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Protein metabolic effects of a prolonged fast and hypocaloric refeeding.

In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underwent a 3-wk fast followed by random allocation to a 1-wk refeeding regimen providing 80 g carbohydrate or protein. Protein metabolism was studied by means of nitrogen (N) balance, urinary 3-methylhistidine excretion, and postabsorptive plasma leucine flux using L-[1-13C]leucine infusions. After the 3-wk fast, plasma leucine flux and 3-methylhistidine excretion both decreased by 31% from control diet values (P less than 0.01), and N balance was -5.9 g/day. After protein refeeding, N balance was positive (+1.7 g/day, P less than 0.05) whereas leucine flux was unchanged from prolonged fasting values. After carbohydrate refeeding, N balance improved to -3.1 g N/day, whereas leucine flux decreased by a further 18% (P less than 0.05). Protein and carbohydrate refeeding were associated with further 23 and 31% reductions of 3-methylhistidine excretion compared with prolonged fasting (P less than 0.05). The results support the hypothesis that improved efficiency of protein retention in starvation is intimately associated with a decreased rate of protein turnover.

3-Hydroxybutyric Acid↗

Effect of the benzodiazepine derivative estazolam in patients with auditory hallucinations. A multicentre double-blind, cross-over study.

The main aim of this study was to test the effect of the triazolobenzodiazepine, estazolam, on auditory hallucinations. Fifty-eight patients (28 male, 30 female) with auditory hallucinosis that had responded poorly to neuroleptics alone, were included; most patients were chronic schizophrenics, and most patients were maintained on previous neuroleptic treatment during the trial. Each patient was treated for three consecutive 3-week periods, and randomly allocated to receive estazolam (1 + 1 + 4 mg) either in the first and third, or in the second period. Similar-looking placebo tablets were given in the control periods. These were seven drop-outs, three of them due to somnolence on estazolam. In both treatment groups there was a significant (but not significantly different) improvement during the first 3-week period, with regard to both global clinical state and auditory hallucinations. During the second and third periods, however, the two groups differed significantly, in that improvement of global state and hallucinosis was seen on estazolam, and deterioration on placebo. It is concluded that estazolam (as an addition to neuroleptics) had a significantly better effect than placebo on the global clinical state, on the frequency of, and attitude towards the hallucinations, and also on the single symptoms "Compulsive thoughts" and "Visual hallucinations" (items in the Comprehensive Psychopathological Rating Scale). There were few side effects except drowsiness. Possible pharmacokinetic and pharmacodynamic interactions between benzodiazepines and neuroleptics are discussed briefly.

Adult↗

Impact of doramectin treatment at the time of feedlot entry on the productivity of yearling steers with natural nematode infections.

OBJECTIVE: To measure the reduction in fecal nematode egg counts and productivity impact of treatment of yearling steers with doramectin at entry into the feedlot, compared with control steers treated only with fenthion. ANIMALS: 6,096 crossbred yearling steers with a mean (+/- SD) body weight of 377.0 (+/- 37) kg. PROCEDURE: Steers were implanted with zeranol and alternately separated to fill each of 24 pens. Groups of steers within 12 matched pairs of pens were randomly allocated to treatment with doramectin or no treatment with doramectin for internal nematodes. Fecal samples were collected from approximately every twentieth steer from each pen at day 0 and at reimplant (approx day 60). Each steer was weighed on day 0 and at reimplant and then mean body weights of steers per pen were determined at 120 to 140 days after trial initiation. RESULTS: Treatment steers had a significantly lower fecal egg count at reimplant than control steers. Treatment steers had a significantly greater mean daily gain during the study, significantly greater feed consumption, significantly lower feed-to-gain ratio, and significantly better quality carcass grades at slaughter. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of our trial, there was a significant fecal egg count reduction response to doramectin treatment, which resulted in significantly improved productivity. Results of economic analysis of return on investment indicated that even with low egg counts in heavy body weight cattle, nematode egg count reduction with doramectin significantly improved returns.

Anabolic Agents↗

Endoscopic sclerotherapy versus medical treatment for bleeding esophageal varices in patients with schistosomal liver disease.

