The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomised-controlled trial.

OBJECTIVE: ischaemic lower-extremity ulcers in the diabetic population are a source of major concern because of the associated high risk of limb-threatening complications. The aim of this study was to evaluate the role of hyperbaric oxygen in the management of these ulcers. METHOD: eighteen diabetic patients with ischaemic, non-healing lower-extremity ulcers were recruited in a double-blind study. Patients were randomly assigned either to receive 100% oxygen (treatment group) or air (control group), at 2.4 atmospheres of absolute pressure for 90 min daily (total of 30 treatments). RESULTS: healing with complete epithelialisation was achieved in five out of eight ulcers in the treatment group compared to one out of eight ulcers in the control group. The median decrease of the wound areas in the treatment group was 100% and in the control group was 52% (p=0.027). Cost-effectiveness analysis has shown that despite the extra cost involved in using hyperbaric oxygen, there was a potential saving in the total cost of treatment for each patient during the study. CONCLUSION: hyperbaric oxygen enhanced the healing of ischaemic, non-healing diabetic leg ulcers and may be used as a valuable adjunct to conventional therapy when reconstructive surgery is not possible.

A design for testing interventions to improve adherence within a hypertension clinical trial.

The Potassium Adherence Clinical Trial (PACT) incorporates one randomized clinical trial within another. A randomized trial of interventions to increase adherence to medication is nested within a second randomized clinical trial testing hypotensive effect of supplemental oral potassium. The trial aims principally to compare the effects of three intervention strategies: two sessions of individual patient counseling, two telephone contacts, or standard care. The trial aims secondarily to evaluate the effect of 60 mEq supplemental oral potassium daily on sitting systolic and diastolic blood pressure in hypertensive patients on established drug therapy. Therefore, it organizes the patients given potassium into three study groups for adherence interventions, and the patients assigned to placebo into a further three. We evaluate adherence primarily by means of the Medication Event Monitoring System (MEMS), an electronic system that records the date and time that the container of study medication is opened. Additional measurements, such as assessments of change in levels of urinary potassium, pill counts, appointment records, self-reporting by patients, and estimates by physician of adherence, are used and correlated with MEMS data. At a single center, the trial enrolled 107 participants between the ages of 26 and 80. This paper describes the background to this trial within a trial, details its design, documents the baseline characteristics of participants enrolled, and describes issues experienced during implementation of the trial.

Medium-induced fragility of Schwanniomyces.

Schwanniomyces occidentalis has attracted interest because of its ability to metabolize starch and similar complex carbohydrates. Studies have been undertaken, mostly using defined media, to ascertain conditions for optimal production and secretion of hydrolytic enzymes. Here we demonstrate the fragility of Schw. occidentalis in many defined media. We especially examined viability in YNB (Yeast Nitrogen Base) plus 1% glucose. Without phosphate supplementation, viability was routinely very low at stationary phase (usually less than 37%), whereas viability of stationary-phase cultures in phosphate-supplemented YNB usually exceeded 97%. The negative implications of having many, presumably permeabilized, dead cells present in assays for secretion of enzymes by living yeast cells are discussed.

Dietary supplementation with omega-3 fatty acids prolongs platelet survival in hyperlipidemic patients with atherosclerosis.

Enhanced dietary omega-3 fatty acid consumption is thought to be associated with a reduced incidence of atherothrombotic disorders. This effect may be mediated in part through suppression of in vivo platelet activity by omega-3 fatty acids. We observed that platelet survival, a sensitive indicator of in vivo platelet activity was prolonged from 6.4 +/- 1.5 days to 7.7 +/- 1.4 days by moderate amounts of dietary omega-3 fatty acid supplementation for 6 weeks in a group of hyperlipidemic patients with preexisting, established atherothrombotic disorders. This effect on platelet survival was associated with a decrease in platelet arachidonic acid levels from 26.7 +/- 3.5% to 20.9% +/- 2.5% and a rise in platelet eicosapentaenoic and docosahexaenoic acid measurements from essentially undetectable to 2.8% +/- 1.6% and 1.9% +/- 1.0%. Plasma total cholesterol, low-density lipoprotein cholesterol, and serum apolipoprotein B levels rose significantly during the omega-3 fatty acid supplementation period. Platelet aggregation did not change. This study demonstrates that a modest amount of dietary omega-3 fatty acid supplementation can significantly effect in vivo platelet activity in a population at high risk for recurrent atherothrombotic disorders.

