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The debil? with nonsignificant lymphocytosis (especially if rash or ity sometimes lingers for 2-3 months. Myco? A glycoprotein vaccine and a protein vaccine are under plasma infection may also present as pharyngitis, though developmentwith the former reducing the rate of infectious lower respiratory symptoms usually predominate. Neither vac? sensitivity syndrome induced by carbamazepine or phe? cine is currently commercially available. Treatment (Duncan disease), lymphomatoid granulomatosis, and a fatal T cell lymphoproliferative disorder in children. After primary infection, the virus remains latent in treating more than two-thirds of cases. Transmission occurs through sexual contact, while peripheral T cell lymphomas and diffse large B cell breastfeeding, blood products, or transplantation; it may lymphomas are more common in the elderly due to waning also occur person-to-person (eg, day care centers) or be immunity. Transmission is much higher from mothers with primary Severe thrombocytopenia; significant hemolysis. About l0% ofinfected newborns will be symptomatic with Airway obstruction from severe adenitis. Age-specifc prevalence of Epstein-Barr In immunocompromised persons, solid organ and virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition. Epstein-Barr virus in systemic autoimmune the first 100 days afterward) and in particular when graf? diseases. Epstein-Barr virus infection and posttransplant on the serostatus of the donor and recipient, disease may lymphoproliferative disorder. Symptoms and Signs ventriculoencephalitis (suspected with ependymitis), and focal encephalitis. Perina? confrmed by presence of the virus in amniotic fuid or an tal infection acquired through breastfeeding or blood IgM assay from fetal blood. Complications include mucosal gastrointestinal damage, encephalitis, severe hep? 2. Immunocompetent persons-The acute mononucleo? atitis, thrombocytopenia (on occasion, refractory), the sis-like syndrome is characterized by initial leukopenia; Guillain-Barre syndrome, pericarditis, and myocarditis. Abnormal liver function postsplenectomy, often years later and associated with a tests are common in the first 2 weeks of the disease protracted fever, marked lymphocytosis, and impaired (often 2 weeks after the fever). Reduction of immunosuppression should be attempted when possible (especially for muromonab, aza? D. In situations where histopathologic or immu? artesunate and adoptive immunotherapy. Intravit? tact with respiratory secretions; avoiding kissing young real injections of ganciclovir or foscarnet may be used as children on the face; and avoiding sharing utensils, fo od, adjunct therapy. Treatment is effective in improving and cleansing objects that have been in contact with chil? survival and preventing dissemination. The encephalitis, pneumonia) involves valganciclovir, ganciclo? appropriate management of transplant patients is based on vir with foscarnet, and cidofovir reserved for treatment of the serostatus of the donor and the recipient. Acyclovir ary prophylaxis is typically maintained until immune res? may also be used. Ganciclovir, cidofovir, and foscarnet (but not acyclovir) appear to be clinically Boekh M et a!. Exposure 10-14 days before onset in an unvacci? cause of exanthema subitum (roseola infantum, sixth dis? nated patient. Prodrome of fever, coryza, cough, conjunctivitis, children under 2 years of age and is a major cause ofinfantile malaise, irritability, photophobia, Koplikspots. Rash: brick red, irregular, maculopapular; onset tions) and with acute liver failure. Most cases of reactivation, however, 1A general guide for vaccine preventable diseases is available at occur in immunocompromised persons. General Considerations Hyperpigmentation remains in fair-skinned individuals and severe cases. Measles isa reportable acute systemic paramyxoviral infec? Other fndings in measles include pharyngeal ery? tion transmitted by inhalation of infective droplets. It is a thema, tonsillar yellowish exudate, coating of the tongue in major worldwide cause of pediatric morbidity and mortal? the center with a red tip and margins, moderate general? ity, although vaccination programs successfully reduced ized lymphadenopathy and, at times, splenomegaly. Columbia in at least 5 outbreaks with 113 (60%) part of a Proteinuria is often observed. Although technically diffi? multi-state outbreak associated with an amusement park in cult, virus can be cultured from nasopharyngeal washings Southern California. The virologic clearance of measles be decreasing in four of six World Health Organization can take months, leading to false-positive results. It is highly conta? Measles is usually diagnosed clinically but may be mis? gious and communicability is greatest during the preemp? taken for other exanthematous infections (Table 32-2). Despite high community vaccination coverage, measles may be more prevalent than is recognized. Central Nervous System of suspected measles infection is especially important in countries that report the elimination of measles. Higher rates of encephalitis occur in adoles? cinated preschool children in dense urban areas, and sport? cents and adults than in school-aged children. Its onset is ing event participants emphasize the need for specific usually 3-7 days after the rash. There is an appreciable mortality (10 20%) and morbidity (33% of survivors are left with A. Coryza (nasal obstruction, sneez? occur after measles vaccination in patients with inadequate ing, and sore throat) resemblesthat seen with upper respira? cellular immunity but is associated with isolation of the tory infections. They appear about 2 days before the rash and last acute progressive encephalitis (subacute measles encepha? 1-4 days as tiny "table salt crystals" on the buccal mucosa litis), characterized by seizures, neurologic deficits, and opposite the molars and vaginal membranes. The rash lasts stupor progressing to death, can occur among immuno? for 3-7 days and fades in the same manner it appeared. In the last decade, the case-fatality rate in the United States stayed around 3 per 1000 reported cases, with Early in the course of the disease, bronchopneumonia or deaths principally due to encephalitis (15% mortality rate) bronchiolitis due to the measles virus may occur in up to and secondary bacterial pneumonia. Deaths in the devel? 5% ofpatients and result in serious respiratory difficulties. Secondary Bacterial Infections In the United States, children receive their first vaccine Immediately following measles, secondary bacterial infec? dose at 12-15 months and a second at age 4-6 years, prior tion, particularly cervical adenitis, otitis media (the most to entry into school. The clustering of unvaccinated individuals also increases the likelihood of an outbreak. Susceptibility to Diarrhea and protein-losing enteropathy (prodromal rectal measles is 2. Other complications include conjunctivitis, keratitis, and American students beyond high school and medical otosclerosis. General Measures Health care workers, immigrants, and refgees should be screened and vaccinated if necessary regardless of date of the patient should be isolated for the week following onset birth. International travelers (if immunocompetent and of rash and kept at bed rest until afebrile. Treatment is born afer 1956) to the developing world and teachers symptomatic including antipyretics and fuids as needed. Vitamin A, 200,000 units/day orally for 2 days (the benefit At 6 months of age, more than 99% of infants of vacci? being maintenance of gastrointestinal and respiratory epi? nated women and 95% of infants of naturally immune thelial mucosa) reduces pediatric morbidity (diarrhea, night women lose maternal antibodies. Therefore, in outbreaks blindness, xerophthalmia) and measles-associated mortality that include infants less than 1 year of age, initial vaccina? for infants between 6 months and 5 years of age, although tion may be given at 6 months, with repeat at 15 months. Measles tutions, or colleges and universities, revaccination is prob? virus is susceptible to ribavirin in vitro and has been used in ably indicated for all, in particular for students and their selected severe cases of pneumonitis (35 mg/kg/day intrave? siblings born after 1956who do not have documentation of nously in three divided doses for 2 days, followed by 20 mg/ immunity as defined above. Susceptible personnel who kg/day intravenously in three divided doses for 5 days). Treatment of Complications regardless of whether they were vaccinated or given Secondary bacterial infections, including pneumonia, are immune globulin. If measles develops in these persons, treated with appropriate antibacterial antibiotics. When susceptible individuals are exposed to measles, Repeated studies fail to show an association between live virusvaccine can prevent disease if given within 5 days vaccination and autism.