A prospective controlled trial was conducted at Ain-Shams and Benha University Hospitals. One-hundred and eighteen chronic liver disease patients, mostly schistosomal in origin and presenting with recent proven variceal hemorrhage, were randomly allocated to injection sclerotherapy or medical therapy. The follow-up period extended to 21 months. Sixty-three patients received injection sclerotherapy using ethanolamine oleate (5% wt/vol) paravariceally while 55 received medical treatment in the form of general resuscitative measures, blood transfusion, vasopressin intravenous drip, and insertion of a Sengstaken-Blakemore tube if bleeding continued. The first 30-day mortality was 7 (11%) in the injection sclerotherapy group compared with 11 (20%) in the medical treatment group. This difference was not statistically significant. During the entire observation period 9 (14.3%) died in the sclerosed group and 16 (29%) died in the medically treated group, and this difference was statistically significant at the 5% level. Comparison of recurrent bleeding among both groups revealed that the difference was statistically not significant. It was concluded that injection sclerotherapy was no better than medical treatment in the control of acute variceal bleeding, but injection sclerotherapy did increase significantly long-term survival of sclerosed patients.

Adult↗

Cardioselective and nonselective beta-adrenoceptor blocking drugs in hypertension: a comparison of their effect on blood pressure during mental and physical activity.

The ability of cardioselective and nonselective beta-adrenoceptor blocking drugs, with and without partial agonist activity, to control increases in blood pressure associated with mental and physical activity was compared in 35 subjects with hypertension. Direct measurements of blood pressure and radioenzymatic determinations of plasma norepinephrine were obtained before, during and after four activities, and were repeated after random allocation to treatment with atenolol, metoprolol, pindolol or propranolol. Cardioselective and nonselective drugs modestly reduced the pressor response to reaction time testing, but not to mental arithmetic or isometric exercise. The increase in systolic blood pressure during bicycling was attenuated significantly by the cardioselective drugs atenolol (by 23 mm Hg, or 38%) and metoprolol (21 mm Hg, or 41%), but not by the nonselective agents pindolol (with partial agonist activity) (13 mm Hg, or 20%) and propranolol (10 mm Hg, or 17%) (p less than 0.02 cardioselective versus nonselective; p = NS pindolol versus propranolol). Only bicycle exercise increased plasma norepinephrine concentrations (by 80%). These results suggest that beta-adrenoceptor blocking drugs will not attenuate increases in blood pressure during mental or physical activities unless intense sympathoadrenal activation also occurs. Marked elevations in circulating epinephrine, with or without norepinephrine, and peripheral beta 2-blockade appear necessary for alpha-mediated vasoconstriction to predominate and for the contrasting effects of cardioselective and nonselective drugs to be appreciated.

Adolescent↗

Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment. Medical Research Council Working Party on Mild Hypertension.

A series of 1418 men and 1,347 women with mild hypertension (diastolic phase V 90-109 mm Hg) aged 35-64 who had either had long term antihypertensive treatment with bendrofluazide or propranolol or taken placebo tablets for a similar period were randomly allocated to groups in which their tablets were either stopped or continued. The course of blood pressure and of biochemical variables was followed up for two years. Mean blood pressures rose rapidly after the withdrawal of active treatment, and between nine months and one year after stopping treatment the antihypertensive effect had almost disappeared. The effect persisting longer than this, and possibly due to resetting of the baroreceptors or of other blood pressure control mechanisms, was very small, and as the rise in mean pressure was due to an upward movement in general distribution there was no evidence of a subgroup in whom these mechanisms had been permanently reset to a clinically important extent. After withdrawal of propranolol the rise in pressure was more rapid in younger than in older people. After stopping bendrofluazide pressure rose more rapidly in men who had had higher pressures before and during treatment; this effect was not seen in women. Disturbances in biochemical variables associated with drug treatment had largely resolved by the end of two years after withdrawal. Stopping placebo tablets made no consistent difference to blood pressure.

Adolescent↗

Intravenous nitroglycerin therapy to limit myocardial infarct size, expansion, and complications. Effect of timing, dosage, and infarct location.

