The treatment of hypertension in diabetic patients.
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Biomedical subjects
Publications and source records attributed to H Ross.
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Common seal populations around the Scottish coast were less severly devastated by phocine distemper than those on the Continent. Nevertheless, over a 4-month period, 59 common seals were examined postmortem. The macroscopic and histopathological lesions are described. Forty-two per cent of these seals were considered to be suffering from phocine distemper. Serology on 29 of the 59 seals was undertaken and the results are discussed in relation to the histopathological findings. Bordetella bronchiseptica proved to be an important secondary invader in phocine distemper virus infected seals. Verminous pneumonia was shown to be a frequent problem, particularly in juveniles.
Origin of a pulmonary artery from the aorta is a rare congenital defect which usually is fatal if not surgically corrected in infancy. Medical treatment often is unsatisfactory because of progressive heart failure. Described is a 19-year follow-up of a patient who underwent surgery at age three weeks to correct a right pulmonary artery from the aorta.
A prospective, randomized, single-blind, controlled clinical trial was undertaken to determine whether two doses of systemic Timentin provided superior prophylaxis against postoperative sepsis in elective colorectal surgery compared with a single dose of the same antibiotic. Timentin, a combination of ticarcillin and clavulanic acid was administered intravenously (3.1 g) at the commencement of operation to all patients, and this was repeated after 2 hours in those patients randomized to receive a second dose. The wound infection rate was 11 percent in the 143 patients completing follow-up and receiving a single dose, and 13 percent in the 128 patients receiving two doses of Timentin (P greater than 0.05). The rates of postoperative septicemia 3 vs. 4 percent and intra-abdominal abscess 5 vs. 8 percent were similar. Multivariate analysis of the factors likely to affect postoperative would infection rate demonstrated an association with the type of hospital, public or private, wound infection rate 16 and 6 percent, respectively (P less than 0.01), and the surgeon group defined by the number of patients contributed greater than 25 or less than 25, wound infection rate 6 and 18 percent, respectively (P less than 0.05). We concluded that a single dose of intravenous Timentin was as effective as two doses for prophylaxis against surgical infection and that the surgeon group and the hospital in which the operation took place were statistically significant predictors of postoperative wound infection.
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The case histories of three patients with hyperthyroidism due to overproduction of thyroid-stimulating hormone (TSH) by the pituitary gland are described. In the first patient treatment with the T3-metabolite 3,5,3'-triiodothyroacetic acid (TRIAC) led to complete clinical and biochemical normalization. In the second patient treatment with the dopaminergic agonist bromocriptine led to a temporal amelioration of hyperthyroidism. In the third patient, who was the only one with a proven pituitary adenoma, hypersecretion of TSH could be controlled by administration of the somatostatin analogue octreotide. It is emphasized that patients with this disorder should preferably not be treated with thyrostatic drugs, radioactive iodine or thyroid surgery. The success rate of these treatment modalities is lower than normal, they may lead to an increase of goiter size, and they potentially may promote growth or development of a TSH-producing adenoma. Treatment should be aimed at diminishing TSH hypersecretion.
Many of the complications of diabetes appear to be closely linked to increased conversion of tissue glucose to sorbitol which is catalysed by aldose reductase (aldehyde reductase 2, ALR2). Inhibition of ALR2 could, therefore, lead to a reduction in the development of diabetic complications. Ponalrestat ["Statil" (a trademark, the property of Imperical Chemical Industries PLC), "Prodiax" (a trademark, the property of Merck, Sharp and Dohme), ICI 128436, MK538] inhibits ALR2 from a number of sources. Until now, the mechanism of this inhibition has not been fully elucidated. In this paper, we present a detailed mechanism for inhibition of bovine lens ALR2 by ponalrestat. Treatment of humans with some ALR2 inhibitors leads to side-effects, some of which may result from interactions with other enzymes. Aldehyde reductase (ALR1) is probably the most closely related enzyme to ALR2. Inhibition of ALR1 from bovine kidney was, therefore, investigated in order to assess the specificity of ponalrestat. The values of Ki and Kies (apparent dissociation constants for inhibitor from enzyme-inhibitor and enzyme-inhibitor-substrate complexes, respectively) for the interactions of ponalrestat with ALR1 and ALR2 has been calculated by non-linear fitting of kinetic data. These values indicate that ponalrestat does not compete with binding of glucose of NADPH to ALR2, nor with binding of glucuronate or NADPH to ALR1. Lack of competition and the structural dissimilarity of substrates and inhibitor make it unlikely that ponalrestat will utilize substrate binding sites on other enzymes, and so produce undesirable side-effects via such a mechanism. Ponalrestat is a potent inhibitor (Ki = Kies = 7.7 nM) of ALR2 and follows a pure noncompetitive mechanism with respect to glucose. Efficacy, therefore, will not be decreased by development of hyperglycaemia. The compound is a mixed noncompetitive inhibitor of ALR1 when glucuronate is varied. The values of Ki and Kies are 60 microM and 3 microM, respectively, so that inhibition tends towards uncompetitive. The selectivity of ponalrestat in favour of ALR2, therefore, lies in the range 390 to 7,800-fold, being higher at lower concentrations of glucuronate. The high selectivity of ponalrestat in favour of ALR2 rather than ALR1 suggests that the compound is unlikely to inhibit other enzymes which have less homology with ALR2.
