How should we monitor gold therapy?
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Biomedical subjects
Publications and source records attributed to R I Harris.
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A sample of 930 children, between 9 years and 15 years old from six Italian towns, were studied. Their family history of allergy, personal allergy and medical history, current allergy symptoms, exposure to environmental allergens, feeding as infants, and their parents' occupations were recorded. They were skin-prick tested (SPT) with a range of common allergens. A subject was defined as atopic if at least one SPT caused a weal greater than 3 mm diameter. The association between the recorded information and atopy was investigated by logistic multiple regression. Atopy was positively associated with: high density housing; medium or high exposure to environmental allergens; a history of rhinitis, asthma or atopic eczema; male gender; and a history of breastfeeding. It was independent of infectious diseases, vaccinations and operations, social class and family history. Thus, there was no evidence of a genetic factor in atopy, other than sex.
Twenty-six Dermatophagoides pteronyssinus (D.pt.) sensitive subjects were skin prick tested in duplicate with 15 concentrations of D.pt. ranging from 0.0018 to 17.8 mg/ml, 15 concentrations of the major allergen of D.pt., antigen P1, ranging from 0.0002 to 1.88 mg/ml and 15 concentrations of histamine dihydrochloride solution ranging from 0.048 to 114.0 mg/ml. Weal areas and concentrations were transformed by taking logs and linear and non-linear regression curves fitted, allowing for confounding variables, such as subject, and interactions. The weal areas over all concentrations fitted "S" shaped curves with essentially straight central portions, parallel between materials, with differences between subjects but parallel within subjects. The dose response curves of P1 and D.pt. were coincident when the concentrations were adjusted to allow for differences in potency. The concentrations of allergen and histamine commonly used for standardisation purposes will give weals that can be plotted along a straight line, but at higher and lower concentrations the response will tail off. This accounts for previously ambiguous results. Standardisation of allergens using 10 mg/ml histamine is preferable to 1 mg/mg.
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One hundred and two febrile episodes in neutropenic patients were treated with intravenous tobramycin and latamoxef. After 48 h latamoxef at 6 g day-1, patients were randomized to continue this regimen or latamoxef at 3 g day-1. Infections responded to these regimens in 67% and 71% of patients, respectively. Two-thirds of the infections which failed to respond were due to coagulase-negative staphylococci in Hickman catheters, a trend which may necessitate the inclusion of additional antibiotics in future empirical regimens. Prolonged prothrombin times due to antibiotic therapy were seen in nine patients but there was only one episode of bleeding and this responded quickly to treatment with vitamin K and fresh frozen plasma. In 35 patients, coagulopathy was present before antibiotics were started, and these cases also responded to vitamin K. The study shows that the response to tobramycin and latamoxef is comparable to other broad-spectrum antibiotic regimens and that a reduction in the dose of latamoxef after 48 h treatment may safely permit cost savings.
We report the case of a young female patient presenting with a clinical picture of pulmonary embolism, in whom widespread deposits of metallic mercury were demonstrated throughout both lungs and in a lesion on the wrist. These resulted from intravenous injection of mercury by the patient in a suicide attempt.
Five patients with mild hypertension were given single oral doses of Ro 31-1118 (10,20,40, and 80 mg) and placebo in a randomized, double-blind, within-patient study. Plasma concentrations of Ro 31-1118 and supine, standing, exercise, and post-exercise heart rates and blood pressures were measured before and at regular intervals after drug administration. The pharmacokinetic data were consistent with a one-compartment model with first-order absorption and a variable time lag. Peak plasma concentrations and area under curve were linearly related to dose, whereas time to peak concentration, half-time, clearance and apparent volume of distribution were dose-independent. There was a reduction in exercise and post-exercise heart rate of approximately 10% after 10 mg and 20 mg Ro 31-1118, and of approximately 15% after 40 mg and 80 mg. At all doses standing systolic blood pressure was reduced by approximately 5%. A similar fall was seen in exercise and post-exercise systolic blood pressures. There was no substantial effect of Ro 31-1118 on supine or standing heart rates nor on diastolic blood pressure. No adverse effects were reported. It is concluded that Ro 31-1118 has linear pharmacokinetics over the dose range 10-80 mg, and has a weak antihypertensive effect when administered in single doses to patients with mild hypertension.
A 26-year-old man was found to have incomplete polyostotic fibrous dysplasia of bone and elevated growth hormone and prolactin levels. There was roentgenographic evidence of a pituitary tumor. The natural history of fibrous dysplasia in relationship to excess growth hormone secretion since childhood is described.
A total of 617 patients diagnosed by their general practitioner, according to set criteria, as having premenstrual symptoms were treated in general practice for three menstrual cycles with either pyridoxine or placebo. Treatment was randomized and administered blind. In the 434 patients analyzed, an improvement was found in 7 of the 9 symptoms assessed for both treatments, but the differences between treatments did not reach conventional significance levels. However, improvement as measured by global assessment after three cycles was significantly greater in the patients treated with pyridoxine (p less than 0.02).
