Aberrant deltaPKC activation in the spinal cord of Wobbler mouse: a model of motor neuron disease

Protein kinase C (PKC) was suggested to play a role in the pathology of amyotrophic lateral sclerosis (ALS) patients. Activation of PKC delta (deltaPKC) modulates mitochondrially induced apoptosis. The goal of the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease). The level of deltaPKC in the soluble fraction was significantly decreased in the spinal cord of Wobbler mice, which was associated with a significant increase in deltaPKC cleavage. Since caspase-3 is known to cleave deltaPKC, we determined caspase-3 activation in the Wobbler mice spinal cord, immunohistochemically. The results demonstrated intense immunoreactivity for activated caspase-3 in corticospinal tract motor neurons of Wobbler mice spinal cord. We hypothesize from these results that caspase-3 activation cleaves deltaPKC, which in turn promotes an aberrant signal transduction pathway in the Wobbler spinal cord.     

Remission of hormone-refractory prostate cancer attributed to Essiac

Essiac is a popular complementary and alternative medicine (CAM) that is utilized by many cancer patients in North America. Much anecdotal reporting exists about its cancer-fighting qualities, but so far no clinical trials have been preformed to validate those claims. We describe here the case of a 64-year-old man whose hormone-refractory prostate cancer responded well to Essiac tea.     

Ischemic preconditioning ameliorates excitotoxicity by shifting glutamate/gamma-aminobutyric acid release and biosynthesis

Excitotoxicity is recognized to play a major role in cerebral ischemia-induced cell death. The main goal of the present study was to define whether our model of ischemic preconditioning (IPC) promotes a shift from excitatory to inhibitory neurotransmission during the test ischemia to diminish metabolic demand during the reperfusion phase. We also determined whether gamma-aminobutyric acid (GABA) played a role in IPC-induced neuroprotection. Ten minutes of cerebral ischemia was produced by tightening the carotid ligatures bilaterally following hypotension. Samples of microdialysis perfusate, representing extracellular fluid, were analyzed for amino acid content by HPLC. IPC promoted a robust release of GABA after lethal ischemia compared with control rats. We also observed that the activity of glutamate decarboxylase (the predominant pathway of GABA synthesis in the brain) was higher in the IPC group compared with control and ischemic groups. Because GABAA receptor up-regulation has been shown to occur following IPC, and GABAA receptor activation has been implicated in neuroprotection against ischemic insults, we tested the hypothesis that GABAA or GABAB receptor activation was neuroprotective during ischemia or early reperfusion by using an in vitro model (organotypic hippocampal slice culture). Administration of the GABAB agonist baclofen during test ischemia and for 1 hr of reperfusion provided significant neuroprotection. We concluded that increased GABA release in preconditioned animals after ischemia might be one of the factors responsible for IPC neuroprotection. Specific activation of GABAB receptor contributes significantly to neuroprotection against ischemia in organotypic hippocampal slices.     

Three Diagnostic Approaches to Asperger Syndrome: Implications for Research

Objective: To examine the implications for research of the use of three alternative definitions for Asperger syndrome (AS). Differences across the three nosologic systems were examined in terms of diagnostic assignment, IQ profiles, comorbid symptoms, and familial aggregation of social and other psychiatric symptoms. Method: Standard data on diagnosis, intellectual functioning, comorbidity patterns, and family history were obtained on 65 individuals screened for a very high probability of having autism without mental retardation (or higher functioning autism, HFA) or AS. Diagnoses of AS were established based on three different approaches: DSM-IV, presence/absence of communicative phrase speech by 3 years, and a system designed to highlight prototypical features of AS. Results: Agreement between the three diagnostic systems was poor. AS could be differentiated from HFA (but not from PDD-NOS) on the basis of IQ profiles in two of the three systems. Differences in patterns of comorbid symptomatology were obtained in two of the three systems, although differences were primarily driven by the PDD-NOS category. Only one of the approaches yielded differences relative to aggregation of the broader phenotype in family members. Conclusions: Diagnostic assignments of AS based on three commonly used approaches have low agreement and lead to different results in comparisons of IQ profiles, patterns of comorbidity, and familial aggregation of psychiatric symptoms across the approach-specific resultant groups of HFA, AS, and PDD-NOS.     