To determine 1) whether the effect of intravenous nitroglycerin (NG) therapy during acute myocardial infarction on creatine kinase infarct size is influenced by infarct location (anterior vs. inferior), timing (therapy less than 4 hours vs. greater than or equal to 4 hours after onset of pain), and dose response (mean blood pressure greater than or equal to 80 mm Hg vs. less than 80 mm Hg during the first 12 hours) and 2) whether NG therapy modifies infarct expansion, 310 patients were randomly allocated to NG (n = 154) and control (n = 156) groups. NG infusion was titrated to lower mean blood pressure by 10% in normotensive and 30% in hypertensive patients, but not below 80 mm Hg, and was maintained for 39 hours. Measurements included clinical variables, creatine kinase infarct size (geq) as well as left ventricular (LV) asynergy, LV ejection fraction, expansion index, and thinning ratio on serial two-dimensional echocardiography. Compared with controls, creatine kinase infarct size was less in the NG group (41 vs. 55 geq, p less than 0.001), in anterior (44 vs. 58 geq, p less than 0.05), and inferior (39 vs. 53 geq, p less than 0.025) NG subgroups, and in early than late NG subgroups (43% vs. 22% decrease). Other indexes of infarct size also improved (p less than or equal to 0.05) with NG compared with controls. Thus, by 10 days, LV asynergy was 40% less, LV ejection fraction was 22% more, and Killip class score was 41% less. A negative effect of mean blood pressure less than 80 mm Hg with NG was reflected in these indexes. In addition, expansion index increased (p less than 0.001) by 31% and thinning ratio decreased (p less than 0.001) by 17% in controls by 10 days but remained unchanged with NG. Infarct-related major complications were less frequent in the NG than the control groups: infarct expansion syndrome (2% vs. 15%, p less than 0.0005), LV thrombus (5% vs. 22%, p less than 0.0005), cardiogenic shock (5% vs. 15%, p less than 0.005), and infarct extension (11% vs. 22%, p less than 0.025). Mortality was less in NG than in control groups in-hospital (14% vs. 26%, p less than 0.01), at 3 months (16% vs. 28%, p less than 0.025) and 12 months (21% vs. 31%, p less than 0.05), but this advantage was only found in the anterior subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine Kinase↗

Oral ciprofloxacin compared with conventional intravenous treatment for Pseudomonas aeruginosa infection in adults with cystic fibrosis.

40 adult patients with cystic fibrosis (CF) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated (20 per group) to receive intravenous azlocillin 5 g and gentamicin 80 mg, or oral ciprofloxacin 500 mg. Both treatments were given three times a day for 10 days. The patients were assessed on days 1 and 10, and at 6 weeks. There was a significant improvement in lung function between days 1 and 10 in both groups (p less than 0.001). Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group. Improvement after ciprofloxacin was superior at day 10. Sputum weight decreased in both groups (p less than 0.001). Patient-recorded symptoms also improved in both groups. There was no serious toxicity or side-effects. Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy. 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy. Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa.

Acute Disease↗

Postoperative pulmonary complications: general anesthesia with postoperative parenteral morphine compared with epidural analgesia.

In a prospective study, patients undergoing abdominal cancer surgery were randomly allocated to receive either general anesthesia with fentanyl intravenously and postoperative analgesia with parenteral morphine (GA group) or general anesthesia combined with epidural bupivacaine and epidural morphine for postoperative pain relief (EP group). Analgesia was tested on a visual pain scale. Pulmonary complications were evaluated by clinical complications, blood gas analysis, x-ray film changes, and pulmonary volumes (vital capacity, forced expiratory volume in 1 second). Measurements were performed on the day before the operation and on the first 5 postoperative days. In the EP group the pain relief was significantly better on the first day (p less than 0.03). Whatever the criteria used, the rates of pulmonary complications were similar in the two groups: clinical complications 21% versus 26%, radiologic complications 50% versus 64% for GA and EP groups, respectively. Postoperative PaO2 and spirometric values were similar in the two groups. Postoperative epidural analgesia may improve the patient's comfort but does not decrease the incidence of pulmonary complications.

Abdomen↗

[A pharmacologic respiratory stimulant, doxapram, used in acute deterioration in patients with chronic respiratory failure].

In a controlled study with random allocation, the effect of doxapram (Dopram), a respiratory stimulant, was evaluated in 25 patients with acute on chronic respiratory failure requiring ventilator support. Eleven patients were allocated to mechanical ventilation and 14 to treatment with doxapram given as a variable rate infusion. In the doxapram group only four were transferred to mechanical ventilation after 1 1/2 to three days of treatment. In these patients, the problem giving rise to the acute exacerbation, was not under control at the time of ventilator intervention. In the remainder of the group, antibiotics, diuretics and bronchodilators had successfully treated the exacerbation. All patients were discharged alive. In the doxapram-treated group duration of hospitalization was nine days compared to 14 days (median values) in the ventilator-treated group. Only minor side-effects from doxapram were observed, and it is concluded that this respiratory stimulant can be used as a primary drug in patients with acute respiratory failure and chronic airflow limitation.

