Role of cervical cerclage and prolonged antibiotic therapy with azithromycin in patients with previous perinatal loss amnionitis.

In the group of 35 patients with cerclage, intermediate fetal mortality was reduced from 37.1% to 0 (p < 0.001); late fetal mortality rate from 8.5% to 2.8% (p = 0.606); prematurity from 65.7% to 5.7% (p < 0.001); newborn underweight from 11.4% to 5.7% (p = 0.671); newborns with very low weight from 34.2% to 0 (p < 0.001) and the abortion rate from 8.5% to 0 ( p < 0.001). In the group of 19 patients without buckling, intermediate fetal mortality was reduced from 26.3% to 10.5% (p = 402); late fetal mortality from 63.1% to 0 (p < 0.001); prematurity 78.9% to 31.5% (p < 0.009); the newborn of low weight from 31.5% to 10.5% (p = 0.234); newborns with very low weight from 68.4% to 15.7% (p < 0.003) and the abortion rate from 36.8 to 0 (p < 0.001). In conclusion, we believe the results of this study demonstrate the effectiveness of therapeutic and prophylactic cervical cerclage associated with prolonged antibiotic therapy.

Novel bacterial acetyl coenzyme A carboxylase inhibitors with antibiotic efficacy in vivo.

The pseudopeptide pyrrolidinedione antibiotics, such as moiramide B, have recently been discovered to target the multisubunit acetyl coenzyme A (acetyl-CoA) carboxylases of bacteria. In this paper, we describe synthetic variations of each moiety of the modularly composed pyrrolidinediones, providing insight into structure-activity relationships of biochemical target activity, in vitro potency, and in vivo efficacy. The novel derivatives showed highly improved activities against gram-positive bacteria compared to those of previously reported variants. The compounds exhibited a MIC(90) value of 0.1 microg/ml against a broad spectrum of Staphylococcus aureus clinical isolates. No cross-resistance to antibiotics currently used in clinical practice was observed. Resistance mutations induced by pyrrolidinediones are exclusively located in the carboxyltransferase subunits of the bacterial acetyl-CoA carboxylase, indicating the identical mechanisms of action of all derivatives tested. Improvement of the physicochemical profile was achieved by salt formation, leading to aqueous solubilities of up to 5 g/liter. For the first time, the in vitro activity of this compound class was compared with its in vivo efficacy, demonstrating a path from compounds weakly active in vivo to agents with significant efficacy. In a murine model of S. aureus sepsis, the 100% effective dose of the best compound reported was 25 mg/kg of body weight, only fourfold higher than that of the comparator molecule linezolid. The obvious improvements achieved by chemical derivatization reflect the potential of this novel antibiotic compound class for future therapy.

Intraperitoneal hyperthermic chemotherapy in ovarian cancer.

We investigated the effect of intraperitoneal hyperthermic perfusion chemotherapy as consolidation therapy in stage IIIB-IIIC ovarian cancer, following cytoreductive surgery and systemic chemotherapy (cisplatin-cyclophosphamide--six cycles). Disease-free survival, overall survival, and side effects were compared with a control group of patients who refused a second-look surgery and intraperitoneal chemotherapy. In a multicenter prospective trial, 29 patients with complete or optimal cytoreductive surgery and systemic treatment were included in the consolidation group and received intraperitoneal hyperthermic perfusion chemotherapy. Patients were recruited between January 1991 and December 1997. The intraperitoneal hyperthermic perfusion was performed with open-abdomen technique, using physiologic solution containing cisplatin 100 mg/m2, for 60 min in hyperthermic phase (41-43 degrees C). Intraperitoneal hyperthermic perfusion chemotherapy was locally and systemically well tolerated. The consolidation therapy group showed a better 5-year survival rate and lower recurrent disease rate, but differences were not statistically significant. Our results suggest that intraperitoneal hyperthermic perfusion chemotherapy is a feasible, well-tolerated, and promising alternative as consolidation therapy in ovarian cancer.

Quimioterapia intraperitoneal con hipertermia en el cáncer de ovario / Intraperitoneal Hyperthermic Chemotherapy in ovarian cancer treatment

Se presentan los resultados de un estudio prospctivo multicéntrico, con la administración de qimioterapia intraperito a cielo abierto, como tratamiento de consolidación en pacientes con cáncer de ovario Estadios IIIB y IIIC; posterior a una cirugía de citorreducción completa u óptima y 6 ciclos de Platino y ciclofosfamina. Se analiza tolerancia y se comparan tiempo libre de fermedad y sobrevida con los de un grupo control, con iguales estadios, posibilidades de citorreducción y terapia sistémica, que no aceptaron el second look y quimioterapia intraperitonal

Drug use and adverse event monitoring in German children.

OBJECTIVE: To assess drug use and the incidence of mild to moderate adverse drug effects (AE) in children aged 0 - 16 years, with 2 different approaches. METHODS: All 185 pediatric practices in the State of Brandenburg, Germany, were surveyed (95% positive response). A random sample of 50 practices servicing 36,000 children participated in the study as sentinel physicians reporting any AE among their patients. Twenty practices servicing 14,000 children were included in a drug utilization component (DUC) which documented diagnoses, prescribing and AE in all children seen in a 3-month period. RESULTS: The results on the DUC are based on 12,628 children with 26,168 physician contacts, 34,465 diagnoses and 33,140 drug prescriptions given to 85% of the children seen (average age: 6.7 years). Practice size ranged from 94 to 1,473 children seen in a 3-month period. The average number of physician contacts per child was 2. 1, with 10% seeing a physician 5 times and more. The diagnoses were respiratory ailments (30%), skin- (12%), injection- (11%) and trauma- (10%) related diagnoses. Major drug uses were respiratory (34% of prescriptions), anti-infective (22%), dermatological (13%), gastrointestinal (9%) and psychotropic agents (8%). One hundred and fifty-two AE affecting 150 children were documented in the DUC, 60% of these occurring within 3 days after treatment initiation. 83% of AE were mild (up to 4 on a scale from I -6), and 85% were considered by physicians to be attributable. Only 4 reports of very severe events were received. 47% of reports were related to antibiotic uses, 31% to immunizations, 11% to respiratory, and 4% to gastrointestinal agents. While there are no differences in the occurrence of AE by gender, AE decreases significantly by age, maintaining the same patterns of AE type and causative medication. Over a 3-month period, the incidence of mild to moderate ADR in children given medications is estimated as 1,200 per 100,000, or about 1%. CONCLUSIONS: Underreporting of AE remains an issue even when a monitoring scheme suggests compliance. The results of this study show that while AE in children are generally non-serious, 1% of treatments might elicit mild AE leading to a consultation. Direct practice recording produces more reports than a sentinel system.

A novel peptide aldehyde with activity against human cytomegalovirus in two different in vivo models.

Novel peptide aldehydes (PAs) were identified as potent inhibitors of human cytomegalovirus (HCMV) in vitro. Although these compounds were highly effective against HCMV, they did not exhibit any activity against murine cytomegalovirus (MCMV). The purpose of this study was to test the antiviral activity of PA 8 as a representative of this novel class of inhibitors against HCMV in vivo. Because of the strict species specificity of HCMV we had to use two artificial animal models. In the first model, HCMV-infected human cells were entrapped into agarose plugs and transplanted into mice. In the second model, SCID mice were transplanted with human tissues that were subsequently infected with a clinical isolate of HCMV. In these two models the antiviral activity of PA 8 was clearly demonstrated, ganciclovir only being slightly superior in its in vivo antiviral activity.