Biomedical subjects
Publications and source records attributed to V Miller.
A 7-year-old boy presented with acute ascites due to mesenteric fibromatosis. The pathophysiological mechanisms for formation of ascitic fluid and some aspects of the aetiology of intra-abdominal fibromatosis and its association with Gardener's syndrome are discussed.
A new technique to estimate water uptake by the gastrointestinal tract was tested in infants undergoing elective surgery. Patients were randomly allocated to receive either sterile water or a glucose-electrolyte solution labeled with the stable isotope H2O18. After absorption, the isotopic O18 comes to rapid equilibrium with plasma bicarbonate and subsequently appears in the breath as C18O2. Breath and blood samples were collected at five-minute intervals after administration of the test solution. Mass spectrometric analysis enabled detection of isotopic O18 enrichment at parts per million levels in blood and in breath CO2. Enrichment of blood and breath C18O2 above baseline levels is detectable within five minutes of administration of the labeled test solution and rises to a plateau between 30 and 90 minutes. It is hypothesized that the rate of increase of enrichment is proportional to the unidirectional flux of water from lumen to gut.
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The thickness of a tumor has been identified as the principal prognostic factor in cutaneous malignant melanoma. However, time to recurrence has not conclusively been related to thickness. A retrospective study of 216 patients with a primary cutaneous malignant melanoma that recurred was conducted to clarify this relationship and investigate possible independent relationships between age at diagnosis and sex of patients to time to recurrence. The results of analysis of linear regression revealed an inverse linear relationship between thickness and time to recurrence (p less than 0.001). Patients more than 50 years of age at the time of diagnosis were shown to relapse sooner than those less than 50 years of age (p = 0.014). Sex was not a significant factor in predicting time to recurrence (p greater than 0.10). These results suggest that thickness of tumor provides an indication of time to recurrence in those patients destined to recur and stress the need for long term surveillance in patients with a history of malignant melanoma because of the possibility of late relapse even with thin lesions.
Simvastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was compared with cholestyramine resin in a randomized open-label 12-week multicenter study of 251 high-risk patients with familial or nonfamilial hypercholesterolemia. Simvastatin, 20 mg and 40 mg daily, produced mean reductions in total cholesterol of 26% and 33%, respectively, and reductions in low-density lipoprotein cholesterol level of 32% and 40%. Cholestyramine resin, 4 to 12 g twice daily, reduced total cholesterol and low-density lipoprotein cholesterol levels 15% and 21%, respectively. High-density lipoprotein cholesterol levels were increased 8% to 10% by all treatments. Plasma triglyceride levels were moderately decreased by simvastatin treatment, while triglyceride levels increased with cholestyramine treatment. Simvastatin was better tolerated than cholestyramine, which had numerous gastrointestinal tract side effects. No patient had a serious drug-related adverse event.
CSF-1 and granulocyte/monocyte CSF (GM-CSF) were shown to modulate the levels of Ia gene and protein expression in bone marrow-derived macrophages (BMM). Recombinant GM-CSF induced high levels of Ia expression, similar to the levels induced by INF-gamma, while IL-3 had no effect. In contrast, recombinant CSF-1 not only suppressed the basal levels of Ia gene and protein expression in BMM, but also inhibited the induction of Ia by IFN-gamma and GM-CSF. Basal levels of Ia were not inhibited by recombinant CSF-1 until after 16-24 h of culture, suggesting an indirect mechanism of suppression. IFN-alpha/beta and PGE2 were shown not to be involved in the CSF-1 inhibition of basal levels of Ia expression. However, the CSF-1-mediated suppression of both the basal levels of Ia expression and the induction of Ia in BMM by IFN-gamma and GM-CSF did correlate with the induction of cellular proliferation. These data imply that in addition to regulating hematopoiesis, CSFs may regulate the initiation of the immune response through their effects on Ia expression in macrophages.
A 3-month-old girl with intractable diarrhoea had protein-losing enteropathy secondary to a lymphangiomyoma. This is the first reported case of lymphangiomyoma in an infant. As enteral feeds were not tolerated, she was maintained on parenteral nutrition for 2 months. Pancreatic enzyme supplementation produced a rapid clinical improvement and normalization of serum albumin level. Weaning was subsequently tolerated and the vitamin, mineral, and trace element deficiencies improved. Subsequent recurrence was associated with normal pancreatic function and has proved refractory to treatment.
A provisional set of standards of care was derived from a quality assurance strand of a wider research project, which reported the development of evaluation strategies for area integrated mental health services (AIMHS). In contrast to most published standards, they apply to all facets of care in a comprehensive catchment area mental health service, whether clinical or functional, community or hospital based, urban or rural, or managed by the public, private or voluntary sectors. We review briefly existing sets of standards of mental health services and report the process of development of standards of care, each with sub-sets of performance indicators and examples. While the AIMHS standards and a companion quality assurance manual are still undergoing refinement, they offer a guide for mental health professionals to the provision of services, and a checklist to service-users of services that should be available to them at every stage of care in a mental health system.
