Broxaterol (Z.1170), a new oral beta 2-agonist compared with salbutamol

The bronchodilating activity and tolerability of a single 0.5-mg oral dose of broxaterol (Z.1170) were evaluated in 18 patients with reversible bronchial obstruction. Salbutamol 4.0 mg and placebo were used as controls. The study design was double-blind within patients. The forced expiratory volume in 1 s (FEV1), pulse rate, and blood pressure were measured immediately before and 0.5, 1, 2, 3, 4, 5, and 6 h after each treatment. At the same time clinical controls were made to detect the possible presence of side effects. Both broxaterol and salbutamol caused significant increases in FEV1 until the 5th hour as compared to baseline values and until the 2nd hour as compared to placebo. No significant difference was reported between the effects of broxaterol and those of salbutamol at all the times considered. The tolerability of broxaterol was good, as was that of salbutamol. The pulse rate and blood pressure did not show any significant clinical variations. The side effect reported most frequently was tremor.     

聚合白蛋白和32P胶体局部放射治疗肝癌30例分析

目的 探讨局部注射32P胶体和聚合白蛋白(MAA)治疗中晚期肝癌的可行性。方法 超声引导下瘤内注射MAA和32P胶体治疗中晚期肝癌30例，并观察其疗效和毒副作用。结果 治疗后所有患者临床症状均减轻，AFP水平明显下降；平均肿块缩小率为53．25％，组织学检查显示治疗区内肿瘤组织完全或部分坏死、纤维化。6个月、1年、2年和3年生存率分别为100％、90％、76．67％和43．33％，平均生存期19．5个月。治疗前后肝肾功能、血常规和免疫功能均无明显变化，局部无并发症发生。结论 对于晚期肝癌患者，局部注射放射性核素32P胶体和聚合白蛋白是一种简单、安全和有效的新方法，副作用低、适应证广。     

Single dose mebendazole therapy for soil-transmitted nematodes

Four hundred and fifty subjects were included in a study of the prevalence of soil-transmitted nematodes in Ujung Pandang, South-Sulawesi, Indonesia. Trichuriasis was the most prevalent infection (93.3%), followed by ascariasis (80.2%) and hookworm infection (19.5%). Among 156 subjects who were given 500 mg of mebendazole in a single dose, treatment resulted in cure rates of 93.4%, 77.6%, and 91.1%, and average egg-count reduction rates of 99.0%, 92.8%, and 98.3%, for ascariasis, trichuriasis, and hookworm infections, respectively. Mebendazole appeared to be equally effective against necatoriasis and ancylostomiasis. The drug was well tolerated and almost no side effects were observed. Single dose mebendazole treatment appears to be relatively inexpensive, convenient, and effective in mass treatment for the control of intestinal nematode infections, especially in highly infected communities.     

Efficacy of disopyramide and mexiletine used alone or in combination in the treatment of ventricular premature beats

The efficacy of oral disopyramide and mexiletine used alone or in combination was studied in 75 patients with frequent ventricular premature beats (VPBs). The efficacy was evaluated with 24-hour ambulatory ECG and 75% reduction in the number of VPBs was defined as effective. When disopyramide or mexiletine were ineffective or not tolerated, the alternative drug was administered and the efficacy was again evaluated. If the single administration of neither drug was effective, the combination of disopyramide and mexiletine was then given. Either disopyramide or mexiletine was effective in 48 patients, and neither drug was effective in 19 patients. In 19 patients unresponsive to both drugs, combination therapy was effective in six patients (32%). Both drugs caused side effects or one drug caused side effects and another drug was ineffective in eight patients. In five out of those patients, we attempted combined therapy with a reduced dosage of those drugs that caused side effects. This therapy was effective in two patients without intolerable side effects. Thus, when the single use of neither disopyramide nor mexiletine single-drug therapy is effective, it is worth-while to try combination therapy. Also, combination therapy with a reduced dosage of the drugs that caused side effects might be the therapy of choice in patients who have developed dose-dependent side effects.     

