Biomedical subjects
D Matthews
Publications and source records attributed to D Matthews.
Felodipine in type II diabetes mellitus.
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Alagille syndrome and deletion of 20p.
We add five cases of 20p deletion to the 10 cases already published. Four had craniofacial, vertebral, ocular, and cardiovascular features of Alagille syndrome, which adds weight to the assignment of this disorder to the short arm of chromosome 20. Included in our series is the first report of familial transmission of a 20p deletion.
A trial of the calcium antagonist felodipine in hypertensive type 2 diabetic patients.
Although calcium antagonists may impair insulin release in vitro, clinical studies have produced conflicting results. Felodipine is a highly selective dihydropyridine calcium antagonist effective in the treatment of hypertension. The efficacy of felodipine was assessed in a double-blind randomized placebo cross-over study of 21 Type 2 diabetic patients with primary hypertension, 13 men and 8 women, with an age of 61 (range 46-73) years. Thirteen were controlled on oral hypoglycaemic therapy and 8 on diet alone. Mean (SD) blood pressure (mmHg) was 176(20)/102(8) after a 2-4 week placebo run-in period, 169(21)/101(8) during the subsequent placebo period compared with 151(15)/88(9) after 4 weeks felodipine therapy (p less than 0.001). Nineteen patients required 5 mg twice daily and 2 patients 10 mg twice daily to achieve a target diastolic pressure of 95 mmHg. Side-effects seen with felodipine included ankle oedema, facial flushing, headache, and dizziness. During oral glucose tolerance tests performed after the felodipine and placebo phases, mean (SD) fasting blood glucose was 9.5(3.1) and 9.0(3.0) mmol l-1, respectively (NS), and the 90 min (peak) blood glucose was 19.1(4.8) and 18.1(4.8) mmol l-1, respectively (NS). Glycosylated haemoglobin and fructosamine concentrations likewise showed no significant changes.
Glucocorticosteroids increase leucine oxidation and impair leucine balance in humans.
High-dose glucocorticoid treatment results in protein wasting. To determine whether such therapy affects leucine oxidation in the postabsorptive state and the disposal of dietary amino acids, eight normal subjects were studied twice in random order, once after 5 days of prednisone (20 mg three times daily) and on a second occasion without prednisone as a control. In the postabsorptive state prednisone therapy increased (P less than 0.05) plasma concentrations of leucine, alpha-ketoisocaproate, glucose, insulin, and C-peptide, as well as leucine carbon flux and oxidation calculated by means of isotope dilution techniques and [1-13C]leucine. During infusion of a chemically defined meal, total leucine carbon flux and oxidation increased similarly on both study days, but leucine oxidation was greater (P less than 0.01) during prednisone treatment; net leucine balance became positive on the control day but remained negative or zero on the prednisone study day despite higher (P less than 0.05) plasma insulin concentrations. These studies demonstrate that high-dose glucocorticoid treatment impairs the balance of the essential amino acid leucine in both the postabsorptive and absorptive states in humans.
Medically unexplained physical symptoms, somatization disorder and abridged somatization: studies with the Diagnostic Interview Schedule.
This paper reviews recent research that used the Diagnostic Interview Schedule (DIS) to characterize medically unexplained symptoms and their clustering in clinical and community populations. While the type of symptom(s) differed little across samples, the distribution of a less restrictive construct of somatization ('abridged' somatization) showed interesting differences across the various groups. The authors propose that in view of its relatively high prevalence, abundant psychiatric comorbidity and the simple and unintrusive nature of the assessment, use of the abridged construct may have practical value particularly when exploring psychopathology among medical and community populations.
Occupational health in a meat-processing plant.
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Mountain man. Interview by Tim Rice.
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Outbreaks of classical swine fever in Great Britain in 1986.
Classical swine fever was confirmed in 10 herds in Britain between April 10 and June 25, 1986 and typical acute disease was seen in nine of them. Serological evidence of exposure to classical swine fever virus was found in a further seven herds which, together with another nine, were slaughtered as dangerous contacts. Altogether 7781 pigs in 26 herds were slaughtered at a cost of 450,101 pounds for compensation alone. In order to detect subclinical disease, the majority of traced herds were blood sampled as well as inspected. A total of 119,169 pigs were inspected in 506 herds and 8302 blood samples were collected. Three primary outbreaks were identified, all attributed to the feeding of unprocessed waste food containing imported pig meat products. There was no spread of disease from two of these primary outbreaks.
Homing receptors and metastasis.
As discussed in the preceding sections, there are several indications that the lymphocyte homing receptors involved in the normal process of lymphocyte recirculation are also relevant to the behavior of metastatic cells. Cell fusion experiments indicate that previously nonmetastatic cells can acquire metastatic capacity from fusion with normal lymphocytes. Murine T lymphomas that bear high levels of functional homing receptors can metastasize to peripheral lymphoid organs, whereas those lymphomas lacking homing receptors cannot. Virtually all lymph node metastases of lymphomas contain a high proportion of MEL-14hi cells, even if the primary tumor has been selected to be relatively deficient in these cells. Further investigations of the biology of lymphocyte homing receptors will reveal whether or not there are additional lymphocyte homing receptors and will clarify the role of lymphocyte homing receptors in metastasis. Antibodies against three lymphocyte homing receptors could therefore be useful for diagnosis and treatment of metastatic disease.
Some aspects of in vivo human protein and amino acid metabolism, with particular reference to nutritional modulation.
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Phenotypic and functional analysis of B cell lines from patients with multiple myeloma.