Aged↗

[Prevention of deep venous thrombosis with defibrotide in chest surgery. Controlled multicenter study versus heparin].

The effectiveness and tolerability of defibrotide in the prevention of post-surgery deep vein thrombosis (DVT) were compared with those of heparin in a multicentric randomized controlled study. One hundred-eight-four both sexes patients submitted to thoracic surgery were randomly allocated to defibrotide (400 mg b.i.d. by IV route, n = 94) or to calcium heparin (5000 I.U. t.i.d. s.c., n = 90); both treatments were started the day before the operation and withdrawn when patients were allowed to stand up (i.e., after 7 days). No patients developed DVT in the defibrotide group, while a single case of DVT was detected in the heparin group; furthermore, a more prominent bleeding was observed in the latter, in the early post-operative period (normal bleeding: 2nd day: defibrotide 70/92 pts, heparin 53/90 pts, p less than 0.02; 3rd day: defibrotide 87/92 pts, heparin 76/90 pts, p less than 0.05, chi 2 test), while the healing rate of surgical wounds was similar in the two groups. No relevant modifications in laboratory parameters were seen throughout the observation period. Thus, these preliminary data suggest that defibrotide is at least as effective as heparin in the prevention of post-thoracic surgery DVT and that the former drug has a possibly better tolerability profile, due to a lesser tendency to bleeding.

Adult↗

Single dose administration of propranolol in hypertension: a comparison of two formulations using clinic and home blood pressure measurements.

The effect of once daily conventional or long acting propranolol on blood pressure was examined in a double-blind crossover trial in 15 patients with moderate hypertension previously responsive to beta-blocking drugs. After a washout period, patients were randomly allocated to receive either conventional or long acting propranolol (160 or 320 mg once daily) and matching placebo for four weeks. Each treatment period was followed by two weeks during which only placebo was given. Clinic and home blood pressure measurements, taken 24 hours after dosing, indicated adequate and similar control during the two treatment periods. The onset of the antihypertensive action was of similar duration and no "rebound" effect was observed after withdrawing treatment. There was a similar reduction in exercise tachycardia 24 hours after dosing. No difference in the incidence of side effects was detected. These results demonstrate satisfactory blood pressure control with propranolol administered once daily, but do not support any therapeutic advantage of long acting over the conventional formulation of the drug.

Blood Pressure Determination↗

Randomized controlled trial of injection sclerotherapy for bleeding oesophageal varices--an interim report.

Oesophageal varices are the commonest cause of acute upper gastrointestinal bleeding in Egypt, due to the prevalence not only of schistosomiasis but also chronic hepatitis. Poor results of conventional treatment and shunt surgery led us to evaluate injection sclerotherapy, using fibreoptic endoscopy. In a controlled trial, 108 patients were randomly allocated to injection sclerotherapy or to conventional treatment (medical measures, with modified splenectomy and oesophagogastric devascularization in selected cases). We report the results in the first 108 patients, with a follow-up of 1-35 months. Fifty-three patients received injection sclerotherapy; 5 died (2 of recurrent bleeding) and 5 others had recurrent bleeding but were controlled by further injections. Thirty-six of the 55 control patients underwent surgery; 5 died (2 of recurrent bleeding) and 2 others developed recurrent bleeding. Further bleeding occurred in 12 of the 19 patients who were managed by medical measures alone, with 7 dying. These early results indicate that injection sclerotherapy can be effective in urgent and elective situations and that it appears to have advantages over conventional medical and surgical treatments.

Acute Disease↗

Dose-response relationships for edrophonium and neostigmine as antagonists of atracurium and vecuronium neuromuscular blockade.

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.

Atracurium↗

Short-term study of quazepam 15 milligrams in the treatment of insomnia.

The hypnotic efficacy and safety of quazepam 15 mg was compared with placebo in thirty-six out-patients with insomnia. The study was double-blind, with two comparable groups of patients established by random allocation. Following a placebo baseline period, patients took placebo or quazepam for 5 consecutive nights and completed sleep questionnaires the next day. Quazepam was rated better than placebo in terms of sleep quality, sleep induction time, total sleep time, and early morning awakenings. Quazepam treatment was rated as good or excellent by the physician and the patients who received it almost three times more often was placebo. Quazepam was proved to be safe, with no reports of unexpected or serious adverse experiences.

