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Clinical and echocardiographic data from 12 patients with pulmonary valve endocarditis are described. Seven patients had isolated pulmonary endocarditis and in 5 patients other valves were infected (aortic, tricuspid, mitral or all 3). Two patients were heroin addicts and 4 had underlying heart disease (congenital heart disease in 3 and aortic regurgitation in 1 patient). The organisms involved were alpha streptococci in 3 patients (all with underlying heart disease), Staphylococcus aureus in 4, Streptococcus D bovis in 1 patient and Candida guillermondii in 1. M-mode and 2-dimensional echocardiography was performed in 10 patients and revealed vegetations in 8. Pulsed Doppler echocardiography was performed in 6 patients and revealed pulmonary regurgitation in all 6. Seven patients had pulmonary emboli. Four patients underwent surgery. Four patients died, including 1 after cardiac surgery. Five patients, including the patient infected with Candida guillermondii, recovered with antibiotic treatment.

The pharmacokinetics of teicoplanin were studied in 15 adult patients in the acute phase of severe infections caused by gram-positive cocci. All the subjects were given a daily intravenous bolus dose of 6 mg of teicoplanin kg-1 (body weight). The pharmacokinetic study was performed over a 48-h period after injection 4. The subjects were categorized according to their mean creatinine clearances (ml.min-1.kg-1) during the study period: group 1 (n = 3), greater than 1.6; group 2 (n = 6), 0.8 to 1.6; and group 3 (n = 6), 0.15 to 0.8. Mean concentrations of teicoplanin in serum at 1, 24, and 48 h were 33 +/- 8, 9 +/- 3, and 6 +/- 2.5 micrograms.ml-1, respectively. The mean half-lives of the concentration-time curve from 12 to 48 h were 28 +/- 4, 44 +/- 24, and 48 +/- 14 h in groups 1, 2, and 3, respectively (group 3 versus group 1: P less than 0.05). The mean area under the serum concentration-time curve from time zero to 24 h was 344 +/- 92 mg.h.liter-1, and the mean hybrid volume of distribution was 1.09 +/- 0.46 liter.kg-1. These values were similar for the three groups, with a trend for larger areas under the curve in group 3. Creatinine clearance correlated directly with the total body clearance of teicoplanin (r = 0.70) and with the renal clearance of teicoplanin (r = 0.82). However, in critically ill patients, the wide interindividual variations in pharmacokinetic parameters are more relevant than those related to the variations in renal function when creatinine clearance is above 0.30 ml.min-1.kg-1. We concluded that, in such conditions, monitoring of concentrations of teicoplanin in serum is mandatory.

Forty-seven nosocomial cases of legionellosis due to Legionella pneumophila serogroup 1 were diagnosed in one major outbreak from November 1982 to March 1983 in a 960-bed teaching hospital. Contaminated water was considered to be a possible source of infection because, during that period, monthly samples were found to be positive with averages of 10(4) CFU/l. After chlorination of hot water associated with flushing of outlets, nearly all samples taken in the next two years were found to be negative. A case-control study was performed to examine potential risk factors. Three groups of controls were randomly selected among eligible patients. In a multivariate analysis, only three clinical factors were found to be associated with legionellosis patients: malignant illness (relative risk, RR = 3.5), presence of an ultimately fatal disease (RR = 2.6), and exposure to corticosteroids prior to admission (RR = 7.9). Investigations of in-hospital exposures suggest that during this nosocomial outbreak diagnostic or therapeutic respiratory procedures had not increased the risk of illness. Although the epidemiological association between water contamination and disease remains unclear, the eradication of L. pneumophila from the identified supply seems to have been effective in preventing disease in this hospital.

Twenty-two adult patients who had required catheterization with a Swan-Ganz catheter and had thrombosis of the internal jugular vein were investigated for pulmonary embolism. In 4 of these, pulmonary embolism was detected by angiography, and 2 patients who died with the catheter in situ had also pulmonary embolism. In 5 out of these 6 patients prophylactic heparin treatment failed to prevent this complication. This study suggests that the Swan-Ganz catheter placement is indicated only when the value of the information to be gained exceeds the potential risk.

The penetration of roxithromycin (RU 28965), an ether oxime derivative of erythromycin, into the cells and fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiber-optic bronchoscopy with bronchoalveolar lavage on eight patients who had received roxithromycin at 300 mg perorally every 12 h for 5 days. The apparent volume of epithelial lining fluid recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. There was a significant relationship (r = 0.75; P less than 0.02) between roxithromycin levels in plasma and epithelial lining fluid, with a correlation whose slope suggested that the level of drug penetration into the lining fluid was 0.2. Concentrations of the antibiotic in cells recovered by bronchoalveolar lavage (21 +/- 10 micrograms/ml) were 2 and 10 times higher than in plasma (11.4 +/- 5.7 micrograms/ml) and epithelial lining fluid (2.0 +/- 1.7 micrograms/ml), respectively. Thus, when administered perorally in humans, roxithromycin is markedly accumulated by resident alveolar macrophages in concentrations largely exceeding the MBCs of the drug for most facultative intracellular pathogens including Legionella pneumophila, despite low concentrations in the epithelial lining fluid.

The onset of hepatic necrosis and a hemorrhagic syndrome, leading to a fatal outcome, was attributed to the toxicity of mithramycin prescribed for an iatrogenic hypercalcemia. This toxicity limits the use of mithramycin for the treatment of hypercalcemias.

19 critically ill adults with acute mediastinitis after cardiac surgery were treated with granulated sugar, either directly (11 patients) or after failure of continuous irrigation (8 patients). Mediastinal tissue cultures were positive in 18 patients. Packing the mediastinal cavity with granulated sugar every 3 or 4 h resulted in near-complete debridement of the wound and rapid formation of granulation tissue in all patients and sterilisation of the wound after an average of 7.6 days. Dressings were easy and painless to change. 5/19 (26%) patients died before discharge, but none because of wound complications. The rest were discharged on average 54.2 days (range 29-120) after initial debridement of the wound; 11 underwent secondary surgical closure of the wound and in 3 the wound healed by granulation tissue formation alone. No recurrence of sternal infection has occurred after a mean follow-up of 8.2 months (range 3 to 17).

Lonapalene was studied as a topical antipsoriatic agent on the basis of its inhibitory effect on 5-lipoxygenase. We studied the effect of lonapalene on the metabolism of exogenous arachidonic acid in washed platelet suspensions by RP-HPLC. Lonapalene was shown to inhibit platelet cyclooxygenase, with substrate diversion towards 12-HETE production. The pattern of inhibition was similar to that of indometacin, although lonapalene was about 1,000 times weaker. The dual inhibition of lonapalene and concomitant deviation of arachidonic acid metabolism may have potential implications, with regard to therapeutic indications and side effects, which deserve further study.

During a five-week period in 1981, six cases of legionellosis due to Legionella pneumophila serogroup 1 were recognized in a hospital in Paris, France. Four cases were clearly nosocomial in origin. There was a direct association between development of disease and exposure to potable hot water (p = 0.003). The entire hot water system was contaminated with L. pneumophila serogroup 1; monoclonal antibody testing demonstrated that the case isolate and the potable water isolates belonged to the same subgroup. Although serogroup 1 was isolated from both the cooling tower and its drift, the cooling tower isolate was antigenically distant from the case isolate. In other nosocomial outbreaks of legionellosis, multiple sources have been found within the hospital environment, but an epidemiologic association of disease with potable water had not been shown. The significant association of cases with exposure to the potable hot water supply, and the identification of case and potable water isolates of the same subtype, suggest that the potable hot water was responsible for transmission of disease in this outbreak.