Clinico-parasitological research in a focus of intestinal nematodiasis in Habak Province (the Socialist Republic of Vietnam) and the efficacy of medamine treatment in these infestations

The authors described the focus of intestinal nematodiasis in Vietnam with the rate of infestation on the average 74.6% for ascaridiasis, 30.8 for trichocephaliasis and 20.2% for ancylostomiasis. The high rate of the geohelminthic infestation was related with the use of untreated feces for the vegetables rearing. The clinical symptoms of intestinal nematodiasis were featured by dyspepsia, pain and asthenoneurotic syndromes. The first field trials of mediamine treatment were performed for 267 patients in the high-intense foci of intestinal nematodiasis in the tropics. In trichocephaliasis patients therapeutic efficacy of the drug was 74%, in ancylostomiasis patients it was 71.9, in ascaridiasis patients 68.4%. Retrograde ascarid migration was noted in two patients.     

Use of recombinant human gamma interferon in patients with rheumatoid arthritis

In a clinical phase II trial the efficacy and side effects of recombinant human interferon gamma in 13 patients with rheumatoid arthritis (RA) are reported. 2 patients (15.3%) showed a marked improvement of rest- and motion pains and of their general motility after a 6 and 8 month treatment. Only a temporary improvement within 2-3 months was observed in 4 patients (30.7%). In 2 cases a reduction of the erythrocyte sedimentation rate and in 4 cases a reduction of the alpha-1 acid glycoprotein and of the number of thrombocytes was documented parallel to the clinical improvement. 3 patients developed new antinuclear antibodies (ANA) or showed an increased titer of ANA. Fever was the most common side effect followed by lymphopenia and increased liver values. All side effects were reversible after dosage reduction. Our results confirm the relatively good short term efficacy of human recombinant interferon gamma in RA. In contrast, the clinical long term benefit remains doubtful.     

Efficacy and complications of argon plasma coagulation for hematochezia related to radiation proctopathy.

BACKGROUND: Endoscopic treatments effectively control bleeding caused by radiation proctopathy. The aims of this study were to determine the efficacy and side effects of argon plasma coagulation in the treatment of this type of bleeding. METHODS: Records of 21 consecutive patients in whom argon plasma coagulation was used to treat hemorrhagic radiation proctopathy were reviewed. RESULTS: Pharmacologic measures had been unsuccessful in 12 patients. Endoscopic treatment had been unsuccessful in 5 patients. All patients were anemic and 4 had received blood transfusions. The mean number of treatment sessions was 1.7, and 10 patients were successfully treated in single session. Rectal bleeding resolved within 1 month of the last treatment in 19 patients, usually on the day of the last procedure. Bleeding resolved 2 months after cessation of therapy in another patient. Short-term side effects occurred in 3 (14%) patients (rectal pain, tenesmus, and/or abdominal distention); long-term complications (rectal pain, tenesmus, diarrhea) developed in 4 patients (19%). CONCLUSIONS: Hematochezia caused by radiation proctopathy is effectively controlled by argon plasma coagulation, in some cases after a single treatment session. Treatment may result in protracted bowel symptoms.     

