Adesh K. Jain

Can garlic reduce levels of serum lipids? a controlled clinical study

PURPOSE To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS Forty-two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p < 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p < 0.05). There were no significant changes in high-density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems.

Evaluation of Intramuscular Levonantradol and Placebo in Acute Postoperative Pain

Abstract: Double‐blind administration of a single intramuscular dose of 1.5, 2.0, 2.5, or 3.0 mg levonantradol or placebo to 56 patients with moderate to severe postoperative or trauma pain showed significant analgesic effects of each dose of levonantradol as compared to placebo (P < 0.05). However, no significant dose response was observed. Compared to 2/16 patients on placebo, 23/40 patients (57 per cent) on levonantradol reported one or more side effect. Drowsiness was most frequent. Dry mouth, dizziness, “weird dreams,” mild hallucinations, nervousness, apprehension and confusion occurred less frequently. Changes in resting heart rate and blood pressure were minor and general acceptability was good.

ANALGESIC EFFICACY OF LOW-DOSE IBUPROFEN IN DENTAL EXTRACTION PAIN

A single‐dose, double‐blind, randomized, parallel trial was conducted to compare the analgesic efficacy of oral ibuprofen (I) 100, 200, or 400 mg, aspirin (ASA) 650 mg, and placebo in moderate to severe pain after extraction of impacted teeth. Subjective, self‐evaluated pain intensity and pain relief reports, hourly for 6 hours, were used as indexes of analgesic response. Data on 227 evaluable patients showed significant differences among the 4 active treatments and placebo (p < 0.001) by most measurements of analgesia. Although no consistent, significant differences were observed among the active drugs, I 400 mg performed the best, followed by I 200 mg, ASA 650 mg, and I 100 mg. Remedication was required by 59% patients receiving I 400 mg, 67% taking I 200 mg, 73% taking ASA 650 mg, 74% taking I 100 mg, and 96% receiving placebo. Differences between I 400 mg and I 100 mg were significant for remedication data (p < 0.05). Side effects were minor, infrequent, and not dose related. In this study, I 100 mg was distinctly superior to placebo and probably as effective as ASA 650 mg in relieving pain. Only a shallow dose response of ibuprofen was observed.

Efficacy and Tolerability of Valsartan in Combination with Hydrochlorothiazide in Essential Hypertension

AbstractObjective: This study compared the efficacy and tolerability of two combination regimens of valsartan and hydrochlorothiazide (HCTZ) with valsartan monotherapy in patients with essential hypertension inadequately controlled with valsartan 80mg once daily. Patients and Methods: A total of 708 patients with inadequately controlled blood pressure after 4 weeks’ treatment with valsartan 80mg once daily participated in this double-blind comparative trial. Patients were randomly allocated once-daily treatment with valsartan 80mg, valsartan 160mg, valsartan 80mg + HCTZ 12.5mg or valsartan 80mg + HCTZ 25mg for 8 weeks. Results: Statistically significant decreases in mean sitting diastolic blood pressure (SDBP) and mean sitting systolic blood pressure (SSBP) from baseline were seen in all treatment groups (least squares mean change from baseline SDBP: −5.1mm Hg, −6.2mm Hg, −8.2mm Hg, −10.8mm Hg; SSBP: −3.9mm Hg, −6.5mm Hg, −9.8mm Hg, −16.0mm Hg for valsartan 80mg, valsartan 160mg, HCTZ 12.5mg combination, HCTZ 25mg combination, respectively). A significant difference for mean SDBP, SSBP and responder rates in favour of the combination regimens was observed compared with either valsartan monotherapy. All treatments were well tolerated with the percentage of patients reporting treatment-related adverse experiences at any time ranging from 9.9% (valsartan 160mg) to 21.0% (HCTZ 25mg combination). Conclusion: The study demonstrated that a combination of valsartan 80mg and HCTZ 12.5mg or 25mg provides an effective and well tolerated treatment in patients who need additional blood pressure control beyond valsartan monotherapy.

Potentiation of Hypoglycemic Effect of Sulfonylureas by Halofenate

We investigated the possibility of a drug interaction between the antilipemic agent halofenate and sulfonylureas. Twelve young, healthy men were given 1 g of tolbutamide by mouth before and after 12 days of double-blind treatment with 1 g per day of halofenate, or placebo. There was a significant increase in serum tolbutamide at eight, 10 and 12 hours (P less than 0.01) and a significant (P less than 0.01) decrease in serum glucose at one, four and six hours after halofenate treatment, but not after placebo. In a long-term, double-blind study of halofenate or clofibrate treatment of patients with Type IV hyperlipoproteinemia, diabetic patients receiving a sulfonylurea and halofenate either required a reduction in the dose of the sulfonylurea or demonstrated significantly improved control of hyperglycemia (P less than 0.05) or both. No appreciable decrease in serum glucose levels was noted in diabetic patients receiving sulfonylurea and clofibrate. This interaction between halofenate and sulfonylureas is clinically important, especially in view of the association of hyperlipemia and diabetes.