Photodynamic therapy (PDT) utilizes a photoactivatable preparation, Photofrin II, which selectively localizes in cancerous tissue and produces substances toxic to that tissue when activated by light. Whether PDT would be able to selectively destroy human malignant mesothelioma was investigated by using a human-derived malignant mesothelioma tumor subcutaneously implanted in nude mice. Human malignant mesothelioma was grown subcutaneously to a size of 0.2-0.4 cm3. Selective retention of Photofrin II was studied by measuring light-induced inhibition of cytochrome c oxidase activity in tumor, heart, and lung. Photofrin II was retained in greater quantities in tumor than in heart or lung at 24 hr after injection. Using laser light at 630 nm under varying conditions, tumor growth was measured every 2 days following PDT for 18 days. All PDT regimens were successful in destroying malignant mesothelioma. Photofrin II at 5 mg/kg was superior to 2 mg/kg (P less than 0.005), light delivered at 50 mW/cm2 x 2 hr was superior to that delivered at 200 mW/cm2 x 30 min (P less than 0.05), and a total fluence of 180 J/cm2 was equivalent to 360 J/cm2 in affecting tumor growth. Ten of 12 mice treated at 50 mW/cm2 became tumor-free and remained so for 30 days following treatment. We concluded that PDT was effective against human malignant mesothelioma in a nude mouse model without adversely affecting the animal. A role for PDT in treating patients with malignant mesothelioma may exist.
Pseudomonas cepacia infection has become increasingly common among patients with cystic fibrosis in North America. In a large cystic fibrosis centre in the United Kingdom 11 cases have been identified during the last six years, with a maximum prevalence of 7% in 1988. Three patients have died, two of whom deteriorated rapidly shortly after acquisition of the organism despite intensive treatment with appropriate antibiotics. Analysis of possible causes of the increase in P cepacia infection suggested that neither patient to patient transmission nor the use of nebulised antibiotics was associated with an increased risk of infection.
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A 50 year old man presented with a pyrexial illness following a holiday abroad. Yersinia pseudotuberculosis was isolated from blood culture. Response to appropriate antibiotic therapy was prompt and complete, but full recovery was complicated by an episode of hyperkalaemia, hyponatraemia and the passing of large volumes of dilute urine. Three years previously he had developed diabetes mellitus and hypogonadotrophic hypogonadism. Investigation on recovery showed underlying haemochromatosis and aldosterone deficiency.
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Given the context of a rapidly changing demography and an evolving health care system, the project described in this article was designed to address the system-wide need for changes in allied health service delivery to minority populations. A multidisciplinary, multicultural, and participative model was adopted to initiate attitudinal and behavioral changes among three groups: faculty from three allied health departments, students preparing for careers in these three professions, and community health care practitioners. This paper briefly describes the major objectives, activities, and outcomes of the project as well as insight into the factors and dynamics that affected its immediate and long-range success. The idea that significant and lasting change requires strategies that incorporate the interactive dynamics of individuals and groups of the inclusive health care system was supported in the outcomes of the project.
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Pernasal swabs were obtained on 3 consecutive days from 146 children referred for hospital admission with suspected whooping cough, and immunoglobulin A and immunoglobulin M antibodies to Bordetella pertussis were measured by enzyme-linked immunosorbent assay. The clinical features in 113 of the children were considered consistent with the diagnosis. Sixty-four cases were confirmed by serology, which showed a greater sensitivity (57% vs. 35%) than pernasal swab culture with no loss of specificity (100%). Paired serum samples were necessary for diagnosis in 30 (47%) of these 64 cases. Seventeen (43%) of 40 cases confirmed by pernasal swab culture had negative serologic results. Most of these were young infants who showed a less reliable antibody response. Detection of antibodies to B. pertussis by enzyme-linked immunosorbent assay can be a valuable additional test in the differential diagnosis of whooping cough but is not appropriate as the sole diagnostic test.