MR cholangiography in children after liver transplantation from living related donors

A highly specific anti-glutamate monoclonal antibody, mAb2D7, was used together with light and electron microscopy to elucidate the role played by the amino acid glutamate in the projection from the olfactory bulb to the piriform cortex in the rat. By light microscopy, glutamate-like immunoreactivity was observed in neuronal cell bodies and in the neuropil of the piriform cortex. Double labelling experiments which involved injections of wheat germ agglutinin-horse--radish peroxidase into the olfactory bulb and a post-embedding immunogold method for electron microscopy revealed anterogradely labelled terminals making asymmetric synaptic contacts on dendrites in the piriform cortex which contained high levels of glutamate as assessed by quantification. These results further support a role for glutamate as a neurotransmitter in the efferent pathway of the rat olfactory bulb.     

Metastasizing pleomorphic adenoma: a report of three cases

BACKGROUND: This study evaluates the diagnosis and treatment of women with pathologic nipple discharge caused by ductal carcinoma in situ (DCIS). METHODS: Women with unilateral spontaneous bloody, serous, or brown nipple discharge who presented between January 1, 1988 and August 1, 1996 were identified by retrospective chart review. Women with nonspontaneous, physiologic discharge were excluded. RESULTS: Two hundred seventy-seven women with a mean age of 59.5 years (range, 24 to 88 years) underwent duct exploration and biopsy for pathologic discharge, with 43 (15.5%) found to have DCIS. The discharge was bloody in 29, clear in eight, and brown in six women. Seven of 12 (58%) women with an associated breast mass were found to have a microinvasive component with the DCIS. Discharge cytology showed malignant cells in only two of 12 (16%) women examined. A ductogram was performed on 20 women, with filling defects seen in 10, ectasia in 3, narrowing in 4, and normal ducts in 3. The DCIS included 17 (40%) specimens with cribriform pattern, 17 (40%) micropapillary, 8 (18%) comedo, and 2 (2%) solid. Twelve microinvasive cancers were found in combination with DCIS. After duct exploration, 37 (86%) patients were found to have extensive or multifocal DCIS to the margin, or both, with 32 (74%) patients requiring mastectomy to achieve free surgical margins. There was residual disease in 27 of 32 (84%) mastectomy specimens after initial biopsy. Breast conservation was possible in only 11 (26%) women. Forty of 43 (93%) are disease-free with a median follow-up of 37 months. CONCLUSION: Women presenting with pathologic nipple discharge require duct exploration regardless of cytologic or radiologic findings. When discharge is the result of DCIS, extensiveness of disease in relation to central location and intraductal spread may preclude breast conservation in as many as 27 of 43 (63%) cases.     

Choroidal blastomycosis. A report of two cases

Isolated resting platelets are able to limit neutrophil activation and then can control the tissue-damaging potential of activated neutrophils. In the present study, platelet-neutrophil interactions have been evaluated in 10 uremic patients; the blood samples have been collected before the hemodialysis session. Twelve normal subjects served as controls. Platelets and neutrophils have been isolated and recombined in an autologous ex vivo system. Anion superoxide production and chemiluminescence (which is related to hypochlorous acid production) have been evaluated after stimulation with N-formyl-methionyl-leucyl-phenylalanine. Coincubation of platelets from normal subjects with autologous neutrophils led to a dose-dependent inhibition of both superoxide anion generation induced by N-formyl-methionyl-leucyl-phenylalanine and chemiluminescence. Instead, platelets from uremic patients have not affected superoxide anion production by autologous neutrophils. The chemiluminescence was reduced by coincubation with autologous platelets only at the highest platelet-neutrophil ratio (100:1). In conclusion, the modulation exerted by platelets towards neutrophil activation can be impaired in chronic uremia. Therefore, the tissue-damaging potential of circulating neutrophils, due to toxicity by superoxide anion and hypochlorous acid, may be increased.     

Reflex sympathetic dystrophy: result of autonomic denervation?