Sixty patients suffering from Parkinson's disease, irrespective of previous treatment, were recruited and treated with benserazide/l-dopa or carbidopa/l-dopa, randomly allocated, in a double-blind comparative study. Duration of disease on entry was 1 year or less in 70% of patients and was graded as moderate in 55% of patients. Mean age of patients on entry was 76 years for males and 80 years for females. Assessments were made before treatment and after 1 week, 3 weeks, 6 weeks and, finally, at 12 weeks. The dosage of drug was titrated at each visit to give minimum risk with acceptable benefit. Both drugs effectively improved the disability scores of the parkinsonian symptoms and the Sheffield Unit's Activities of Daily Living scores, the latter showing the immediate benefit for the patient in terms of independence. More patients improved in the benserazide/l-dopa-treated group. Furthermore, apart from one activity the improvement in each individual symptom and activity was greater in the benserazide/l-dopa-treated group, but none of the differences reached a statistically significant level. Adverse events recorded during the study were few and in many cases transient. Two patients defaulted (1 on each treatment) and 7 patients died during the study from non-drug-related causes.
Using a recently developed chromogenic substrate assay sensitive to 10 pg/ml Escherichia coli endotoxin in plasma, systemic endotoxaemia was found in 52% of 21 episodes of fever in patients with a haematological malignancy who were infected. Endotoxaemia was also found in 27% of 22 episodes of fever of unknown origin. In 45 afebrile patients neither neutropenia nor cytotoxic chemotherapy was a cause of endotoxaemia. Passage of endotoxin from portal blood into the systemic circulation can contribute to unexplained fever in immunosuppressed patients.
Three rapid assay techniques (latex agglutination, laser nephelometry, and EMIT enzyme immunoassay) have been evaluated for serial monitoring of the serum C reactive protein (CRP) concentration in immunosuppressed patients with fever. Radial immunodiffusion assay was used as a reference method. Latex agglutination reliably distinguished between normal and raised serum CRP concentrations. Enzyme immunoassay also provided a result within minutes, showed particularly close correlation (r = 0.967) with the reference method, and was free from interference by lipaemic or icteric sera. In 27% of 55 episodes of fever studied serially in immunosuppressed patients, the enzyme immunoassay provided clinically useful information by indicating incomplete resolution of infection despite resolution of fever.
A double-blind study was carried out in 312 patients seen by their general practitioner for a sleep disorder requiring hypnotic treatment to compare the efficacy and event profile of flunitrazepam and triazolam. Patients were allocated at random to receive a night-time dose of 1 mg flunitrazepam or 0.25 mg triazolam for a minimum of 7 and a maximum of 14 nights. Sleep disturbances, classified as difficulty in falling asleep, troublesome awakenings in the first or the second half of the night, and early morning awakening, were assessed on the initial and final visits and details of any events recorded. The results showed no significant difference between the two treatments with respect to efficacy and event profile and the findings are discussed in the context of the differing pharmacokinetics of the two drugs.
An improved quantitative assay for endotoxin in plasma was developed after evaluating three different chromogenic substrates and seven methods for removal of plasma inhibitors. Optimal storage conditions for plasma samples prior to assay were also determined. Using chromogenic substrate S2423 with plasma diluted 1/10 in water and heated to 75 degrees C for 5 min to remove inhibitors, a within-batch coefficient of variation of 4% was obtained at levels of endotoxin likely to be encountered clinically. The limit of assay sensitivity was less than 10 pg/ml. This assay provides a sensitive quantitative test for single episodes of endotoxaemia in individual patients but variable activation of the Limulus proenzyme by endotoxin from different bacterial strains limits quantitative comparisons between patients.
Ten men who had FSH-secreting pituitary adenomas were evaluated before and 4-6 weeks after transsphenoidal surgery to determine whether reduction of adenoma mass would ameliorate the hormonal abnormalities associated with these adenomas. Nine of the 10 men exhibited marked reduction in adenoma size, as judged by computerized tomography, an 7 had improvement in vision. The same 9 men also had decreases in basal serum FSH concentrations to within the normal range after surgery. The 1 man who had no reduction in adenoma size by computed tomographic scan and whose serum FSH concentration did not decrease to normal after surgery was also the only patient whose abnormal FSH and LH responses to TRH did not improve after surgery. Another man, who had a reduction in adenoma size and serum FSH concentration after surgery, subsequently had regrowth of the adenoma and concomitant resurgence of the FSH concentration. Two men had increases in their serum testosterone concentrations from subnormal to well within the normal range after surgery, suggesting that gonadotroph cell adenomas may impair LH secretion from normal gonadotroph cells. We conclude that the correlation of reduction in adenoma size with reduction in hormonal hypersecretion after surgery suggests that the hormonal hypersecretion is a direct consequence of the adenomatous tissue.
A linear logistic model is used to compare the performance of a series of head injured patients treated in Auckland with a series obtained from the International Data Bank (IDB), on head injured patients. The IDB patients were treated along conventional lines of neurosurgical management. The Auckland patients were submitted to a regime of elective artificial ventilation of the lungs and heavy sedation, directed against diffuse brain swelling. Two types of comparison were used. First, a model was constructed from the Auckland data of the relationship of outcome to factors relating to the severity of the head injury. This input-output relationship was used to predict the distributions of outcome in the IDB series. Secondly, a descriptive model on the combined Auckland and IDB data was given the option of selecting a dummy variable to indicate whether the source of the patient, Auckland or IDB, had significantly influenced outcome for a given set of other determinants. Differences between Auckland and IDB were only significant if the severity of the head injury in the IDB cases was represented by the set of scores indicating their best condition over the first 24 hours of coma. The scores indicating the condition of the Auckland patients might be comparable to either the 24 hour best or the 24 hour worst IDB scores. One cannot say whether any differences in input-output relationships between the two series arise from differences in coding the input data or from real differences in outcome for given sets of determinants of outcome.
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