One hundred and twenty-one cases of murine typhus and spotted fever in Israel between 1976 and 1985 in the Chaim Sheba Medical Center are reviewed. Clinical manifestations of murine typhus were similar to those described previously, but those of spotted fever were different from classical Mediterranean spotted fever: rash was present in 87% but eschar was noted in only two out of 38 patients. The occurrence of relapse in eight of the 16 patients treated with chloramphenicol (seven cases of murine typhus and one case of spotted fever) was striking, particularly since none occurred in 86 patients treated with tetracycline hydrochloride (p less than 0.01). Relapses were milder than the primary illness, except for one which did not receive specific therapy and was fatal.

Chloramphenicol↗

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Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.

BACKGROUND: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients. METHODS: Non-neutropenic patients with a positive blood culture for a species of candida and clinical evidence of infection were enrolled. Patients were randomly assigned, in a 2:1 ratio, either voriconazole (n=283) or amphotericin B followed by fluconazole (n=139). The primary efficacy analysis was based on clinical and mycological response 12 weeks after the end of treatment, assessed by an independent data-review committee unaware of treatment assignment. FINDINGS: Of 422 patients randomised, 370 were included in the modified intention-to-treat population. Voriconazole was non-inferior to amphotericin B/fluconazole in the primary efficacy analysis, with successful outcomes in 41% of patients in both treatment groups (95% CI for difference -10.6% to 10.6%). At the last evaluable assessment, outcome was successful in 162 (65%) patients assigned voriconazole and 87 (71%) assigned amphotericin B/fluconazole (p=0.25). Voriconazole cleared blood cultures as quickly as amphotericin B/fluconazole (median time to negative blood culture, 2.0 days). Treatment discontinuations due to all-cause adverse events were more frequent in the voriconazole group, although most discontinuations were due to non-drug-related events and there were significantly fewer serious adverse events and cases of renal toxicity than in the amphotericin B/fluconazole group. INTERPRETATION: Voriconazole was as effective as the regimen of amphotericin B followed by fluconazole in the treatment of candidaemia in non-neutropenic patients, and with fewer toxic effects. RELEVANCE TO PRACTICE: There are several options for treatment of candidaemia in non-neutropenic patients, including amphotericin B, fluconazole, voriconazole, and echinocandins. Voriconazole can be given both as initial intravenous treatment and as an oral stepdown agent.

APACHE↗

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Chimeric CD46/DAF molecules reveal a cryptic functional role for SCR1 of DAF in regulating complement activation.

Chimeric proteins using membrane cofactor (CD46) and decay accelerating factor (DAF or CD55) were generated to further investigate the functional domains involved in the regulation of human serum complement. Following activation of the classical pathway, the isolated substitution of CD46 SCR III (x3DAF) exhibited a modest regulatory activity comparable to that of CD46. The isolated substitution of CD46 SCR IV (x4DAF), and the combined CD46 SCR III+IV substitutions (x3/4DAF) were essentially as efficient as DAF. No regulation of C3b deposition was observed with the combined CD46 SCR I+II substitutions (x1/2DAF). When tested after activation of the alternative pathway, both the x3DAF and x3/4DAF chimeras failed to regulate C3b deposition, while the x4DAF chimera still displayed some activity. In contrast to that observed following classical pathway activation, the x1/2DAF chimera exhibited a similar efficiency to wild type CD46 and DAF in controlling C3b deposition. Using SCR specific antibodies, the regulatory activity of the x1/2DAF chimera against the alternative pathway was mapped to the first three distal SCR (i.e. DAF 1, DAF 2 and CD46 III). These data demonstrate that several combinations of SCR domains from two related complement regulators can result in functional molecules, and reveal a novel and cryptic functional role for DAF SCR1.

Animals↗

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Anthrax post-vaccinal cell-mediated immunity in humans: kinetics pattern.

Seven groups (2596 subjects) were vaccinated with a human live anthrax vaccine (HLAV) by three different routes (scarification, subcutaneous and aerosol). The vaccinees were tested for anthrax cell-mediated immunity using the "Anthraxin" skin test at 7, 15, 30, 90, 180 and 365 days following vaccination. The kinetic pattern obtained from all groups, shows a significant, five-phased curve: phase I (2-6 days post-vaccination) shows a slow increase in positive Anthraxin skin reactions. Phase II (7-15 days post-vaccination) shows an exponential rise to a maximum at day 15. Phase III (16-30 days post-vaccination) shows a decrease to day 30. Phase IV (31-90 days post-vaccination) leads to a relative restoration of the positive skin reactions. During phase V (91-365 days post-vaccination) there is a continuous decrease in positive Anthraxin skin reactions. The loss of the skin test reaction on day 30 is a characteristic feature of post vaccination anthrax cell-mediated immunity. It may be due to a blockade of macrophages by lethal anthrax toxin released by the multiplying vaccine strain. Epidemiological observations of HLAV protective rates correlate with the phases of the skin reaction kinetics.