Bacteremia due to Clostridium hathewayi in a patient with acute appendicitis

Clostridium hathewayi is a newly described Clostridium species isolated from the feces of healthy human individuals, but its clinical significance is not known. We describe a case of human infection associated with C. hathewayi. The bacterium (strain HKU18) was isolated from the blood culture of a 39-year-old patient with acute gangrenous appendicitis complicated by septic shock. The cells were strictly anaerobic, nonmotile rods that stained gram negative. Conventional phenotypic tests and commercial identification systems failed to identify HKU18 to the species level. 16S rRNA gene analysis showed 1.4% nucleotide difference between the sequence of HKU18 and that of C. hathewayi, indicating that HKU18 was a strain of C. hathewayi. The patient responded to appendectomy and antibiotic treatment. 16S rRNA gene sequencing would be useful in further characterizing the clinical disease spectrum of C. hathewayi.     

Annotation: Hyperlexia: disability or superability?

BACKGROUND: Hyperlexia is the phenomenon of spontaneous and precocious mastery of single-word reading that has been of interest to clinicians and researchers since the beginning of the last century. METHODS: An extensive search of publications on the subject of hyperlexia was undertaken and all available publications were reviewed. RESULTS: The literature can be subdivided into discussions of the following issues: (1) whether hyperlexia is a phenomenon that is characteristic only of specific clinical populations (e.g., children with developmental delays) or whether it can also be observed in the general population; (2) whether hyperlexia is a distinct syndrome comorbid with a number of different disorders or whether it is a part of the spectrum of some other clinical condition(s); (3) whether hyperlexia should be defined through single-word reading superiority with regard to reading comprehension, vocabulary, general intelligence, any combination of the three, or all three characteristics; (4) whether there is a specific neuropsychological profile associated with hyperlexia; (5) whether hyperlexia is characterized by a particular developmental profile; and (6) whether hyperlexia should be viewed as a disability (deficit) or superability (talent). CONCLUSIONS: We interpret the literature as supporting the view that hyperlexia is a superability demonstrated by a very specific group of individuals with developmental disorders (defined through unexpected single-word reading in the context of otherwise suppressed intellectual functioning) rather than as a disability exhibited by a portion of the general population (defined through a discrepancy between levels of single-word reading and comprehension). We simultaneously argue, however, that multifaceted and multi-methodological approaches to studying the phenomenon of hyperlexia, defined within the research framework of understanding single-word reading, are warranted and encouraged.     

Palliative surgery for bowel obstruction in recurrent ovarian cancer:an updated series

OBJECTIVE: Intestinal obstruction is a frequent sequela of recurrent ovarian cancer. Previous series report median survivals of 3-6 months in patients undergoing surgery for obstruction due to recurrent disease. We analyze a contemporary series of patients to determine if outcomes have changed in patients undergoing palliative surgery. METHODS: We retrospectively reviewed all patients undergoing surgery for intestinal obstruction due to recurrent ovarian cancer from 1994 to 1999. RESULTS: During the study period, 68 operations were performed on 64 patients. Mean age at the time of obstruction was 57.3 years. Mean time from original diagnosis of ovarian cancer to obstruction was 2.8 years. Surgical correction (intestinal surgery performed for relief of obstruction) was attained in 57 of 68 (84%) cases. Successful palliation (the ability to tolerate a regular or low-residue diet at least 60 days postoperatively) was achieved in 71% of cases where surgical correction was possible. The rate of major surgical morbidity was 22%. There was one death from pulmonary embolus and one from peritonitis. Two other deaths occurred due to progression of disease, for an overall perioperative mortality rate of 6%. Postoperative chemotherapy was administered in 45 of 57 (79%) cases where surgical correction was possible. The median survival of the entire cohort was 8 months. If surgery resulted in successful palliation, median survival was 11.6 months, versus 3.9 months for all other patients (P <.01). CONCLUSIONS: The majority of our patients undergoing surgery had successful palliation, and were able to receive further chemotherapy. They were discharged home, and could tolerate solid food.