Comparison of the single-dose pharmacokinetics and tolerability of modafinil and dextroamphetamine administered alone or in combination in healthy male volunteers.

An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of modafinil, the acid and sulfone metabolites of modafinil, and dextroamphetamine at intervals through 48 hours after administration for each treatment. Vital signs (blood pressure and pulse rate) were measured through 48 hours, and electrocardiograms were measured through 24 hours after administration. Pharmacokinetic parameters were determined using noncompartmental methods. The data collected in this study of 24 healthy volunteers suggest that concomitant administration of single oral doses of modafinil and dextroamphetamine has no clinically significant effects on the pharmacokinetic profile of either agent. Although there was a slightly greater incidence of adverse events when modafinil and dextroamphetamine were administered together, the concomitant administration of the two drugs was well tolerated.

Primary atherosclerotic aneurysm of the profunda femoris artery associated with distal embolization.

A rare case of an isolated atherosclerotic aneurysm of the profunda femoris artery associated with emboli to the distal leg and foot is reported. A mechanism for such distal embolization is proposed and the management of the condition discussed.

The role of computed tomography in assessing the operability of oesophageal carcinoma.

The reliability of CT scanning in assessing resectability in carcinoma of the oesophagus was investigated prospectively by direct comparison with the operative findings. Over 11 months, 38 patients judged potentially operable following conventional investigation underwent CT scanning from the thoracic inlet to the level of the adrenal glands. These patients were then explored surgically with a view to resection. The CT findings were assessed by two radiologists without access to clinical information. Operative findings were recorded by the surgeon. Comparison was made between the tomographic and surgical findings specifically assessing: longitudinal tumour extent, direct mediastinal infiltration, invasion of other mediastinal structures, lymph node involvement and the presence of hepatic and pulmonary metastases. The sensitivity and specificity of the scan for each feature was then calculated. Scan sensitivity was poor, ranging from 0%-66.7%. Specificity was better with a range of 70.8%-100% according to the criterion studied. We conclude that the poor sensitivity means that CT scanning is of little value in the preoperative assessment of resectability in oesophageal carcinoma.

Role of cryoanalgesia in the control of pain after thoracotomy.

Thoracotomy causes severe postoperative pain, which is difficult to manage since the use of systemic analgesics often causes respiratory depression. Cryoanalgesia of the intercostal nerves has been advocated as an effective means of local analgesia without serious side effects. A prospective randomised blind trial to investigate the efficacy of the technique was carried out. A total of 53 patients undergoing thoracotomy were allocated to either the trial or a control group. At thoracotomy the surgeon was informed of the patient's trial allocation. The trial group received one minute of direct cryotherapy to at least five intercostal nerves related to the incision. All patients received methadone via the lumbar epidural route in a dose calculated according to their weight. A linear analogue assessment of postoperative pain was made by the patients as soon as they were sufficiently awake. An independent record of all postoperative analgesia was kept. After discharge from hospital further assessments were made at least six weeks after operation. Statistical analysis of the scores of postoperative pain and analgesic consumption showed that there was no significant difference between the trial and the control group. There was, however, a suggestion of an increase in the long term morbidity, although these figures were not amenable to statistical analysis. Thus is has not been possible to demonstrate a role for cryoanalgesia in the control of post thoracotomy pain.

Posterior urethral valves managed by cutaneous ureterostomy with subsequent ureteral reconstruction.

Six boys, 2 weeks to 5 years old, underwent cutaneous ureterostomy for massively dilated upper urinary tracts secondary to obstruction by posterior urethral valves. Cutaneous ureterostomies had been performed elsewhere in 2 patients. Two patients underwent transurethral fulguration of the valves initially with no improvement. Blood urea nitrogen, creatinine and serum electrolyte values continued to increase and, therefore, cutaneous ureterostomies were performed with dramatic improvement. Two patients presented with sepsis, one of whom had a positive blood culture. Both children had severe pyonephrosis and after the conditions improved with medical treatment cutaneous ureterostomies were done. The total number of surgical procedures required for all patients was 59, including renal biopsies, nephrostomies and cystoscopies. No kidneys, except for the severely dysplastic ones, were lost and all patients resumed normal growth rates and have had no urinary tract infections. All laboratory values are within normal limits.

Leydig cell hypoplasia: a cause of male pseudohermaphroditism.

A patient with male pseudohermaphroditism is presented whose testicular biopsy showed marked paucity of the Leydig cell populations to which is attributed testosterone deficiency and impaired spermatogenesis.

The effect of pharmacological agents on ejaculation.

Infertility in a patient on pharmacological agents with sympatholoytic activity was found to be caused by ejaculatory failure owing to absent contraction of the seminal vesicle, ampulla and ductus deferens, rather than the previously accepted reason of retrograde ejaculation. These findings suggest that pharmacological agents producing alpha-adrenergic blockage may produce temporary interference with ejaculation, suggesting investigation of their use as reversible male contraceptives.

Sexual function following high retroperitoneal lymphadenectomy.

The mechanism of infertility after high retroperitoneal lymphadenectomy was studied in 36 patients. In 35 patients infertility occurred because of unavoidable seminal vesicular and ductus deferential sympathetic denervation, with consequent aspermia. Potency and orgasm were unchanged in all patients and there was no evidence of retrograde ejaculation. The findings suggest that sympatholytic drugs be studied for possible application as reversible male contraceptives.

Calculi complicating renal transplantation into ileal conduits.

In 2 patients with renal transplants into ileal conduits renal calculi developed proximal to stenosis of the ureteral-ileal anastomosis, These are the only cases of urinary calculi in 600 consecutive transplants. The pathogenetic factors contributing to sepsis and stasis in such cases are reviewed and precautions suggested.