Adolescent↗

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Corynebacterium diphtheriae endocarditis.

Two patients with Corynebacterium diphtheriae endocarditis have been observed in the past ten years. Both cases occurred sporadically. In one case toxigenic C. diphtheriae caused endocarditis in an immunized child with congenital heart disease. The second patient developed rapidly progressive valve destruction caused by a nontoxigenic strain of C. diphtheriae. These cases illustrate that C. diphtheriae may produce endocarditis in addition to its previously described diseases spectrum.

Child, Preschool↗

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Therapeutic effects of roxithromycin and azithromycin in experimental murine brucellosis.

Mice infected with Brucella melitensis were treated with azithromycin or roxithromycin at a dose of 50 mg/kg/day i.p. alone and in combination with streptomycin 75 mg/kg/day for 14 days. Streptomycin at this dose was previously documented to be ineffective against murine brucellosis. Azithromycin- and azithromycin/streptomycin-treated animals demonstrated a significantly better cure rate than controls. Therapy failure was observed in all mice treated with roxithromycin 50 mg/kg/day i.p. alone or in combination with streptomycin 75 mg/kg/day. Our findings demonstrate that azithromycin cures experimental murine brucellosis and may be an effective alternative in the therapy of human brucellosis.

Animals↗

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Acute gram-negative bacillary infections of middle ear and mastoid.

Thirty-three patients with acute purulent otitis media and mastoiditis caused by Gram-negative bacilli are presented. The main features of the disease include: predilection for young male infants, a high rate of complications that include sepsis, mastoiditis and osteomyelitis of the base of the skull. Patients that are diagnosed early respond well to drainage and ventilation of the infected middle ear combined with in vitro effective antibacterial therapy. Patients that receive prior inappropriate antibacterial therapy tend to have prolonged courses and require mastoid surgery. It is suggested that early myringotomy and bacterial cultures be performed in all patients with acute middle ear infections.

Acute Disease↗

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West Nile fever outbreak, Israel, 2000: epidemiologic aspects.

From August 1 to October 31, 2000, 417 cases of West Nile (WN) fever were serologically confirmed throughout Israel; 326 (78%) were hospitalized patients. Cases were distributed throughout the country; the highest incidence was in central Israel, the most populated part. Men and women were equally affected, and their mean age was 54+/-23.8 years (range 6 months to 95 years). Incidence per 1,000 population increased from 0.01 in the 1st decade of life to 0.87 in the 9th decade. There were 35 deaths (case-fatality rate 8.4%), all in patients >50 years of age. Age-specific case-fatality rate increased with age. Central nervous system involvement occurred in 170 (73%) of 233 hospitalized patients. The countrywide spread, number of hospitalizations, severity of the disease, and high death rate contrast with previously reported outbreaks in Israel.

Adolescent↗

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Managing prescription drug costs in medical groups.

Explore the source record for details and available documents.

Cost Control↗

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Development of stress ulcers assessed by gastric electrical potential difference, pH of gastric juice, and endoscopy in patients in the intensive care unit.

OBJECTIVE: To assess measurement of gastric electrical potential difference, pH of gastric mucosa, and endoscopic findings in patients in intensive care units who are at risk of developing stress ulcers. DESIGN: Open comparison with age- and sex-matched control subjects. SETTING: Herlev Hospital, Denmark. SUBJECTS: Sixteen consecutive patients with no history of gastrointestinal haemorrhage, coagulopathy, or ulcer disease who had been admitted to the intensive care unit, and 16 age- and sex-matched outpatients with normal endoscopic findings. INTERVENTIONS: Upper gastrointestinal endoscopy, during which any lesions that were found were scored according to severity, the gastric potential difference, and the pH of gastric juice were measured. OUTCOME MEASURES: Correlation between the incidence of stress ulceration found at endoscopy, gastric potential difference, and gastric pH. RESULTS: Gastric potential difference was significantly reduced and gastric pH significantly increased in the patients in the intensive care unit (p less than 0.05 in both cases), all of whom had stress ulcers in more than one gastric segment. Nine of the patients had gastric pH readings of greater than 4. CONCLUSION: Gastric electrical potential difference may be useful measurement for the assessment of stress ulceration in patients in intensive care units.

Adult↗