Estimates are that 2 million women are battered each year by their male partner. To prevent battering and promote physical safety, Planned Parenthood of Houston and Southeast Texas added four abuse-assessment questions to the standard intake form for all initial and annual-visit clients. To establish the prevalence of battering, all intake forms completed at four clinics during a one-month period were analyzed. A total of 793 forms were reviewed. The prevalence of physical battering was 8.2 percent. When the characteristics of the battered women were compared with the non-battered, statistically significant differences existed. Information on the health consequences of battering are presented along with suggested assessment questions.
Diagnosis of Crohn's disease in children may be delayed because of obscure presentation and inappropriate investigation. The clinical and radiological features in 35 children with Crohn's disease were reviewed retrospectively. The distal ileum and proximal colon were the most common sites of disease. Intestinal symptoms and signs were often overshadowed by nonspecific complaints. Proximal small bowel disease was characterised by oedema, clubbing, anaemia, and stunting of growth. The delay in diagnosis was less than in other series, although most prolonged in the group with proximal disease. We have identified a group of clinical features that strongly suggests Crohn's disease. In these patients, we believe a small bowel enema is justified. Small bowel enema, although invasive, is more effective than barium meal and follow-through for demonstrating Crohn's disease. Severity of radiological changes did not correlate with clinical assessment. Neither bowel stricture nor fistula was found. Radiology of the colon was insensitive and colonoscopy is better for assessing colonic disease.
The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum orosomucoid were measured in children with Crohn's disease and ulcerative colitis in various states of disease activity. Results were matched with a clinical assessment to determine the correlation between laboratory test values and disease activity. Regression analysis showed that serum orosomucoid reflected disease activity better than ESR in both diseases. Orosomucoid but not ESR discriminated between disease in remission and mild disease in ulcerative colitis. No test invariably predicted presence or absence of active disease. Orosomucoid and ESR were complementary, but CRP was of no additional value. The usefulness of orosomucoid and ESR as objective measures of inflammatory activity was not masked by corticosteroid medication.
The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects.
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As was previously shown, a mutation rendering Chinese hamster ovary (CHO) cells concanavalin A (Con A) resistant (Con AR) resulted in enhanced binding and susceptibility to lysis by natural killer (NK) cells. In the present study altered cell surface carbohydrate expression on the Con AR CR-7 cell line was demonstrated. This could be detected by flow cytometry with the use of fluorescein isothiocyanate-conjugated lectins Con A, wheat-germ agglutinin, and peanut agglutinin, and by a radiolabeled monoclonal antibody (49H.8) that recognizes a phenyl-P-galactose determinant. Two other independently selected Con AR CHO lines (BCR-2 and ECR-1) also exhibited increased NK cell reactivity, which suggests that a similar and, likely, a single mutation has altered the phenotype of these cells. Tunicamycin, an inhibitor of N-linked glycosylation, was able to reverse the binding to the CHO lines with the use of conditions that did not affect protein or DNA synthesis. The mutation rendering the CR-7 line Con AR and more sensitive to NK cell lysis and binding resulted in reduced killing and adhesion by activated bone marrow-derived macrophages from DBA/2J and CBA/CaJ mouse strains. Inhibition of macrophage and NK cell lysis by simple monosaccharides was demonstrated; however, macrophage killing was inhibited only by D-mannose, whereas NK cell lysis was reduced by all sugars tested. Neither macrophage nor NK cell adherence to tumor monolayers was affected by any of the monosaccharides. These results suggest that complex N-linked oligosaccharides are important for NK cell and macrophage binding and lysis.
The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn's disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn's disease. The scans of two patients with inactive Crohn's disease were negative. There were two false negative scans in patients with Crohn's colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity.
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The mitotic activity of epithelial lymphocytes (expressed as percentage mitotic figures/3,000 lymphocytes/mucosal biopsy) was determined in a random sample of jejunal biopsies performed on 44 children with malabsorption, diarrhoea, or failure to thrive. The mitotic index (MI) exceeded 0.2% in 19 biopsies obtained from children with untreated celiac sprue (CS); there were no false positives. The remaining 25 biopsies (MI of less than 0.2%) were considered to be "nonceliac" in origin, among which were several with a severe degree of villous flattening. Conditions in this latter category excluded by a low MI included cow's milk protein enteropathy, selective immunoglobulin A deficiency, combined variable immunodeficiency, Crohn's jejunitis, and intractable diarrhoea of infancy. A high MI (greater than 0.2%) prospectively distinguishes mucosal lesions due to untreated CS from other causes of malabsorption, particularly those associated with villous flattening, but in which the MI is less than 0.2%. This index is therefore proposed as a simple, reliable, and prospective histological marker of CS, and one that could: reduce the need to perform multiple biopsies during a gluten-free diet; and avoid the necessity for follow-up "diagnostic" gluten challenges, especially in very young children.
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