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Biomedical subjects

D Mitchell

Publications and source records attributed to D Mitchell.

At least 199 records · Page 11Linked to original sources
PubMed1990

Historical and contemporary issues in nursing home reform.

Historical developments leading to the enactment of nursing home reform legislation (P.L. 100-203) were discussed. The results of the nursing home component of a nationwide University of Illinois at Chicago study of public mental retardation/developmental disabilities spending were also presented. Approximately 51,000 individuals with mental retardation and related conditions resided in nursing homes in 1989. The cost of their care was approximately $900 million annually. Within the first 12 months of the enactment of P.L. 100-203, 46 states had requested an extension to the original mandated services deadline imposed under that legislation. Under P.L. 100-203 guidelines, state agencies estimated that nearly 40% of all nursing home residents with mental retardation might need to be relocated to alternative settings. Implementation issues were also discussed.

Eligibility Determination↗
PubMed1990

Sezary cell-like leukemia: a distinct type of mature T cell malignancy.

We describe the clinical, ultrastructural, and immunophenotypical characteristics of four cases of an unusual type of T cell leukemia. Clinical features included high WBC, ranging from 26-148 x 10(9)/liter, bone marrow infiltration, splenomegaly, and lymphadenopathy. Skin involvement was not documented at presentation, but it was seen as a terminal event in one patient with a pattern of dermal lymphocytic infiltration different from that usually seen in Sezary syndrome. By ultrastructural analysis, the circulating lymphoid cells were indistinguishable from small Sezary cells in two cases, resembled large Sezary cells in one case, and consisted of a mixture of small Sezary cells and prolymphocytes in the remaining case. The cells from all cases had a mature T cell phenotype, TdT-, CD1a-, CD2+/-, CD3+, CD5+. In addition, the cells were either CD8+, CD4- or CD8+, CD4+ or CD4-, CD8-; and, in only one case, the findings were similar to those of Sezary syndrome cells: CD4+, CD8-, CD7-, BE-2+. In the latter case, serological and immunological assays were positive for HTLV-I while these were negative in two other patients investigated. The features of these patients suggest that Sezary cell leukemia is a distinct clinico-pathological entity although the alternative diagnosis of adult T cell leukemia/lymphoma could not be excluded in the HTLV-I+ case. Sezary cell leukemia appears to be resistant to current chemotherapy regimens and is associated with an aggressive clinical course and short survival.

Adult↗
PubMed1989

Clinical experience with zidovudine for patients with acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex.

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

AIDS-Related Complex↗
PubMed1989

Ath-2, a second gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.

Strain C57BL/6J and A/J differ at two genes determining atherosclerosis susceptibility. The first gene, Ath-1, was described earlier and this report characterizes Ath-2. The alleles at Ath-2 are r for resistance and s for susceptibility to atherosclerosis. The resistant phenotype in female mice is characterized by high plasma high density lipoprotein-cholesterol levels (74 mg/dl +/- SEM 2) and very few lesions/mouse after 14 weeks of consumption of an atherogenic diet (0.1 +/- SEM 0.1 in a predetermined region of the aorta). The susceptible phenotype in female mice is characterized by low levels of high density lipoprotein-cholesterol (35 mg/dl +/- SEM 1) and 1.2 lesions/mouse +/- SEM 0.2 in the same region of the aorta. In Ath-2 heterozygotes, resistance is dominant to susceptibility. Recombinant inbred strains derived from C57BL/6 and A were characterized for Apoa 1, Apoa 2 and susceptibility to atherosclerosis. Ath-1 and Ath-2 interact with each other so that resistant alleles at either locus confer a resistant phenotype to the animal. The map position of Ath-2 is not known, but Ath-2 does not map near genes determining the apolipoproteins for A-I, A-II, or E.

Alleles↗
PubMed1989

Functional evidence for the recognition of endogenous peptides by autoreactive T cell clones.

