Observational Study of Methotrexate in the Treatment of Bronchiolitis Obliterans Syndrome.

BACKGROUND: Methotrexate (MTX) is potential change in immunosuppression after lung transplantation that may help to slow down the decline in lung function in bronchiolitis obliterans syndrome (BOS). METHODS: We sought to analyze the safety and efficacy of MTX in patients with BOS, by retrospective case review. RESULTS: Thirty lung allograft patients were treated with MTX for BOS after one bilateral lower lobe, nine single, 16 bilateral, and four heart-lung transplants. Twenty-one patients had MTX treatment for a minimum of 6 months, and their serial lung function was analyzed for efficacy. In these patients, there was a significant overall increase in mean forced expiratory volume in 1 second (FEV1) of 149 mL (P < .02) at 3 months, with an increase observed in 14 of 21 patients. At 6 months, there was a mean increase in FEV1 of 117 mL (P < .05). At 12 months, there was a mean non-significant increase of FEV1 of 60 mL (P = .19) observed in 18 patients who had MTX for this time period. The rate of decline in FEV1 before MTX was 118.5 mL/month and at 3 months after MTX increased to 49.5 mL/months (P < .0005) in the FEV1. Nine patients had been treated with MTX for less than 6 months; two died within 6 months of starting MTX, five tolerated the drug poorly with nausea and tiredness, and one developed leucopenia. One patient requested discontinuation of the medication after failing to halt the rapid progressive decline in lung function after 1 month. CONCLUSIONS: Methotrexate therapy provides a potential therapeutic strategy in managing the progressive decline in lung function observed in BOS. This is hampered by the observation of poor tolerability and side effects.

Growth restriction in pregnancies of opioid-dependent mothers.

BACKGROUND AND AIMS: Intrauterine growth restriction (IUGR) can lead to significant intellectual and behavioural problems in later life. IUGR represents a frequent feature of pregnancies of opioid-dependent mothers (ODMs), the causes of which are largely unknown. The objective of this study was to determine the independent risk factors for IUGR in ODMs. DESIGN AND SUBJECTS: We performed a retrospective study analysing maternal and neonatal parameters from pregnancies of ODM maintained on methadone (n=215). These were compared to smoking non-ODM and non-smoking non-ODM control groups matched for maternal age, gestational age at delivery, infant birth date and sex. Logistic regression analysis was performed on all parameters with the outcome of IUGR. RESULTS: Fifty-seven infants (27%) of ODMs showed IUGR. Compared to non-smoking non-ODMs, the risk of IUGR in non-smoking ODMs was almost four times higher (relative risk 3.48, 95% CI 1.70 to 7.14). Growth restriction was independent of the last maternal methadone dose and the cumulative methadone dose during pregnancy. In addition, whereas nicotine and female sex impacted on IUGR in non-ODMs (nicotine: OR 3.45, 95% CI 1.82 to 6.67; sex: OR 2.37, 95% CI 1.25 to 4.50), these parameters had no influence on IUGR in ODMs. Maternal body mass index (BMI) was identified as the only independent risk factor for IUGR in infants of ODMs (OR 1.15, 95% CI 1.03 to 1.28). CONCLUSIONS: IUGR in pregnancies of ODM is related to maternal BMI rather than to opiate dosing, nicotine use or infant sex. BMI may itself be an indirect marker of several other genetic, nutritional and/or social determinants of IUGR.

Characterization of gabaergic neurons within the human medial mamillary nucleus.

The morphology, distribution and relative frequency of GABAergic neurons in the medial mamillary nucleus (MMN) of normal human individuals was studied using a glutamic acid decarboxylase (GAD) antiserum. GAD-immunoreactive (GAD-IR) neurons were found sparsely distributed throughout the MMN and most displayed a simple bipolar morphology. A small population of large diameter GAD-IR neurons was found in the white matter capsule adjacent to the ventral border of the MMN. Results of double-labeling experiments revealed no evidence of calretinin, parvalbumin or calbindin immunoreactivities co-localizing with GAD-IR neurons. GAD-IR neurons of the MMN had an average somal area of 138+/-41 microm2, compared with the average somal area of 384+/-137 microm2 for the population of MMN neurons as a whole. GAD-IR neurons had a tendency to cluster in groups of two (and occasionally three) and showed a distribution gradient across the MMN with higher densities being found near the insertion of the fornix, the origin of the mamillo-thalamic tract and toward the medial MMN border. Quantitative estimates of GAD-IR neuron frequency revealed the GAD-IR phenotype to constitute an average of 1.7% percent of the total neuron population within the human MMN. These findings suggest that inhibitory activity within the human MMN is regulated in part by a small population of intrinsic GABAergic interneurons.