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Zatebridine selectively reduces resting and exercise heart rate without any other myocardial effects. In this study, despite significant reductions in resting and exercise heart rate, there were no clinically significant effects on myocardial ischemia, suggesting that the anti-ischemic effect of heart rate reduction should be reevaluated.

Study Objective: To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water-soluble phenytoin prodrug, after intramuscular and intravenous administration., Design: Open-label study of intramuscular administration, and double-blind, randomized study of intravenous administration., Setting: Six and ten hospitals throughout the United States for the intramuscular and intravenous multicenter studies, respectively., Patients: Neurosurgical patients who required anticonvulsant prophylaxis or treatment., Interventions: In the intramuscular study, 118 patients received loading doses ranging from 480-1500 mg phenytoin equivalents (PE) and daily maintenance doses ranging from 130-1250 mg PE for 3-14 days. In the intravenous study, 88 patients received fosphenytoin and 28 received phenytoin sodium for 3-14 days. Mean +/- SD loading doses and maintenance doses of intravenous fosphenytoin and phenytoin were 1082 +/- 299 mg PE and 411 +/- 221 mg PE, and 1082 +/- 299 mg and 422 +/- 197 mg, respectively. Trough phenytoin concentrations were measured daily in all patients., Measurements and Main Results: Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations. Adverse events associated with the drug occurred in 9% of patients, commonly those typical of the parent drug. For intravenous treatment, the frequency of mild irritation at the infusion site was significantly lower in the fosphenytoin group (6%) than in the phenytoin group (25%, p < 0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 micrograms/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days., Conclusion: Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.

This survey was undertaken to ascertain what clinical investigators liked and disliked about the meetings that precede the initiation of clinical trials and to determine if there are any differences in opinion between those investigators engaged in private practice and those affiliated with academic institutions. A 16-item multiple choice survey was mailed to 565 clinical investigators. Sixty-three percent of those polled returned the survey. A majority of respondents (67%) believes that attendance at investigators' meetings is beneficial to themselves and to their coordinators. Seventy percent prefer to attend a multicenter meeting in lieu of having an on-site initiation. Private practitioners prefer weekend meetings (59%) held at resorts (54%) where as academicians favored meetings to be held mid-week (42%) and were less unified as to the type of facility. The last choice for a meeting's location was the Northeast. More investigators prefer to make their own travel arrangement than to use a central travel planner. Both groups of investigators believe that the most beneficial parts of the meeting for themselves and for their coordinators are a formal presentation of the protocol and a discussion/answer session about the study. There was generalized agreement that the study's coordinator is the principal beneficiary of a discussion about the central laboratory. It is less clear who actually benefits from discussions of the drug brochure, FDA guidelines, case report form, etc.

After elective surgery, 28 patients with 40 wounds were enrolled in a controlled clinical study to assess the effects of two different dressings on incisional healing. Patients served as their own control with one-half of each incision covered with an impregnated gauze (Xeroform) and the other half of the incision covered with a thin occlusive hydrocolloid dressing (DuoDerm Extra Thin CGF). All wounds were evaluated 2 to 3 days, 7 to 10 days, 4 weeks, and 7 months postoperatively. None of the incisions segments showed any evidence of infection. At the time of suture removal, the hydrocolloid dressing's ability to contain exudate, protect the wound, and facilitate mobility and personal hygiene were rated higher compared with the gauze-type dressing (p < 0.001, for all variables). At the 4-week visit, both the patient and the surgeon rated the scar segments covered with the hydrocolloid dressing better with respect to color, evenness, and suppleness (p < or = 0.04, for all variables). These differences were no longer apparent 7 months after surgery.

Innervated (Pavlov) gastric fundic pouches were constructed in dogs. One group of dogs served as controls, and another group of dogs had their pouch submucosa infiltrated with 25 per cent ethyl alcohol. The alcohol infiltration of the gastric pouch submucosa eliminated the gastric secretory responses to histamine, pentagastrin, a meat meal, and insulin-induced hypoglycemia. The alcohol infusion of the gastric pouch submucosa did not modify the elevated serum gastrin levels to a meat meal, alter the basal or stimulated mean splenic arterial blood flow to the pouch, nor alter the histologic appearance of the pouch with hematoxylin and eosin or histochemical fluorescence of catecholamines. Transplantation of 75 per cent of the gastric antrum into the colon caused a basal and a meal-augmented hypergastrinemia in all dogs. In the control Pavlov pouches the hypergastrinemia induced elevated gastric secretory responses to histamine, pentagastrin, and insulin-induced hypoglycemia. In those Pavlov pouches in which the submucosa had been infiltrated with alcohol, the hypergastrinemia could not induce any gastric secretory response to histamine, pentagastrin, or insulin-induced hypoglycemia.

Thirteen femoral vein autografts were placed into the corresponding ipsilateral femoral arteries of 8 mongrel dogs. Cuff-type Doppler (ultrasonic) flowmeters were placed around six of the grafts. None of the vessels thrombosed. Blood flow velocities were measured in all vessels up until the time of sacrifice (mean 95 +/- 5 days after surgery) or accidental death (one dog, 49 days after surgery). The only case of graft failure was attributed to infection at the flowmeter site. With this single exception, the vein grafts exhibited uniformity in histological appearance from dog to dog. These data suggest that implantation of properly designed Doppler flow transducers may have clinical applications. This technique permits continuous or intermittent assessment of blood flow characteristics through a graft without additional trauma or cost to the patient. It is free of the many inherent disadvantages of chronically implanted electromagnetic flowmeters and may negate the need in some instances for followup angiographic studies.