We characterized phenotypic and functional properties of B cell lines obtained from patients with multiple myeloma to determine how well they conform to particular stages of B cell differentiation. This information is a prerequisite for using such lines as tools for studying B cell growth and the regulation thereof. Two lines, GM1312 and GM1500, expressed B1 and Ia, determinants on early B cells, but expressed little, if any, T10, a determinant expressed on plasma cells. By contrast, B1 and Ia were poorly expressed on two other lines, GM2132 and U266. T10 was expressed on GM2132 but not on U266. Using a reverse hemolytic plaque assay, we also assessed the numbers of cells actively secreting immunoglobulin (IgSCs) in such cultures to provide a functional marker of B cell differentiation. We observed consistently higher numbers of IgSCs in cultures of GM2132 than in GM1500 and GM1312. These phenotypic and functional markers were stable over several months. The data suggest that such cell lines represent early (GM1312, GM1500) and later stages (GM2132, U266) of B cell differentiation, although all lines were derived from patients with multiple myeloma.
Recovery of in vivo cellular immunity after human marrow grafting. Influence of time postgrafting and acute graft-versus-host disease.
Three hundred thirty-two marrow graft recipients and 241 healthy marrow donors were studied by skin testing with recall and neoantigens. Two hundred thirty patients with leukemia and seventy-eight patients with aplastic anemia received allogeneic HLA-identical sibling marrow. Twenty-four patients with leukemia received syngeneic marrow. The conditioning regimen prior to marrow infusion consisted of 120 mg/kg cyclophosphamide and 9.2-15.75 Gy total-body irradiation (leukemia) or 200 mg/kg cyclophosphamide (aplastic anemia). The patients were skin-tested with the neoantigens dinitrochlorobenzene (DNCB), keyhole limpet hemocyanin, and a battery of five recall antigens around 100, 150, 365, 730, 1095, 1460, and 1825 days after grafting. A binary logistic regression analysis was used to investigate the factors thought to influence immunocompetence. At 3 months postgrafting, the proportion of patients positive to DNCB was equal to that of normal marrow donors, but thereafter it was lower until 2 years. The proportion of patients positive to keyhole limpet hemocyanin was lower than normal regardless of the time after grafting. The proportion of patients positive to recall antigens was lower than that of normal marrow donors until 4 years after grafting. Patients with a history of acute graft-versus-host disease had the lowest probability of a positive reaction to recall antigens. None of the other factors was significantly associated with an increased or reduced level of response.
Effect of immunoglobulin on hepatitis A in day-care centers.
Over a 21-month interval, we investigated the effectiveness of immunoglobulin (lg) in preventing hepatitis A spread in day-care centers. Immunoglobulin was given to all center and employees whenever hepatitis occurred in one center child or employee or parents in two families. Immunoglobulin programs were completed in 91 centers during the trial within an average of 17 days of onset of illness in the index case. Immunoglobulin intervention caused significant reduction in the average size of a day-care hepatitis outbreaks, from 7.3 cases in historically untreated centers to 6.0 cases in Ig-treated centers. Cases in center children and employees virtually ceased two weeks after Ig intervention, while those in household contacts decreased significantly within six weeks. Reported cases of hepatitis type A or unspecified in the community decreased 75%, and the number of new hepatitis outbreaks decreased 77% during the trial. A decrease occurred not only in day-care-associated cases, but in cases not directly associated with centers, probably due to decreased tertiary spread from day-care families into the community. Use of Ig to prevent hepatitis spread in day-care centers seems to be an excellent means of controlling this disease, both within the centers and the general community.
In vitro measurement of antithyroid compounds and environmental goitrogens.
A specific, sensitive, and reproducible in vitro assay for antithyroid compounds and environmental goitrogens has been used to investigate antithyroid activity (AA) in small samples of water supplying 15 localities in endemic and nonendemic goiter areas of western Colombia. A significant positive correlation was observed between goiter prevalence and AA in water collected from the pipelines of these localities. Samples at the water source showed only borderline significance. No significant correlation was observed in waters between AA and total hardness (ppm) or concentrations of Ca, Mg, sulfates, chlorides, silicates, nitrates, and iodine. AA was also demonstrated by this in vitro assay in well water previously shown experimentally to be goitrogenic and that supplied the endemic goiter district of Candelaria town in western Colombia. In contrast, water from the well supplying the area of lower endemicity was found to possess little AA. These results provide experimental support for epidemiological observations that demonstrate a relationship between the sources of drinking water and goiter prevalence rates, and are consistent with previous findings indicating that organic antithyroid compounds contaminate water supplies in areas where goiter persists despite adequate iodine supplementation.
Debt financing: an alternative for hospital construction funding.
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Inpatient medical rehabilitation: results of the 1981 survey of hospitals and units.
This paper analyzed the results of the American Hospital Association's (AHA) 1981 survey of inpatient medical rehabilitation hospitals and units, which obtained information for 1980, and notes important differences from the patterns revealed by the survey when it was first conducted in 1979. The survey sample consisted of 554 hospitals, 334 of which responded to the questionnaire. Three categories of these hospitals (independent rehabilitation hospitals, self-contained rehabilitation hospitals within larger medical centers, and defined rehabilitation units of institutions) are examined in terms of utilization, referral sources of their admissions, places to which their patients were discharged, composition of their full-time equivalent professional medical staff, and sources of payment for inpatient claims.
Parkinson's disease: long-term results of levodopa therapy.
The long-term results of levodopa therapy in Parkinsonian patients is described. Between January 1969 and December 1972, dopaminergic therapy was started in 186 patients with Parkinson's disease. Their progress after six months, five years and in the autumn of 1980, was assessed. The initial benefit in the majority of patients was followed by a gradual loss of efficacy in most patients with increasing side effects of central-mediated type. We suggest that it may be wise to delay the onset of levodopa therapy until progress of the disease makes treatment imperative.