THRM forum: My boss.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Hewitt.
Explore the source record for details and available documents.
1. Using the isolated perfused lung preparation we have demonstrated a low-activity ureolytic enzyme present in rodent lung tissue. The enzyme shares four characteristic features with jack bean urease (EC 3.5.1.5). 2. Ureolytic activity was inhibited by fluoride ions and methionine hydroxamic acid; using the latter inhibitor, the I50 value and maximum inhibition were similar to those reported for jack bean urease. The apparent Km for rat lung urease was similar to the plasma urea level. 3. The low level of urease activity in the rat lung and in that of Notomys alexis, a desert rodent, suggests that the enzyme is not involved in urea excretion, rather that pulmonary ammonia production may influence fluid balance at the alveolus.
25 patients with mixed autoimmune haemolysis are described; in these cases the combined criteria for warm antibody autoimmune haemolysis and also the cold agglutinin syndrome were present. The direct antiglobulin tests were positive with IgG and complement coating of the red cells. The IgM and IgG components could be separated. The cold autoantibodies were active at 30 degrees C or above and often showed blood group specificity within the Ii system; specificity was not usually evident in the warm component. Haemolysins were found in 18 patients. Serologically, the condition maintained its mixed nature throughout; only 2 cases later changed to a warm type picture. Mixed autoimmune haemolysis was found in all age groups but was more frequent in later life; the male:female ratio was 1:15. The cases were either idiopathic (44%) or secondary; in the latter, systemic lupus erythematosus or lymphoma were the most frequently associated disorders. The patients tended to have severe haemolysis which, although usually responding well to treatment, ran a chronic course with intermittent exacerbations, thus making overall management difficult; plasma exchange may be a useful adjunct to chemotherapy.
Explore the source record for details and available documents.
The clinical and serological records of 20 pregnant patients with erythrocyte autoantibodies were critically reviewed and analysed. This series, the largest reported, confirmed an association between erythrocyte autosensitization and pregnancy, and suggested that this occurred on an average of 1 in 50,000 pregnancies. The clinical presentation varied from severe haemolytic anaemia to serological abnormalities discovered during the routine testing of well patients; overt haemolysis was present in 7 cases. Treatment was only necessary in 3 patients where the haemolysis was severe. 3 infants were mildly affected with haemolytic disease due to the maternal autoantibodies crossing the placenta but no treatment was needed. The risks to the infant were increased when other active autoimmune conditions (e.g., systemic lupus erythematosus) were present. With early diagnosis and appropriate treatment, outlook for mother and child is good.
The Lewis (Lea) blood group substance in alimentary tract liquids is a large molecule. Ileal and jejunal mucosal preparations can act upon it to produce dialysable serologically active Lea. Alimentary tract bacteria cannot produce a similar effect. Plasma, serum and urinary Lea are principally in the form of a dialysable moiety. It is suggested that this dialysable form is produced by mucosal degradation of large-molecule Lea in the alimentary tract. The small-molecule Lea is absorbed, transported in the plasma and then excreted. Both secretor and non-secretor patients with duodenal ulcer and inflammatory bowel disease have normal urinary Lea titres. Non-secretor coeliac patients who have not regenerated normal jejunal mucosa on treatment have significantly reduced urinary Lea titres when compared with healthy individuals. One non-secretor coeliac patient who had regenerated a normal jejunal mucosa on treatment had a normal urinary Lea titre. Coeliac patients have normal titres of salivary Lea.
The clinical pattern of haemolysis associated with Donath-Landsteiner antibodies has undergone a change over the years. In the current study 13 patients developed the acute form of the disease whilst only 1 presented with the classical picture of chronic paroxysmal cold haemoglobinuria. The acute illness typically occurred in young children with a male predominance of about 2.5:1; 10 patients were less than 5 years old. There was often a history of a preceding infection, the onset was sudden, prostration, haemoglobinuria and pallor were prominent. The patients were very ill but rapid and complete recovery usually occurred within a few days; however, 1 patient died. Treatment consisted of rest and warmth; in addition blood transfusion was needed in 7 patients. The chronic disease (which was non-syphilitic in origin) followed a benign course, warmth and avoidance of cold being all that were necessary to maintain the patient's well-being. It is felt that the general term for this disorder should be Donath-Landsteiner haemolysis rather than the traditional paroxysmal cold haemoglobinuria.