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

AIM:To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride(PLC) in colonic inflammatory bowel disease.METHODS:Patients suffering from mild to moderate ulcerative colitis(UC) or Crohn's disease(CD) colitis,with disease activity index(DAI) between 3 and 10 and under stable therapy with oral aminosalicylates,mercaptopurine or azathioprine,for at least 8 wk prior to baseline assessments,were considered suitable for enrollment.Fourteen patients were enrolled to assume PLC 2 g/d(two active tablets twice daily) orally.Clinical-endoscopic and histological activity were assessed by DAI and histological index(HI),respectively,following a colonoscopy performed immediately before and after 4 wk treatment.Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2.Histological response was defined as an improvement of HI of at least 1 point.We used median values for the analysis.Differences pre-and post-treatment were analyzed by Wilcoxon signed rank test.RESULTS:All patients enrolled completed the study.One patient,despite medical advice,took deflazacort 5 d before follow-up colonoscopy examination.No side effects were reported by patients during the trial.After treatment,71%(SE 12%) of patients achieved clinical response,while 64%(SE 13%) obtained remission.Separating UC from CD patients,we observed a clinical response in 60%(SE 16%) and 100%,respectively.Furthermore 60%(SE 16%) of UC patients and 75%(SE 25%) of CD patients were in clinical remission after therapy.The median DAI was 7 [interquartile range(IQR):4-8] before treatment and decreased to 2(IQR:1-3)(P 0.01) after treatment.Only patients with UC showed a significant reduction of DAI,from a median 6.5(IQR:4-9) before treatment to 2(IQR:1-3) after treatment(P 0.01).Conversely,in CD patients,although displaying a clear reduction of DAI from 7(IQR:5.5-7.5) before therapy to 1.5(IQR:0.5-2.5) after therapy,differences observed were not significant(P = 0.06).Seventy-nine percent(SE 11%) of patients showed improvement of HI of at least 1 point,while only one CD and two UC patients showed HI stability;none showed HI worsening.Median HI decreased from 1(IQR:1-2),to 0.5(IQR:0-1) at the endoscopic control in the whole population(P 0.01),while it changed from 1(IQR:1-2) to 0.5(IQR:0-1) in UC patients(P 0.01) and from 1.5(IQR:1-2) to 0.5(IQR:0-1) in CD patients(P = not significant).The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients.No side effects were reported during treatment or at 4 wk follow-up visit.CONCLUSION:PLC improves endoscopic and histological activity of mild to moderate UC.Further studies are required to evaluate PLC efficacy in colonic CD patients.     

THE EFFECT OF A NEW ERGOLINE DERIVATIVE, CU 32-085, IN THE TREATMENT OF ACROMEGALY. A CONTROLLED STUDY

The effect of a new dopamine agonist, CU 32-085 (8 alpha-amino-ergoline), on pituitary function in acromegaly was evaluated by a controlled, single blind study of 12 acromegalics. The study included a single dose placebo/drug (0.5 mg CU 32-085) trial and a long-term crossover trial with 3 month periods (placebo/CU 32-085 8 mg daily). The patients were evaluated clinically and biochemically (oral glucose tolerance (OGTT), TRH- and LHRH-tests) before and after each 3 month period. Nine patients completed this long-term trial; one died from myocardial infarction during the placebo period, and two dropped out because of side effects. The release of GH, judged from more than 9 h suppression of serum GH following the single dose, and from the response to OGTT after the long-term treatment, was significantly inhibited by CU 32-085. Serum GH reached normal values in 4 of 9 patients. Serum PRL was also markedly suppressed, to subnormal values after the 3 months in all but one hyperprolactinemic patient. Serum TSH, cortisol, FSH and LH were generally unaffected. Glucose tolerance was not significantly altered, although an improvement was found in six of nine patients. A semiquantitative evaluation of subjective symptoms showed a significant improvement following the long-term treatment, while objective signs of acromegaly were unaffected. The blood pressure was slightly lowered, both after a single dose and after 3 months' treatment. Seven patients experienced nausea and dizziness, two of them with vomiting, after a single dose of the drug. Four of these had similar symptoms initially during the long-term treatment, which forced two to interrupt the trial. We conclude that CU 32-085 caused a marked suppression of the release of GH and PRL and an improvement of the major symptoms of acromegaly, a therapeutic effect that is comparable to the previous experience with bromocriptine.     

The efficacy and safety of leflunomide therapy in lupus nephritis by repeat kidney biopsy

To evaluate the clinical and pathological efficacy, and safety of leflunomide as a new immunosuppressive medicine in lupus nephritis (LN). A total of 31 patients were all determined as LN by kidney biopsy. SLE disease activity index (SLEDAI), clinical and immunological tests of these patients were performed. Meanwhile, the pathological presentation and LN activity of before and after leflunomide therapy were evaluated by repeat biopsy. The patients of LN usually have a bit response by the first or second month visit and have a good response by the third month visit after leflunomide therapy. One year later SLEDAI scores of all patients were significantly improved and 13 patients of them were transformed from complex pathological types to simple types (the transformed ratio was 41.9%). For the other patients not transformed, the pathological presentation took a favorable turn, the pathological active index (AI) of LN were significantly improved. There was not anyone relapsed or aggravated. The side effects of leflunomide were less and mild, and could be improved by symptomatic management with or without decreasing dosage. The clinical and pathological activity of LN can be apparently inhibited and the relapse can be prevented through leflunomide therapy. The side effects of leflunomide are mild and transient. Leflunomide is now a new ideal immunosuppressive medicine in the therapy of LN.     