The safety and efficacy of bepridil plus propranolol therapy were investigated in a placebo-controlled, parallel-design, double-blind trial in 56 patients who were not responding to propranolol alone. Patients entering the study were receiving an average propranolol dosage of 131 mg/day (range 20 to 240). For the first 2 weeks of the study they were given placebo in addition to their propranolol dose, and then were randomized to receive continued placebo plus propranolol or bepridil plus propranolol therapy. The bepridil dosage was adjusted over the 8 weeks of active treatment to an average of 273 mg/day (range 200 to 400). The double-blind treatment period was followed by a 3-week washout period during which all patients received propranolol and placebo. The effects of treatment on the frequency of angina attacks, nitroglycerin consumption, exercise performance (treadmill-modified Bruce protocol) and Holter electrocardiogram (ECG) were assessed. Propranolol and bepridil plasma levels also were obtained. Improved antianginal efficacy and reduced nitroglycerin consumption were noted when bepridil was added to propranolol (p less than 0.01). During 8 weeks of combination treatment, exercise tolerance increased 1.0 +/- 1.2 minutes from a baseline of 7.3 +/- 2.2 with bepridil plus propranolol compared with an increase of 0.02 +/- 1.3 minutes from a baseline of 7.6 +/- 2.9 with placebo plus propranolol (p less than 0.01). With bepridil plus propranolol, there were also increases in exercise time to onset of angina (p less than 0.04), exercise time to 1-mm electrocardiographic ST-segment depression (p less than 0.06) and total work (p less than 0.03) compared with placebo plus propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A problem associated with some patients undergoing hemodialysis is the presence of muscle cramps. As the etiology of these cramps is still unknown, the purpose of this study was to evaluate tonic muscle activity and muscle cramps during hemodialysis. Forty-six complete dialysis treatment sessions were studied. Electromyographic (EMG) activity was recorded from a leg muscle in patients who cramped and control patients who did not cramp. EMG was analyzed via a minicomputer for each minute of recording time. Results indicated the mean muscle cramp latency from start of dialysis was 248 minutes. Average muscle cramp was 10 minutes in duration and took three minutes to develop and seven minutes to fully dissipate. Tonic EMG activity in patients with muscle cramps showed a continued increase throughout the latter part of dialysis whereas the control patients showed a continual decline. The results suggest that the latent increase in EMG activity may be causally related to muscle cramps and may be a useful predictor as to the onset of muscle cramps during hemodialysis.

The effect of ethaverine hydrochloride on exercise tolerance of patients with intermittent claudication was evaluated in a double-blind, placebo-controlled study conducted at three sites. Forty-five patients with symptoms of occlusive arterial insufficiency of the lower extremities were randomly assigned to receive ethaverine 200 mg or placebo four times daily. The patients were evaluated biweekly for 12 weeks with treadmill claudication tests, patient and investigator assessments of symptom severity, and reports of adverse reactions. Doppler ankle/brachial pressure ratios were recorded for 26 patients. Walking tolerance improved for patients in both groups during the course of the study. Increases in distance-to-claudication were significantly greater for patients receiving ethaverine after 6, 8, 10, and 12 weeks of therapy. Ankle/brachial pressure index after exercise was unchanged in both groups. Incidence of adverse reactions was similar for the two groups. Although patients were generally unaware of any improvement in symptoms, the investigators judged significant relief of claudication among those receiving ethaverine compared to those receiving placebo. It was concluded that ethaverine safely increased distance-to-claudication in patients with intermittent claudication.

Plasma zinc levels in premature infants receiving parenteral nutrition without supplementation of trace elements were evaluated. The mean +/- SE for plasma zinc concentration prior to the start of parenteral nutrition was 53 +/- 6 microgram/dl. During the first two weeks of parenteral nutrition the levels remained low, but did not change significantly. However, from day 14 through day 32 there was a statistically significant (P less than 0.05), progressive decline in plasma zinc values. Perhaps the shortened gestational periods were etiologic in producing the initial low plasma zinc concentration in these patients. Since low-birth-weight infants apparently have a high requirement for zinc, the reduced growth rates of these patients may be related to their apparent zinc deficiencies.

A method of inducing slow gradual constriction of a renal artery is described. A metal constrictor is partially filled with ameroid, a hydroscopic material. Over a period of weeks, the ameroid expands, causing increasing obstruction to the renal artery. Data revealed a progressive decrease in function as measured by p-aminohippurate, inulin, and creatinine clearance on the affected side with an increase in function in the contralateral side.

Short segments of Chemfluor flexible Teflon tubing (2.38 mm ID) previously coated with sodium heparin (1,000 units/ml) serve as ideal containers in which blood from neonates can be collected for zinc analysis. The ends of the tube are plugged with Teflon TFE round beading so that the sample comes in contact only with Teflon and the risk of contamination is minimized. The heparin coating facilitates easy collection of the sample and separation of plasma by centrifugation. It does not contribute zinc to the specimen.

Present knowledge of trace element nutritional requirements and the effects of TPN solutions unsupplemented with zinc indicate that zinc supplementation must be considered for any patient receiving prolonged TPN. Zinc sulfate appears to be the supplement of choice, and infusions of freeze-dried plasma appear to be an unsatisfactory method for supplying zinc, even during short-term therapy. As long as accepted dosage regimens are followed, there appears to be little risk of toxicity when TPN solutions are supplemented with zinc.

Scanning electron micrographs of the endothelium of the pulmonary artery reveal that the entire surface is covered by a meshwork of irregular projections which vastly increase the surface area. The size and density of the projections suggest that they may function to direct an eddying flow of plasma along the endothelial surface.