Biomedical subjects
R Sheridan
Publications and source records attributed to R Sheridan.
Self-inflicted abdominal gunshot wounds with the 0.357 magnum handgun.
In an 18-month period, three self-inflicted abdominal gunshot wounds with 0.357 magnum handguns were managed in a community hospital. This clinical experience is described and certain unique aspects of these injuries are noted.
Creating an endoscopy capability in Army community hospitals.
The purchase of gastrointestinal endoscopic services can be a fiscal drain on the Army Community Hospital. We describe a method whereby a quality endoscopic service can be created at the Army Community Hospital level.
Probing the role of two hydrophobic active site residues in the human dihydrofolate reductase by site-directed mutagenesis.
In the x-ray structure of the human dihydrofolate reductase, phenylalanine 31 and phenylalanine 34 have been shown to be involved in hydrophobic interactions with bound substrates and inhibitors. Using oligonucleotide-directed mutagenesis and a bacterial expression system producing the wild-type and mutant human dihydrofolate reductases at levels of 10% of the bacterial protein, we have constructed, expressed, and purified a serine 31 (S31) mutant and a serine 34 (S34) mutant. Fluorescence titration experiments indicated that S31 bound the substrate H2folate 10-fold tighter and the coenzyme NADPH 2-fold tighter than the wild-type human dihydrofolate reductase. The serine 31 mutation had little effect on the steady-state kinetic properties of the enzyme but produced a 100-fold increase in the dissociation constant (Kd) for the inhibitor methotrexate. The serine 34 mutant had much greater alterations in its properties than S31; specifically, S34 had a 3-fold reduction in the Km for NADPH, a 24-fold increase in the Km for H2folate, a 3-fold reduction in the overall reaction rate kcat, and an 80,000-fold increase in the Kd for methotrexate. In addition, the pH dependence of the steady-state kinetic parameters of S34 were different from that of the wild-type enzyme. These results suggest that phenylalanine 31 and phenylalanine 34 make very different contributions to ligand binding and catalysis in the human dihydrofolate reductase.
Fertility in a male with trisomy 21.
We review the published reports on reproduction in cases of non-mosaic trisomy 21 (Down's syndrome) and present the first fully documented case of a non-mosaic male with Down's syndrome fathering a pregnancy, a fact which has important implications in the light of caring for these people in the community.
AIDS-related small bowel lymphoma presenting with perforation.
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Prenatal testing for Duchenne and Becker muscular dystrophy.
DNA studies were undertaken following 53 requests from pregnant women at risk for Duchenne and Becker muscular dystrophy, including 32 in whom there was only 1 affected individual in the family (sporadic cases). The DNA restriction fragment length polymorphisms were informative in 51 of the 53 cases. In 10 of 25 pregnancies with male fetuses the risk to the fetus was reduced to 5% or less. Referral of possible carriers before onset of pregnancy is strongly advisable on both medical and economic grounds. The banking of DNA from affected individuals for future use in the estimation of risks to their relatives should be encouraged.
Chromosome banding in direct preparations of chorionic villi.
Chorionic villus sampling (CVS) is now currently offered for first trimester prenatal diagnosis of genetic disorders. Chromosome analysis of CVS in direct and culture preparations is possible using modifications of standard banding techniques. We summarize our experience in applying QFQ, GTG, RBG, CBG, DA/DAPI, NOR, and SC differentiation protocols to direct preparations. Characteristic chromosome regions are properly labelled by these techniques, and analysis of 300 band stage karyotypes is consistently achievable on GTG banded direct preparations. However, banding of CVS direct chromosomes has proved to be difficult, and the analysis needs to be backed up by culture preparations.
First-trimester diagnosis of metachromatic leucodystrophy.
Two pregnancies at risk for late infantile metachromatic leucodystrophy were monitored by assaying arylsulphatase A at 0 degrees C in homogenates of chorionic villi. In one, the very low activity recorded indicated the fetus to be affected, and this was confirmed by demonstration of low arylsulphatase A activity in cultured villi and cultured fetal fibroblasts after termination. In the other pregnancy, normal activity was found in the villi and the pregnancy is continuing. This simple chromogenic assay appears to be reliable for first-trimester diagnosis of metachromatic leucodystrophy. However, there is a probability of mis-diagnosis if the standard assay at 37 degrees C is used.
Resolution of epidermolysis bullosa aquisita with resection of intraabdominal Crohn's disease.
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Spindle cell carcinoma of the breast: case report and review.
Spindle cell carcinoma is a distinct, but unusual, variant of squamous cell carcinoma. It is seen most frequently in the upper aerodigestive tract and esophagus. The natural history seems to be similar to that of the more typical squamous cell carcinoma. A case of spindle cell carcinoma arising from the ductal epithelium of the breast is reported. The light and electron microscopic histology is described. A review of the literature suggests that this rare neoplasm should be managed in a fashion similar to that for more common types of epithelial breast duct malignancies.
Massive abdominal wall desmoid tumor. Treatment by resection and abdominal wall reconstruction.
The management of a massive abdominal wall desmoid tumor in a young woman with Gardner's syndrome is discussed. Treatment options included primary radiation, subtotal excision with radiation, primary chemotherapy, or radical resection with abdominal wall reconstruction. The advantages and disadvantages of the various treatment options are discussed, and the technique of resection and reconstruction is explained.
Aetiology of non-immune hydrops: the value of echocardiography.
Forty-eight pregnancies, five of them multiple, were referred for fetal cardiac assessment following the detection of non-immune hydrops fetalis; there were 52 hydropic fetuses in total. A cardiovascular aetiology was found in 21 of these 52 (40%); structural heart disease was present in 13, tachyarrhythmia in the remaining eight. The accurate delineation of these causes was possible using fetal echocardiography, and enabled rational management to be instituted. This included termination of pregnancy, pharmacological control of arrhythmias and appropriate timing of delivery.
Implementing an equal opportunities policy--a matter of good management practice?
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Echocardiographic detection of early cardiac involvement in juvenile rheumatoid arthritis.
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Impact of regulations on artificial organs research.
From a research perspective, some of the primary problems created by the FDA regulations include: the amount of time necessary to comply with the regulations and to obtain FDA and IRB review of the studies. The cost of such delays may be great in terms of statistical death. Lack of understanding of the regulations on the part of investigators. Escalated costs and extra restrictions on the use of animals. Benefits of the regulations appear to be: better preclinical testing performed prior to initiating clinical trials, and improved testing protocols, both of which may result in lower risks to patients.
Mouse monoclonal anti-A and anti-B as routine blood grouping reagents: an evaluation.
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The efficiency of Myklebust's pupil rating scale for detecting reading and arithmetic difficulties.
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