The fine specificity of two human T cell clones responding to autologous HLA-DR1 expressing antigen-presenting cells (APC) in the absence of nominal antigen has been investigated using Epstein-Barr virus-transformed B cells (BCL) of known DR beta 1 domain sequence. It was found that responsiveness was markedly affected by changes in a limited number of residues in this domain. Substitution of the DR1 beta sequence at one residue, position 74, even conservatively, was found to be particularly significant. Located on the beta 1 domain alpha-helix, this residue is predicted to point into the antigen-binding groove and is therefore unlikely to make contact with the T cell receptor. This finding suggests that these T cells are specific for a bound endogenous peptide within the autologous major histocompatibility (MHC) binding groove. The autospecific T cell clones also responded to murine L cell transfectants expressing DR alpha DR1 beta as well as to transfectants expressing the mouse/human hybrid MHC molecule I-E alpha DR1 beta but not to the reciprocal combination DR alpha I-E beta, thus confirming the importance of the beta 1 domain to T cell recognition. In contrast to the autocytotoxicity observed with BCL, cytolysis of the murine L cells expressing the HLA-DR1 molecule was slight and only found at high effector-target ratios. In addition, although fixation enhanced the recognition of BCL, capacity of the murine L cells bearing the HLA-DR1 molecule to stimulate T cell clone proliferation was markedly reduced by aldehyde fixation. When taken together, these results suggest that the endogenous peptides recognized by these autoreactive T cells are of human origin.

Amino Acid Sequence↗
PubMed1989

Partial zona dissection of human oocytes when failure of zona pellucida penetration is anticipated.

Partial zona dissection (PZD) of human oocytes facilitates sperm penetration through mechanically made holes in the zona pellucida. Only 1 of 69 eggs was damaged when sucrose was used to shrink the ooplasm during micromanipulation. The fertilization rate of micromanipulated oocytes in 18 couples with male factor infertility was 68% (34/50), which compared favourably with insemination of non-micromanipulated controls (21/45, 47%). PZD was advantageous in oligozoospermic patients, but not in cases of asthenozoospermia, combined semen problems or immunological infertility. Three twin and two singleton pregnancies resulted following replacement of 23 micromanipulated and eight control embryos in 14 patients. No differences in embryo morphology and development rates were found between the micromanipulated and control groups. The incidence of polyspermy in couples with abnormal semen analyses was relatively low (less than 20%) possibly due to partial activation of the oocytes following exposure to sucrose. Polyspermy was high (57%) in normozoospermic patients with either immunological infertility (n = 3) or failure of fertilization in previous cycles (n = 4). In the three immunological patients, nine of 11 hyaluronidase and sucrose-exposed control embryos fertilized and six implanted, possibly indicating that cumulus and corona cells are contributing factors inhibiting fertilization in such cases.

Embryo Transfer↗
PubMed1989

Does 99Tcm human serum albumin alter the characteristics of nebulized pentamidine isethionate?

Nebulized pentamidine has been used as therapy for Pneumocystis carinii pneumonia. The lung dose delivered using different nebulizer systems and doses of pentamidine from 50-600 mg is unknown. To measure this a marker which does not alter the characteristics of the nebulized pentamidine solution must be found. We have assessed the aerosol characteristics of four jet nebulizers (System 22, System 22 Mizer, Optimist, Respigard II) and one ultrasonic device (Pulmosonic) using two concentrations of pentamidine isethionate (50 mg and 300 mg) in 3 ml of solution. The jet nebulizers were operated at a flow rate of 6 l min-1, a rate suitable for home use. These measurements were repeated with 99Tcm labelled human serum albumin (HSA) added to the solutions. A linear relationship between 99Tcm-HSA activity and pentamidine concentration was demonstrated by using a nine stage cascade impactor. The Respigard II and Optimist produced the best results in terms of particle size (96% less than 5 microns), but the addition of the tracer to the latter led to a smaller particle size range and a reduction in the amount of aerosol present at the mouthpiece. The Mizer system had 52% of particles less than 5 microns, the Pulmosonic 46%. The Respigard II had a total output of 8.7 mg for the 50 mg concentration and 30.9 mg for the 300 mg concentration. The System 22 produced corresponding outputs of 18.0 mg and 67.1 mg with 54% of the aerosol particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1989

First trimester maternal serum lysosomal enzymes: implications for carrier testing and prenatal diagnosis.

Carrier detection for lysosomal storage diseases is sometimes possible by evaluating maternal serum levels of specific enzymes. However, lysosomal enzymes (LE) can be modified by maternal hormonal changes in pregnancy or embryonic contributions. Maternal serum was obtained prospectively in the follicular phase and at 2-5 and 7-11 weeks after conception from 13 infertility patients with precisely known ovulation dates. Eleven enzyme activities were determined fluorimetrically using 4-methylumbelliferyl substrates. Using repeated measures ANOVA, alpha-N-acetyl-glucosaminidase (p less than 0.05), hexosaminidase A (p less than 0.005) and hexosaminidase A and B (p less than 0.005) increased during the first trimester, and 8 enzymes did not change significantly. Our data show differing patterns of LE in the first trimester. These may be explained by: (1) variability of maternal reaction to hormonal changes of pregnancy, or (2) variable embryonic contributions suggesting differential ontogeny and placental transfer of these enzymes. The increase in levels of the 3 specific LE in maternal serum may interfere with the accuracy of carrier testing in early pregnancy, but pregnancy should not interfere with the other 8.

Adult↗
PubMed1989

Diurnal variation in TSH and free thyroid hormones in patients on thyroxine replacement.

Eleven patients with treated hypothyroidism were investigated to examine the effects of time on their thyroid function tests. Each patient was clinically and biochemically euthyroid on once daily thyroxine replacement therapy, taken in the morning. TSH followed a diurnal rhythm with a peak level at 23.30 h and a trough level at 14.30 h. Four subjects had TSH trough levels within the normal range, but with peak levels outside this range. FT4 and FT3 levels fell from their highest levels some three hours after ingestion to the lowest levels just prior to the next dose. This study shows that there are significant time-related variabilities in TSH and thyroid hormone levels in treated hypothyroid patients. This should be taken into account when interpreting results of their thyroid function tests.

Aged↗
PubMed1989

Streptococcus faecalis arthritis.

Septic arthritis due to Streptococcus faecalis is rare. We describe a case in which synovial biopsy was required for diagnosis and a new longterm antibiotic combination using ciprofloxacin and amoxicillin was successful in treating the infection. Comparison is made with previous reported cases and the usual poor outcome in this condition.

Amoxicillin↗
PubMed1988

Selection of medical students--effect on class composition of using non-academic criteria.

The attributes of 2,304 applicants for admission to the University of the Witwatersrand Medical School were analysed. Those measured by previous academic performance, biographical history and assessment at interview were significantly different. Inclusion of non-academic criteria in admission decisions broadens the personal attributes of the class, and alters the ethnic and gender composition, without affecting subsequent failure rate.

Educational Measurement↗
PubMed1988

Radiation sensitivity and DNA repair in Caenorhabditis elegans strains with different mean life spans.

The sensitivities to three DNA damaging agents (UV and gamma-radiation, methyl methanesulfonate) were measured in four recombinant inbred (RI) strains of Caenorhabditis elegans with mean life spans ranging from 13 to 30.9 days, as well as in the wild-type strains used to derive these RI's. Sensitivities at several stages in the developmental cycle were tested. There were no significant correlations between mean life span and the lethal effects of these 3 agents. Excision of two UV-radiation-induced DNA photoproducts was also measured. Long-lived strains were no more repair competent than shorter-lived strains. These data indicate that DNA repair plays at best a minor role in the aging process of C. elegans.

Animals↗