Comparison between nafarelin acetate andd-Trp6-LHRH for temporary pituitary suppression in in vitro fertilization (IVF) patients: A prospective crossover study

Purpose Nafarelin acetate is a new gonadotropin releasing (GnRH) agonist analogue with unique potency, intranasal administration, and convenient storage. Hence, nafarelin was considered as an alternative for temporary pituitary suppression in patients undergoing ovulation induction in IVF. A crossover treatment in a prospective study was performed including 40 women with bilateral obstructed tubes and normal ovarian function, treated in 80 ovulation induction cycles using the long protocol. Twenty patients used nafarelin acetate 600 g/daily in their first cycle and received d-Trp6-LHRH, 0.5 mg/daily, in their following cycle. The other 20 women used decapeptyl in their first cycle and received nafarelin in the second.Results Estradiol suppression was achieved by both d-Trp6-LHRH and nafarelin at equal time intervals. The average total number of ampoules (P=0.0005) and the length of administration of hMG required for ovarian stimulation (P=0.0002) and the time interval between GnRHa initiation to oocyte retrieval (P=0.04) was significantly lower in nafarelin cycles. The number and the distribution between large and small follicles as well as the average number of oocytes retrieved did not differ between the two GnRH analogues.Conclusion Our results demonstrate that nafarelin acetate is comparable to d-Trp6-LHRH for temporary pituitary suppression used for controlled ovarian stimulation in IVF patients. However, using nafarelin ovarian stimulation was achieved with fewer ampoules of hMG, administered for a shorter period of time, thus with a lesser cost.     

MRI of the Stener lesion

Objective. To assess the utility of MR in detecting surgically induced Stener lesions (displaced thumb ulnar collateral ligaments) in cadaveric models. Design. Six cadaver thumbs had ulnar collateral ligament (UCL) tears created surgically. MR examinations (2D STIR and 3D GRASS) were performed identically on all specimens both before displacement (non-Stener) and after displacement (Stener lesion) of the UCL. The MR images were then randomly numbered. Each image was evaluated separately in blinded fashion by four musculoskeletal radiologists for the presence or absence of a Stener lesion. Each radiologist reinterpreted the images after an interval of several days. The interpretation was based on previously published criteria for Stener lesion diagnosis by MR. Results. The sensitivity of GRASS ranged from 0.17 to 0.67 with the most experienced reader scoring the lowest. The specificity of GRASS ranged from 0.33 to 1.0 (most experienced reader 0.67, 0.83). STIR had a sensitivity of 0.00–0.17 and a specificity of 0.53–0.83. The values for inter- and intraobserver agreement were measured. The intraobserver for GRASS was 0.27–0.75 (most experienced reader 0.75). Conclusions. 2D imaging is probably inadequate for the evaluation of Stener lesions. The most likely reason is that the STIR slice thickness of 3 mm limits resolution of small UCLs. The poor sensitivity and specificity of GRASS as well as poor interobserver agreement suggest that MR may not be sufficiently accurate for Stener lesion evaluation.     

Pregnancy Outcome in Gestational Diabetes with Preconceptional Diabetes Counselling

One hundred and thirty-six women with known previous gestational diabetes and normal glucose tolerance between pregnancies attended a preconceptional clinic at least 2 months before conception, and were regularly consulted by a diabetological team. Evaluation consisted of oral glucose tolerance test (OGTT), mean blood glucose, glycosylated haemoglobin and management by self-blood-glucose monitoring (SBGM) and nutritional counselling. When these patients were compared to a group of 154 patients with gestational diabetes who attended our clinic at different stages of pregnancy, the former had improved glucose homeostasis whereas the latter had more frequent elevations of fasting and postprandial glucose levels throughout pregnancy. This group had also more maternal complications and higher Caesarean section rates. Congenital anomalies were 0.65% among offspring of nonattenders, while none occurred in those with preconceptional counselling. Macrosomia and hypoglycaemia were significant neonatal complications in infants of nonattending mothers. We concur with the recommendation that preconceptional counselling in gestational diabetics is required to improve glucose homeostasis throughout pregnancy, and that appropriate evaluation of glucose intolerance should be included as part of prospective family planning.     

Antibiotic-resistant invasive pediatric Streptococcus pneumoniae clones in Israel

Antibiotic-resistant international clones of Streptococcus pneumoniae are increasingly reported in different parts of the world. We investigated the spread of these clones through an active surveillance performed at the Israeli Streptococcal National Center during 1998 and 1999. Isolates were tested for antibiotic susceptibility, serotyped, and genotyped by random amplified polymorphic DNA analysis and pulsed-field gel electrophoresis. Of 437 isolates, 276 (63.4%) were antibiotic resistant and 156 (35%) were penicillin nonsusceptible (PNS). The PNS isolates were less frequently encountered in southern Israel (27 of 136 [20%]) than in other regions (127 of 301 [42%]). Among 276 antibiotic-resistant isolates, 43 fingerprint patterns were observed. The most common clones were 9V/14-a (19.2%), 5-a (17.8%), and 1-a (10%). The 9V/14-a clone was less common, while the 1-a clone was more frequent in the south than in other regions. The 5-a clone was more common in Jerusalem than in other regions. Among the Jewish and Arab populations the most frequent clones were 9V/14-a (20%) and 1-a (25%), respectively. Three international clones, 9V/14-a-Spain(9V)-3, 6B-a-Spain(6B)-2, and 5-a-Colombia(5)-19, comprised 40% of all antibiotic-resistant isolates and 56% of all PNS isolates. The seven-valent conjugate vaccine covers 58% of the most common clones, all highly PNS clones, and 94% of the multidrug-resistant clones in Israel, while the nine-valent vaccine covers all of them. The most common antibiotic-resistant invasive pediatric S. pneumoniae clones-mainly the three international ones-contribute significantly to increases in antibiotic resistance. Their geographic distribution varies within the country and between the different populations.     