The estimation of endogenous creatinine clearance yields information useful to the renal physiologist without the need to introduce a marker compound. The method has been limited in its application to mammalian species of bodyweight 200 g and above due to the blood sample size required. A modification is described whereby this procedure may be applied to animals of bodyweight as low as 25 g. Use of this microassay is illustrated in an investigation of the effect of salt and urea loading on renal function in an Australian desert mouse, Notomys alexis.
Clinical and serological records of 865 patients with confirmed autoimmune haemolysis (AIH)--a much larger series than any previously reported--were critically reviewed nd analysed. A proposed new classification for AIH based on serological findings differs from traditional classifications in that a new category of "mixed" AIH has been defined in which both "warm" and "cold" autoantibodies are present, and both are capable of causing haemolysis. Patients in this mixed group tend to have severe disease that may run a chronic intermittent course. The presentation of cold agglutinin disease is much more variable than has been seen in previous studies, haemolysis due to low titre autoantibodies being common. The AIH associated with pregnancy, usually considered as being of bad prognosis, is often mild and self limiting in the absence of other associated disorders.
Two new cases of G gamma delta beta thalassaemia and G gamma HPFH (Hb Kenya type) have been characterised in detail and compared with regard to haematological data, globin chains biosynthesis, and intracellular distribution of Hb F. The similarities and differences between these two conditions are discussed in relation to the possible underlying defects at the molecular level and to the control of the gamma delta beta gene complex in general.
Percentage and absolute levels of circulating T lymphocytes were measured in 48 patients with bronchial carcinoma. These were compared with control values from nine healthy adults and 19 age-matched patients with benign disorders. A further 20 patients who had been given postoperative immunotherapy after complete resection of bronchial carcinoma were also studied. There was no significant difference in the mean percentage T cells between the groups. Lymphopenia, however, was a feature of the bronchial cancer patients with metastatic disease. This resulted in a significant diminution of absolute T cells in this group. There is no evidence, with the technique employed in this study, of a total T-cell deficiency in early bronchial carcinoma.
1. We have investigated the water transport and short-circuit current (s.c.c.) response to vasopressin (1 mu./ml. and 100 mu./ml.) in isolated toad urinary bladders (Bufo marinus) following overnight incubation in the presence or absence of steroid-containing Ringer solution. 2. The water transport response to the lower dose of vasopressin (1 mu./ml.) was considerably reduced in 'steroid depleted' conditions, wheras the response to the higher dose of vasopressin (100 mu./ml.) was not similarly affected. 3. Aldosterone 3. Aldosterone 3. Aldosterone (10(-7)M) potentiated the water transport response to the lower dose of vasopressin (1 mu./ml.) but had no effect on the response to the higher dose (100 mu./ml.). 4. There was no effect of 'steroid depletion' or aldosterone treatment on the vasopressin s.c.c. response when measured as a percentage increase above basal levels. 5. In 'steroid depleted' conditions vasopressin (1 mu./ml.) maximally stimulated Na+ transport (s.c.c.) but a higher dose of vasopressin (100 mu./ml.) was required for maximum water transport. 6. We have failed to obtain any potentiation effect of corticosterone (10(-7)M) on the water transport or s.c.c. response to vasopressin (1 mu./ml.).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Anthroponotic cutaneous leishmaniasis (ACL) is a significant public health problem in many towns and cities of south central Asia and the Middle East, resulting in disfigurement and disability which warrants preventive action. A randomized controlled trial was conducted in 1997/98 amongst a non-immune study population of 3666 people in Kabul, Afghanistan, to compare the efficacy of insecticide-treated nets (ITNs), insecticide-treated Islamic cloth wraps (chaddars) used to sleep in, and residual pyrethroid spraying of individual houses for the prevention of ACL. Dosages of insecticide were: ITNs with permethrin, 0.5 g/m2; chaddars with permethrin, 1 g/m2; rooms with lambdacyhalothrin, 30 mg/m2. Cases of ACL were diagnosed on clinical criteria. At the end of the trial period (15 months) the incidence of ACL amongst controls was 7.2%, amongst ITN users 2.4% (OR 0.31, 95% CI 0.2-0.5), amongst impregnated chaddar users 2.5% (OR 0.33, 95% CI 0.2-0.6) and amongst residents of sprayed houses 4.4% (OR 0.60, 95% CI 0.3-0.95). ITNs and impregnated chaddars were equally effective, providing about 65% protective efficacy, with approximately 40% protective efficacy attributable to individual house spraying. No significant differences for age or sex were found between new cases in the intervention and control groups. No serious side-effects were reported and interventions were generally popular; ITNs were the most popular, followed by residual spraying and then impregnated chaddars.
