Host Serotonin Axons Innervate Intrastriatal Ventral Mesencephalic Grafts After Implantation in Newborn Rats

This study investigated the potential of immature and adult serotonin (5HT) neurons for axonal growth into intrastriatal grafts of ventral mesencephalic tissue. Implantation of dissociated fetal (embryonic days 14–15) ventral mesencephalic tissue was carried out in immature [postnatal days (P) 5–14] and adult rat neostriatum. The brains were processed 2–6 months later for dopamine and 5-HT immunocytochemistry. A few grafts implanted into adult and P7 recipients contained small numbers of cotransplanted 5HT cell bodies. These also displayed a rich network of 5-HT axons, even in adult rats prelesioned with 5,7-dihydroxytryptamine, indicating the graft origin of these axons. All other grafts were totally devoid of 5-HT cell bodies. After implantation in adults, such grafts contained rare 5-HT axons. In contrast, in P5-P7 recipients, they displayed many 5-HT fibres, which were uniformly distributed. Such was no longer the case after implantation in P14 recipients, which showed minimal 5HT innervation, as in adult recipients. Processing of naïve rat brain at different ages for 5-HT immunocytochemistry showed that 5-HT axons were still clearly less numerous in the neostriatum at P21 than in adults, whereas in the substantia nigra the 5-HT innervation developed more rapidly and was comparable, at P21, to that of adults. It was concluded that 5-HT axons are able to grow into ventral mesencephalic grafts, but mainly at the fetal stage and with decreasing capacity after birth. Since 5-HT axons are still normally growing in the developing striatum beyond P21, it appears that their inability to innervate mesencephalic grafts after P14 is not the result of a developmental decrease in growth capacity. Rather, the better temporal correlation with the maturation of the 5-HT innervation in the substantia nigra suggests that this inability reflects an ontogenic change in the affinity of these axons for nigral tissue.     

Transient bilirubin encephalopathy and apnea of prematurity in 28 to 32 weeks gestational age infants.

OBJECTIVE: Apnea of prematurity (AoP) is, in part, a reflection of brainstem-mediated respiratory control system maturation. We previously demonstrated changes in brainstem function in relation to hyperbilirubinemia (bilirubin encephalopathy, (BE)) as evaluated by auditory brainstem evoked responses (ABR) in infants 28 to 32 weeks gestational age (GA). We hypothesized that in this population, as bilirubin increases and causes auditory brainstem dysfunction, respiratory control system may also be adversely affected leading to increased frequency of AoP. STUDY DESIGN: We studied 100, 28 to 32 weeks GA infants and identified 66 with normal and 34 with abnormal ABR progression in temporal relation to hyperbilirubinemia (BE). The abnormal ABR progression was associated with elevated bilirubin, specifically elevated unbound bilirubin levels. A blinded, retrospective chart review quantified the amount of weekly apnea and bradycardia events during the hospital stay, total duration of methylxanthine treatment, total duration of mechanical ventilation, CPAP, and/or nasal cannula, and risk factors for apnea (sepsis, IVH grade >II, asphyxia). Since mechanical ventilation confounds the identification of apnea, infants requiring mechanical ventilation were excluded from further review (n = 60; 21 with BE and 39 with normal ABR progression). Data from the remaining 40 infants were analyzed. Student's t-test was used to analyze continuous variables if the distribution was normal otherwise Wilcoxon-ranked-sum test was used. chi(2) was used to analyze nominal variables. A p < or =0.05 was considered significant. RESULTS: There was no difference in risk factors between infants with and without BE. BE was identified on day 3 (median; range 1 to 6 days). Patients with BE had significantly more apneic events (15 vs 2, p = 0.0009), bradycardic events (14 vs 1, p = 0.02), and required more prolonged treatment with CPAP (2.2 vs 0.5 days, p = 0.007), nasal cannula (6.6 vs 2.2 days, p = 0.02), and methylxanthines (9.5 vs. 1.9 days, p = 0.002) than those with normal ABR progression. The difference in the incidence of apnea and bradycardia between infants with and without BE was most pronounced during the first week. CONCLUSIONS: Premature infants with transient bilirubin encephalopathy as defined by abnormal ABR progression in relation to hyperbilirubinemia have more concurrent apneic events and require more prolonged respiratory support and medications.     