Beneficial effects of low dose amiodarone in patients with congestive cardiac failure: a placebo-controlled trial

The effects of amiodarone in a low dosage (200 mg every 8 h for 2 weeks, then 200 mg/day) was assessed in a double-blind placebo-controlled trial in 34 patients with a history of severe congestive heart failure but no sustained ventricular arrhythmia. Left ventricular ejection fraction, treadmill exercise tolerance and 48 h electrocardiographic monitoring were assessed before and repeatedly after beginning amiodarone or placebo therapy over 6 months, and side effects were monitored. In patients receiving amiodarone, the ejection fraction increased significantly from 19 +/- 7 to 29 +/- 15% at 6 months (p less than 0.01 from baseline), but not significantly in 14 placebo-treated patients (18 +/- 5 to 22 +/- 9%). Exercise tolerance increased significantly in amiodarone-treated patients (median 433 s to 907 s, p less than 0.05), but not significantly in placebo-treated patients (757 to 918 s). Nonsustained ventricular tachycardia was present in 88% of amiodarone-treated patients before, but in only 21% of patients after 6 months of treatment (p = 0.06); it was seen in 43% of placebo-treated patients at baseline and in 50% after 6 months. Fifty percent of amiodarone-treated patients had side effects (principally nausea) and the drug was withdrawn in 28% of cases; no life-threatening effects were seen. Low dose amiodarone appears to have a multifaceted potential to produce benefits in arrhythmia control, exercise tolerance and ventricular function in patients with a history of severe congestive heart failure, but better control of side effects (principally nausea) appears essential. Effects on mortality could not be determined from this study; such assessment requires a larger cohort of patients.     

Intravenous clonidine in acute myocardial infarction in men

We studied the effects of intravenous clonidine treatment in a group of 24 patients with acute myocardial transmural anterior and/or lateral wall infarction. Clonidine, known as an antihypertonic agent, was administered as a bolus of 1–2 μg/kg body weight and repeated every 2–3 hr. However, maximal range of the time interval was 20 min to 4 hr, maximal range of doses 37 to 150 μg, depending on the hemodynamic status. The effects were measured by precordial electrocardiographic mapping as well as serial creatine phosphokinase determinations. A big decrease in ST-segment elevation was observed: ΣST reduction after 24 hr was 37% of initial value (140% in control group), after 48 hr - 30% (120% - control). NST fall after 24 hr - 45% (145% - control), after 48 hr - 41% (142% - control). NQ increased after 24 hr to 135% of initial value (156% - control), after 72 hr to 137% (167% - control). Detailed analysis revealed undoubted correlation between the dosage and favourable dynamics of precordial mapping parameters.Hemodynamic, antiarrhythmic and above all adrenolytic activity were noted. The treatment caused a distinct deterioration in daily adrenalinuria mean values to 5.99 μg in the first day (14.20 - control) and lower in the following days. No side effects were observed but sudden discontinuation of the therapy caused an unfavorable reaction. A temporal association between diminished adrenalinuria and both clinical improvement and limitation of infarct size was observed. Therapy with intravenous clonidine requires meticulous individualization of clonidine dosage depending on the patient's initial hemodynamic status.     

Effect of orally administered 15(R)-15-methyl prostaglandin E2 and/or an anticholinergic drug on meal-induced gastric acid secretion and serum gastrin level in patients with duodenal ulcers.

