Prostaglandin-Priming der Zervix: Wirkung auf die fetoplazentare Einheit

Ohne Zusammenfassung     

Follow-up of the use of local health department clinics for preventive care among young children.

We followed 18,490 infants from their first visit to a county child health clinic (CHC) in Maryland through visits through their third year of age to investigate whether their continued use of the CHCs was related to their characteristics or to the services they were provided as an infant. We classified as provided services immunization, an Early and Periodic Screening, Diagnosis, and Treatment Program (EPSDT) recommended screening, and number of visits. Immunization was associated with an increased percentage of infants who returned to the CHCs at two and three years of age. Half of the children, on the other hand, never returned to the clinics if they were not immunized as infants. These findings persisted, regardless of race, Medicaid status, completion of a screening, or number of visits in the first year of life. One-fifth of infants did not receive an immunization during one or more visits to CHCs in their first year. Failure to administer an immunization to infants appears to impede subsequent use of public health clinics for well child care.     

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.      

Safety and efficacy of omadacycline for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in patients with mild-to-moderate renal impairment

BackgroundMany antibiotics require dosage adjustments in patients with renal impairment. In Phase III studies, omadacycline was non-inferior to moxifloxacin and linezolid in adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), respectively. This analysis evaluated efficacy and safety measures from three omadacycline studies by patient renal function.MethodsPatients were stratified as having normal renal function (creatinine clearance >89 mL/min), mild renal impairment (creatinine clearance 60–89 mL/min) or moderate renal impairment (creatinine clearance <60 mL/min); creatine clearance ≤30 mL/min (severe renal impairment) was an exclusion criterion. Efficacy endpoints were clinical success at the early clinical response (ECR) and post-treatment evaluation (PTE) time-points. Safety was evaluated as treatment-emergent adverse events (TEAEs) and laboratory measures.ResultsThis subgroup analysis included 773 patients with CABP and 1339 patients with ABSSSI in intent-to-treat (ITT) and modified ITT populations, respectively. Clinical success rates were high at ECR and PTE across the studies (CABP 75–90%; ABSSSI 74–95%), and broadly similar between treatments, irrespective of renal function. Rates of TEAEs in patients with ABSSSI ranged from 33% to 52%, and were similar across renal function groups. In patients with CABP, higher rates were observed in patients with moderate renal impairment (56–61%) compared with patients with normal renal function or mild renal impairment (35–49%). The most common TEAEs were nausea and vomiting.ConclusionsClinical success was similar across renal function groups, indicating no notable difference in the efficacy of omadacycline in patients with mild or moderate renal impairment. Omadacycline and comparators displayed similar safety profiles.ClinicalTrials.gov registryOPTIC (NCT02531438); OASIS-1 (NCT02378480); OASIS-2 (NCT02877927).     

Foscarnet and ganciclovir combination therapy for CMV disease in HIV-infected patients

Summary An open prospective trial of combined ganciclovir and foscarnet therapy for 3 weeks was initiated in 14 episodes of severe CMV-disease in 13 HIV-infected patients (all CDC class IV, age 30–42, median 34 years, CD4+ cell count 0–80, median 10/µl). In seven episodes of gastrointestinal disease (five colitis, two esophagitis) remission of symptoms and mucosal changes was achieved in five. In seven episodes of retinitis, scarring was achieved in six. Renal toxicity was seen in two patients, moderate hematologic toxicity in eight patients. Overall efficacy was comparable to monotherapy; no new toxicities were seen with the combination of these two drugs.

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Kombinationstherapie mit Ganciclovir und Foscarnet bei schwerer CMV-Erkrankung bei HIV-infizierten Patienten

Zusammenfassung In 14 Episoden einer CMV-Erkrankung bei 13 HIV-infizierten Patienten wurde eine Kombinationstherapie mit Ganciclovir und Foscarnet in einer offenen, prospektiven, nicht randomisierten Studie durchgeführt. Alle Patienten (n=13, Alter 30–42, Median 34 Jahre; CD4+Lymphozyten 0–80, Median 10/µl; alle Stadium IV CDC) wurden über 3 Wochen mit 2 × 5 mg/kg/d Ganciclovir und 2 × 90 mg/kg/d Foscarnet behandelt. In sieben Episoden einer gastrointestinalen CMV-Erkrankung (Colitis fünf, Ösophagitis zwei) wurde eine Remission in fünf Episoden erzielt, bei CMV-Retinitis in sechs von sieben Fällen. Nephrotoxizität trat bei zwei Patienten auf, mäßige Hämatotoxizität bei acht Patienten, sämtlich reversibel. Die Wirksamkeit der Therapie ist ähnlich der Monotherapie, die Nebenwirkungen sind additiv.