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Intervention (no real-time characterisation) A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection. High Comparator (histopathology not compared definition plus colonoscopy combined with i-scan tone enhancement vs. Dig Liver in size) Dis 2014;46: 991?6 Hoffman A, Sar F, Goetz M, Tresch A, Mudter J, Biesterfeld S, et al. Intervention (detection only, no Comparative study of conventional colonoscopy and pan-colonic narrow characterisation) band imaging system in the detection of neoplastic colonic polyps: a randomized, controlled trial. Pol Arch Med Wewn 2013;123: 519?25 in size) Kaltenbach T, Sano Y, Friedland S, Soetikno R. Increased detection of Intervention (detection only, no colorectal polyps in screening colonoscopy using high definition i-scan characterisation) compared with standard white light. Differentiating Intervention (used magnification) small polyp histologies using real-time screening colonoscopy with Fuji Intelligent Color Enhancement. Kominami Y, Yoshida S, Tanaka S, Sanomura Y, Hirakawa T, Raytchev B, Intervention (used magnification) et al. Computer-aided diagnosis of colorectal polyp histology by using a real-time image recognition system and narrow-band imaging magnifying colonoscopy. Intervention (used magnification) Endoscopic trimodal imaging detects colonic neoplasia as well as standard video endoscopy. Feasibility and Patient group (polyposis syndromes accuracy of confocal endomicroscopy in comparison with narrow-band included) imaging and chromoendoscopy for the differentiation of colorectal lesions. Am J Gastroenterol 2012;107: 543?50 Kumar S, Fioritto A, Mitani A, Desai M, Gunaratnam N, Ladabaum U. A Intervention (used magnification) prospective dual-center proof-of-principle study evaluating the incremental benefit of narrow-band imaging with a fixed zoom function in real-time prediction of polyp histology. Does Intervention chromoendoscopy with structure enhancement improve the colonoscopic adenoma detection rate? The role of standard Intervention videochromocolonoscopy in distinguishing adenomatous from nonadenomatous diminutive colorectal polyps. Acta Clinica Croatica 2001;40: 197?201 Machida H, Sano Y, Hamamoto Y, Muto M, Kozu T, Tajiri H, et al. Narrow Intervention (used magnification) band imaging in the diagnosis of colorectal mucosal lesions: a pilot study. Endoscopy 2004;36: 1094?8 Mayr M, Treszl A, Balzer K, Wegscheider K, Aschenbeck J, Aminalai A, et al. Outcomes Endoscopic versus histological characterisation of polyps during screening colonoscopy Guido Schachschal,1. Improved detection of Outcomes proximal colon adenomas with i-scan in comparison to high-definition white light endoscopy. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 283 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Int J in size) Colorectal Dis 2012;27: 331?6 Sakamoto T, Matsuda T, Aoki T, Nakajima T, Saito Y. Time saving with Intervention (used magnification) narrow-band imaging for distinguishing between neoplastic and non neoplastic small colorectal lesions. J Gastroenterol Hepatol 2012;27: 351?5 Sakatani A, Fujiya M, Tanaka K, Dokoshi T, Fujibayashi S, Ando K, et al. Accuracy of visual prediction of pathology of Intervention colorectal polyps: how accurate are we? Intervention (used magnification) Narrow-band imaging with dual focus magnification in differentiating colorectal neoplasia. Comparative study of Intervention (not real time) conventional colonoscopy, chromoendoscopy, and narrow-band imaging systems in differential diagnosis of neoplastic and nonneoplastic colonic polyps. Am J Gastroenterol 2006;101: 2711?16 Szura M, Pasternak A, Bucki K, Urbanczyk K, Matyja A. Two-stage optical Intervention (used magnification) system for colorectal polyp assessments. Value of magnifying endoscopy in classifying colorectal polyps based on vascular pattern. Endoscopy 2010;42: 22?7 Togashi K, Osawa H, Koinuma K, Hayashi Y, Miyata T, Sunada K, et al. A Intervention (used magnification) comparison of conventional endoscopy, chromoendoscopy, and the optimal band imaging system for the differentiation of neoplastic and non-neoplastic colonic polyps. Time requirements and health effects of participation in colorectal cancer screening with colonoscopy or computed tomography colonography in a randomized controlled trial. World J Gastroenterol 2011;17: 666?70 in size) a the first item in the flow chart that the reviewers agreed would be a reason for exclusion was recorded as the primary reason for exclusion. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 285 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Reviewers decided during study selection that it was unclear if these conference abstracts met the inclusion criteria for the review. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 287 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Lancet Oncol 2009;10: 1171?8 Chandran S, Parker F, Lontos S, Vaughan R, Efthymiou M. Using real-time endoscopic assessment of polyp histology to predict surveillance intervals. The cost impact of in vivo diagnosis of diminutive polyps: Abstract experience from a screening endoscopy programme. The cost impact of in-vivo diagnosis of diminuitive colonic Abstract polyps in screening colonoscopy: results from a large prospective western study. Optical Abstract diagnosis of small colorectal polyps with resect and discard strategy is cost saving. Economic value of narrow band imaging versus white Outcome light endoscopy for the characterization of diminutive polyps in the colon: systematic literature review and cost-consequence model. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 289 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. No additional examination and training time or any other additional material costs were assumed. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 291 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Population characteristic taken from a database of 10,060 consecutive colonoscopies from 1999 to 2004 13 Intervention(s), No pathological examination of diminutive polyps (resect and discard) vs. The number needed to harm because of perforation, major bleed or missed cancer is 7979. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 293 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 295 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. What currency are costs expressed in and does the publication give the base year to which those costs relate? Analytical perspective What is the perspective adopted for the evaluation health service, health and personal social services, third-party payer, societal. Effectiveness Were the effectiveness data derived from a single study, a review/synthesis of previous studies or expert opinion? Give the size of the treatment effect used in the evaluation Parameter Value Source Diminutive polyp optical diagnosis feasibility rate 75. Indirect costs (costs as a result of lost productivity, unpaid inputs to patient care) Were indirect costs included? This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that 297 suitable acknowledgement is made and the reproduction is not associated with any form of advertising. The model begins with an at-risk cohort of 551,000 people and increases this population by 20% in each of the 7 years of the model. Colonoscopy identifies three mutually exclusive patient groups: patients with no polyps, patients with one or more polyps of? Extract transition probabilities for (natural history/disease progression) model and show sources (or refer to table in text) the model does not include disease progression. Give results of any statistical analysis of the results of the evaluation Not applicable.

Diseases

  • Hydrops ectrodactyly syndactyly
  • Glycosuria
  • Adrenogenital syndrome
  • Punctate acrokeratoderma freckle like pigmentation
  • Grand Kaine Fulling syndrome
  • Alexander disease
  • Gemss syndrome
  • Dentinogenesis imperfecta
  • Epidermolysis bullosa
  • Methylcobalamin deficiency cbl G type

