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Biomedical subjects

E Shore

Publications and source records attributed to E Shore.

At least 19 recordsLinked to original sources

Urinary basic fibroblast growth factor. A biochemical marker for preosseous fibroproliferative lesions in patients with fibrodysplasia ossificans progressiva.

Angiogenesis is a prominent histopathologic feature of preosseous fibroproliferative lesions in patients who have fibrodysplasia ossificans progressiva. Basic fibroblast growth factor is an extremely potent in vivo stimulator of angiogenesis, and has been implicated in the growth of solid tumors. An enzyme linked immunosorbent assay for basic fibroblast growth factor was performed on urine samples from patients who had active (n = 28) and inactive (n = 39) fibrodysplasia ossificans progressiva, and compared with urine samples from normal age and gender matched control subjects (n = 54). Median basic fibroblast growth factor levels were 2705 pg/g of creatinine in the normal control group, 5058 pg/g of creatinine in patients with inactive fibrodysplasia ossificans progressiva (no significant difference), and 8793 pg/g of creatinine in patients with active fibrodysplasia ossificans progressiva. Female subjects, both normal and with fibrodysplasia ossificans progressiva, had higher levels of urinary basic fibroblast growth factor than did male subjects. There was no correlation of urinary basic fibroblast growth factor levels with age or severity of preexisting disability. These data document an elevation of urinary basic fibroblast growth factor during acute flareups of fibrodysplasia ossificans progressiva and provide a biochemical basis for considering antiangiogenic therapy for inhibiting endochondral osteogenesis in this disorder.

Adolescent

Bone morphogenetic protein 2/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by congenital malformation of the great toes and progressive heterotopic ossification in distinct anatomic patterns. Early preosseous lesions in FOP are clinically and histologically indistinguishable from the lesions of aggressive juvenile fibromatosis (AJF). Although the genetic defect in FOP is unknown, bone morphogenetic proteins (BMPs) 2 and 4 are plausible candidates genes. To determine if there is a difference in BMP 2/4 expression in the early fibromatous lesions of the two conditions, we performed immunohistochemical studies with a monoclonal antibody to BMP 2/4 on the earliest detectable fibromatous lesions of FOP and compared them with histologically identical lesions resected from children who had AJF. Fibromatous cells from the early FOP lesions exhibited immunostaining for BMP 2/4, whereas histologically indistinguishable fibromatous cells from AJF lesions showed no evidence of BMP 2/4 immunostaining. It is incumbent on all physicians who treat patients with suspected fibromatosis to examine the toes to rule out FOP and to avoid unnecessary diagnostic biopsies because surgical trauma induces further bone formation in patients who have FOP. However, if diagnostic confusion still exists and a biopsy is performed, immunostaining with BMP 2/4 antibody may resolve the diagnostic dilemma between FOP and AJF before the appearance of heterotopic ossification is observed in the FOP lesions. Our data suggest that the BMP 2/4 subfamily of secreted proteins may be involved in the pathogenesis of the FOP lesions.

Alkaline Phosphatase

Zero tolerance.

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Humans

A prospective study of carbon dioxide-digital subtraction vs standard contrast arteriography in the evaluation of the renal arteries.

OBJECTIVE: To compare carbon dioxide-digital subtraction arteriographic (CO2-DSA) images of renal artery anatomy with standard iodinated contrast arteriographic (ICA) images. DESIGN: One hundred patients with vascular disease who required abdominal aortography were evaluated by both CO2-DSA and ICA modalities. Two blinded readers interpreted arteriograms for the degree of renal artery stenosis, and a third reader was employed to resolve differences in reader interpretations. SETTING: University medical center. MAIN OUTCOME MEASURES: The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were calculated for the ability of CO2-DSA to demonstrate a 60% or greater stenosis of the main renal artery; kappa values for CO2-DSA and ICA were calculated to assess intraobserver variability. RESULTS: Of the 200 main renal arteries imaged, 17 (9 by means of CO2-DSA), 8 means of ICA) were eliminated because of inadequate visualization of the renal artery. In identifying a renal artery stenosis of 60% or greater, CO2-DSA had a sensitivity of 0.83, specificity of 0.99, positive predictive value of 0.94, and negative predictive value of 0.98. The overall accuracy was 0.97. The kappa was 0.75 for CO2-DSA and 0.70 for ICA, hence, the variation in the interpretations of CO2-DSA and ICA were comparable. CONCLUSION: Images by means of CO2-DSA accurately reflect pathologic changes in renal arteries and are thus useful in the diagnosis of clinically occult occlusive renal artery disease in patients at risk of contrast medium-related nephrotoxicity.

Adult

A two-week sleep extension in sleepy normals.

Thirty-four healthy, normal young men and women (21-35 years), with no sleep complaints and a normal screening polysomnogram, some with short (< or = 6-minute) and some with long (> or = 16-minute) average daily sleep latencies on a screening multiple sleep latency test, were studied on two baseline nights (8 hours) and in the "sleepy" group, for 14 consecutive nights of extended (10-hour) or habitual (7.8 +/- 0.7-hour) bedtimes. The screening differences between the groups in average daily sleep latency were consistently seen on the two further baseline nights and days. The extension of bedtime in sleepy subjects was followed by an increase in average daily sleep latency relative to randomly chosen sleepy subjects maintained on their habitual sleep schedule for the 14 nights. The increase in average daily sleep latency was associated with a gradual reduction in sleep efficiency over the 14 nights. Some (36%) of the sleepy subjects did not have increased average sleep latencies during the 10-hour bedtime extension. Those showing no increase in average daily sleep latency had an immediate drop in sleep efficiency when the bedtime was increased to 10 hours, suggesting they were unable to sleep longer during the extension. Their short average daily sleep latency was a result of causes other than chronic insufficient sleep.