The purpose of the present series of tests was to measure and compare the effects of ingestion of gelatin capsules containing 15(R)-15-methyl PGE2 (PG) and/or an anticholinergic drug (methscopolamine bromide, Pamine) on meal-induced gastric acid secretion and serum gastrin level. Eleven duodenal ulcer patients were stimulated by a 5% peptone meal. Acid secretion was determined by the intragastric titration technique, and serum gastrin was measured by radioimmunoassay. The tests were randomized and double-blind. PG alone given 30 min before a test meal at a dose of 50 micrograms or 100 micrograms produced no side effects and inhibited meal-stimulated acid secretion by about 43% and 55%, respectively. Gastric acid inhibition after a single dose of PG was most pronounced in the first hour of a test meal and was accompanied by almost complete suppression of the meal-induced serum gastrin level. Pamine alone in a dose of 2.5 mg reduced gastric acid response to a meal by about 29% but caused a further rise of postprandial serum gastrin level over control values. The combination of PG, 50 micrograms, and Pamine, 2.5 mg, did not result in significantly greater acid inhibition (about 48%) than when either compound was given alone. When the higher dose of PG (100 micrograms) was given together with Pamine (2.5 mg), the degree of inhibition produced by PG alone was not changed. It is concluded that PG given orally in capsules is a potent inhibitor of gastric acid and serum gastrin response to a meal and that this effect may be of potential value in the treatment of peptic ulcer disease.     

Pulmonary side effects of interferon-alpha therapy in patients with hematological malignancies

Several side effects of interferon-alpha-2b (IFN-alpha) therapy have been described. Pulmonary side effects have seldom been reported. The four patients we describe all developed respiratory disorders while being treated with IFN-alpha for hematological malignancies. We point out the similarities and differences noticed concerning the clinical course, pathological findings, and prognosis in the four different cases. Also, in addition to our review of the literature, we discuss the possible mechanisms involved in development of lung symptoms. In three patients the pulmonary disorder seems to have been caused by a cell-mediated immunological side effect in the form of interstitial pneumonitis. In one patient the symptoms were most likely caused by an autoimmunologic reaction, primarily engaging the vascular system, initially in the lungs. The single pathological finding existing in all four cases was the marked decrease in carbon monoxide diffusion capacity when performing spirometry. This was not necessarily associated with the existence of radiological findings. The decrease in diffusion capacity and the clinical symptoms were completely reversible in three of the patients, either spontaneously after the withdrawal of IFN-alpha or after treatment with corticosteroids. Our conclusion is that IFN-alpha, on rare occasions, can cause serious pulmonary side effects when used to treat both lympho- and myeloproliferative hematological malignancies. When pulmonary symptoms are evaluated during IFN-alpha therapy, spirometry, including estimation of carbon monoxide diffusion capacity, high-resolution computerized tomography, and ultracardiography should be used.     

依那西普对难治性强直性脊柱炎相关髋关节病变治疗的临床疗效观察

目的 观察肿瘤坏死因子拮抗剂(依那西普)治疗难治性强直性脊柱炎(AS)相关髋关节病变的疗效.方法 35例AS患者同时伴有单侧或舣侧髋关节疼痛及活动受限,既往接受规范非甾体抗炎药及缓解病情抗风湿药治疗病情仍不能控制.我们采用前瞻性开放性临床研究,对35例患者给予依那西普治疗,即依那西普50mg皮下注射,每周1次,疗程12周;同时联合每周甲氨蝶呤(MTX)10 mg治疗.评价指标有Harris髋关节评分、Bath AS髋关节X线指数(BASRI-hip)、Bath AS疾病活动指数(BASDAI)、Bath AS功能指数(BASFI)、红细胞沉降率(ESR)、C反应蛋向(CRP),评价治疗前和治疗12周后以上指标的变化.结果 35例患者中15例为单髋关节受累,20例为双侧髋关节受累,共有55个髋关节受累.Harris髋关节评分治疗后明显升高,治疗前和治疗后分别为(51±4)分和(86±5)分(P=0.000);BASDAI治疗前后分别为6.4±1.2和4.4±0.8(P=0.000);BASFI治疗前后分别为6.3±1.1和3.4±0.8(P=0.000);ESR治疗前后平均分别为(68±28)mm/l h和(25±)mm/l h(P=0.001);CRP治疗前后分别为(59.1±22.3)mg/L和(6.9±1.1)mg/L(P=0.000);但BASRI-hip治疗前后改变不明显.本研究治疗和随访过程中患者未出现结核和其他严重感染.结论 依那西普联合MTX治疗难治性AS髋关节病变能明显改善髋关节功能、很好控制疾病活动度,未见明显不良反应.     

