Lupus anticoagulant, anticardiolipin antibodies and hepatitis C virus infection in thalassaemia

Anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) have been detected in patients with hepatitis C virus (HCV) infection and have been associated in autoimmune diseases (i.e. systemic lupus erythematosus) with an increased risk of thromboembolic events. Because of the high prevalence of HCV infection and the thrombotic risk described in thalassaemia we decided to investigate the prevalence of ACA and LA in a cohort of 68 thalassaemia patients. We found a high prevalence (34%) of beta2-glycoprotein I independent ACA in our thalassaemia patients which was related to HCV infection. None of patients developed any complications related to antiphospholipid antibodies (APL); therefore the clinical significance of positivity for APL in patients with HCV infection is at present unclear. In conclusion, the results of our study indicate that ACA in the serum of HCV-infected thalassaemic patients exhibit the characteristics of natural autoantibodies rather than those of the pathogenic autoantibodies that are found in patients with systemic lupus erythematosus.     

Laryngeal atresia or stenosis presenting as second-trimester fetal ascites--diagnosis and pathology in three independent cases

Congenital atresia of the larynx is a rare abnormality. We describe three cases where prenatal diagnosis during the second trimester showed massive abdominal fetal ascites and at post-mortem, laryngeal atresia was identified in two cases, and severe laryngeal stenosis in the third. All were associated with pulmonary hyperplasia. No additional abnormalities were found in other systems. Overdistended lung tissue and ascites are resultant from aberrant laryngeal growth; laryngeal anomalies are a cause of isolated fetal ascites. The association of ascites and voluminous lungs should arouse suspicion of laryngeal atresia and should be an indication for careful pathological study of the fetal larynx.     

Antinociceptive analogs of orphanin FQ/nociceptin(1-11)

The presence of pairs of basic amino acids within the sequence of orphanin FQ/nociceptin (OFQ/N) peptide, the endogenous ligand for the ORL1/KOR-3 receptor, has raised the possibility that processing might generate pharmacologically important truncated peptides, including OFQ/N(1-11). OFQ/N(1-11) is pharmacologically active in vivo with a potency comparable to OFQ/N. Several tyrosine-containing analogs of OFQ/N(1-11) have been synthesized and examined for antinociceptive activity. Like OFQ/N(1-11), [Tyr1]OFQ/N(1-11), [Tyr10]OFQ/N(1-11) and [IodoTyr10]OFQ/N(1-11) given supraspinally in mice were antinociceptive in the tailflick assay in mice. The tyrosine analogs showed similar potencies as OFQ/N(1-11) but longer durations of action. This response was readily reversed by the opioid antagonist naloxone despite poor affinities for these analogs at opioid receptors. Another compound, [Tyr11]OFQ/N(1-11) was highly epileptogenic, inducing naloxone-sensitive seizures in greater than 50% of the mice tested at doses comparable to those examined with the other analogs. These results indicate that it is possible to make analgesic OFQ/N(1-11) analogs. The activity of [IodoTyr10]OFQ/N(1-11) suggests that it may prove useful as a radioligand in exploring potential OFQ/N(1-11) binding sites.     

Enteropathogenic E. coli: intimacy redefined

A 42 yr old male presented with left facial weakness. MRI showed lesions affecting the distal seventh nerve and third division of the trigeminal nerve. The seventh nerve was biopsied and showed a malignant epithelioid schwannoma. The patient underwent extensive resection followed by irradiation. This is one of very few examples of intracranial malignant peripheral nerve sheath tumors and the first reported example of an intracranial malignant epithelioid schwannoma. The literature is reviewed and completeness of resection appears to be the most pertinent prognostic factor.     

Effects of chronic ethanol consumption and withdrawal on the neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one in male and female rats

Prolonged alcohol (ethanol) consumption leads to the development of alcohol tolerance and cross-tolerance to some benzodiazepines and barbiturates. In contrast, rats undergoing alcohol withdrawal are sensitized to the anticonvulsant effects of the endogenous GABA(A) receptor modulator, 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP). Alterations in endogenous, cerebral cortical levels of 3alpha,5alpha-THP during alcohol withdrawal could contribute to the observed sensitization to 3alpha,5alpha-THP. Therefore, this study investigated plasma and brain levels of 3alpha,5alpha-THP, progesterone, and corticosterone during alcohol dependence and withdrawal in the rat. Plasma corticosterone, progesterone (a precursor of 3alpha,5alpha-THP) and 3alpha,5alpha-THP levels were unchanged in alcohol-dependent animals. Cerebral cortical levels of 3alpha,5alpha-THP decreased in dependent male animals, but not in dependent female rats. During alcohol withdrawal, plasma corticosterone and progesterone levels increased in male, but not female rats. However, neither plasma nor cerebral cortical 3alpha,5alpha-THP levels were altered from control levels in male or female rats during alcohol withdrawal. Plasma and brain levels of 3alpha,5alpha-THP were markedly higher in female compared with male rats. Cerebral cortical levels of 3alpha,5alpha-THP during the diestrus phase of the estrus cycle were approximately 4 to 6 ng/g, a concentration that may approach physiological relevance. These findings suggest that sensitization to 3alpha,5alpha-THP during alcohol withdrawal is not mediated by elevations in brain levels of endogenous 3alpha,5alpha-THP in male or female rats. However, elevations in circulating corticosterone and progesterone levels during ethanol withdrawal in male rats may underlie gender differences in allopregnanolone sensitivity during ethanol withdrawal.     

Hypertonic-hyperoncotic solutions in open-heart surgery

PURPOSE: To examine relationships between tobacco use and use of other substances among U.S. high school students, by gender and racial/ethnic subgroups. METHODS: Data about tobacco and other substance use were analyzed from the 1995 national Youth Risk Behavior Survey implemented by the Centers for Disease Control and Prevention. RESULTS: Compared to nonsmokers, current smokers were significantly more likely to report use of all other substances we examined, including lifetime use of cocaine, inhalants, other illegal substances, and multiple substances and current alcohol use, episodic heavy drinking, marijuana use, and cocaine use. A strong dose-dependent relationship between current cigarette smoking and other substance use was identified. Among smokeless tobacco users, a strong dose-dependent relationship was found for all examined substances with the exception of lifetime and current cocaine use. Finally, a pattern of risk emerged suggesting that the likelihood of other substance use increases as students move from no tobacco use to smokeless tobacco use only, to cigarette smoking only, and to use of both smokeless tobacco and cigarettes. CONCLUSIONS: Programs designed to prevent tobacco or other substance use should consider that such use often occurs concomitantly.