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Genetic influences have some role in the v) Ulcer-cancer etiology of gastric cancer. Not more than 4% of patients of In addition to the above classification, gastric gastric cancer have a family history of this disease. A, Conventional classification, showing correlation of the macroscopic subtypes with the main histological patterns. Infiltrating (formerly diffuse type) carcinomas have certain related terms as under: poorly-defined invasive border. The tumour cells are loose Epithelial dysplasia is cellular atypia seen in intestinal and invade singly or in small group. The diagnosis of this carcinoma crosses the basement membrane into the condition has been made possible by extensive work on muscularis propria or beyond, it is referred to as advanced histogenesis of gastric cancer by Japanese pathologists by gastric carcinoma. It is seen more commonly in the region of Type I : Polypoid type gastric canal (Fig. Direct spread by local extension is the most well-differentiated adenocarcinomas, commonly papillary common feature of gastric carcinoma. The involvement may more commonly, referred to as Krukenberg tumours (Chapter be localised to pyloric antrum, or diffuse affecting whole 24). Submucosal spread occurs more often upwards into the of the stomach from the cardia to pylorus. The lumen of oesophagus due to continuity of the layers of stomach with the stomach is reduced. There are no ulcers but rugae are those of oesophagus, while the spread downwards into the prominent (Fig. The tumour ring cell carcinoma, extensively infiltrating the stomach may directly involve other neighbouring structures and wall, but due to marked desmoplasia cancer cells may be organs like lesser and greater omentum, pancreas, liver, difficult to find (Fig. The groups like masses having gelatinous appearance due to secretion of lymph nodes involved are along the lesser and greater of large quantities of mucus. Blood spread of gastric chronic gastric ulcer is a rare occurrence (less than 1%). Location Commonly lesser curvature of pylorus and antrum Commonly greater curvature of pylorus and antrum 5. Gross features a) Size Small Large b) Shape Regular Irregular c) Mucosal folds Radiating Interrupted d) Ulcer bed Haemorrhagic Necrotic 6. Therapy Responds well to medical therapy Usually does not respond to medical therapy 558 Figure 20. Therefore, the prognosis is generally iv) Loss of appetite (anorexia) poor; 5-year survival rate being 5-15% from the time of v) Anaemia, weakness, malaise. However, 5-year the most common complication of gastric cancer is survival rate for early gastric carcinoma is far higher haemorrhage (in the form of haematemesis and/or melaena); (93-99%) and hence the need for early diagnosis of the others are obstruction, perforation and jaundice. Gastric carcinoma, gross appearance of subtypes and their corresponding dominant histological patterns. Other Carcinomas Carcinoid Tumour Besides the various morphologic patterns of adenocarcinoma Carcinoid tumours are rare in the stomach and are usually just described, other carcinomas that occur rarely in the non-argentaffin type but argentaffinomas also occur. Their stomach are: adenosquamous carcinoma, squamous cell behaviour is usually malignant; they are described on carcinoma and undifferentiated carcinoma, all of which are page 579. Lymphomas of Gut Leiomyosarcoma Primary gastrointestinal lymphomas are defined as lymphomas arising in the gut without any evidence of Leiomyosarcoma, though rare, is the commonest soft tissue systemic involvement at the time of presentation. Grossly, the tumour may be of variable size but is usually Gastric lymphomas constitute over 50% of all bowel quite large, pedunculated and lobulated mass into the lymphomas; other sites being small and large bowel in lumen. Prognosis of primary gastric Microscopically, leiomyosarcoma is characterised by high lymphoma is better than for intestinal lymphomas. Tumour is lymphoma of stomach is the most common malignant gastric usually well-differentiated. Clinical manifestations of gastric lymphomas may be Leiomyoblastoma (Epithelioid Leiomyoma) similar to gastric carcinoma. Age incidence for lymphomas of the gastrointestinal tract is usually lower than that for this is a rare tumour, the behaviour of which is intermediate carcinoma (30-40 years as compared to 40-60 years in gastric between clearly benign and malignant tumour. Microscopically, it is characterised by round to polygonal Grossly, gastric lymphomas have 2 types of appearances: cells with clear perinuclear halos. Diffusely infiltrating type, producing thickening of the determines the biological behaviour of the tumour. The luminal surface of the stomach in the region of pyloric canal shows an elevated irregular growth with ulcerated surface and raised margins. B, Malignant cells forming irregular glands with stratification are seen invading the layers of the stomach wall. The wall of the stomach in the region of pyloric canal is markedly thickened and fibrotic while the mucosal folds are lost. D, Microscopy shows characteristic signet ring tumour cells having abundant mucinous cytoplasm positive for mucicarmine (inbox). Histologically, the small bowel is identified by recognition Low-grade small lymphocytic well-differentiated B-cell of villi. The serosa is the outer covering of the small bowel which frequency (arising from Mucosa Associated Lymphoid is complete except over a part of the duodenum. The muscularis propria is composed of 2 layers of smooth the blood supply of the whole of small intestine, except 561 muscle tissue?outer thinner longitudinal and inner thicker the first part of the duodenum, is by the superior mesenteric circular layer. These muscles are functionally important for artery which supplies blood by mesenteric arterial arcades peristalsis. The main functions of the small intestine are digestion and absorption so that ultimately nutrients passing into the 3. The submucosa is composed of loose fibrous tissue with bloodstream are utilised by the cells in metabolism. It is Intestinal atresia is congenital absence of lumen, most supported externally by thin layer of smooth muscle fibres, commonly affecting the ileum or duodenum. The mucous membrane is thrown into segment has a blind end which is separated from distal folds or plicae which are more in the jejunum and less in the segment freely, or the two segments are joined by a fibrous ileum, thus increasing the absorptive surface enormously. The condition must be recognised early and treated the absorptive surface is further increased by the intestinal surgically, as otherwise it is incompatible with life. Villi are finger-like or leaf-like projections which contain 3 types of cells: Intestinal stenosis is congenital narrowing of the lumen i) Simple columnar cells. Intestinal segment due to the presence of brush border consisting of large above the level of obstruction is dilated and that below it is number of microvilli. It is almost always lined by small cells, on the other hand, require the addition of exogenous intestinal type of epithelium; rarely it may contain islands of reducing substance for staining). These are commonly multiple (diverticulosis), frequently located on the hypothalamus, pituitary and sympathetic ganglia. The deeper layer of the mucosa of the small flexure and the middle of transverse colon). Due to failure of intestine elsewhere contains intestinal glands or crypts of normal rotation of midgut, the following consequences can Lieberkuhn. They are lined by columnar cells, goblet cells, occur: endocrine cells and Paneth cells. B, Resected segment of the small intestine shows an outpouching which on section is seen communicating with the intestinal lumen. The causes of intestinal obstruction can be fibrous adhesions and bands may be without any preceding classified under the following 3 broad groups: peritoneal inflammation and are of congenital origin. It can occur as a result of the complete intestinal obstruction by outside pressure on the following causes: bowel wall. Meconium in mucoviscidosis External hernia is the protrusion of the bowel through a Roundworms defect or weakness in the peritoneum. Gallstones, faecoliths, foreign bodies Internal hernia is the term applied for herniation that Ulceration induced by potassium chloride tablets does not present on the external surface. Two major factors involved in the formation of a hernia ii) External compression: are as under: Peritoneal adhesions and bands i) Local weakness which may be congenital. Volvulus ii) Increased intra-abdominal pressure that is produced by Intra-abdominal tumour. Obstruction of the superior mesen Direct when hernia passes medial to the inferior teric artery or its branches may result in infarction causing epigastric artery and it appears through the external paralysis. Thrombosis Indirect when it follows the inguinal canal lateral to the Embolism inferior epigastric artery.