The effect of MK‐185 on some aspects of uric acid metabolism

Following oral administration of MK‐185 to 10 patients with types III, IV, or V hyperlipoproteinemia at doses of 10, 15, and 20 mg. per kilogram per day for a period of 4 weeks at each of the 3 dose levels, the serum uric acid decreased significantly with the progression of dosage. A specific metabolic study designed to evaluate the mechanism of this hypouricemic action showed that MK‐185, 20 mg. per kilogram per day for 3 days, produced a gradually increasing (p < 0.05) uricosuria in the 3 patients studied. The results of the other drugs used in metabolic study, namely, probenecid, allopurinol, and clofibrate are discussed in relation to those of MK‐185.

Efficacy and acceptability of different dosage schedules of clonidine

In 12 hospitalized patients with hypertension, clonidine 3 times a day led to better control of blood pressure than did the same total dose administered once daily. Compared to the uniform control of blood pressure on divided dose regimen, the single daily 8 p.m. dose led to wider fluctuations and inadequate control 18 hr after dosing. However, 10 of the 12 patients preferred the single daily dose at 8:00 p.m. to the divided dose regimen because of no drowsiness during the day. In 2 patients administration of clonidine twice daily resulted in better control of blood pressure than that du ring the single or thrice‐daily dose regimens. Since there appeared to be a correlation between the dose and the duration of adequate blood pressure control, administration of clonidine twice a day with a larger dose at bedtime and a sm aller dose before noon could limit unwanted drowsiness and combine the convenience of less frequent dosing with superior blood pressure control.

Comparison of oral nalbuphine acetaminophen and their combination in postoperative pain

This double‐blind, randomized, parallel, placebo‐controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine, 650 mg acetaminophen, and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain. Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response. Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia. The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements, indicating an additive effect of the components. The combination was the most effective treatment, followed by nalbuphine, acetaminophen, and placebo. Effects of the combination were significantly different from those of acetaminophen at 4, 5, and 6 hours and from those of placebo at 1 to 6 hours. There was no significant difference in the frequency or intensity of side effects among the groups. The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination.

Guanabenz in essential hypertension.

Fifty‐five patients with mild to moderately severe essential hypertension were treated with guanabenz (2,6‐dichlorobenzylidene aminoguanidine acetate) in doses from 4 to 16 mg twice daily in a randomized, placebo‐controlled study. The patients treated with placebo in the initial phase of the study were subsequently treated with guanabenz. The mean arterial pressure in the guanabenz group decreased from 130.6 to 107.6; that in the placebo group decreased from 129.6 to 126.6 standing and from 126.6 to 109.9 and 128.8 to 120.5, respectively, supine. The principle adverse effects included sedation, dry mouth, weakness, and tiredness. Of the guanabenz‐treated patients 84% had sustained decrease in supine diastolic blood pressure of 10 mm Hg or more, whereas in the placebo‐treated patients only 32% had such a response. There was no signijicant orthostatic hypotension. Guanabenz thus appears to be an effective antihypertensive drug in patients with mild to moderately severe hypertension.

Clonidine and guanfacine in hypertension

Guanfacine, 1 to 3 mg/day, and clonidine, 0.1 to 0.3 mg twice a day, were compared in a 24‐week double‐blind, randomized, parallel study of 42 patients with hypertension that was inadequately treated by chlorthalidone, 25 mg/day. Mean reduction of blood pressure was 18/9 mm Hg after guanfacine and 14/8 mm Hg after clonidine. To determine the incidence of rebound hypertension, subjects were hospitalized for 7 days during chlorthalidone therapy for collection of baseline data and once again immediately after abrupt withdrawal of the α‐agonist after 24 weeks of dosing. Although blood pressure and heart rate rose significantly in both groups, the changes after clonidine withdrawal were greater and occurred earlier (day 2) than those after guanfacine withdrawal (day 4). Forty percent of the subjects receiving guanfacine and 64% of subjects receiving clonidine had diastolic blood pressure elevations ≥10 mm Hg from baseline. There were increases in urinary norepinephrine levels in both groups after drug withdrawal, but these correlated poorly with blood pressure rise. Side effects after guanfacine were much the same as those after clonidine. Guanfacine taken once a day provides an effective and safe alternative to clonidine in the management of essential hypertension.