Synthesis and pharmacological investigation of beta-substituted pyrrolo derivatives

A series of pyrroles bearing an ethanol- or an iso-propanolamine side-chain in the beta-position was prepared and their adrenergic activity evaluated. The absence of any appreciable activity suggests that the pyrrole ring is not suitable for replacing the phenol nucleus in derivatives possessing an adrenergic activity. Noteworthy is the amphetamine-like activity observed in amino-ketone (XXIII).     

Prospective epidemiological study of invasiveHaemophilus influenzae disease in adults

The incidence and characteristics of invasiveHaemophilus influenzae disease were studied in 43 adult patients admitted to the acute care hospitals in El Vallés County (Barcelona, Spain) between January 1987 and June 1992. The annual incidence ofHaemophilus influenzae disease was 1.2 per 100,000 inhabitants. Pneumonia occurred in 24 patients, meningitis in five, intraabdominal infections in three, obstetric infections in two, epiglottitis in two and cellulitis in one. In six patients the source of infection was unknown. Ten (23 %) of the infections were hospital acquired. Underlying conditions were diagnosed in 30 (70 %) patients. NontypeableHaemophilus influenzae strains predominated in all adult age groups. Sixty-one percent of type b and 34 % of nontypeable strains were ampicillin resistant (p=0.08). Multiple antibiotic resistance was also high among type b (53 %) and nontypeable (18 %) strains. The mortality rate was significantly higher in patients with pneumonia, bactaeremia from an unidentified focus or shock at presentation.     

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen.

BACKGROUND. Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported. METHODS AND RESULTS. We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001). CONCLUSIONS. In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women.     

Efficacy and tolerability of prolonged linezolid therapy in the treatment of orthopedic implant infections

The aim of the study presented here was to assess the efficacy and tolerability of linezolid in the treatment of orthopedic implant infections (OII). Eighty-five patients with an OII treated with linezolid were prospectively followed up for a minimum of 12 months from the end of antibiotic therapy. Outcome was evaluated in relation to the duration and type of symptoms (acute or chronic) and the retention or removal of the implant. For acute and chronic infections, the respective success rates were 100 and 92.3% when the implant was removed and 72.2 and 42.8% when it was not. The median length of linezolid treatment in acute and chronic infections was 47 and 60 days, respectively. Thrombocytopenia was observed in four (4.7%) patients and anemia in five (5.8%). The results suggest oral linezolid is an effective and well-tolerated alternative for treating OII.     

Expression of gastrin-releasing peptide (GRP) in the bovine uterus during the estrous cycle

Gastrin-releasing peptide (GRP) has been proposed as a novel regulatory peptide in the reproductive tract. We previously demonstrated that GRP immunoreactivities are found predominantly in the uterine gland epithelial cells of nonpregnant and pregnant cows. The present study focused on the distribution of GRP immunoreactivity and the expression of GRP mRNA in the bovine endometrium during the estrous cycle. Tissues were collected from 21 uterine horns and bodies during the estrous cycle. RT-PCR showed the expected GRP mRNA fragments (284 bp) in the tissues from all stages of the cycle. In situ hybridization results ascertained the expression of the GRP mRNA in the uterine gland epithelial cells and superficial epithelial cells of the endometrium. Positive staining of GRP immunoreactivity in the uterine gland epithelial cells was detected in both the uterine horn and body from all stages of the cycle. In metestrus and diestrus stages, GRP was also detected in the superficial epithelial cells of horn, but not in the body. The degrees of GRP mRNA expression and intensities of GRP immunoreactivity in the endometrium increased from proestrus to diestrus stages. These findings suggest that GRP may be important both in the endometrial remodeling during the estrous cycle and in the implantation and development of blastocysts.