Chromosomal defects in infertile men with poor semen quality

Purpose

To assess the incidence and the type of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 76 Tunisian infertile men (54 nonobstructive azoospermia and 22 oligo-asthenospermia).

Methods

Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Molecular diagnosis of classical and partial Y-chromosomal microdeletions was performed by amplifying Y-specific STSs markers.

Results

Various numerical and structural chromosome abnormalities were identified in 15 patients (19.48%). The occurrence of chromosomal abnormality in the azoospermics and severe oligo-asthnospermic was 21.7% and 13.5%, respectively. The most common was Klinefelter syndrome, accounting for 10 of the 15 cytogenetic defects. The total frequency of Y chromosomal microdeletions was 17.1%, with respective frequencies in azoospermic and severe oligospermic groups, 11.1% and 31.8%. The most frequent of Y chromosomal deletions were the partial ones (11.1% in azoospermic and 27.2% in oligospermic).

Conclusion

The occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques.     

TMC1 but not TMC2 is responsible for autosomal recessive nonsyndromic hearing impairment in Tunisian families

Hereditary nonsyndromic hearing impairment (HI) is extremely heterogeneous. Mutations of the transmembrane channel-like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of nonsyndromic HI linked to the loci DFNA36 and DFNB7/B11, respectively. TMC1 is 1 member of a family of 8 genes encoding transmembrane proteins. In the mouse, MmTmc1 and MmTmc2 are both members of Tmc subfamily A and are highly and almost exclusively expressed in the cochlea. The restricted expression of Tmc2 in the cochlea and its close phylogenetic relationship to Tmc1 makes it a candidate gene for nonsyndromic HI. We analyzed 3 microsatellite markers linked to the TMC1 and TMC2 genes in 85 Tunisian families with autosomal recessive nonsyndromic HI and without mutations in the protein-coding region of the GJB2 gene. Autozygosity by descent analysis of 2 markers bordering the TMC2 gene allowed us to rule out its association with deafness within these families. However, 5 families were found to segregate deafness with 3 different alleles of marker D9S1837, located within the first intron of the TMC1 gene. By DNA sequencing of coding exons of TMC1 in affected individuals, we identified 3 homozygous mutations, c.100C-->T (p.R34X), c.1165C-->T (p.R389X) and the novel mutation c.1764G-->A (p.W588X). We additionally tested 60 unrelated deaf Tunisian individuals for the c.100C-->T mutation. We detected this mutation in a homozygous state in 2 cases. This study confirms that mutations in the TMC1 gene may be a common cause for autosomal recessive nonsyndromic HI.     

Optimal post-contrast timing of breast MR image acquisition for architectural feature analysis

PURPOSE: To define a post-contrast imaging time span during which diagnostic accuracy of breast magnetic resonance (MR) architectural feature analysis is maintained. MATERIALS AND METHODS: Seventy-five patients with mammographically-visible or palpable findings underwent MR examination. Three sequential post-contrast, fat-saturated, three-dimensional gradient-echo imaging runs were acquired spanning 0-90, 90-180, and 180-270 seconds after contrast injection. Five readers independently predicted the malignant potential of the MR abnormalities. RESULTS: Receiver-operator characteristics (ROC) curves were our primary measure of diagnostic accuracy. The accuracy of four readers was unchanged over the three post-contrast runs. One reader was slightly more accurate using the second and third runs than using the first. CONCLUSION: For most readers, a single post-contrast run performed at any point during the first four minutes and 30 seconds following injection should yield an equivalent diagnostic accuracy. If any time period is less optimal, it is that of our first run, performed between 0-90 seconds after contrast injection.     

