Hyperexcitability associated with localizable lesions in epileptic patients

Intracellular recordings from neurons were carried out in cortical slices obtained from tissue removed from patients suffering from intractable seizures. The patients were divided into two groups based on the presence or absence of an anatomical abnormality that could be imaged preoperatively. The lesion or its surround was the presumptive epileptogenic area. The tissue removed from the patients without lesions was removed either for biopsy purposes or for access to epileptic tissue and was not considered epileptogenic. All neurons from patients without an imageable lesion, and some (19%) from patients with an imageable lesion, responded to orthodromic stimuli with a sequence of synaptic excitation followed by inhibition; these properties resembled those of normal rodent cortical slices. Different responses, classified as abnormal, were observed in 81% of the neurons in tissue specimens obtained near lesions. The most common was prolonged synaptic excitation with no noticeable inhibition, even at high stimulus strengths. In three resections, long latency all-or-none depolarization shifts were observed that resemble the classic paradoxical depolarization shift seen in in vivo extracellular recordings. Loss of specific inhibitory systems within the cortex may contribute in part to these abnormal responses.     

Smoking in Pregnancy and Parenthood: What is the Role of Depression, Anxiety and Nicotine Addiction?

This paper presents some of the findings from the Smoking in Pregnancy study of attitudes towards smoking among pregnant women, mothers of young children and their partners in East Surrey. As part of the study, respondents completed a General Health Questionnaire to identify mental health difficulties and, if they were smoking at the time of the study, they also completed the Fagerstrom nicotine addiction test. Eleven female respondents had high scores on the General Health Questionnaire, suggesting symptoms of depression, anxiety and/or social dysfunction for these women. There was no evidence that smokers were suffering from greater mental health difficulties than ex-smokers or non-smokers. However, the General Health Questionnaire scores of smokers were positively associated with their level of nicotine dependence. Furthermore, when General Health Questionnaire scores of all respondents were compared with self-reported health status there was a marked discrepancy suggesting under-reporting of symptoms by women.     

Agouti-related peptide-expressing neurons are mandatory for feeding

Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.     

Three distinct loci on human chromosome 21 contribute to interferon-α/β responsiveness

The species specificity of interferons (IFNs) depends on restricted recognition of these ligands by multisubunit cell surface receptors. Expression of the human receptor subunit IFNAR in mouse cells conferred sensitivity only to one subtype of human IFN, IFN-B. Other genes on human chromosome 21 were required for responses to other subtypes of type I IFN. In contrast, IFNAR expression in hamster cells did not confer sensitivity to any human IFN tested, including IFN-B. Using human-hamster somatic cell hybrids, we mapped theIfnabr gene, encoding a ligand-binding subunit of the IFN-/ (type I) receptor, to human chromosome 21.Ifnabr colocalized withIfnar to the distal region of q22.1. The presence of a chromosomal fragment encoding IFNABR and IFNAR was also not sufficient to confer sensitivity to human IFN. In contrast, hybrids carrying in addition the region 21q22.2 showed a full response to human IFN-B, suggesting that a gene located in this region encodes a third factor required for type I IFN receptor activity.     

Gastrointestinal graft-versus-host disease in recipients of autologous hematopoietic stem cells: incidence, risk factors, and outcome.

Graft-versus-host disease (GVHD) is seen in skin, intestinal mucosa, and liver after autologous stem cell transplantation. We reviewed 681 consecutive patients to estimate the probability of gastrointestinal (GI) GVHD, response to treatment, risk factors for development, and effect on survival. GI GVHD was defined by persistent symptoms, mucosal abnormalities at endoscopy, and histology showing apoptotic crypt cells with or without lymphoid infiltrates. The proportion of patients with GI GVHD was 90/681 (13%). Nausea and vomiting occurred in 90% and diarrhea in 40%. The mean time to developing symptoms was day +15, that to histologically proven diagnosis was day +42, and that to starting prednisone treatment was day +45 after stem cell infusion. Treatment with a short course of prednisone effected durable responses in 79% of patients, and an additional 18% responded to a second course of prednisone. A multivariable logistic regression model demonstrated that the combined factor of a diagnosis of breast cancer or hematologic malignancy and female sex was statistically significantly associated with the probability of GI GVHD (P = .003). Survival in patients with GI GVHD was not statistically different than that in those without GVHD. We conclude that women with breast cancer or hematologic malignancy are more likely to develop GI GVHD after autologous transplantation, and that treatment with prednisone was effective.     

Maturation,Mores and Morals

The two approaches to the treatment of ulcerative colitis presented here are of special interest not only because they exemplify the differing points of view of gastroenterologist and surgeon, but also because Dr. Bargen's medical approach is exceedingly conservative and Mr. Aylett's approach tends toward the radical. Moreover, Mr. Aylett is the chief exponent of ileorectal anastomosis in the presence of ulcerative colitis, an operation which is controversial, to say the least. Both authors have had unusually extensive experience in treating ulcerative colitis.