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However, in general, 2 factors appear to definite treatment is available for hereditary and idiopathic play significant role in the pathogenesis of anaemia in chronic types of sideroblastic anaemias. These are: defective red cell production and reduced administered routinely to all cases of sideroblastic anaemia red cell lifespan. Though there is abun Differential diagnosis of various types of hypochromic dance of storage iron in these conditions but the amount of anaemias by laboratory tests is summarised in Table 12. A defect in One of the commonly encountered anaemia is in patients of the transfer of iron from macrophages to the developing a variety of chronic systemic diseases in which anaemia erythroid cells in the marrow leads to reduced availability develops secondary to a disease process but there is no actual of iron for haem synthesis despite adequate iron stores, invasion of the bone marrow. In general, anaemia in chronic of erythropoieitn by inflammatory cytokines at some stage disorders is usually normocytic normochromic but can have in erythropoiesis, and hepcidin which is the key iron mild degree of microcytosis and hypochromia unrelated to regulatory hormone. Decreased survival of circulating red cells in chronic renal disease is attributed to A number of factors may contribute to the development of hyperplastic mononuclear phagocyte system. Since cell division is slow but cytoplasmic development progresses normally, the nucleated red cell precursors tend to be larger which Ehrlich in 1880 termed megaloblasts. Megaloblasts are both morphologically and functionally abnormal with the result that the mature red cells formed from them and released into the peripheral blood are also abnormal in shape and size, the most prominent abnormality being macrocytosis. Measurement of erythrocyte survival anaemia, an outline of vitamin B and folic acid metabolism 12 generally reveals mild to moderate shortening of their is given for a better understanding of the subject. Examination of the marrow generally of vitamin B12 and folic acid are summarised in Table12. Cases of chronic infection often organometallic compound having a cobalt atom situated have myeloid hyperplasia and increase in plasma cells. The only dietary sources of vitamin B12 are foods between true iron-deficiency anaemia and iron-deficient of animal protein origin such as kidney, liver, heart, muscle erythropoieisis in anemia of chronic diseases. In addition, certain other and vegetables contain practically no vitamin B unless 12 plasma proteins called phase reactants? are raised in contaminated with bacteria. Cooking has little effect on its patients with chronic inflammation, probably under the activity. Body stores 2-3 mg (enough for 2-4 yrs) 10-12 mg (enough for 4 months) 304 thus, the humans are entirely dependent upon dietary sources. After ingestion, vitamin B12 in food is released and forms a stable complex with gastric R-binder. Vitamin B12 plays an important role in general action as co-enzyme, polyglutamates must be reduced to cell metabolism, particulary essential for normal dihydro and tetrahydrofolate forms. Folate exists in different plants, bacteria and 12 biochemical reactions in the body: animal tissues. Its main dietary sources are fresh green leafy vegetables, fruits, liver, kidney, and to a lesser extent, muscle Firstly, as methyl cobalamin (methyl B12) in the methylation meats, cereals and milk. Folate is labile and is largely of homocysteine to methionine by methyl tetrahydrofolate destroyed by cooking and canning. The homocysteine-methionine reaction is closely synthesised by bacteria in the human large bowel is not linked to folate metabolism (Fig. However, Secondly, as adenosyl cobalamin (adenosyl B12) in propionate absorption depends upon the form of folate in the diet. Synthetic folic Adenosyl B12 acid preparations in polyglutamate form are also absorbed Propionyl CoA > Methyl malonyl CoA > Succinyl CoA as rapidly as mono and diglutamate form because of the absence of natural inhibitors. An alternative hypothesis of inter-relationship a carrier protein, it is reconverted to polyglutamate (see of B12 and folate is the formate-saturation hypothesis. Normally, folate is lost from the sweat, Etiology and Classification of Megaloblastic Anaemia saliva, urine and faeces. It acts as a co-enzyme for 2 important bio anaemia is classified into 3 broad groups: vitamin B12 chemical reactions involving transfer of 1-carbon units (viz. This reaction is Indian Hindus and breast-fed infants have dietary lack of linked to vitamin B metabolism (Fig. Gastrectomy by lack of intrinsic factor, and small 12 these biochemical reactions are considered in detail intestinal lesions involving distal ileum where absorption of below together with biochemical basis of the megaloblastic vitamin B12 occurs, may cause deficiency of the vitamin. Deficiency of vitamin B12 takes at least 2 years to develop when the body stores are totally depleted. Folate deficiency is more often the basic biochemical abnormality common to both vitamin due to poor dietary intake. This reaction requires the presence such as methotrexate and pyrimethamine; alcohol, congenital enzyme deficiencies. In addition to the cardinal features mentioned and in various disease states, chronic alcoholism, and excess above, patients may have various other symptoms. Combined deficiency of vitamin B Laboratory Findings 12 12 and folate may occur from severe deficiency of vitamin B12 the investigations of a suspected case of megaloblastic because of the biochemical interrelationship with folate anaemia are aimed at 2 aspects: metabolism. In addition to deficiency of vitamin blood picture, red cell indices, bone marrow findings, and B and folate, megaloblastic anaemias may occasionally be biochemical tests. Based on these principles, the following scheme of investigations is followed: Clinical Features A. General Laboratory Findings Deficiency of vitamin B12 and folate may cause following clinical manifestations which may be present singly or in 1. Esti combination and in varying severity: mation of haemoglobin, examination of a blood film and evaluation of absolute values are essential preliminary 1. Typically, the patient has a smooth, beefy, red concentration may be of a variable degree. Vitamin B12 deficiency, parti cularly in patients of pernicious anaemia, is associated with macrocytosis can also be seen in several other disorders significant neurological manifestations in the form of such as: haemolysis, liver disease, chronic alcoholism, subacute combined, degeneration of the spinal cord and hypothyroidism, aplastic anaemia, myeloproliferative peripheral neuropathy (Chapter 30), while folate deficiency disorders and reticulocytosis. The underlying demonstrates marked anisocytosis, poikilocytosis and pathologic process consists of demyelination of the peripheral presence of macroovalocytes. The reticulocyte count is generally ataxia, poor finger coordination and diminished reflexes. The total white blood cell count may be be decreased and show abnormal morphology such as reduced. Presence of characteristic hypersegmented hypersegmented nuclei and agranular cytoplasm. Prussian blue staining for iron in the blood film should raise the suspicion of megaloblastic marrow shows an increase in the number and size of iron anaemia. Significant findings of marrow blood and marrow investigations and specific tests to examination are as under (Fig. The marrow is hypercellular with following biochemical abnormalities are observed in cases a decreased myeloid-erythroid ratio. Megaloblasts a result of ineffective erythropoiesis causing marrow cell are abnormal, large, nucleated erythroid precursors, breakdown. Special Tests for Cause of Specific Deficiency stains lightly, while the haemoglobinisation of the cytoplasm proceeds normally or at a faster rate i. Megaloblasts with abnormal mitoses laboratories, currently automated multiparametric, may be seen. Features of ineffective erythropoiesis such random access analysers are employed based on separa as presence of degenerated erythroid precursors may be tion techniques by chemiluminescence and enzyme-linked present. The normal Patients with pernicious anaemia have abnormal test range of vitamin B12 in serum is 280-1000 pg/ml. Assay of vitamin B12 in patients absorb vitamin B12 in water as was stipulated in blood can be done by 2 methods?microbiological assay the original Schilling test. In this test, the serum sample to causing malabsorption, the test is repeated after a course be assayed is added to a medium containing all other of treatment with antibiotics or anti-inflammatory drugs. The medium along with another way of distinguishing whether megaloblastic microorganism is incubated and the amount of vitamin anaemia is due to cobalamine or folate is by serum B12 is determined turbimetrically which is then compared determination of methylmalonic acid and homocysteine with the growth produced by a known amount of vitamin by sophisticated enzymatic assays. Several organisms have been used for this test such cobalamine deficiency, while in folate deficiency there is as Euglena gracilis, Lactobacillus leichmannii, Escherichia coli only elevation of homocysteine and not of methylmalonic and Ochromonas malhamensis. Values of 4 ng/ml or less are generally considered to be diagnostic of folate ii) Radioassay. These tests are more sensitive and have the formerly for assessing folate status but it is less specific advantage over microbiologic assays in that they are and less sensitive than the serum assays. Radioisotope used for labeling B12 is either Co 57 estimated by 2 methods?microbiological assay and or Co. Other pathologic changes are Most cases of megaloblastic anaemia need therapy with secondary to vitamin B deficiency and include 12 appropriate vitamin. This includes: hydroxycobalamin as megaloblastoid alterations in the gastric and intestinal intramuscular injection 1000? Blood transfusion should be avoided the disease has insidious onset and progresses slowly.

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After the swelling has Septic arthritis resolved, the patient can walk with a "stiff-knee" gait or Gout or other inflammatory disorder quadriceps avoidance gait because of the instability. More Lateral knee pain importantly, patients describe symptoms of instability Lateral meniscal injury while performing side-to-side maneuvers or descending Iliotibial band syndrome (pain superficially along the distal stairs. Stability tests assess the amount oflaxity of the knee iliotibial band near lateral femoral condyle or lateral tibial while performing side-to-side maneuvers or descending insertion) stairs. The Lachman test (84-87% sensitivity and 93% Lateral collateral ligament sprain (rare) specificity) is performed with the patient lying supine and Posterior knee pain the knee fexed to 20-30 degrees (Table 41-9). The clini? Popliteal (Baker) cyst cian grasps the distal femur from the lateral side and the Osteoarthritis proximal tibia with the other hand on the medial side. Performed with the patient lying supine, and the Fu fiJrur knee flexed to 20-30 degrees. The examiner " graspsthe distal femurfrom the lateral side, and the proximal tibia with the other hand on the medial side. With the knee in neutral position, sta? bilize the femur, and pull the tibia anteriorly using a similar force to lifing a 10-15 pound weight. Excessive anterior translation of the tibia com? pared with the other side indicates injury to the anterior cruciate ligament. Anterior drawer Performed with the patient lying supine and the knee flexed to 90 degrees. A positivetest finds anterior cruciate ligament laxity compared with the unafected side. With one hand, the clinician should hold the ankle while the other hand is supporting the leg at the level of the knee joint. A valgus stress is applied at the ankle to determine pain and laxity of the medial collateral ligament. The test should be performed at both 30 degrees and at 0 degrees of knee extension. For the right knee, the clinician should be standing on the right side of the patient. The left hand ofthe examiner should be holding the ankle while the right hand is supporting the lateral thigh. A varus stress is applied at the ankle to determine pain and laxity of the lateral collateral ligament. Because of gravity, the posterior cruciate ligament-injured knee will have an obvious set-off at the anterior tibia that is"sagging" posteriorly. Posterior drawer the patient is placed supine with the knee flexed at 90 degrees (see Anterior drawer figure above). The clinician can grasp the proximal tibia with both hands and push the tibia posteriorly. The movement, indicating laxity and possible tear of the posterior cruciate ligament, is compared with the uninjured knee. To test the lateral meniscus, the same maneuver is repeated while rotating the foot internally (53% sensitivity and 59-97% specificity). The knee is then flexed maximally with internal or external rotation ofthe lower leg. The knee can then be rotated with the lower leg in internal or external rotation to capture thetorn meniscus underneath the condyles. A positive test is pain overthe joint line while the knee is being flexed and internally or externally rotated. Patellofemoral joint test Apprehension sign Suggests instability of the patellofemoral joint and is positive when the patient becomes apprehensive when the patella is deviated laterally. Treatment the proximal tibia with both hands around the calf and Most young and active patients will require surgical recon? pulls anteriorly. The patient must remain very relaxed to have a cadaver graft (allograft) to arthroscopically reconstruct the positive test. Different patients groups experienced improved results with specific surgical graft choices. This is called a "Segond" fracture and is pathogno? patients or those with a very sedentary lifestyle. Longitudinal patient may have limited range of motion due to pain, espe? studies have demonstrated that nonoperative management cially during the first 2 weeks following the injury. Treatment for acute anterior cruciate ligament right hand is supporting the lateral thigh. The American Academy of Orthopaedic Surgeons and the knee shows instability at 30 degrees ofknee fexion. Collateral ligament Injury Radiographs are usually nondiagnostic except for avul? sion injuries. However, radiographs should be used to rule out fractures that can occur with collateral ligament injuries. It is usually injured 2 injuries, the patient can usually bear weight as tolerated with a valgus stress to the partially fexed knee. Patients can ments are extra-articular, injuries to these ligaments may weight-bear but only with the knee locked in extension not lead to any intra-articular effusion. The motion can then be increased with the may have difficulty walking initially, but this can improve brace unlocked. Usually follows an anterior trauma to the tibia, the knee extension; the patient uses crutches for ambula? such as a dashboard injury during a motorvehicle tion. Meniscus Injuries should be high suspicion for neurovascular injuries and a thorough neurovascular examination of the limb should be performed. Most meniscus injuries occur with acute injuries rior drawer test (90% sensitivity and 99% specificity) (usually in younger patients) or repeated microtrauma, (Table 41-9). The patient is placed supine with the knee such as squatting or twisting (usually in older patients). In a normal knee, the anterior tibia should be positioned about 10 mm anterior to the femoral condyle. He or she may complain of catching since the tibia is subluxed posteriorly in a sagged position or locking of the meniscal fragment. Physical findings can and can be abnormally translated forward, yielding a include effusion or joint line tenderness. Meniscus tears rarely lead to the sus sham surgery for a degenerative meniscal tear. Provocative tests, including the McMurray test, the modified McMurray test, and the Thessaly test, can be performed to confirm the diagnosis (Table 41-9). Most symptomatic meniscus tears cause pain with deep squat? ting and when waddling (performing a "duck walk"). Pain experienced with bending activities (kneel? ing, squatting, climbing stairs). High signal through the meniscus (bright on T2 images) represents a meniscal tear. The pain affects any or all ofthe anterior knee structures, including the medial and Conservative treatment can be used for degenerative tears lateral aspects of the patella as well as the quadriceps and in older patients. Forces on the patellofemoral joint increase up to trolled trial showed that physical therapy compared to three times body weight as the knee fexes to 90 degrees arthrosopic partial meniscectomy had similar outcomes at (eg, climbing stairs), and five times body weight when 6 months. However, 30% of the patients who were assigned going into full knee fexion (eg, squatting). Abnormal to physical therapy alone underwent surgery within patellar tracking during flexion can lead to abnormal 6 months. When the patient has arthroscopic surgery has no benefit over sham operation ligamentous hyerlaxity, the patella can sublux out of the for patients who have meniscus tears in osteoarthritic groove, usually laterally. A 2013 randomized controlled study has further ated with muscle strength and flexibility imbalances as well demonstrated no beneft for arthroscopic meniscectomy as altered hip and ankle biomechanics. Clinical Findings Acute tears in young and active patients with signs of internal derangement and without signs of arthritis on A. Symptoms and Signs imaging can be best treated arthroscopically with meniscus Patients usually complain of pain inthe anterior knee with repair or debridement. When to Refer can sometimes bereferred to the posterior knee or over the medial or lateral inferior patella. Symptoms may begin If the patient has symptoms of internal derangement after a trauma or after repetitive physical activity, such as suspected as meniscus injury.