Preconception Health Assessment in China,Lebanon and the Philippines: Applicability to Other Countries

To test the utility of a preconception checklist tool in identifying preconception health needs of women in three countries; China, Lebanon and the Philippines. An academic medical center within each country participated in the development and testing of a preconception checklist tool, which was administered over a 6 month period to selected target groups in each country. The checklist provided valuable data on the preconception health of 6,530 women. Aggregated data identified common preconception health needs across all countries, including provision of modern contraceptives and adequate immunization coverage; HIV and STI screening; treatment for anemia; and counseling for maintenance of a healthy weight. A preconception checklist tool was found to be useful in distinct cultural settings. The study was a pilot. Future steps include validation and standardization of the checklist, data from which could be used to help shape preconception care policies and implementation strategies.     

Autoimmune hepatitis as an adverse effect of long-term methotrexate therapy

Methotrexate (MTX) is one of the most commonly used medicines in the treatment of psoriatic arthritis. The drug can produce steatosis and cirrhosis. Autoimmune hepatitis is a rare and serious adverse effect. We describe the case of a 53-year-old woman who developed autoimmune hepatitis after a long-term use of MTX for psoriatic arthritis. Hepatitis was completely resolved 4 months after stopping this drug. The pathophysiologic mechanisms of a drug-induced autoimmunity are unclear and complex. This report confirms the need to monitor liver enzymes carefully in patients using long-term treatment with MTX for psoriasis or rheumatoid arthritis.KEY WORDS: Autoimmune hepatitis, drug-induced autoimmunity, methotrexate, psoriatic arthritis     

Retractable Syringes in a Swiss Prison Needle and Syringe Exchange Program: Experiences of Drug-using Inmates and Prison Staff Perceptions

Needle and Syringe Exchange Programs (NSP) prevent infectious diseases in community and prisons. Less than 1 % of prisons worldwide have NSP. One barrier is organizational concern for needle stick injuries from used syringes. Given these concerns, we introduced retractable syringes into our prison NSP and evaluated 1) injection drug users’ experiences with retractable syringes and 2) beliefs and knowledge about NSP among prison officers (PO) and healthcare staff (HS). In 2010, we replaced usual syringes with retractable needle devices in the prison of Champ-Dollon, Geneva, Switzerland. We examined demographics, clinical profiles and NSP use among NSP participants, and asked about ease and safety of retractable syringes use in interviews. We distributed questionnaires to PO and HS, to assess knowledge and general opinions on NSP. The majority of participants expressed that retractable syringes were acceptable alternatives, but needed improvements. Of the questionnaires, 90.3 % of PO and 9.6 % of HS were still concerned about misuse of soiled syringes as weapons. Improving the quality and ease of use of use may increase the acceptance of retractable syringes. Continuing to address PO and HS safety concerns is an important step towards more disseminated NSP implementation and useful innovation.     

Does the association between smoking and mortality differ by educational level?

Some researchers suggest that the effect of smoking on health depends on socioeconomic status; while others purport that the effect of smoking on health is similar across all social groups. This question of the interaction between smoking and socioeconomic status is important to an improved understanding of the role of smoking in the social gradient in mortality and morbidity. For this purpose, we examined whether educational level modifies the association between smoking and mortality. Information on smoking by age, gender and educational level was extracted from the Belgian Health Interview Surveys of 1997 and 2001. The mortality follow up of the survey respondents was reported until December 2010. A Poisson regression was used to estimate the hazard ratio of mortality for heavy smokers, light smokers, and former smokers compared with never smokers by educational level controlling for age and other confounders. Among men, we found lower hazard ratios in the lowest educational category compared with the intermediate and high-educated categories. For instance, for heavy smokers, the hazard ratios were 2.59 (1.18-5.70) for those with low levels of education, 4.03 (2.59-6.26) for those with intermediate levels of education and 3.78 (1.52-9.43) for the highly educated. However, the interaction between smoking and education was not statistically significant. For women, the hazard ratios were not significant for any educational category except for heavy smokers with intermediate levels of education. Also here the interaction was not statistically significant. Our results support the hypothesis that educational attainment does not substantially influence the association between smoking and mortality.