The Impact of Gabapentin Administration on Brain GABA and Glutamate Concentrations: A 7T 1H-MRS Study

Gamma-aminobutyric acid (GABA) and glutamate are implicated in numerous neuropsychiatric and substance abuse conditions, but their spectral overlap with other resonances makes them a challenge to quantify in humans. Gabapentin, marketed for the treatment of seizures and neuropathic pain, has been shown to increase in vivo GABA concentration in the brain of both rodents and humans. Gabapentin effects on glutamate are not known. We conducted a gabapentin (900 mg) challenge in healthy human subjects to confirm and explore its effects on GABA and glutamate concentrations, respectively, and to test the ability of single voxel localized proton magnetic resonance spectroscopy (¹H-MRS) to reliably measure GABA and glutamate in the visual cortex at the ultra-high magnetic field of 7 Tesla. Reproducibility of GABA and glutamate measurements was determined in a comparison group without drug twice within day and 2 weeks apart. Although GABA concentration changes were small both within day (average 5.6%) and between day (average 4.8%), gabapentin administration was associated with an average increase in GABA concentration of 55.7% (6.9–91.0%). Importantly, drug-induced change in GABA levels was inversely correlated to the individual''s baseline GABA level (R²=0.72). Mean glutamate concentrations did not change significantly with or without drug administration. In conclusion, localized ¹H-MRS at 7 Tesla can be successfully applied to the measurement of GABA concentration and is sensitive to acute drug-induced changes in cortical GABA. Whether baseline GABA concentrations predict clinical efficacy of gabapentin is an area worthy of exploration.     

Knowledge and attitudes of young people in Guyana to HIV/AIDS

HIV prevalence in Guyana is the third highest in the Caribbean which, in turn, is the second-most-affected region in the world. Over 2000 young people aged 12-20 years completed self-report questionnaires that examined their knowledge of HIV/AIDS, their attitudes to sexual behaviours and their intentions with regard to virginity and use of condoms. Nearly one-quarter of young people aged 12-14 were sexually active and this rose to over one-third for youths aged 15 years and over, but condoms were only used consistently by two in five of these persons. Attitudes and intentions towards sexual behaviour were significantly influenced by religious teaching as well as by gender and age. Hence, prevention strategies for the spread of HIV/AIDS should harness religious belief and practice, especially in societies such as Guyana where religious affiliation remains strong.     

A study on motility of sphincter of Oddi in postcholecystectomy syndrome

Endoscop c manometry of sphincter of Oddi(SO)and serumlevels of gastrin,glucagon,and somatostatin were measured in patients withpostcholecystectomy syndrome(n=12),asymptomatic cholecystectomised pa-tients(n=6),and controlled subjects(n=14).Pentagastrin-stimulated gastricacid secretion test was also performed in part of patients who had symptoms orno symptoms after gallbladder resection.The results showed that the patientsof symptomatic group had hypertonic dyskinesia of SO as shown by deep andwide waves superimposed on high basal pressure plateau of SO.The symptoma-tic group also had a higher serum level of gastrin and a greater BAO than tho-se of other two groups.No difference of serum levels of glucagon and soma-tostatin was found among these three groups.The hypertonic dyskinesia of SOand hypergastrinemia are considered as possibly important factors in the patho-genesis of postcholecystectomy syndrome.     

Rat myometrial smooth muscle cells express endothelial nitric oxide synthase

We examined if rat myometrial cells in culture generate nitric oxide (NO) and express various isoforms of NO synthase (NOS). Myometrial cells isolated from rats on day 18 of gestation were incubated with various stimulators and inhibitors of NOS for 24 and 48 h, and NO production was evaluated by measuring nitrites in the media and NOS proteins in the cell lysates. NO was produced by myometrial cells and its production inhibited by N(G)-methyl-L-arginine (L-NMMA). This inhibition was reversed by L-arginine (3 mM). Interleukin-1beta (IL- 1beta) significantly stimulated NO production, in a dose-dependent manner. The IL-1beta-stimulated NO production was inhibited by the NOS inhibitor, L-NMMA, whose effects were reversed by L-arginine. Abundant NOS III protein was detectable in freshly isolated myometrial cells, and this was maintained in culture in the presence of fetal bovine serum (FBS; 10%). In the absence of FBS, NOS III levels decreased significantly (by 90%) within 24 h. In contrast, NOS I and NOS II proteins were undetectable in freshly isolated muscle cells and in cells cultured without IL-1beta. However, NOS II protein in these cells was induced by IL-1beta. Thus, NO is produced by myometrial cells through the NOS III isoform, and the myometrial NO may be important in maintaining uterine quiescence during pregnancy.      

