摘要:

To try to explain the wide therapeutic range of cyclosporin A, we examined its effects on physiological functions of skin and responses to immunological and inflammatory stimuli during and before or after administration of 5 mg/kg/day of cyclosporin A in the treatment of various skin diseases.Pilocarpine-stimulated sweat rate (10 patients), sebum excretion rate (10), scalp hair growth rate (8) and epidermal proliferation in response to tape-stripping (7) were not affected by cyclosporin A; nail growth rate was unaltered in patients without psoriasis (12), but was significantly slowed by treatment in patients with psoriasis (7) who had abnormally rapid growth before treatment.Induction of cell-mediated sensitisation to 2,4-dinitrochlorobenzene (DNCB) was inhibited by cyclosporin A treatment (22 patients), but 7 patients sensitised to DNCB before cyclosporin treatment reacted normally to DNCB challenge during treatment. The immediate hypersensitivity response to intradermal house dust mite antigen was increased during treatment in 8 patients with atopy.Weal responses to histamine (9 patients) and compound 48/80 (12), the 24 hour erythemal response to ultraviolet B (UVB) irradiation (10) and the inflammatory response to topical leukotriene B4(16) were not affected, but cyclosporin A produced a striking inhibition of anthralin inflammation (21).Since the methods we used will have detected all but minor changes, we conclude that cyclosporin A has no gross physiological effects on the skin and is not cytostatic; hypertrichosis must be due to a prolonged hair cycle. Secondly, cyclosporin A (a) impairs induction of cell-mediated sensitisation in doses which permit some continued expression, but (b) increases immediate hypersensitivity. Thirdly, cyclosporin A has no general anti-inflammatory effect, but we have found a novel and specific inhibitory effect on anthralin inflammation, the mechanism of which may underlie some of its therapeutic effects. The therapeutic effect of cyclosporin A may not be due solely to its immune effects, and other activities such as the anti-inflammatory effect we found need further exploration.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

In a double-blind randomised parallel group trial comprising 146 patients, a new calcium antagonist, isradipine, was compared with hydrochlorothiazide with regard to blood pressure lowering effect and adverse events during treatment of mild to moderate hypertension. Isradipine was given in doses between 2.5 and 10mg twice daily, and hydrochlorothiazide at a dosage of 25 to 50mg once daily for 10 weeks. Both treatments reduced blood pressure, with no difference between the treatment groups, and the number of responders did not differ. Patients not obtaining a diastolic blood pressure ⩽ 90mm Hg on monotherapy received the second drug, with a further relevant lowering of blood pressure. More patients experienced newly occurring adverse events during treatment with isradipine (44) than with hydrochlorothiazide (28; p < 0.05). Palpitation, flushing and oedema were all more common in the isradipine group. Mean doses during therapy were isradipine 11.7 mg/day and hydrochlorothiazide 39.8 mg/day. During treatment with isradipine, white blood cells (p < 0.01), alkaline phosphatase (p < 0.0001), albumin (p < 0.05) and serum calcium (p < 0.05) increased, whereas serum potassium (p < 0.05) decreased. Hydrochlorothiazide decreased serum sodium (p < 0.01) and serum potassium (p < 0.01), but increased serum uric acid (p < 0.001).It is concluded that isradipine lowers blood pressure as effectively as hydrochlorothiazide, but produces more subjective adverse events at the doses used. Combining the 2 treatments results in additional blood pressure reductions. Whether isradipine is as useful as hydrochlorothiazide for the treatment of arterial hypertension cannot be established from the present study.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

From a total of 50 healthy male Filipino subjects enrolled in the study, 34 completed a 10-month open-label evaluation of 2% topical minoxidil. The remaining 16 withdrew because of disinterest or noncompliance with the regular monthly follow-ups. Both objective measurement of hair growth by counting of indeterminate and terminal hairs in the target balding area and subjective evaluation by subjects and investigators were made, and photographs taken to document the efficacy of new hair growth.52% of subjects noted minimal new hair growth, while 42% noted moderate new hair growth. In comparison, the investigators rated 79% of subjects as having minimal new hair growth and 21% as having moderate new hair growth. Overall, 70.5% of subjects noted decreased shedding at the end of treatment. Furthermore, terminal hair counts at the end of treatment showed statistically significant (paired t-test) growth. No significant physical findings or laboratory abnormalities were seen.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

The barrier properties of an alginate antireflux agent (Liquid Gaviscon®, Reckitt and Colman, UK) were investigated using a portable cadmium telluride detector worn on the chest wall over the oesophagus to detect the reflux of radiolabelled food, with simultaneous oesophageal pH monitoring. A crossover study was performed in 12 healthy nonpatient volunteers.An oesophageal pH probe was placed coincident with a small &ggr;-detector strapped to the chest wall and the positioning verified using &ggr;-scintigraphy. A test meal designed to promote reflux was radiolabelled and administered to the subjects. On 1 occasion, subjects received only the meal, and on the second occasion the subjects also received a 20ml dose of alginate antireflux agent (Liquid Gaviscon®) 30 minutes after the meal had been consumed. The reflux of radiolabel and acid was monitored for 3 hours post-prandially.The antireflux agent was found to significantly reduce the amount of both acid and food reflux. The length of time for which the pH in the oesophagus was below 4 was 19.9 ± 1.6 minutes (mean ± SEM) in the untreated group, but 3.0 ± 4.0 minutes for the treated group. Although the absolute amounts of acid refluxed cannot be measured, it is possible to estimate the ratio of amounts of acid refluxed in treated and untreated groups. This ratio was 0.119 ± 0.028, indicating that the antireflux agent prevented the reflux of 88% of the acid refluxed by the untreated group. The ratio of the amount of food reaching the oesophagus in treated and untreated groups could be similarly estimated from the refluxed activity data as 0.095 ± 0.024, indicating suppression of food reflux by 90%. This study demonstrates that Liquid Gaviscon® significantly reduces the reflux of both food and acid.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