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Partial exchange transfusion may be administered via an umbilical venous catheter. If all other disease entities are ruled out, these infants may indeed be polycythemic and hyperviscous. Use clinical judgment and institutional guidelines to decide whether or not this infant should have a partial exchange transfusion. Observe for complications of polycythemia and disorders that are more common in polycythemic infants. Note that a partial exchange transfusion decreases viscosity and ameliorates most symptoms but has not been shown to significantly affect or improve long-term neurologic outcomes. Hypoplastic left heart syndrome may cause poor perfusion and a mottled appearance. Associated risk factors for sepsis are premature rupture of membranes or maternal infection and fever. If the temperature is lower than normal, cold stress or hypothermia associated with sepsis may be present. Hypotension may cause poor perfusion (see normal blood pressure values in Appendix C). Decreased urine output (<2 mL/kg/h) may indicate depleted intravascular volume or shock. Is the liver enlarged and are metabolic acidosis, a poor peripheral pulse rate, and gallop present? These problems are signs of failure of the left side of the heart (eg, hypoplastic left heart syndrome). If mechanical ventilation is being used, are chest movements adequate and are blood gas levels improving? Left-sided heart lesions such as hypoplastic left heart syndrome, coarctation of the aorta, and aortic stenosis. Cutis marmorata, a marbling pattern of the skin (the infant appears poorly perfused), may occur in a healthy infant, especially when exposed to cold stress. The cardiovascular and pulmonary examinations are important because they may suggest cardiac problems or pneumothorax. Signs of trisomy 18 include micrognathia and overlapping digits; signs of trisomy 21 include a single palmar transverse crease and epicanthal folds. These studies reveal inadequate ventilation or the presence of acidosis, which may be seen in sepsis or necrotizing enterocolitis. If sepsis is suspected, a complete workup should be considered, especially if antibiotics are to be started. This study can be performed quickly to help determine whether or not a pneumothorax is present (see Chapter 51, Pneumothorax). A chest x-ray study should be obtained if pneumonia, pneumothorax, congenital heart lesion, or hypoventilation is suspected. In left-sided heart lesions, the x-ray film shows cardiomegaly with pulmonary venous congestion (except in hypoplastic left heart syndrome, in which the size of the heart may be normal). If a view taken during lung expansion shows that the lungs are down only to the sixth rib or less, hypoventilation should be considered. A flat plate x-ray film of the abdomen should be obtained if necrotizing enterocolitis is suspected. In hypoplastic left heart syndrome, a large right ventricle and a small left ventricle are seen on the echocardiogram, and there is failure to visualize the mitral or aortic valve. While checking vital signs and quickly examining the patient, order stat blood gas levels and a chest x-ray study. Transillumination of the chest may need to be done if a pneumothorax is suspected. It can be accomplished by means of a radiant warmer or incubator or a heating pad. If the blood pressure is low because of depleted intravascular volume, give crystalloid (normal saline), 10 mL/kg intravenously for 5-10 min. If hypoventilation is suspected, it may be necessary to increase the pressure being given by the ventilator. One method is to increase the pressure by 2-4 cm H2O and then obtain blood gas levels in 20 min. Another method is to use bag-and-mask ventilation, observing the manometer to determine the amount of pressure needed to move the chest. Treat with oxygen, possibly diuretics and digoxin if congestive heart failure is present, and infusion of prostaglandin E1. Surgery is usually indicated in all these patients, except those with hypoplastic left heart syndrome, for whom it is controversial. If this condition is secondary to cold stress, treat the patient as described in section V,B,2. If the condition persists, consider formal karyotyping to rule out trisomies 18 and 21. Should a sepsis workup be done, and should antibiotics be started in either of these newborns? The incidence of sepsis is 1-10 in 1000 live births and 1 in 250 live premature births. Low socioeconomic status and asymptomatic bacteriuria in the mother are associated with increased prematurity and sepsis. The use of fetal scalp electrodes in the intrapartum period increases the risk of infection in the infant. Neonatal risk factors include male sex, twin birth, prematurity, low birth weight, and presence of the metabolic disorder galactosemia (which increases the risk of gram-negative sepsis). Fetal tachycardia (>160 beats/ min), especially sustained, and decelerations (usually late) can be associated with neonatal infection. Prolonged duration of intrauterine monitoring is a risk factor for early-onset group B streptococcal disease. Signs of sepsis include apnea and bradycardia, temperature instability (hypothermia or hyperthermia), feeding intolerance, tachypnea, jaundice, cyanosis, poor peripheral perfusion, hypoglycemia, lethargy, poor sucking reflex, increased gastric aspirates, and irritability. Other signs include tachycardia, shock, vomiting, seizures, abnormal rash, abdominal distention, and hepatomegaly. Studies have shown an increase in maternal intrapartum fever with the use of epidural analgesia. Because of this fever, an increase in sepsis evaluations and antibiotic treatment was found. However, the study did not find that epidurals caused infections or even increased the risk of infections. Complete maternal, perinatal, and birth history should be obtained and reviewed in an attempt to identify risk factors. One study found that affect, peripheral perfusion, and respiratory status were key predictors in sepsis compared with feeding patterns, level of activity, and level of alertness. The total neutrophil count can be calculated, and normal reference ranges can be found in Tables 54-1 and 54-2. Many institutions do not perform this procedure in newborn infants with possible sepsis on day 1 of life because newborns rarely present with a urinary tract infection the first day. Lumbar puncture for cerebrospinal fluid examination is indicated if a decision is made to give antibiotics. This measure is controversial; some institutions perform a lumbar puncture only if the infant has signs of central nervous system infection. If used together, or repeated values become more abnormal, they may help in deciding who should receive antibiotics. Total neutrophil count (is more sensitive than the total leukocyte count but too often normal in case of infection). Total immature neutrophil count (is poorly sensitive; could have a better positive predictive value). Ratio of immature to total neutrophils (I-T) (greatest value relies on good negative predictive value; likelihood of infection is minimal if I-T ratio is normal).