医学生心理健康状况与人格特征的相关分析

目的 :了解在校医学生的心理健康状况 ,为今后开展心理健教育提供有益的依据。方法 :采用 SCL-90和 EPQ量表对在校 5 88名医学生调查并作相关分析。结果 :医学生出现各类心理问题的比例为 6.80 %～ 3 2 .11% ,以强迫、人际敏感、抑郁和偏执为主。临医和护理专业学生心理问题的侧重点不同。女生在人际敏感、抑郁和恐怖等方面均高于男性。情绪稳定性 N和精神质 P与各因子及总均分呈正相关关系 (P<0 .0 1) ,掩饰度 L 与各因子呈显著负相关 (P<0 .0 1)。多因素回归分析表明 ,情绪稳定性 N和掩饰度 L对心理健康的影响起着重要作用。结论 :搞好学生的心理健康 ,加强健全人格教育是关键 ,同时要根据不同性别和专业区别地对待     

A phase II trial of preoperative mitomycin, cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus

The effect of neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of mitomycin, cisplatin and 5-fluorouracil (MCF) were given, followed by a radiological evaluation of response. Twenty-two of 25 patients completed both courses. Two showed a complete response and 12 a partial response. There was a pathological complete response of the primary tumour in only one patient (although there was residual secondary tumour in a local lymph node). The main toxicity was myelosuppression, with 9/22 patients having the second chemotherapy course delayed. There were three sudden deaths, one due to a pulmonary embolus and two due to complications of infections. Twenty-one patients underwent surgical exploration; there were 18 resections. Although the radiological response rate of MCF (14/25 56%; 95% CI 37–75) appeared promising, there were no pathological complete responders. Further Phase II trials are needed to identify more efficacious agents and regimens that will yield a pathological response rate of at least 10%, before proceeding to randomized trials of neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.     

Changes in gap junctional intercellular communication in mouse skin carcinogenesis

Gap junction intercellular communication (GJIC) has been measured in cell lines that represent different stages of chemically induced mouse skin carcinogenesis. No significant difference in GJIC, as measured by dye spread, was found in cultures of normal keratinocyte, papilloma or squamous carcinoma cell lines. There was no correlation, in this system, between the presence of a mutant Ha-ras gene and down- regulation of communication. There was, however, a marked decrease in GJIC (80-90%) on progression from squamous to spindle carcinoma cells. Measurement of GJIC in somatic cell hybrids shows that the genetic defect responsible for this down-regulation is recessive and is common to two independently isolated spindle cell lines. No abnormalities were found in the spindle cells in expression of connexin 43, a cell component involved in gap junction formation and permeability. However, expression of E-cadherin, a cell-cell adhesion molecule implicated in the process of gap junction formation, was missing in the spindle carcinoma cells. Introduction of an E-cadherin cDNA into the spindle cells partially restored junctional communication without causing any noticeable alterations in cell morphology. During the study a non- tumourigenic keratinocyte line, a sub-clone of a normal keratinocyte line, was also found to have a low level of GJIC. However, the defect in this line was shown, by genetic complementation in somatic cell hybrids, to be different from that in the spindle carcinoma cell lines. Consistent with these data, analysis by immunofluorescence shows an abnormal distribution of connexin 43 in these cells.      

Percutaneous cecostomy: controlled transperitoneal approach

The authors present two cases of percutaneous cecostomy performed with a modified approach previously described for percutaneous gastrostomy and cholecystostomy. T-fastener devices were used to affix the cecum to the anterior abdominal wall; thus, the potential problem of fecal spillage was prevented. In both cases, adequate fecal drainage was provided without complication.