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Biomedical subjects

A Knight

Publications and source records attributed to A Knight.

At least 55 records · Page 3Linked to original sources
PubMed1992

Can autoimmune mechanisms account for the genetic predisposition to schizophrenia?

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.

Autoantibodies↗
PubMed1992

Sustained improvement in asthma with long-term use of formoterol fumarate.

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.

Adolescent↗
PubMed1991

Clinical evaluation of the efficacy and safety of noberastine, a new H1 antagonist, in seasonal allergic rhinitis: a placebo-controlled, dose-response study.

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.

Adolescent↗
PubMed1991

A three-month comparison of twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma.

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)

Administration, Inhalation↗
PubMed1991

A successful modification of ultrafiltration for cardiopulmonary bypass in children.

Total body water (TBW) is increased after cardiopulmonary bypass (CPB) resulting in tissue oedema and organ dysfunction. Ultrafiltration has been used to reduce this accumulation of water, although conventional ultrafiltration seemed ineffective in reducing the rise in TBW after CPB in our clinical experience. We describe a modified technique in which ultrafiltration is performed in the first 10 minutes after the patient is weaned from bypass, returning nearly all the blood in the circuit to the patient and elevating the haematocrit (Hct) to any predetermined level. We carried out a pilot study on 21 children aged 4-144 months undergoing open-heart surgery and CPB for congenital heart defects. They were divided into three comparable groups: (1) controls (n = 6); (2) conventional ultrafiltration (n = 7); and (3) modified ultrafiltration (n = 8). TBW (bio-impedance), Hct, osmolality, mean corpuscular volume and mean corpuscular haemoglobin concentration were recorded at frequent intervals. Control patients showed elevation of TBW by 18.2% median (range 14.5-20.3), conventional ultrafiltration by 12.4% (7.9-15.0), modified ultrafiltration by 5.7% (4.5-7.1) (p less than 0.0001 compared to controls, p. less than 0.005 compared to conventional ultrafiltration, Mann-Whitney U test). Hct could be elevated to preoperative levels only by the modified method. Mean corpuscular volume, and mean corpuscular haemoglobin concentration osmolality were unaltered. Ultrafiltration by the modified method was more effective than conventional ultrafiltration in reducing the rise in TBW and elevating Hct after CPB.

Blood Volume↗
PubMed1991

A prospective randomized study of a modified technique of ultrafiltration during pediatric open-heart surgery.

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.

Body Water↗
PubMed1990

Autoantibodies against brain septal region antigens specific to unmedicated schizophrenia?

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.

Adolescent↗
PubMed1990

The cost of acquired immunodeficiency syndrome in northern California. The experience of a large prepaid health plan.

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.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A Canadian multicenter study with Zaditen (ketotifen) in the treatment of bronchial asthma in children aged 5 to 17 years.

One hundred thirty-eight children with chronic asthma, requiring daily treatment with bronchodilators, took part in a 7-month, double-blind, multicenter clinical study. Patients were randomized into two groups, and after a 1-month baseline, were administered Zaditen (ketotifen), 1.0 mg twice daily, or an identical placebo for a period of 6 months. After 10 weeks of receiving the study medication, bronchodilator use was reduced or stopped. In the Zaditen-treated group, 60% of the children taking theophylline were able to stop its use completely, compared to 34% of the patients taking placebo (p less than 0.05). Of the patients who were unable to stop taking theophylline, the Zaditen-and placebo-treated groups recorded average dosage reductions of 62% and 26%, respectively. These differences were statistically significant (p less than 0.05). Thus, a high percentage of patients in the placebo-treated group maintained asthma symptom control with theophylline, whereas most of the Zaditen-treated patients could stop using this medication. Although pulmonary function readings improved in both groups, those patients taking Zaditen demonstrated earlier improvement and greater changes from baseline. Significant differences (p less than 0.05) in favor of Zaditen were found for reduction of concomitant medications, patient's global evaluation, physician's clinical evaluations, incidence of emergency room visits for asthma, and upper respiratory tract infections. No unexpected side effects were observed. It is concluded that Zaditen is an effective medication for long-term control of asthma in children.

Adolescent↗
PubMed1989

Novel benzodiazepine receptor partial agonists: oxadiazolylimidazobenzodiazepines.

The synthesis and biochemical evaluation of a series of oxadiazole derivatives of imidazobenzodiazepines related to the benzodiazepine antagonist Ro 15-1788 (2a) are reported. Although the oxadiazole ring is seen as an isosteric replacement for the ester linkage, significant differences in structure-activity trends were observed. Specifically, oxadiazoles 9-12 invariably had increased receptor efficacy (as witnessed by measurements of the GABA shift) relative to the corresponding ester. Additionally, and in direct contrast to the classical agonists such as diazepam, affinity for the benzodiazepine receptor was enhanced by a 7- rather than 8-halo substituent. The results are discussed in terms of a six-point receptor-binding model originally based on the X-ray structure of 2a. For comparison, the crystal structures of two representative oxadiazole derivatives, 10h and 12o, having a 6-oxo and 6-phenyl group, respectively, were determined and the data incorporated into a modified binding model to account for the greater efficacy of these compounds. It is concluded that the antagonist behavior of 2a relies upon the hydrogen-bond-acceptor properties of the ester carbonyl oxygen whereas for the oxadiazole series this site is localized at the imidazole nitrogen.

Animals↗