A dose-response study of intravenous enoximone in congestive heart failure

Previous clinical studies with intravenous enoximone have used cumulative dosing to quantify enoximone's hemodynamic effects. The magnitude and duration of the hemodynamic effects of single intravenous doses of enoximone were evaluated in patients with congestive heart failure. Sixty patients, who were in New York Heart Association functional classes III and IV, received single intravenous doses of enoximone, either 0.25 (12 patients), 0.5 (13 patients), 1 (14 patients), 1.5 (10 patients) or 2 mg/kg (11 patients). Cardiac index was increased by 20% with the 0.25 mg/kg dose and by 48% and 42% with the 1.5 and 2 mg/kg doses, respectively. These increases were statistically significant (Student's paired t test with Bonferroni's correction, p less than 0.007) for 1 hour after 0.25 and 0.5 mg/kg, for 2 hours after 1 mg/kg and for 4 hours after 1.5 and 2 mg/kg. Enoximone also reduced pulmonary artery diastolic pressure by 19% with 0.25 mg/kg and by 29% with 2 mg/kg. The duration of effect varied from 1 hour with 0.25 mg/kg to 4 hours with 2 mg/kg. Enoximone produced no consistent or dose-related effects on heart rate or blood pressure. Eighteen adverse reactions were reported by 15 patients, of which 11 were minor and transient (vein pain, flushes, nausea). In 5 patients ventricular or supraventricular arrhythmias were observed, including nonsustained ventricular tachycardia and extrasystoles; 3 of these patients had evidence of arrhythmias before enoximone. Laboratory studies before and after treatment showed no drug-related effects. Dose-related effects on the magnitude and duration of hemodynamic responses to intravenous enoximone were evident within the dose range of 0.25 to 2 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients

AIM: The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients, with a specific attention to cardiovascular effects and to side effects because of this treatment. METHODS: Patients were enrolled, evaluated and followed at three Italian Centres of Internal Medicine. We evaluated 115 obese and hypertensive patients. (55 males and 60 females; 26 males and 29 females, aged 50 +/- 4 with orlistat; 28 males and 30 females, aged 51 +/- 5 with sibutramine). All patients took antihypertensive therapy for at least 6 months before the study. We administered orlistat or sibutramine in a randomized, controlled, double-blind clinical study. We evaluated anthropometric variables, blood pressure and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 113 completed the 4 weeks with controlled energy diet and were randomized to double-blind treatment with orlistat (n = 55) or sibutramine (n = 58). Significant body mass index (BMI) improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups, and body weight (BW) improvement was obtained after 9 (p < 0.05) and 12 (p < 0.02) months in both groups. Significant waist circumference (WC), hip circumference (HC) and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p < 0.05, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05) was present in orlistat group after 12 months. Lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides] reduction (p < 0.05, respectively) was observed in orlistat group and triglyceride reduction (p < 0.05) in sibutramine group after 12 months. No significant change was observed in sibutramine group during the study. No significant HR variation was obtained during the study in both groups. Of the 109 patients who completed the study, 48.1% of patients in the orlistat group and 17.5% of patients in the sibutramine group had side effects (p < 0.05 vs. orlistat group). Side-effect profiles were different in the two treatment groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pressure (both SBP and DBP) in two patients, but it has been controlled by antihypertensive treatment. The vitamin changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation. CONCLUSIONS: Both orlistat and sibutramine are effective on anthropometric variables during the 12-month treatment; in our sample, orlistat has been associated to a mild reduction in blood pressure, while sibutramine assumption has not be associated to any cardiovascular effect and was generically better tolerated than orlistat.     

Comparison of single 7.5-mg dose treatment vs sequential multidose 2.5-mg treatments with nebulized albuterol in the treatment of acute asthma