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Fetal Abnormalities in Stillbirths Maceration occurs if there is intrauterine fetal retention after fetal death. Mac eration (Latin macerate to soften by soaking) is characterized by softening and peeling of the skin, discoloration and softening of the viscera, and? The extent of maceration in stillborn fetuses may be a rough indicator of the time interval from fetal death to delivery; however, its rate may be in? Maceration may hinder, but does not negate, the pathological investigation of the stillbirth. Placental changes after fetal death appear to be more constant; if cytotrophoblasts are increased without stromal changes, fetal death has occurred in <7 days. Inner one-half of Moderate desquamation myocardium: loss of nuclear basophilia 36 hours Cranial compression 48 hours Desquamation of >50% of Outer one-half of myocardium: Multifocal stem vessel luminal body loss of nuclear basophilia abnormalities 72 hours Desquamation of >75% of body 96 hours Overlapping cranial sutures Loss of nuclear basophilia in (4?5 days) bronchial epithelial cells and in all liver cells 1 week Widely open mouth Gastrointestinal tract: maximal loss of nuclear basophilia Collapse of calvarium Adrenal glands: maximal loss of nuclear basophilia. Laxity and dislocation of joints Trachea: chondrocyte loss of nuclear basophilia 2 weeks Mummification (dehydration, Extensive vascular luminal change compression, tan color) (see 48-hour findings). External fetal examination: A study of 86 stillborns, Obstet Gynecol 80: 593, 1992. If large may cause: fetal death fetal distress hypovolemic shock anemia with cardiac failure hydrops (Figure 2. This test is based on different acid elution characteristics of fetal and adult hemoglobin. The test should be done routinely in all cases of unexplained stillbirth, fetal distress, and neonatal anemia. Immediate transfusion may be lifesaving, and testing of the mother during the puerperium is still important. The size of the hemorrhage can be calculated on the basis of the percentage of fetal red cells present (number of fetal cells in 2,000 total red cells divided by 20), an estimated average maternal blood volume of 5,800 mL, an average maternal hematocrit of 0. For example, if 5% of the red cells in the maternal circulation are fetal in origin, the size of the hemorrhage is calculated as 5,800? Some postdate newborns have no biochemical, physiologic, or other signs of placental dysfunction. Theskiniswrinkled which, after separation breathes or shows any other evidence of life, such as and meconium stained. In the United States, 20% occur in the African-American population and 9% in the white population. The major complications of prematurity are hyaline membrane disease that may progress to bronchopulmonary dysplasia, necrotizing entero colitis, and germinal matrix and intraventricular hemorrhage. The hand and foot show nails extending beyond the tips of the digits and meconium staining of skin and nails. Very-low-birth weight infants weigh 1,500 g or less and constitute 1% to 2% of all live births. Prematurity and complications of preterm birth tissue and low birth weight result Hyaline membrane disease and bronchopulmonary dysplasia Absence of lanugo hair Intracranial hemorrhage Long nails Necrotizing enterocolitis Abundance of scalp hair Diffuse pulmonary hemorrhage Pale skinwith desquamated 2. Maternal complications of pregnancy Dehydration Age Hypoglycemia Parity Complications of placenta/cord/membrane Smoking Hypertension and preeclampsia Postmaturity Diabetes mellitus Thyrotoxicosis Collagen vascular diseases 7. Severe cerebral edema of brain ina cigarette smoking during pregnancy, vigorous motor activity by the fetus, a newborn who sustained severe birth anoxia. Hypoxic Ischemic Encephalopathy Hypoxic ischemic encephalopathy is the result of perinatal asphyxia usually occurring at or shortly before birth. The cortex, basal ganglia hippocampus, brain stem, and cerebellar Purkinje cells are primarily affected. Initially the cysts were separate from the ventricles, but communication subsequently developed. It usually is a complication of hypoxia in a premature infant but may occur in full-term in fants. Porencephaly Perivascular leukomalacia may progress to porencephaly with coalescence of small cysts to form large cystic spaces that may communicate with the ventri cles. In stage I, the infant manifests abdominal distension, vomiting, increased gas tric residual, lethargy, apnea, bradycardia, or guaiac-positive stools. Surgically manifested by shock, disseminated intravascular coagulation, acidosis, throm resected segment of bowel with hemorrhage bocytopenia, and sometimes intestinal perforation. The bowel is grossly distended, dark purple or black in areas containing extensive hemorrhage; the soft, friable wall may perforate when the involvement is severe and transmural. Perforation occurs at a junction between normal and necrotic bowel or in a devitalized region. In neonates with severe anoxic episodes, blood is diverted to the heart and the brain and the bowel are exposed to severe ischemia. Necrosis of the bowel in some cases may be secondary to mesenteric thromboembolism. Microorganisms isolated from the stools include Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Salmonella, Clostridium perfringens, Clostridium dif? Congenital Malformations Congenital malformations are a leading cause of death in neonates. Causes of neonatal deaths from major organ system anomalies include cardiovascular, pulmonary, renal, central nervous system, musculoskeletal, and gastrointesti nal malformations as well as chromosomal defects and multiple congenital anomaly syndromes. Bacterial infections may result in neonatal pneumonia, menin gitis, or encephalitis. Infant of Diabetic Mother the infant of a diabetic mother is at particular risk for severe hypoglycemia, hyperinsulinemia with pancreatic islet cell hyperplasia, malformations, and Table 2. Complications of Amniocentesis (see Chapter 10) Amniotic Fluid and Meconium Aspiration Amniotic? Meconium aspiration occurs in 5?15% of births and is most common in term or postterm infants. It usually improves within 48 hours of birth, but if severe it carries high mortality. Meconium aspiration syndrome occurs in 9 per 1,000 births; 59% have been attributed to severe acute chorioamnionitis and less frequently to low uteroplacental blood? Occipital diastasis (separation of the squamous and lateral parts of the occipital bone) (Figure 2. The squamous and lateral parts of the occipital bonearewidelyseparatedbycartilageuntilabout36weeks?gestationanddonot fuse until the second year of life. The lower Stimulation of uterine contractions edge of the squamous occipital bone is then displaced and rotated forward. Fetal skin puncture with healing to form small scars or dimples Blood Dyscrasia Peritoneal adhesions Ileal atresia 1. Hemolytic disease of the newborn due to blood group incompatibility Fetal intracranial hemorrhage (Figures 2. Metabolic Disorders (see Chapter 24) Metabolic disorders have been related to unexpected death in newborns. In these disorders, there is usually a normal period immediately after birth fol lowed by hypoglycemia, respiratory dif? Bilirubin staining of basal ganglia (left) and the olivary nuclei (right) inan infant with erythroblastosis fetalis. Bergsjo P: Introducing two international studies on perinatal and infant growth, morbidity and mortality. The variety and complexity of the congenital anomalies found in perinatal and fetal autopsies is endless and the prosector must be prepared to spend the necessary time demonstrating these anomalies. This detailed procedure can be altered to preserve any anomaly encountered without deforming the body itself. Together with the clinical information this meticulous examination provides the necessary information to educate the families about future pregnancies. Loss of fetal perfusion leads to stromal fibrosis, loss of capillaries with retention of trophoblasts from maternal perfusion. The villi are eventually clustered more closely together and the intervillous spaces become almost completely obliterated. When the fetus is severely macerated, amniotic membranes can be used for karyotypic analysis. Mammogram films used in the faxitron with a fetus of 18 weeks gestation positioned to obtain anteroposterior (A) and lateral (B) views. The faxitron is not limited to bony surveys and can be used to demonstrate visceral anomalies through injection studies. The external features may provide the only information necessary to make the diagnosis of a malformation syndrome.