A randomized placebo-controlled comparison of amlodipine and atenolol in mild to moderate systemic hypertension.

Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with placebo and atenolol in 125 patients with mild to moderate systemic hypertension [supine diastolic blood pressure (DBP) 90-114 mm Hg]. Patients received placebo for 4 weeks, followed by a random allocation to an 8-week double-blind, once-daily treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The changes in 24-h post-dose blood pressure (BP) from baseline to final visit for amlodipine (mean daily dose 8.8 mg, range 5-10 mg) were -12.8 +/- 2.0/ -10.1 +/- 1.2 mm Hg in supine BP and -11.5 +/- 2.3/-9.8 +/- 1.1 mm Hg in standing BP (p less than 0.001); for atenolol (mean daily dose 83.7 mg, range 50-100 mg), the changes from baseline were -11.3 +/- 2.3/-11.7 +/- 1.3 mm Hg in supine BP and -13.3 +/- 3.1/-12.3 +/- 1.5 mm Hg in standing BP (p less than 0.001); for placebo, the changes from baseline were -0.9 +/- 2.8/-3.5 +/- 0.9 mm Hg in supine BP and -1.6 +/- -2.6/-4.0 +/- 1.0 mm Hg in standing BP. In the study, goal response was defined as a supine DBP of less than 90 mm Hg or its decrease by greater than or equal to 10 mm Hg. The response rates were similar for atenolol (65%) and amlodipine (61%). Both active therapies were significantly more effective than placebo. Heart rate was significantly lowered by atenolol only.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of atherosclerosis by cod-liver oil in a hyperlipidemic swine model.

We studied the effect of cod-liver oil on the development and progression of coronary artery disease in swine subjected to coronary balloon abrasion and fed an atherogenic diet for eight months. Sections from serial 3-mm segments of the coronary arteries were analyzed morphometrically in 7 pigs given a cod-liver-oil supplement and 11 control animals not given the supplement. Significantly less disease was seen in the sections from the animals fed cod-liver oil. The mean lesion area per vessel, mean luminal encroachment per vessel, and mean maximal luminal encroachment per vessel were reduced in animals fed cod-liver oil, as compared with controls, (P = 0.05, P = 0.016, and P = 0.011, respectively). Both groups of animals had severe hyperlipidemia throughout the study. Differences in the extent of coronary atherosclerosis were not related to differences in plasma lipid levels. Platelet arachidonate was markedly reduced, platelet eicosapentaenoic acid was increased, and serum thromboxane was decreased in the oil-fed group as compared with the control group. We conclude that in our animal mode, dietary cod-liver oil retarded the development of coronary artery disease, possibly through changes in prostaglandin metabolism.

Hemodynamic and metabolic effects of the calcium channel blocking agent nitrendipine.

In an open crossover comparison of propranolol and nitrendipine, 19 patients with hypertension received 40 to 160 mg propranolol and 5 to 20 mg nitrendipine twice a day. Mean (+/- SD) predose supine blood pressure fell from 145/98 +/- 11/7 to 132/88 +/- 12/8 mm Hg with propranolol and to 135/92 +/- 11/9 mm Hg with nitrendipine. Resting heart rate was reduced by propranolol but was unchanged 12 hours after nitrendipine dosing. Neither propranolol nor nitrendipine altered plasma glucose or insulin after oral glucose. Propranolol significantly increased fasting triglyceride levels and reduced high-density lipoprotein cholesterol levels, but nitrendipine induced no change. Propranolol reduced and nitrendipine increased plasma renin activity after exercise. Peak plasma nitrendipine levels were dose proportional and occurred at 1 to 2 hours after dosing, whereas peak blood pressure reductions occurred 4 hours after the last dose of nitrendipine and were associated with mean increases in heart rate. Nitrendipine is almost equivalent in hypotensive effect to propranolol, but nitrendipine increases plasma renin activity after exertion and may produce transient tachycardia. However, nitrendipine does not cause unwanted metabolic effects.