To assess the antimalarial sensitivity of Plasmodium falciparum in vivo and in vitro in a highly endemic area of southern Viet Nam, a field study was conducted (in 1999) at a rubber plantation in Binh Phuoc Province north of Ho Chi Minh City. Fifty patients were treated with either artesunate (4 mg/kg on day 0, then 2 mg/kg on day 1 to 4) or mefloquine (10 mg/kg at 0 h, then 5 mg/kg at 6 h), and their progress was followed for 28 days under standard WHO protocols. Blood spots were taken at baseline from all patients, as well as from those who redeveloped parasitaemia during follow-up, for polymerase chain reaction (PCR) determination of parasite genotypes to assist differentiation of re-infection from recrudescence. Both treatments cleared parasites within 5 days. Of the 25 mefloquine-treated patients, 2 (8%) re-presented with probable re-infections. For artesunate, 4 patients (16%) had re-infections and 5 (20%) had recrudescences. Sensitivity tests in vitro of pre-treatment P. falciparum isolates showed geometric mean IC50 values of 29, 38, 209 and 15 nmol/L for chloroquine (n = 32), mefloquine (n = 33), quinine (n = 31) and artemisinin (n = 31), respectively. There were significant correlations between IC50s for artemisinin and mefloquine (r = 0.72, P = 0.004), and chloroquine and quinine (r = 0.44, P = 0.05). These data show that, although mefloquine has been used for 10 years in Binh Phuoc Province, it remains fully effective, perhaps because an artemisinin derivative is commonly given at the same time. The recrudescence rate for artesunate is similar to those reported in other epidemiological contexts. The present in-vitro data imply that quinine remains effective and that reduced drug pressure has been associated with increased sensitivity of local strains of P. falciparum to chloroquine. Although from one hyperendemic area, these results may have implications for antimalarial prophylaxis and treatment strategies for residents and travellers to southern Viet Nam.
Regular biting collections were conducted in 1993-1994 to investigate seasonal fluctuations in the abundance of anophelines in Afghan refugee villages in north-western Pakistan. Enzyme-linked immunosorbent assay were used to test heads-plus-thoraces for the presence of malaria sporozoites. Anophelines giving positive results for Plasmodium vivax were captured in every month except January. Nine species were positive. Biting rates showed a marked increase in May, after the spring rains, and thus spring transmission of vivax malaria seems certain. However, transmission of vivax malaria reached its peak only after the monsoon in July. To determine the optimal time to control vivax malaria by indoor spraying with residual insecticide, spray campaigns were conducted in either spring or summer in 14 refugee villages. Villages sprayed in July 1994 showed a mean reduction in annual incidence of 62% (95% confidence interval [CI] +/-6%) relative to the previous year, whereas villages sprayed in April 1994 showed only a 15% reduction (95% CI +/- 32%). Parasite prevalence surveys conducted in April and October 1994 confirmed the greater efficacy of spray campaigns waged in July. The insecticide malathion proved as effective as the pyrethroid lambdacyhalothrin, even though several species of anopheline were resistant to malathion.