A modern disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A Knight.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Applications of molecular genetic techniques to schizophrenia have shown great initial promise but have then proved disappointing. In order to maximise chances of elucidating the genetic mechanism underlying schizophrenia, diverse strategies and diverse perspectives must be adopted. Most studies begin with the premise that, although schizophrenia may be a heterogeneous collection of diseases, some subtypes will be primarily single-gene disorders. We are concerned that this single-gene hypothesis may be incorrect. Schizophrenia research may benefit from application of knowledge from other disciplines and from other diseases which, in terms of epidemiology and apparent genetic mechanisms, bear some resemblance to schizophrenia.
Inhaled formoterol fumarate, a long acting beta 2 agonist, produces bronchodilatation that is sustained for approximately 12 hours. To determine whether such bronchodilator effects are maintained and asthma control sustained during chronic administration, we monitored airflow indices and clinical control in 112 asthmatic patients who self administered formoterol twice daily for periods ranging from 9 to 12 months. Subjects were recruited immediately following completion of a 3-month double-blind comparison of formoterol, 12 micrograms, bid versus salbutamol, 200 micrograms, qid. Assessments were conducted at baseline, 3, 6, and 9 months, where baseline represents the final visit of the 3-month comparative study. Patients were asked to complete diary cards and twice daily PEFR for a 2-week period before each assessment. Throughout the follow-up study, there was no indication of worsening of asthma control or deteriorating lung function. For the patients who continued to receive formoterol, the previous improvement in asthma control and lung function was maintained at the level reached in the 3-month study. There was an improvement in flow rates and asthma symptoms in the group switched from salbutamol to formoterol by the first clinic visit. This improvement in asthma control and lung function was maintained over the subsequent 6 months. Formoterol was well tolerated during the study period. We conclude that prolonged use of formoterol fumarate twice daily results in sustained improvement in symptoms and flow rates in asthma with no evidence of tachyphylaxis.
Noberastine (NOB), a new histamine H1 antagonist, has potent and specific peripheral antihistaminic activity. To evaluate the efficacy and safety of NOB in ragweed seasonal allergic rhinitis, 250 eligible patients were randomized to one of four parallel, double-blind treatment groups: NOB, 10, 20, and 30 mg, or placebo, each administered once daily for 3 weeks. Rescue medication was prohibited. Efficacy parameters included global response rate (percentage of responders), physician visit, patient-diary symptom scores, and onset of action. Efficacy analyses used alpha = 0.0167 (adjusted for multiple comparisons). Efficacy parameters demonstrated universal superiority of NOB therapy over placebo therapy with statistical significance achieved frequently; no statistically or clinically significant separation was demonstrated among NOB-treated groups. Global-response rates for all active-treatment groups (range, 62.7% to 71.1%) were statistically significantly greater than rates for the placebo-treated group (39.6%). Median time to first relief of symptoms was within 2 to 4 hours for NOB-treated groups versus 72 hours for the placebo-treated group. No significant abnormalities in safety parameters were ascribed to NOB treatment. Incidence and severity of adverse experiences of NOB-treated groups were comparable in incidence and severity to placebo treatment. NOB treatment did not appear to cause weight gain or sedation. Once-daily NOB, 10, 20, and 30 mg, is equally and highly effective and safe in the symptomatic management of seasonal allergic rhinitis compared to placebo.
We compared the efficacy of inhaled formoterol, a long-acting beta 2-agonist, with inhaled albuterol in 145 stable adult asthmatics in a 12-wk multicenter trial. Patients were allocated in randomized double-blind fashion to maintenance therapy with either formoterol 12 micrograms twice a day or albuterol 200 micrograms four times a day in addition to their other asthma medications. Patients were allowed to use "rescue" 100-micrograms albuterol puffs on an as-needed basis. Mean baseline FEV, in the morning before bronchodilator was 2.14 +/- 0.76 L and 1.98 +/- 0.71 L for the formoterol and albuterol groups, respectively, these values being used as baseline covariates in subsequent analysis of predrug and postdrug FEV1. Measured at each clinic visit, morning predrug FEV1 rose significantly with formoterol treatment and was significantly greater at all visits than in the albuterol group, the greatest difference being in Week 8 (2.40 +/- 0.77 versus 1.92 +/- 0.66 L, p less than 0.001). Morning FEV1 30 min postdrug was significantly higher in the formoterol group at Weeks 2 and 8, the trend not reaching statistical significance at other times. Diurnal variation in prebronchodilator peak flow rates was significantly reduced in the formoterol group throughout the trial (17 versus 42 L/min at Week 12, p less than 0.0001). The number of asthma episodes per week was significantly less in the formoterol group during Weeks 4, 8, and 12 as were the number of sleep disruptions during Weeks 2, 4, 6, 8, and 12. Significantly more rescue albuterol was required in the albuterol group by Week 2 and throughout the remainder of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Conventional ultrafiltration (UF) fails to reverse satisfactorily hemodilution and the rise in total body water (TBW) seen