Spread of Streptococcus pneumoniae and antibiotic-resistant S. pneumoniae from day-care center attendees to their younger siblings

A prospective study was conducted to determine the association between pneumococcal carriage among 36 infants and young toddlers cared for at home and carriage among their older siblings who attended 8 day-care centers (DCCs); 71 pneumococcal strains acquired by the younger siblings were compared with those present in the DCCs for 6 months. In 76% of cases, > or =1 strain identical by serotype and antibiogram was isolated in the older siblings' DCC versus 32%-63% in all other DCCs (P<.001). When phenotypically identical strains were compared by pulsed-field gel electrophoresis, the similarity between strains from older siblings' DCCs and the younger siblings' isolates was striking. This was not found when isolates from other DCCs were compared. Vaccinating DCC attendees with a 7-valent pneumococcal conjugate vaccine may play a key role in controlling the spread of antibiotic-resistant pneumococci, because the most resistant serotypes are included in the vaccine.     

Clozapine attenuates disruptions in response inhibition and task efficiency induced by repeated phencyclidine administration in the intracranial self-stimulation procedure

Currently available antipsychotic medications lack satisfactory effectiveness against several symptom clusters of schizophrenia, including affective symptoms (e.g., anhedonia) and cognitive deficits (e.g., impulsivity). Translational animal models analogous to these symptoms are necessary to provide insights into the neurobiological events underlying these impairments and allow the development of improved schizophrenia treatments. We investigated the effects of repeated administration of the psychotomimetic phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate receptor antagonist, on performance in the intracranial self-stimulation (ICSS) procedure, a test of reward function. We also explored how chronic treatment with clozapine, an atypical antipsychotic with limited effectiveness on affective and cognitive schizophrenia symptoms, would affect PCP-induced disruptions of ICSS performance. A single injection of 2 mg/kg PCP elevated ICSS thresholds, suggesting a reward deficit. Repeated PCP administration (2 mg/kg once daily for 2 consecutive days followed by a 10-day drug free period, and then 5 consecutive days of 2 mg/kg PCP daily, s.c., 30 min pretreatment) resulted in a small, but significant, lowering of ICSS reward thresholds, indicating increased reward function. Chronic clozapine did not alter the effects of repeated PCP on ICSS thresholds. Repeated PCP also increased the number of extra and timeout responses performed during the ICSS procedure, reflecting disinhibition of inappropriate responding and decreased task efficiency. Chronic clozapine attenuated the increase in extra responses induced by repeated PCP and tended to reduce the PCP-induced increase in timeout responses. These results suggest that repeated PCP administration does not produce an anhedonia-like state resembling that seen in schizophrenia. However, the increased impulsivity and reduced task efficiency seen with repeated PCP administration, and the sensitivity of these effects to attenuation with an atypical antipsychotic, suggest that repeated PCP administration may be a useful inducing condition for eliciting cognitive deficits with relevance to schizophrenia.     

Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration

Rationale

Nicotine-induced cognitive enhancement may be a factor maintaining tobacco smoking, particularly in psychiatric populations suffering from cognitive deficits. Schizophrenia patients exhibit higher smoking rates compared with the general population, suggesting that attempts to self-medicate cognitive schizophrenia deficits may underlie these high smoking levels.

Objectives

The present study explored pro-cognitive effects of nicotine in a model of schizophrenia-like cognitive dysfunction to test this self-medication hypothesis.

Materials and methods

We investigated whether chronic nicotine (3.16 mg/kg/day, base) would attenuate the performance disruption in the five-choice serial reaction time task (5-CSRTT, a task assessing various cognitive modalities, including attention) induced by repeated administration of phencyclidine (PCP), an N-methyl-d-aspartate receptor antagonist that induces cognitive deficits relevant to schizophrenia.

Results

Chronic nicotine administration shortened 5-CSRTT response latencies under baseline conditions. Nicotine-treated rats also made more correct responses and fewer omissions than vehicle-treated rats. Replicating previous studies, repeated PCP administration (2 mg/kg, 30 min before behavioral testing for two consecutive days followed 2 weeks later by five consecutive days of PCP administration) decreased accuracy and increased response latencies, premature responding, and timeout responding. Chronic nicotine did not attenuate these PCP-induced disruptions.

Conclusions

Chronic nicotine had pro-cognitive effects by itself, supporting the hypothesis that cognitive enhancement may contribute to tobacco smoking. At the doses of nicotine and PCP used, however, no support was found for the hypothesis that the beneficial effects of nicotine on cognitive deficits induced by repeated PCP administration, assessed in the 5-CSRTT, are larger than nicotine effects in the absence of PCP.     

Etiology and Antimicrobial Susceptibility of Middle Ear Fluid Pathogens in Costa Rican Children With Otitis Media Before and After the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine in the National Immunization Program: Acute otitis media microbiology in Costa Rican children

Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009).This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010–2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3–59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction).Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (≥2 PCV7 doses or ≥1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction.Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage.