Americans With Disabilities Act of 1990. Implications for the medical field.
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Biomedical subjects
Publications and source records attributed to M Golden.
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Red cells in oedematous malnutrition (kwashiorkor) have an increased sodium content, 'leakiness' to sodium and enhanced sodium pumping. In non-oedematous malnutrition (marasmus) there is a reduction in the sodium pump activity. The explanation has hitherto been unknown but the glutathione content of red cells is low in kwashiorkor and normal in marasmus. We artificially lowered the glutathione content of normal red cells to values characteristic of mild oedematous malnutrition, using the enzyme inhibitors bischloronitrosourea (BCNU) and buthionine sulfoximine (BSOX). After preincubation, the cells were washed to remove the inhibitors and oxidized glutathione. Cellular content of sodium and potassium, and 86Rb influx were then measured. The reduction in glutathione reproduced the abnormalities of sodium content and flux observed in kwashiorkor. We suggest that oxidant stress in kwashiorkor, by reducing cellular glutathione, may affect cell membrane electrolyte transport. This may act through alterations in membrane sulfhydryl groups. Glutathione depletion may therefore play an important role in the clinical picture and natural history of oedematous malnutrition and may have relevance to other conditions where oxidant stress occurs.
In vivo fertilized hamster one-cell eggs (embryos) were cultured in a simple medium that was modified to provide a wide range of concentrations and ratios of the four major cation components (sodium, potassium, calcium and magnesium) while maintaining total osmotic pressure at 290 +/- 5 mosm. Embryos were cultured in these media to find the optimum cation concentrations for supporting the first cleavage division in vitro and to determine if physiologically abnormal cation concentrations and/or ratios in standard culture media could account for the 'two-cell block' to development in vitro in this species. Despite using a broad range of ratios for sodium:potassium (from 45:1 to 5:1) and for calcium:magnesium (from 17:1 to 1:1), there were no significant differences in the proportions of fertilized eggs that underwent the first cleavage division (approx. 60-80% across all treatments), and none of the two-cell embryos underwent further cleavage during extended culture. These data demonstrate that the first cleavage division of hamster embryos in vitro is insensitive to extracellular concentrations and ratios of the major cations, and that the non-physiological concentrations and/or ratios of these cations in the culture medium are not the primary reason for the failure of hamster zygotes to develop past the two-cell stage in vitro.
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Six adolescents, 12 to 15 years old, with insulin-dependent diabetes mellitus were discovered to be secretively taking extra insulin, not with the intent of improving metabolic control. Large discrepancies between reported and observed insulin requirements were noted. Psychosocial problems antedated the discovery of surreptitious insulin administration in all. Psychological testing and psychiatric evaluation revealed a variety of psychiatric conditions; depression was common. In two patients surreptitious insulin administration was believed to represent suicidal behavior. In others, it appeared to represent symptom substitution when use of other health-threatening behaviors such as recurrent ketoacidosis was made increasingly difficult through appropriate intervention. Surreptitious insulin administration may be one symptom of serious underlying psychiatric dysfunction in adolescents with insulin-dependent diabetes.
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The prognosis of tuberculous meningitis is closely linked to the stage at which treatment is started. At the same time the diagnosis will often have to be made on purely circumstantial evidence. Adenosine deaminase activity in the cerebrospinal fluid was evaluated as a diagnostic aid in 30 cases of tuberculous meningitis. Cerebrospinal fluid adenosine deaminase levels differentiated tuberculous meningitis cases from those with aseptic meningitis being higher than 4 U/l in all and higher than 6 U/l in 90% of cases of tuberculous meningitis, but lower than 6 U/l in aseptic meningitis and less than 4 U/l in normal controls. It could not distinguish bacterial meningitis from tuberculous or aseptic meningitis. In cases of low-cell-count bacterial meningitis, the mean cerebrospinal fluid adenosine deaminase level was significantly lower than in cases of tuberculous meningitis with a similar cell count, but considerable overlap of results in the two groups was still to be found.
The effects of differentiation inducers on the sensitivity of two human myeloid cell lines, K562 and HL-60, to natural killer (NK) cell lysis were examined. K562 cells treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA) and HL-60 cells treated with either TPA or dimethylsulfoxide (DMSO) not only became less sensitive NK targets, but also became less competitive in cold target inhibition experiments. Target binding cell assays revealed that TPA-treated target cells bound fewer NK effector cells than did untreated targets. TPA treatment renders K562 and HL-60 target cells more susceptible to hypotonic lysis, indicating that the decreased NK sensitivity is not due to altered osmotic fragility. The observed reduction in sensitivity to NK lysis was not apparently mediated by interferon (IFN) released by the target cells, as neither alpha nor gamma IFN were detected in culture supernatants. Furthermore, the effects of TPA were additive to the known protective effect of IFN on NK target cells. In contrast to the parent line, a subclone of HL-60 resistant to chemically induced differentiation did not become a less sensitive target after exposure to TPA. These observations with myeloid and erythroid target cells imply that the reduced killing of the TPA-treated cells was secondary to impaired recognition of the target by the effector, and that the state of cellular differentiation is a major determinant of susceptibility to NK cell-mediated lysis.
Although there have been many attempts to discriminate subtypes of reading disabled children, this study provides evidence of two common factors that seem to generalize to the vast majority of children with specific reading disability. The first, a right hemisphere cognitive style, may have some diagnostic utility. The second, a grapheme to phoneme deficit, may be at the heart of the disability. Techniques for diagnosis and remediation are discussed.
Because immune mechanisms are associated with insulin-dependent diabetes, multiple organ specific and xenogeneic cytotoxicity assays were developed. Human cellular and antibody effector systems were incubated with 51Cr-labeled dispersed normal rat islet target cells. In eight of 11 diabetic patients, nonenriched mononuclear cells incubated with islet target cells were more cytotoxic than cells from age- and sex-matched controls (p less than 0.01). When non-T cell-enriched mononuclear cells were used at diabetes onset, seven of 11 patients' cells showed excessive islet cytotoxicity (p less than 0.05). In four patients showing elevated cytotoxicity at diabetes onset, cytotoxicity decreased to control levels during diabetes remission. Islet specificity was suggested in that mononuclear cells derived from diabetic subjects did not mediate cytotoxicity against rat spleen or macrophage target cells. Three cytotoxic antibody mechanisms were also evaluated. C-dependent antibody-mediated cytotoxicity with the use of patient serum-coated islet target cells was elevated above control levels in four of 14 patients. Antibody-dependent cellular cytotoxicity exceeded control values in only two of 16 patients, although four assay systems were evaluated. C-augmented antibody-dependent cellular cytotoxicity was elevated in three of 14 patients. No differences were observed for antibody-mediated mechanisms in four patients evaluated at both diabetes onset and remission. Cytotoxic antibody was present in only about one-half of the patients showing increased cellular cytotoxicity, whereas most patients expressing increased cytotoxic antibody had cellular cytotoxicity. Islet cell cytotoxicity assays with the use of effector systems from patients with recent onset insulin-dependent diabetes suggest that direct cellular cytotoxicity is more active than antibody-mediated cytotoxic mechanisms, and that cellular cytotoxicity can correlate with disease activity.
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Described the development and evaluation of a measure of cognitive belief systems and thinking styles within the context of assertion. The Cognition Scale of Assertiveness comprises eight items and is scored on a 7-point (disagree-agree) scale. In a series of studies, normative, reliability, and validity data were obtained for junior college, university, and nonstudent samples (N = 482). Reliability and validity results were poor for junior college students, but impressive data obtained for university and nonstudent populations. Further, cognition scores for these latter two groups discriminated high vs. low social anxiety, a factor often linked to assertion. Finally, the instrument was sensitive to change via assertion training. Overall, the present findings recommend the use of the Cognition Scale of Assertiveness as a reliable and valid measure of cognitive assertion for university students and for nonstudent samples.