after cardiopulmonary bypass (CPB). We have modified the technique, timing, and placement of UF in the CPB circuit and in pilot studies observed controlled elevation of hematocrit and a significantly reduced rise in TBW. We have carried out a prospective randomized study in 50 children undergoing open-heart surgery, comparing modified UF (MUF) with nonfiltered controls. MUF was carried out for 10 minutes after completion of CPB to a hematocrit of 36-42. Fluid balance, TBW (by bioimpedance), and hemodynamics were recorded for 24 hours postoperatively. The results were analyzed using Mann-Whitney U test, comparing controls (n = 24) to ultrafiltered (n = 24). There was one death in each group. Blood loss (ml/kg/24 hr) was 19.5 median (range, 9-30) in the controls versus 12.5 (8-22) in MUF (p = 0.0002); blood transfused (ml/kg/24 hr) 15.5 (3-35) in controls versus 3 (0-11) in MUF (p = 0.0001); colloid transfused (ml/kg/24 hr) 12 (6-56) in controls versus 12 (0-28) in MUF (p = 0.18); percent rise in TBW 11.1 (4.3-16.8) in controls versus 4.0 (1.6-7.9) in MUF (p = 0.0001). There was rise in arterial blood pressure during MUF. Percent rise of systolic blood pressure was 1 (-4 to +9) in controls versus 49 (5-81) in MUF (p = 0.0001); percent rise in diastolic blood pressure 0 (-5 to +8) in controls versus 28 (3-47) in MUF (p = 0.0001). UF reduced the rise in TBW and donor blood requirement associated with CPB in children. The blood pressure rise observed during UF is as yet unexplained, but if proven safe the technique may permit donor blood-free cardiac surgery and prevent the accumulation of potentially dangerous excess tissue fluid.
Health et al. (1989) reported that serum from 96% of unmedicated schizophrenic patients contained IgG autoantibodies specific for the septal region of rhesus monkey brain, compared with 0% of nonschizophrenic control subjects and 6% of schizophrenic patients who were on neuroleptic medication. Using the same technique of crossed immunoelectrophoresis, we have tried to replicate this finding. In contrast to the original report, we observed "positive" precipitin arcs with IgG concentrates from all 14 serum samples tested. The failure of immunoelectrophoretic methods to provide convincing evidence of pathogenic autoantibodies in schizophrenia in no way detracts from the hypothesis that autoimmune processes are involved in some forms of schizophrenia. Such methods have not proved useful in established autoimmune diseases such as Graves' disease and myasthenia gravis in which the pathogenic autoantibodies against cell-surface receptors can only be detected by assays which measure functional interactions with such receptors.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We studied the cost of acquired immunodeficiency syndrome (AIDS) in the Kaiser Permanente Medical Care Program (KPMCP), northern California region. We report the costs of care to the KPMCP and introduce an innovative application of survival methods to cost analysis. From the beginning of the AIDS epidemic in 1981 to the end of June 1987, 866 cases of AIDS were recorded among members of the KPMCP. Estimates of the costs of care of these patients were derived from comprehensive chart reviews of a random sample of 71 patients whose conditions were diagnosed from January 1984 through June 1987. Total mean lifetime costs per patient were $32,816 (median, $28,677), whereas the mean hospital per diem cost was $20,446 per patient. As more care was shifted to outpatient services overtime, overall costs dropped, despite marked increases in the cost of outpatient medications such as zidovudine. The overall estimate of cost compared closely with other estimates of the cost of care in San Francisco, Calif, and it is lower than estimates from elsewhere in the United States, probably because of the low proportion of cases associated with intravenous drug use and the well-developed social support networks available to patients with AIDS in the San Francisco Bay Area.
As part of a study of the effectiveness of beclomethasone dipropionate in perennial rhinitis five immunologically related parameters were measured. These included skin tests, total IgE, specific IgE, nasal and peripheral blood eosinophil counts. In addition, nasal biopsies were obtained in twenty out of sixty patients. It was apparent that patients with perennial rhinitis formed a heterogeneous group who could be divided into three groups based on the extent of immunological abnormality detected. Group 1 consisted of twenty patients who displayed no abnormality in any of the five parameters studied. Group 2 consisted of twenty-six patients in whom specific IgE was not detected but who had varying degrees of abnormal findings in the other laboratory parameters. The remaining fourteen patients formed a third group in whom specific IgE was detected in addition to abnormalities in other parameters. In general, patients with detectable specific IgE had a higher frequency of abnormal parameters, including abnormal histology of their nasal biopsy, than patients in whom no specific IgE was detected. The heterogeneous nature of perennial rhinitis is discussed. Despite the heterogeneous nature of the total patient group, the majority of patients (80%) treated with beclomethasone dipropionate improved compared to 20% improved in the placebo group. There was no difference in the drug effect between the three groups of patients.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Three patients showing features of both lupus erythematosus and lichen planus are described together with their histological, immunofluorescence and other investigative findings. The similarities between lupus erythematosus and lichen planus are discussed and it is suggested that these may be the result of common pathophysiological pathways.