1. To investigate the nature of sympathetic dysfunction in the pathogenesis of reflex sympathetic dystrophy, the microcirculatory vasoconstrictive responses to dependency were investigated in the skin of the hand of 76 reflex sympathetic dystrophy patients with unilateral disease by means of laser Doppler flowmetry (in perfusion units) and capillary microscopy. The patients were divided into three stages according to their perception of skin temperature (stage I in the case of a stationary warmth sensation, stage II in the case of an intermittent warmth and cold sensation, and stage III in the case of a stationary cold sensation). The vasoconstrictive responses were induced by lowering of the affected hand. 2. As compared to controls, the mainly sympathetically mediated vasoconstrictive response at thermoregulatory level of the skin microcirculation, as measured by laser Doppler flowmetry, was attenuated at stage I (1.82 versus 1.41, P < 0.05), stage II (1.82 versus 1.09, P < 0.0001) and stage III (1.82 versus 1.14, P < 0.01), suggesting the involvement of sympathetic denervation at all stages of the reflex sympathetic dystrophy syndrome. This sympathetic denervation may also account for the observed increase in thermoregulatory skin blood flow at stage I as compared to controls (152 versus 81, P < 0.01). 3. Since sympathetic denervation has been reported to cause increased sensitivity of vascular structures to catecholamines, the decrease in thermoregulatory skin blood flow at stages II (54 versus 81, P < 0.05) and III (31 versus 81, P < 0.05), both as compared to controls, may result from hypersensitivity to catecholamines of skin microvessels. 4. The sympathetically independent vasoconstrictive response at the nutritive level of skin microcirculation, as measured by capillary microscopy, was impaired only at stage III as compared to controls (1.04 versus 2.06, P < 0.05). This divergence in microvascular reactivity upon dependency of the nutritive and thermoregulatory subsystems also supports the hypothesis of sympathetic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Athlete''s heart in elite disabled athletes

Nineteen children with congenital upper alimentary tract malformation were studied prospectively at the Department of Paediatrics, University College Hospital (UCH), Ibadan, over a period of 12 months. There were 20 cases, grouped into six types comprising congenital hypertrophic pyloric stenosis, seven; cleft lip and/or cleft palate, five; oesophagal atresia with or without tracheo-oesophageal fistula, four; jejunal atresia two and a case each of achalasia and annular pancreas. One patient had oesophageal atresia and congenital hypertrophic pyloric stenosis. The mortality rate was 31.51% (six out of nineteen). Low mortality was recorded in cases of cleft lip and/or palate, while mortalities of over 70% were recorded among cases of jejunal atresia, and oesophageal atresia with or without tracheo-oesophageal fistul. The common causes of death were milk feed aspiration (28.6%-two cases), purulent peritonitis (14.3%-one case), and probable septicaemia (14.3%-one case). The cause of death in two cases could not be determined.     

Synthesis, and in vitro and in vivo muscarinic pharmacological properties of a series of 1,6-dihydro-5-(4H)-pyrimidinone oximes

A series of 1,6-dihydro-5-(4H)-pyrimidinone oxime derivatives I was synthesized (Scheme 1, Tables 1 and 2) and tested for muscarinic activity (Table 3) in receptor binding assays using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies that measured their potencies to inhibit the binding of Oxo-M and Pz. Preferential inhibition of Oxo-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. The series produced a wide range of active compounds with differing degrees of selectivity in M1, M2, and M3 functional models. Several compounds that have mixed agonist/antagonist profiles were able to reduce cholinergic-related cognitive impairments in models of mnemonic function. Substitutions (I, e.g. R2 or R3 = Me) at the 1,6-dihydro-5-(4H)pyrimidine ring disrupted binding and efficacy, whereas systematic variation of the oximes substituent R1 resulted in various degrees of potency and selectivity dependent on the nature of the substitution.     

Large intestine obstruction complicated with perforation: a rare manifestation of Schistosoma mansoni infection

The authors report a case of a 25 year old Brazilian man with a history of crampy abdominal pain in the left iliac fossa for 2 weeks, abdominal distention, mucous diarrhea and anorexia. The patient presented signs of hemodynamic instability and a hard mass palpated in the left iliac fossa presented peritoneal irritation. At laparotomy, fecal peritonitis and a punched-out perforation of the midsigmoid colon were found. A left hemicolectomy was performed with terminal colostomy. Specimen examination revealed a thickened rectosigmoid wall, narrow lumen and multiple mucosal polyps. Microscopically, chronic granulomatous colitis with Schistosoma mansoni eggs confirmed the etiology. To the authors' knowledge, this is the first case of obstruction complicated with perforation due to mansoni schistosomiasis reported in the literature.     