A phase I study with the combination of ifosfamide + carboplatin + etoposide (ICE) was conducted in patients with advanced non-small-cell lung cancer (NSCLC). Patients who had had previous therapy were given the following dosages: ifosfamide 2 g/m2on days 1 to 3, carboplatin 75 mg/m2on days 1 and 2, and etoposide 80 mg/m2on days 1 and 2. In those with no previous therapy, carboplatin 75 mg/m2was administered on days 1 to 3. In 15 treated patients, 3 objective responses were documented, all from the 7 patients with no prior therapy. The dose limiting toxicity was leucopenia. A phase II study is required to determine the exact activity of the combination in patients with advanced NSCLC.Two patients with limited NSCLC were treated with high doses ICE (ifosfamide 6 g/m2on day 1; carboplatin 400 mg/m2on days 1 and 2, and etoposide 500 mg/m2on days 1 and 2) and autologous bone marrow infusion followed by local therapy. Toxicity was acceptable. Responses were of short duration (10 months) and both patients died 13 and 15 months, respectively, after the start of therapy.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

The effect of the histamine H2-antagonists cimetidine and ranitidine on aminopyrine accumulation stimulated by forskolin was investigated in isolated guinea pig parietal cells. Forskolin (10−5mol/L) caused a 2.2-fold increase in acid production, assessed as [14C]-aminophenazone (aminopyrine) accumulation, and a 19-fold increase in cyclic AMP. The H2-antagonists (10−4mol/L) almost completely inhibited the forskolin-induced aminopyrine accumulation, without affecting the cyclic AMP level. Histamine released by forskolin from contaminated cells into the media was 5.08 ± 0.28 × 10−8mol/L, which was not sufficient to stimulate acid secretion in parietal cells. Therefore, it is suggested that the H2-antagonists may inhibit acid secretion at the step subsequent to the synthesis of cyclic AMP, in addition to antagonism of the histamine receptors.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

We enrolled 14 human volunteers in a crossoverex vivostudy comparing 6 regimens including amikacin (0.5g), ceftazidime (2g), cefoperazone (2 and 4g) and the combination of each cephalosporin (2g) with amikacin. The antibiotics were given by intravenous infusion over 30 minutes. Blood samples were obtained 1, 4, 6 and 12 hours after the end of infusion to measure serum concentrations, bactericidal titres and killing rates. Two parameters were derived from the killing curves: the initial rate of killing and the relative bioactivity (area under the time-kill curve as a percentage of the control growth curve). The elimination half-life of cefoperazone was decreased by concomitant administration of amikacin, resulting in higher trough levels. Although synergy was seen in the checkerboard method in half of the strains, serum bactericidal titres unusually showed synergy which was more frequent with cefoperazone + amikacin than with ceftazidime + amikacin. For both cephalosporins, the relative bioactivity, but not the killing rate, was dependent on concentration. Ceftazidime had a higher intrinsic activity despite the higher serum concentrations obtained with cefoperazone. The addition of amikacin conferred concentration dependency of the killing rate to the combination. None of the regimens tested provided enough antimicrobial activity to support once daily administration.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

摘要:

A total of 243 patients were entered at 20 general practice centres in the UK in this 6 week, double-blind, randomised, parallel-group study, which was designed to compare the safety and efficacy of nabumetone (1g at night) and slow-release diclofenac (100mg at night) in the treatment of osteoarthritis.Seven parameters of efficacy were measured, adverse events were recorded and laboratory monitoring was carried out.At the end of the study, both treatment groups showed highly significant clinical improvement with no significant intergroup differences.24 patients (20%) in the nabumetone group and 21 (17%) in the slow-release diclofenac group withdrew before the end of 6 weeks, mainly because of adverse events. Although overall the incidences of adverse events were similar in both treatment groups, significantly fewer patients complained of digestive system side effects in the nabumetone group (21) than in the slow-release diclofenac group (35) [p = 0.03].The study was also intended to evaluate the effectiveness of study monitoring by a clinical research associate who attended study centres with a laptop microcomputer to enter trial data. Immediate correction by the trialist of errors and omissions in the data, with on-site data entry on the laptop computer, contributed to trialist motivation and resulted in rapid recruitment of patients, collection of high quality data and speedy analysis at the end of the trial.

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS

ISSN:0114-2402    

出版商:ADIS    

年代:1990

数据来源: ADIS