Adult

Bronchiolitis associated with the finding of the fungus aspergillus. Report of two cases.

We report two cases of necrotizing bronchiolitis and bronchiolitis obliterans associated with the finding of the fungus aspergillus. One of the cases also showed bronchiolocentric granulomas and mucoid impaction of a segmental bronchus. Both patients were immunocompromised and had presented with dyspnea, cough, fever, and pulmonary infiltrates. Systemic antifungal therapy led to symptomatic and radiologic resolution. We surmise that these cases represent unusual examples of chronic necrotizing aspergillosis. The spectrum of pulmonary aspergillus diseases is reviewed.

Aged

Theophylline and antiparasitic drug interactions. A case report and study of the influence of thiabendazole and mebendazole on theophylline pharmacokinetics in adults.

To determine a change in theophylline pharmacokinetics during concomitant thiabendazole or mebendazole therapy, we studied six normal, healthy male volunteers. Aminophylline was administered intravenously, followed by a 30-h blood sampling period. Subjects were randomized to receive thiabendazole or mebendazole, then crossed over to receive the other therapy. Theophylline concentrations were measured utilizing an HPLC technique and a one-compartment model was fit to the data. Theophylline pharmacokinetic parameters were significantly different during thiabendazole therapy. Mean theophylline half-life increased, clearance decreased and elimination rate constant decreased. Two subjects experienced severe nausea and vomiting during thiabendazole therapy. There were no significant differences in theophylline pharmacokinetic parameters during mebendazole therapy. Thiabendazole administration results in a significant decrease in theophylline clearance and beta elimination rate constant. The theophylline half-life increased significantly. Concomitant administration of theophylline and thiabendazole resulted in severe nausea and vomiting. Mebendazole administration did not seem to alter theophylline pharmacokinetics.

Adult

Yohimbine-induced bronchospasm.

Yohimbine is an alpha-2 blocking agent which also increases cholinergic activity. This medication is used to treat male impotence. We report a case of yohimbine-induced bronchospasm.

Bronchial Spasm

Designated trainers.

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Education, Medical, Graduate

Pregnancy during residency.

To identify possible barriers to women physicians who wish to combine parenting with medical careers, we studied 56 of 64 pregnancies from the past 10 years in 63 of 66 Harvard-affiliated residency programs. Pregnancies during residency were common (one in eight married women in 1983) and were usually planned (77 percent). Most institutions were unprepared for pregnancies among members of the house staff; four fifths of the programs had no maternity-leave policy. No one quit a residency program because of pregnancy, and pregnancy rarely affected achievement of board certification. Whether the pregnant women found pregnancy during residency a "pleasant" experience was determined largely by whether the program director was supportive, whether the issue of pregnancy was openly discussed within the program, and whether the woman was permitted to return to work on a part-time basis for the first weeks after maternity leave. We conclude that pregnancy within residency programs should be expected and planned for and that if proper arrangements are made, it need not be a major problem for either the training program or the pregnant resident.

Attitude of Health Personnel

The molecular structure and lubricating activity of lubricin isolated from bovine and human synovial fluids.

Lubricin was isolated from bovine ankle, metacarpophalangeal and knee and human knee synovial fluids. The lubricins isolated from the bovine joint fluids had the same amino acid and carbohydrate compositions, but differences were observed in the relative molecular masses. The Mr values of bovine metacarpophalangeal and ankle lubricin determined by light-scattering measurements were about 200 000, whereas values of 132 000 and 143 000 were obtained for the bovine knee lubricin. The human knee lubricin had a similar carbohydrate composition to bovine knee lubricin except for the higher glucosamine content, and the amino acid composition differed slightly. The human sample had a lower glutamic acid content and a leucine/isoleucine ratio of 2:1 compared with 1:1 in the bovine. The Mr value of the human knee lubricin (166 000) was also lower than that of the bovine metacarpophalangeal and ankle samples. The Mr value of the bovine knee lubricin determined by sedimentation-equilibrium measurements was 171 000. The length measurements determined by electron microscopy and also the sedimentation measurements showed considerable polydispersity and indicate that the degree of extension of lubricin molecules can vary. Friction measurements showed that the human knee synovial-fluid lubricin had equivalent lubricating ability in a test system in vitro to that observed for lubricin isolated from normal bovine synovial fluids. The lubricating ability of lubricin was concentration-dependent, and each lubricin sample was able to act as a lubricant in vitro in an equivalent manner to whole synovial fluid at concentrations that are thought to occur in vivo.

Amino Acids

The lubricating activity of human synovial fluids.

The lubricating abilities of human synovial fluids were measured using a rotating cartilage-on-glass apparatus. A total of 247 human fluids were lubrication-tested. Of these, 20 of the 180 knee fluids from patients with degenerative/traumatic joint disease lubricated less well than normal bovine synovial fluid. The remainder of the fluids from the knee and other joints were equivalent to normal bovine synovial fluid in their lubricating properties. The concentrations of hyaluronic acid, protein, and sialic acid and the relative viscosity of 117 human fluid samples were determined, but no relationships between the gross composition and the lubricating abilities were apparent.

Glycoproteins