STUDY OBJECTIVE:s: The purpose of the current trial was to compare the relief of airway obstruction from treatment with a single dose of albuterol,7.5 mg (single-dose group), with that from three sequential doses of albuterol, 2.5 mg, spaced 20 min apart (multidose group). DESIGN: Randomized clinical trial designed to test equivalence. SETTING: Urban county hospital emergency department. Patients or participants: Adult patients between the ages of 18 and 60 years presenting to the emergency department with acute asthma, as defined by the American Thoracic Society criteria, with FEV (1) on presentation to the emergency department of < or = 75% of predicted were included in the study. INTERVENTIONS: After the initial evaluation, patients were administered either albuterol, 2.5 mg via nebulizer every 20 min for a total of three doses, or albuterol 7.5 mg via nebulizer in a single dose. Measurements and results: Ninety-four patients participated, 46 in the single-dose group and 48 in the multidose group. Patients in both groups had severe obstruction on presentation to the emergency department (single-dose group pretreatment FEV(1), 45% of predicted [SD, 16% of predicted]; multidose group pretreatment FEV(1), 47% of predicted [SD, 17% of predicted]; p = 0.62). The primary outcome measure was the change in FEV(1) percent predicted over time. The secondary outcome measures were disposition after treatment (ie, hospitalization or discharge to home) and the incidence of side effects. We noted a 44.5% improvement (SD, 56.2%) in pretreatment to posttreatment FEV(1) values in the single-dose group and a 38.1% improvement (SD, 37.3%) in the multidose group (p = 0.52). A similar proportion of patients in both groups required hospitalization (single-dose group, 48%; multidose group, 41%; p = 0.51). There was a trend for the patients in the single-dose group to experience more side effects than patients in the multidose group (patients in the single-dose group patients, 40% [SD, 19%]; multidose group patients, 22% [SD, 10%]; p = 0.06). CONCLUSION: A single dose of 7.5 mg nebulized albuterol and sequential doses of 2.5 mg nebulized albuterol are clinically equivalent in the treatment of patients with moderate-to-severe acute asthma and result in similar dispositions from the emergency department.     

Comparison of the cardiopulmonary effects of subcutaneously administered epinephrine and terbutaline in patients with reversible airway obstruction.

The cardiopulmonary effects of epinephrine and terbutaline were compared in a doubleblind crossover study in 23 subjects with chronic obstructive airway disease. On each of three days each subject received a single subcutaneous dose of saline, 0.25 mg of epinephrine or 0.5 mg of terbutaline. Treatment with epinephrine produced significant increases in forced vital capacity (FVC), forced expiratory volume in one second (FEV-1), maximal expiratory flow rate (MEFR) and maximal mid-expiratory flow (MMEF). Terbutaline caused even more pronounced increases in all four parameters and exhibited a longer duration of action. Neither drug altered arterial pH, arterial oxygen pressure (PaO-2), or arterial carbon dioxide pressure (PaCO-2). With regard to cardiovascular effects, no alterations in either systolic or diastolic pressure were observed. Administration of epinephrine and terbutaline caused statistically significant increases in heart rate. The effect of terbutaline was more pronounced that that of epinephrine. In addition, terbutaline caused a heart rate-related depression of the T-wave of the lead 2 ECG. Neither drug altered any of the hematologic, hemochemical or urinary parameters monitored before and after treatment. Side effects were seen in eight subjects after administration of saline solution, in 13 subjects after epinephrine and in 19 subjects after terbutaline. None of these side effects was considered clinically serious and none required treatment. It is concluded from this study that subcutaneously administered terbutaline is a more effective bronchodilator than epinephrine.     

Changes in lymphocyte infiltration of the synovial membrane and the clinical course of rheumatoid arthritis

Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clinical index of disease activity (IDA) and spontaneous in vitro synthesis of IgM rheumatoid factor (IgM-RF) by blood mononuclear cells were also measured before and after treatment. In 16 patients (group A), the IDA indicated 26-69% improvement, and the values for spontaneous IgM-RF decreased substantially. In 8 patients (group B), the IDA indicated deterioration or no improvement, and the values for spontaneous IgM-RF were unchanged. In group A patients, the intensity of the T cell infiltrate decreased from a mean score of 1.3 to a mean score of 0.8 (P = 0.025). The ratio of T helper cells to T suppressor/cytotoxic cells was greater than or equal to 2:1 in 90% of group A patients before treatment, compared with 20% of these patients after treatment (P = 0.016), and the number of biopsy samples that contained identifiable B cells decreased from 36% before treatment to 7% after treatment. In group B patients, there were no changes in the intensity of T cell infiltration, the ratio of T helper cells to T suppressor/cytotoxic cells, or the number of biopsy samples with identifiable B cells.