Molecular characterization of N-methyl-D-aspartate receptors expressed in mammalian cells yields evidence for the coexistence of three subunit types within a discrete receptor molecule

The N-methyl-D-aspartate R1 (NMDA R1), NMDA R2A, and NMDA R2C subunits were expressed transiently in double or triple combinations in human embryonic kidney (HEK) 293 cells. The biochemical and pharmacological properties of the cloned receptors were compared with those of adult mouse forebrain and cerebellum. Under conditions established for maximal expression, cotransfection of the NMDA R1 and R2C subunits yielded a protein detected immunologically with a molecular size of 780,000-850,000 daltons. No cell death was observed in the transfected cells, and the KD for [3H]MK801 binding to the NMDA R1/R2C receptor was 346 +/- 158 nM. This was in contrast to a value of KD = 22 +/- 9 nM found for native cerebellar receptors. Co-transfection with NMDA R1/R2A/R2C subunits with a DNA ratio, 1:3:3, resulted in the expression of a protein with a size similar to the NMDA R1/R2C combination, but the affinity of [3H]MK801 was now 22 +/- 5 nM, and the percentage cell death post-transfection was 89 +/- 17%. Immunoprecipitation assays of detergent-solubilized transfected cells with NMDA R1 subunit-specific antibodies co-precipitated the NMDA R2A and NMDA R2C subunits in 1/2A and 1/2C transfections, respectively. Similarly, immunoprecipitations with either NMDA R1 or NMDA R2C subunit-specific antibodies co-precipitated the NMDA R2A subunit in the R1/2A/2C triple transfections. These results show that the three NMDA receptor subunit types can co-assemble following their co-expression in mammalian cells with a pharmacological profile that is similar to that found for adult cerebellar NMDA receptors.     

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)

We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. The cardinal features of this syndrome are a consequence of P450arom deficiency: 1) the fetal masculinization in this syndrome can be ascribed to defective placental conversion of C19 steroids to estrogens, leading to exposure of the female fetus to excessive amounts of testosterone; 2) the pubertal failure, mild virilization, multicystic ovaries, and hyperstimulation of the ovaries by FSH and LH are the result of the inability of the ovary to aromatize testosterone and androstenedione to estrogens; and 3) the striking delay in bone age at 14 2/12 yr supports the notion that estrogens, in contrast to androgens, are the major sex steroid driving skeletal maturation during puberty. Familial P450arom deficiency, although rare, may be more common than previously suspected.(ABSTRACT TRUNCATED AT 400 WORDS)     

Economic issues in lung cancer: a review

PURPOSE: Lung cancer is a major source of morbidity, mortality, and health care costs in the developed and developing world. It is estimated that lung cancer is responsible for 20% of all cancer care costs. Concerns exist that this expenditure is associated with questionable benefits. DESIGN: The economic literature that relates to smoking was reviewed, followed by a summary of the economics of the diagnosis, treatment, and palliation of lung cancer. Methodologic considerations are also discussed in this section. RESULTS: Published studies suggest that the increased lifetime health care costs from smoking-related illnesses in smokers are partially or fully offset by the higher medical costs that result from increased longevity in nonsmokers. However, lost productivity costs, which result from morbidity and early mortality among smokers, result in an overall net cost of smoking to society. Discounting rates of 3% to 5% do not substantively alter these results. The per-patient cost to treat lung cancer is substantial. The major cost center is hospitalization; palliative or terminal treatment is associated with significant costs. Savings can be obtained through the judicious use of diagnostic and staging procedures. Furthermore, combined modality treatment approaches and the palliative use of combination chemotherapy appear to be associated with acceptable cost-effectiveness compared with commonly used therapies for other diseases. CONCLUSION: Although the increased medical care costs of treating smoking-related diseases are somewhat offset by the higher medical care costs due to increased longevity in nonsmokers, the lost productivity that results from smoking results in a net cost to society. Standard approaches to the management of lung cancer are associated with cost-effectiveness similar to that of other commonly used medical interventions.