Fluconazole: a new triazole antifungal agent

Fluconazole is a recently approved agent for the treatment of certain fungal infections. Based on available studies, the drug is clearly effective in oropharyngeal candidiasis in immunosuppressed hosts. Current evidence suggests it may be more efficacious than other azole drugs for oropharyngeal disease. It is probably also effective in other infections due to Candida species, but controlled studies are lacking. Fluconazole is also efficacious in the treatment of cryptococcal meningitis, but recent reports question its use as initial therapy in HIV-infected patients with this illness. The drug, however, is clearly more effective than amphotericin B in the suppression of cryptococcal meningitis in AIDS patients and is the treatment of choice in this situation.     

The effect of systemic cocaine on the responses to noxious stimuli and spontaneous activity of medial bulboreticular projection neurons

The effect of antinociceptive doses of cocaine (25 mg/kg, i.p.) on unit responses to noxious somatic stimuli and spontaneous activity of antidromically identified projection neurons in the medial medullary reticular formation (MRF) was studied in the rat. Thirty-three antidromically activated neurons were recorded from the medullary raphe, gigantocellular, or paragigantocellular nuclei in an acute anaesthetized preparation; 25 cells projected to the spinal cord and 8 neurons had rostral projections through the medial forebrain bundle (n = 4) or the medial thalamus (n = 4). After cocaine administration, 24 (73%) of these cells showed immediate (less than 5 min) and prolonged (45-70 min) increases in their level of spontaneous activity. Associated with this increased interstimulus activity, 21 of 29 (72%) neurons responsive to noxious somatic stimulation reduced their responsiveness, relative to prestimulus activity, after cocaine administration. In 5 animals tested, the cocaine-induced changes in spontaneous activity and changes in evoked responsiveness were unaffected by naloxone (1 mg/kg, i.p.) but partially reversed within 5 min of the administration of chlorpromazine (3 mg/kg, i.p.). There were no obvious differences in neuronal response characteristics or the effect of cocaine that correlated with anatomical location or direction of axonal projection. Similar results were obtained while recording from 14 somatically responsive units in chronic, unrestrained, lightly anesthetized or awake rats. These findings provide direct evidence that cocaine, in doses that are antinociceptive for the rat, affects both unit responses to noxious stimuli and the spontaneous activity of caudally and rostrally projecting bulboreticular neurons over a time course that parallels the behavioral antinociception. The observation that unit responses to somatic stimuli were reduced while spontaneous activity was unchanged or increased in most cells suggests that cocaine antinociception may be due to the activation of sensory inhibitory mechanisms mediated by the MRF.     

Deficits of gaze stability in multiple axes following unilateral vestibular lesions

 Abnormalities in the vestibulo-ocular reflex (VOR) after unilateral vestibular injury may cause symptomatic gaze instability. We compared five subjects who had unilateral vestibular lesions with normal control subjects. Gaze stability and VOR gain were measured in three axes using scleral magnetic search coils, in light and darkness, testing different planes of rotation (yaw and pitch), types of stimulus (sinusoids from 0.8 to 2.4 Hz, and transient accelerations) and methods of rotation (active and passive). Eye velocity during horizontal tests reached saturation during high-velocity/acceleration ipsilesional rotation. Rapid vertical head movements triggered anomalous torsional rotation of the eyes. Gaze instability was present even during active rotation in the light, resulting in oscillopsia. These abnormal VOR responses are a consequence of saturating nonlinearities, which limit the usefulness of frequency-domain analysis of rotational test data in describing these lesions. Received: 22 April 1996 / Accepted: 18 February 1997     

The role of clinical epidemiology in establishing essential national health research capabilities in developing countries

Health research directly relevant to the needs of the people of developing countries is essential for equity in development as well as for improving health planning and management. the international Commission on Health Research for Development has stressed the need to strengthen the capacity of developing countries, no matter how poor, to carry out essential national health research (ENHR). Clinical epidemiologists in developing countries can significantly contribute to the manpower available for ENHR. They play a major role in the provision and practice of appropriate health care by contributing to the critical assessment of priority health problems and by carrying out scientific evaluation of new and conventional intervention tools. In clinical epidemiology units in developing countries, transdisciplinary collaboration with social scientists and health economics has enhanced the capacity to do research that would influence decision-making and health policy, even as links with ministries of health and other ENHR-committed networks are being strengthened. The potential for carrying out ENHR will be multiplied as national and regional training centers for clinical epidemiology in selected developing countries are established.     

Small bowel obstruction in patients with a prior history of cancer.

To assess the efficacy of operative and nonoperative therapy of small bowel obstruction (SBO) in patients with a previous diagnosis of cancer, a review of 54 cases was carried out. The 32 men and 22 women had a mean age of 58 years. At presentation with SBO, 26 patients (48%) had known recurrent cancer. Forty patients were initially treated nonoperatively; 11 (28%) had resolution of their SBO after a mean of 7 days of nasogastric suction. Five of 11 patients developed recurrent SBO prior to death. Thirty-seven patients underwent laparotomy, 14 on the day of admission and 23 after failure of nasogastric suction. Twenty-five of 37 (68%) had obstruction due to recurrent carcinoma. Small bowel obstruction due to recurrent cancer occurred earlier (21 +/- 5 months) than SBO from benign causes (61 +/- 18 months; p < 0.01). Mean survival for patients with malignant obstruction (5 +/- 1 month) was significantly shorter than for those with benign obstruction (50 +/- 10 months; p < 0.001). The 30-day and in-hospital mortality rates for the 25 surgically treated patients with malignant SBO were 24% and 28%, respectively; in 9 of 25 (36%), the obstruction failed to fully resolve. The only factor predictive of in-hospital mortality was obstruction secondary to cancer (p < 0.05). The median posthospital survival for surgically treated patients with malignant SBO was only 2.5 months. We conclude that: (1) patients should be given an initial trial of nonoperative therapy; (2) patients with no known recurrence or a long interval to the development of SBO should be aggressively treated with early surgery if nonoperative treatment fails; and (3) for patients with known abdominal recurrence in whom nonoperative therapy fails, the results of surgical palliation are grim. Innovative approaches are needed to maximize palliation while also limiting morbidity and mortality.