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Precautions should be taken to avoid exchange transfusion with donor blood from a carrier. If the donor blood with sickle trait becomes acidic, sickling can occur with expected complications to the patient. Preterm infants who have been transfused in utero or who have received more than 50 mL of transfused blood are candidates for irradiated blood. The blood must be type O, Rh-compatible (with the mother and the infant) or Rh-negative, low-titer anti-A, anti-B blood. Hyperbilirubinemia, metabolic imbalance, or hemolysis not caused by isoimmune disorders. For disorders associated with hydrops fetalis or fetal asphyxia, it is best to use blood that is <24 h old. The blood should be agitated periodically during the transfusion to maintain a constant Hct. Potassium levels in the donor blood should be determined if the infant is asphyxiated or in shock and renal impairment is suspected. Warming of blood is especially important in low birth weight and sick newborn infants. Simple 2-volume exchange transfusion is used for uncomplicated hyperbilirubinemia. Low birth weight and the blood volume of extremely premature newborns (which may be up to 95 mL/kg) should be taken into account when calculating exchange volumes. A nasogastric tube should be passed to evacuate the stomach and should be left in place to maintain gastric decompression and prevent regurgitation and aspiration of gastric juices. Perform umbilical vein catheterization and confirm the position by x-ray film (see Figure 9-6). If an isovolumetric exchange is to be performed, then an umbilical artery catheter must also be placed and confirmed by x-ray film (see Figure 9-7). Attach the bag of blood to the tubing and stopcocks according to the directions on the transfusion tray. The orientation of the stopcocks for infusion and withdrawal must be double-checked by the assistant. Isovolumetric 2-volume exchange transfusion is performed using a double setup, with infusion via the umbilical vein and withdrawal via the umbilical artery. This method is preferred when volume shifts during simple exchange might cause or aggravate myocardial insufficiency (eg, hydrops fetalis). Two operators are usually needed: one to perform the infusion and the other to handle the withdrawal. Attach the unit of blood to the tubing and stopcocks attached to the umbilical vein catheter. If the catheter is to be left in place after the exchange transfusion (usually to monitor central venous pressure), it should be placed above the diaphragm, with placement confirmed by chest x-ray film. The tubing and the stopcocks of the second setup are attached to the umbilical artery catheter and to a sterile plastic bag for discarding the exchanged blood. If isovolumetric exchange is being performed because of cardiac failure, the central venous pressure can be determined via the umbilical vein catheter; it should be placed above the diaphragm in the inferior vena cava. A partial exchange transfusion is performed in the same manner as 2 volume exchange transfusion. Blood should be obtained for laboratory studies before and after exchange transfusion. Hematologic studies include hemoglobin, Hct, platelet count, white blood cell count, and differential count. Blood for retyping and cross-matching after exchange is often requested by the blood bank to verify typing and re-cross-matching and for study of transfusion reaction, if needed. Treatment of suspected hypocalcemia in patients receiving transfusions is controversial. Some physicians routinely administer 1-2 mL of 10% calcium gluconate by slow infusion after 100-200 mL of exchange donor blood. Begin or resume phototherapy after exchange transfusion for disorders involving a high bilirubin level. Continue to monitor serum bilirubin levels after transfusion at 2, 4, and 6 h and then at 6-h intervals. Unless the cardiac status is deteriorating or serum digoxin levels are too low, patients receiving digoxin should not be remedicated. Antibiotic prophylaxis after the transfusion should be considered on an individual basis. Clot or air embolism, arteriospasm of the lower limbs, thrombosis, and infarction of major organs may occur. Coagulopathies may result from thrombocytopenia or diminished coagulation factors. Hypoglycemia is especially likely in infants of diabetic mothers and in those with erythroblastosis fetalis. Metabolic alkalosis may occur as a result of delayed clearing of citrate preservative from the donated blood by the liver. An increased incidence of necrotizing enterocolitis after exchange transfusion has been suggested. For this reason, the umbilical vein catheter should be removed after the procedure unless central venous pressure monitoring is required. Also, we recommend that feedings be delayed for at least 24 h to observe the infant for the possibility of postexchange ileus. At some institutions, the infant is given enteric feedings if the respiratory rate is >60 breaths/min to decrease the risk of aspiration pneumonia (controversial). Many premature infants with immature sucking and swallow mechanisms tire before they can take in enough calories with normal feeding to maintain growth. Gastric decompression may be required in infants with necrotizing enterocolitis, bowel obstruction, or ileus. The length of tubing needed is determined by measuring the distance from the nose to the xiphoid process. See Table 22-1 for guidelines on insertion length in infants weighing less than 1500 g. Push the tongue down with a tongue depressor and pass the tube into the oropharynx. One method is to inject air into the tube with a syringe and listen for a rush of air in the stomach. One study found this method unreliable because a rush of air can occur when the tip is in the distal esophagus. Some clinicians recommended either palpating the tube in the abdomen or aspirating the contents to determine the acidity by pH tape. If feedings are to be initiated, the position should also be verified by plain x-ray. Apnea and bradycardia are usually mediated by a vagal response and will usually resolve without specific treatment. Always have bag-and-mask ventilation with 100% oxygen available to treat this problem. Aspiration can occur if feeding has been initiated in a tube that is accidentally inserted into the lung or if the gastrointestinal tract is not passing the feedings out of the stomach. Periodically check the residual volumes in the stomach to prevent overdistention and aspiration. Collection of blood samples when only a small amount of blood is needed or when there is difficulty obtaining samples by venipuncture. Equipment includes a sterile lancet (a 2-mm lancet if the infant weighs <1500 g or if only a small amount of blood is needed, a 4-mm lancet in larger infants or if more blood is required). Although this is not mandatory, it will produce hyperemia, which increases vascularity, making blood collection easier. Do not use the center of the heel because this area is associated with an increased incidence of osteomyelitis. If the area is wet with alcohol, hemolysis may occur, altering the results of blood testing. Gently squeeze the heel, and place the collection tube at the site of the puncture. Maintain pressure on the puncture site with a dry sterile gauze pad until the bleeding stops.

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Jaundice, which may be due to a raised concentration of both unconjugated and conjugated bilirubin in the blood. Ofen also bleeding from puncture sites (due to a disseminated intravascular coagulopathy). Once most of the clinical signs are present and the diagnosis is easily made, it is ofen too late to save the infant. Treatment must be started immediately, however, as it may be a few days before the blood culture results are available. Testing the urine for Streptococcal group B antigen (Wellcogen Strep B kit) is only of limited help in diagnosing septicaemia as it may simply indicate colonisation. Benzyl penicillin 50 000 units/kg/dose plus gentamicin (Garamycin) 5 mg/kg/ dose; or cloxacillin 50 mg/kg/dose plus amikacin (Amikin) 5 mg/kg/dose. Penicillin, cloxacillin and cefotaxime are given in divided doses either intravenously or intramuscularly every 12 hours for infants under one week and every 8 hours afer one week of age. Cefriaxone has the advantage of being given once a day intravenously or intramuscularly. Pneumonia may be acquired as the result of colonisation of the upper airways before, during or afer delivery: 1. Before delivery the fetus may be infected by inhaling liquor that is colonised by bacteria that have spread from a chorioamnionitis. Listening to the chest is not a reliable method of diagnosing pneumonia in infants. A chest X-ray will show the typical features of pneumonia with areas of consolidation. The diagnosis of meningitis in the newborn infant is ofen very difcult as it usually does not present with the signs of neck stifness, full fontanelle, photophobia, vomiting and headache common in older children with meningitis. If meningitis is suspected, a lumbar puncture must be done to confrm or exclude the diagnosis. Bacterial meningitis in the newborn infant is usually caused by Gram negative bacilli. The drugs usually used are either cefotaxime 50 mg/kg/dose intravenously or intramuscularly every 12 hours or cefriaxone 100 mg/kg/dose as a daily dose. To prevent or treat convulsions give phenobarbitone 20 mg/kg intravenously or intramuscularly, then follow with 5 mg/kg orally daily until the infant is clinically well. Chorioamnionitis is a common acute infammation of the chorion, amnion and placenta. Chorioamnionitis may occur with intact membranes, although it is most common afer prolonged rupture of the membranes. Most bacteria causing chorioamnionitis stimulate the chorion and amnion to produce prostaglandins and, thereby, induce labour. Chorioamnionitis is the commonest cause of preterm labour and, therefore, should be suspected in all preterm infants born afer the spontaneous onset of labour or prelabour rupture of the membranes. Chorioamnionitis is usually asymptomatic in the mother and, therefore, is ofen not diagnosed before delivery. Only if the infection is severe will the mother develop fever, abdominal tenderness and possibly an ofensive vaginal discharge. If the infection has spread to the amniotic fuid, the infant may smell ofensive at delivery. Most of these colonised infants will be clinically well but some will develop signs of infection at or soon afer delivery. Severe chorioamnionitis may also cause placental oedema and result in fetal hypoxia. Whether the infant is infected or only colonised must be decided on clinical examination. A chronic intra-uterine infection is an infection of the fetus that is present for weeks or months before delivery and is caused by organisms that cross the placenta from the mother to the fetus during pregnancy. An apparently healthy infant that is, however, infected and will develop signs of disease weeks or months afer delivery. Rubella (German measles), which is very important because it causes congenital malformations if the infection takes place during the frst 16 weeks of pregnancy. As there is no treatment for congenital rubella, it must be prevented by immunising all children especially girls before puberty. If the mother has untreated syphilis during pregnancy, the fetus has a 50% chance of becoming infected. Syphilis causes infection and damage to many organs but, unlike rubella infection, does not cause congenital malformations. It is ofen difcult to confrm a diagnosis of congenital syphilis if the infant appears clinically well at delivery and the X-ray is normal. A positive result in an asymptomatic infant, therefore, indicates that the infant has been exposed to maternal syphilis but does not prove that the infant has congenital syphilis. If tests for specific IgM antibodies are positive in the infant then infection of the infant is confirmed. The method of treatment depends on whether an infant with a positive antibody test for syphilis has or has not clinical signs of congenital syphilis: 1. If the infant has clinical signs of syphilis give 50 000 units/kg of procaine penicillin daily by intramuscular injection for 10 days. Ten days of treatment should be given to these infants even if the mother has been fully treated. Tese infants are ofen very sick and need good general supportive care in a level 2 hospital. Erythromycin given to the mother for syphilis does not cross the placenta and treat the fetus. The risk from exclusive breastfeeding (breast milk only) for 6 months only is much less. Never leave the needle or lancet lying next to the patient as the nurse or doctor may prick themselves when cleaning up afer the procedure. They should then be washed out or irrigated repeatedly until the pus stops forming. In addition, cefotaxime or cefriaxone must be given by intramuscular injection daily for 3 days. Only when the eyes are clean and the frst dose of antibiotic has been given should the infant be referred to hospital for further treatment. The mother reports that the infant refuses the breast and cries when she tries to feed. Mycostatin (Nystatin) drops 1 ml should be placed in the mouth and repeated afer every feed. This infant will need intravenous fuids, nasogastric drainage, incubator care and careful observations. This is suggested by the peeling rash on hands and feet, the hepatosplenomegaly and the heavy, pale placenta in a low birth weight infant. An X-ray of the legs will almost certainly show the typical features of syphilic osteitis. What is the treatment if the infant appears well but the mother has untreated syphilis? If the infant has no clinical signs of syphilis the treatment is a single dose of 50 000 units benzathine penicillin. By placing the needle or lancet into a sharps container immediately afer it has been used. During delivery the infant may be damaged by pressure on the body as it passes down the birth canal. The infant may also be damaged by the person conducting the delivery, either during a vaginal birth or caesarean section. Caput (or caput succedaneum) is oedema of the presenting part caused by pressure on the presenting part during a vaginal delivery. A cephalhaematoma is a collection of blood under the periosteum of the parietal bone of the skull. Bleeding is caused by damage to capillaries under the periosteum of the parietal bone.

