Effects of flunitrazepam on the baroreflex control of heart rate and on adrenergic activity

The effects of intravenous flunitrazepam (25 micrograms . kg-1) on the baroreflex control of heart rate and plasma catecholamine levels were determined in ten ASA 1 unpremedicated patients. Plasma concentrations of flunitrazepam were also measured. The data was obtained before and 5, 10 and 15 min after flunitrazepam administration. The baroreflex gain was significantly decreased at 5 min, the time of the highest flunitrazepam plasma concentration. Catecholamine plasma levels were decreased at each study time. It was concluded that flunitrazepam induced a transient depression in baroreflex function and a sustained decrease in adrenergic activity.     

High dose chemotherapy and autologous bone marrow transplantation in refractory Hodgkin's disease

Seventeen patients with Hodgkin's disease (HD) were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Eleven patients were resistant to initial therapy. Three patients had relapsed and were still responders to second or third line therapy. Three patients had relapsed but were progressing under second or third line therapy. Pre-ABMT chemotherapy included high dose cyclophosphamide in all patients (50 mg Kg-1 day-1 bolus for 4 days), most often associated with BCNU or CCNU, aracytine and 6 thioguanine. Four patients received additional TBI (10 Gy). In 9 patients complete remission (CR) was achieved, 4 failed to respond and 4 cases were not evaluable due to early death. Among CR patients, 2 died from late toxicity, 4 relapsed between the 2nd and 5th months, but 3 patients remain in CR, off therapy at 25+, 43+, and 66+ months, including 1/11 initially resistant and 2/6 who had relapsed. There were 9 treatment related deaths: 6 due to infection, 1 cardiac failure and 2 multiorgan failure. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high dose therapy earlier in resistant HD. Moreover under such conditions, treatment related morbidity would be expected to be lower.     

Current concepts in the pathogenesis of leprosy. Clinical, pathological, immunological and chemotherapeutic aspects.

In recent years there have been notable advances in the laboratory investigation and field management of leprosy. Progress, however, continues to be hindered by the lack of efficient methods for early diagnosis and implementation of control and treatment measures. Diagnosis is still made on the same principles as a century ago (clinical and histopathological findings), and only 1 in 3 known patients worldwide receives optimal chemotherapy. In 1988, nearly 1 in 10 newly diagnosed patients already had debilitating deformities. Contributing factors are operational, administrative and financial difficulties in implementing multidrug therapeutic regimens, inadequately trained personnel, and lack of priority and political commitment to leprosy control. The formulation and implementation of multidrug therapy is the most important development in leprosy in the past 10 years. Dapsone monotherapy was the mainstay for treatment and control for approximately 40 years, but secondary dapsone-resistant strains, first noted in 1964, now infect as many as 50% of all new patients. Multidrug regimens recommended by the WHO consist of various combinations of therapy using dapsone, rifampicin, clofazimine and a thionamide. Duration of therapy is limited to 6 months for paucibacillary and 2 years or more for multibacillary patients; relapse rates thus far are low. The average cost of treatment worldwide, including the cost of drugs, is estimated at $US150 per patient. The recent annual drop of nearly 8% in newly registered patients may be due to the implementation of these therapeutic regimens. Newer drugs that may be introduced into these regimens include fluoroquinolones, minocycline and clarithromycin. While knowledge of the microbiology of the leprosy bacillus and host response has advanced remarkably, there is little improvement in the understanding or amelioration of social aspects of leprosy. Better treatment and control reduces the stigma, but improvements in the attitudes of patients and society towards leprosy are as important as advances in medical science in achieving ultimate eradication of the disease.     

Does the stress of admission to an intensive care unit influence arginine vasopressin secretion and renal diluting ability?

The pathogenesis of excessive arginine vasopressin (AVP) release and hyponatraemia in euvolaemic intensive care unit (ICU) patients is poorly understood. Stress has frequently been proposed as a possible determinant, but its actual responsibility has not been adequately assessed. Therefore, water-load tests were prospectively performed in 11 patients admitted to the ICU for severe or potentially severe diseases, but who had no other condition which could result in excessive AVP release or impairment of renal diluting ability. Renal diluting ability was normal in 9 patients. Two patients exhibited very slight defects, which might be the consequence of subclinical haemodynamic alterations, since one had a pulmonary embolism and the other manifested a gastrointestinal haemorrhage just after the completion of the water load. Nevertheless, plasma AVP levels decreased in response to the water load in all the patients, resulting in a significant decrease in mean values. Plasma norepinephrine values were found to be elevated both before and after water loading. A highly significant correlation existed between the levels of norepinephrine and those of AVP measured before the load, but was lost after it. In addition, norepinephrine values were markedly elevated in two patients who exhibited strictly normal renal diluting abilities, and no correlation was found between plasma norepinephrine values and any parameter of renal water excretion. Our study shows that the stress of a serious illness and of admission to an ICU does not seem to interfere, by itself, with osmotic regulation of AVP secretion and renal diluting ability, and that sympathetic activation is not, under such circumstances, a predominant stimulus for AVP release. Caution is advisable before attributing to medical stress alone the responsibility for hyponatraemia in ICU patients.Presented in part at the 4th European Congress on Intensive Care Medicine, Baveno-Stresa, Italy, June 14–18 1988     

In vitro bactericidal activity of tobramycin and amikacin alone or in combination against Pseudomonas aeruginosa isolated from patients with cystic fibrosis

The bactericidal kinetic of 60 P. aeruginosa isolates (40 from cystic fibrosis sputum and 20 from various origins) was studied. Liquid medium micromethod was performed. Bacteria were incubated with tobramycin and amikacin alone at several concentrations and combined with piperacillin, cefsulodin, ceftazidim, imipenem, and ciprofloxacin at concentrations obtained in vivo. When used alone, tobramycin showed the most rapid bactericidal activity, whatever the concentration used. The bactericidal activity (greater than or equal to 99.99% killing of the inoculum) was obtained in 5 hours, with 1 or 2 x MIC of the majority of the strains, with the 2 aminoglycosides. No difference was found between tobramycin and amikacin, when combinated with an antibiotic which provides a notable increase of the rapidity of the bactericidal activity. The combination of amikacin plus imipenem was more rapidly bactericidal: 48% of strains; 26% were synergistically inhibited by amikacin plus ciprofloxacin. When correlated with the susceptibility patterns of studied micro-organisms, the results were rather unpredictive.