Adult↗

A single-blind, comparative study of hydrochlorothiazide/amiloride ('Moduret' 25) and hydrochlorothiazide/triamterene ('dyazide') in elderly patients with congestive heart failure.

The efficacy and biochemical effects of two low-dose thiazide plus potassium-sparing diuretic preparations were compared in the treatment of elderly patients with stable, mild to moderate congestive heart failure. Sixty patients (mean age 80 years) were randomly allocated to treatment with 1 tablet daily of either 25 mg hydrochlorothiazide/2.5 mg amiloride or 25 mg hydrochlorothiazide/50 mg triamterene. The dose was increased to 2 tablets daily if necessary, after 2 weeks, for a further 6 weeks. Patients' response to treatment was assessed at 2, 4 and 8 weeks using a simple clinical scoring system for signs and symptoms of their condition, and routine biochemical analysis was carried out at baseline and the end of treatment. One patient was withdrawn from the study due to a rash which was probably related to hydrochlorothiazide/amiloride treatment. A further 11 patients were excluded from the analysis because of intercurrent illness or inadequate records. Analysis of the results from 48 patients showed that both treatments resulted in an improvement in clinical score and weight reduction, with more than three-quarters of the patients responding to treatment. No serious biochemical disturbances occurred; in particular, no new cases of hyponatraemia (serum sodium less than 130 mmol/l) developed. Both preparations, therefore, were effective and tolerated forms of treatment for mild to moderate congestive heart failure in the elderly and there were no significant differences between them.

Aged↗

Oral antihistamine or nasal steroid in hay fever: a double-blind double-dummy comparative study of once daily oral astemizole vs twice daily nasal beclomethasone dipropionate.

Seventy-four patients with a well documented history of seasonal allergic rhinitis were randomly allocated to receive either astemizole 10 mg orally per day or beclomethasone 100 micrograms in each nostril twice daily on a double-blind double-dummy basis. The patients were studied in a general practice setting and were seen at entry, during the study and at the end of the study by a single observer, the author. Assessment was by diary card incorporating five 10 cm visual analogue scales related to the four symptoms of sneezing, rhinorrhoea, blocked nose and itchy eyes and an overall assessment of hay fever symptoms. Patients were asked if the medication had upset them in any way at each observer assessment. Symptom severity, as recorded by the visual analogue scales, was not significantly different for sneezing, rhinorrhoea, blocked nose or overall between the two groups but the symptom scores for itchy eyes were significantly better for the astemizole group. Adverse effects were minimal and of a minor nature only. There was no real difference between the two groups regarding adverse effects. The study suggests that oral astemizole is at least as good as nasal beclomethasone in the maintenance treatment of hay fever and that it offers the additional advantage of improved control of eye symptoms.

Administration, Intranasal↗

Omission of nitrous oxide from a propofol-based anesthetic does not affect the recovery of women undergoing outpatient gynecologic surgery.

BACKGROUND: Although nitrous oxide (N2O) is used commonly during anesthesia, clinically relevant advantages-disadvantages of using this agent are not well established in the ambulatory setting. This study in women undergoing ambulatory gynecologic surgery compares outcomes in patients administered total intravenous anesthesia with propofol versus the propofol plus N2O. The primary outcome was the time to home readiness. Secondary outcomes included the incidence of postanesthetic adverse events. METHODS: Women presenting for elective ambulatory termination of pregnancy or gynecologic laparoscopy were induced with an intravenous sleep dose of propofol and fentanyl. After induction, subjects were randomly allocated to maintenance anesthesia with propofol alone or propofol plus 65% N2O. Patients were assessed by a blinded observer in the postanesthetic care unit at 20-min intervals to determine home readiness. Postoperative pain and nausea were measured with visual analog scales. Postoperative analgesics and antiemetics were recorded. The incidence of adverse events occurring after hospital discharge was assessed by a telephone interview 24 h postoperatively. RESULTS: A total of 740 patients received propofol alone, and 750 patients received propofol plus N2O. Mean home readiness times were not significantly different between treatment groups. There were no significant differences between groups in pain scores, nausea scores, analgesia administration, or antiemetic administration before discharge. There were no significant differences in the frequency of adverse events for 24 h after discharge from hospital. CONCLUSIONS: Omission of N2O from a propofol-based anesthetic for ambulatory gynecologic surgery does not affect time to home readiness or the incidence of postoperative adverse events up to 24 h after discharge from hospital. (Key words: Awareness; outpatient surgery; total intravenous anesthesia.)

Abortion, Legal↗