Cataract congenital Volkmann type

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The parison is produced by extruding the plastic at high temperature and pressure. Variations on blow molding include coextrusion blow molding, injection blow molding, and injection stretch molding. This is used for making solid plastic objects such as caps, closures, and plastic toys. This involves heating a plastic sheet until it softens and then shaping it by stamping it between two cooled molds. Plastics are generally slow to degrade under ambient conditions, but they may discolor or become brittle. Films may be used as liners, wraps, or overwraps, depending on how they are applied to the product. Liners are plastic films applied to the inside of the container, often to protect the container from the product, such as plastic lin ings sprayed into the inside of metal drums or cans. Wraps are applied directly to the product, usually by mak ing a tube from the film, sealing one end, filling the tube with product, then sealing the top end. An overwrap is applied around the carton, often heat shrunk onto the carton to provide barrier protection. A common method of closing plastic bags is with plastic clips that can also double as price tags, as in bread packaging. Envelopes are bags sealed on three sides, with the last side folded over and sealed after filling with product, used mainly for flat items. The plastic resin granules and other ingredients are fed into the extruder and compressed and heated until the plastic flows out of the die. This can then be stretched in the machine direction by up to 80 times its original length, which has the effect of thinning the sheet and orienting the molecular structure. The result is that the plastic can be stretched easily in one direction after cooling, but not in the other. The thickness of the film is checked, the film cooled, and then wound onto the mill roll. Biaxially: jaws and rollers are used to stretch the film apart in both directions at once (Tenter process). The molten film is poured onto a casting wheel and then through a series of rollers, which stretch the film in the machine direction. The film then passes through the Tenter sec tion oven, where the jaws are used to grip the softened plastic and pull it apart in the trans verse direction. A second method is called the bubble method, where the plastic is extruded as a continuous cylinder, and a bubble of air is blown up the cen ter of the cylinder, forcing biaxial expansion. The plastic may then be coated prior to the mill roll in several ways to enhance its properties. A com mon example is coating a plastic that is difficult to print with a printable plastic on one or both sides. For this technique, the plastic passes quickly through an evacuated chamber in which aluminum is vapor ized. This deposits a metal layer several molecules thick (i200 A), resulting in a metallized appearance. This material is often used to replace foils as it is cheaper but does not have the same barrier properties as foil (although there will be some improvement over untreated film). However, the metal does not attach firmly to the plastic and may be scraped off (a surface lacquer pre vents this), and the plastic is not sealable on the metallized side. Metallized plastics also suffer from metal oxidation, affecting print adhesion, giving a maximum effective lifetime of about 3 months. The film may also be pearlized, a technique that distributes fine air bubbles throughout the plastic (or cavitating the surface), resulting in a pearly white opaque appearance. This is useful for preventing show-through,? the wet appearance where fats directly contact the plastic, and a particular problem 922 Handbook of Food Preservation, Second Edition with chocolate wrapping. The ideal film should have good bar rier properties, be chemically stable, temperature resistant, heat sealable, resist grease, be strong, not allow migration, have good transparency and gloss, be printable, and be inexpensive to make. Since no plastic will satisfy all these requirements, the actual plastic chosen for a particular function will be a compromise. One key prop erty relevant to packaging equipment, slip, is not covered in detail, and therefore will be explained here. From the perspective of machining, plastic film must have the right friction coefficient to pass smoothly through the packaging equipment. If the slip is too high, the result is different package sizes in tube formed packaging due to the film sliding past the forming rollers as well as a loss of registration in print ing (see below). On the other hand, too low a slip can cause the film to stick to hot surfaces or folding box surfaces and can cause the product not to slide down to the bottom of the pack, also affecting pack sealing and presentation. The product should be able to slide back and forward in the pack relatively easily for tight sealing at both ends. This section also serves to introduce and describe the primary packaging plastics. This results in long branched chains, weakly linked to each other by van der Waals forces (but strong overall force due to length). Thus, neighboring chains can slip past each other, allowing the material to bend easily (flexible). However, many plas tics with poor printability can be made printable by corona treatment, in which an ionic discharge is used to sensitize one side of the plastic. This irregularity in structure also results in a lower melting point and a less crystalline (ordered chain) structure. It resists most chemicals below 60?C, and it resists water moderately, but not gases (poor O2 bar rier). It is used for bag manufacture (bread, diapers), for low-temperature storage (due to its low barrier properties), and for packaging rice. This gives rise to an ordered molecular structure, which is called an isotactic polymer. Higher temperatures are required to produce ther moplasticity (melting point, 134?C). Such films have high strength, flexibility, clarity, and especially barrier properties, and are used for bag-in-the-box, pouches, cups and lids, etc. It has high crystallinity (high clarity and gloss), is Types of Packaging Materials Used for Foods 923 hard, heat resistant (higher softening point, 150?C), exhibits good memory, flex crack resistance, punc ture resistance, and stiffness. It is difficult to cut as it lacks stiffness, so is hard to machine by itself and is too expensive for use as a pure monofilm (except for household use). It resists chemicals, has low water, gas, aroma, and flavor permeability (due to chlo rine ions), and high strength. It is used in laminates and is an important shrink film, with excellent cling properties. This makes coextrusion lamination difficult as well, although it can still be easily used in coating from solution. When used in coextrusion, it must be copolymerized first (for example, with vinyl chloride) to give better temperature stability. Since the bonds C?C and C?F are strong, this material is extremely inert and has a high softening point (340?C). It is used in coating cookware (nonstick surfaces) and forming and packaging where easy-to-clean nonstick surfaces are required. It is often used for loose bulk packaging, especially for packing fragile materials. In general, they have reasonable clarity and poor feel and printability, but are strong, versatile, with good heat resistance. This is useful for boil-in-the-bag-type applications, where the plastic must sus tain temperatures of 100?C without deforming or softening. It is used for blow-molded bottles and some films, increasingly for thermoformed trays, for shrink-wraps, and for boil-in-the-bag products. It is only used in 12 and 15 m gauges for film and is com monly used as the outer layer of a laminate structure due to its gloss and temperature stability (melting point, 254?C). There is a growing interest in recycling poly esters due to their initially high cost.

References:

  • https://aem.asm.org/content/aem/81/21/7350.full.pdf
  • http://www.bio.org/sites/default/files/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf
  • https://www.pearson.com/content/dam/one-dot-com/one-dot-com/us/en/higher-ed/en/products-services/course-products/fremgen-6e-info/pdf/Sample_ch04_final.pdf
  • http://web.brrh.com/msl/GrandRounds/2015/Surviving%20Sepsis/Surviving%20Sepsis%202015.pdf
  • https://www.mmv.org/sites/default/files/uploads/docs/publications/17_-_2009_World_Malaria_Report_12.pdf

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