Innovation in clinical method: diabetes care and negotiating skills

Hepatocellular carcinoma (HCC) with extrahepatic spreading is not uncommon. In order to delineate the clinical and radiological pictures of HCC with intracranial metastasis, 33 documented cases were analysed. Eighteen had brain parenchymal metastasis without skull involvement; the other 15 cases disclosed skull metastasis with brain invasion. The underlying HCC are mainly of expanding (13/33, 39.4%) and multifocal (13/33, 39.4%) types. Eighteen cases (18/33, 54.5%) had mental changes not related to hypoglycaemia or hepatic encephalopathy. Eighteen cases (18/20, 90%) disclosed hyperdense mass lesions by non-contrast computed tomography (CT) scans and 17 cases showed homogeneous enhancement (17/22, 77.3%) by post-contrast CT images. In the non-skull involved group, five cases (5/12, 41.7%) disclosed ring-shape enhancement and 14 cases (14/16, 87.5%) had perifocal oedema, which were not seen in the skull involved group. Eight cases (8/33, 24.2%) presented as intracerebral haemorrhage. Twelve (12/33, 36.4%) died of brain herniation. Most (14/18, 77.8%) non-skull involved cases had simultaneous lung metastasis without bony metastasis, while the skull involved group often (10/15, 66.7%) disclosed extracranial bony metastasis without lung metastasis. The difference in extracranial metastasis was statistically significant (P < 0.05). The multivariate survival analysis disclosed that lower lactate dehydrogenase level (< or = 316 U/L, P = 0.029) and treatments (surgery or radiation, P = 0.001) were positively associated with longer survival. In conclusion, HCC with intracranial metastasis is symptomatic and life-threatening. Half the cases may come from pulmonary metastasis and the other half may be from bony metastasis. Brain irradiation or surgery can prolong their survival.     

Structure-based design of a potent transition state analogue for TEM-1 beta-lactamase

The structure of the plasmid-mediated beta-lactamase TEM-1 has been solved in complex with a designed boronic acid inhibitor (1R)-1-acetamido-2-(3-carboxyphenyl)ethane boronic acid at 1.7 A resolution. The boronate inhibitor was designed based on the crystallographic coordinates of the acyl-enzyme intermediate of TEM-1 bound to the substrate penicillin G. The boronate-TEM-1 complex is highly ordered and defines a novel transition state analogue of the deacylation step in the beta-lactamase reaction pathway. The design principles of this highly effective inhibitor (Ki = 110 nM) and the resulting structural and mechanistic implications are presented.     

Transumbilical use of the endovaginal probe

The endovaginal probe can be used in the umbilicus to improve fetal imaging. In 27 of 31 patients, an optimal ultrasound examination was achieved because of this added technique. The procedure is most useful in obese women and those with prior abdominal surgery.     

Ability of 16 priority PAHs to be directly cytotoxic to a cell line from the rainbow trout gill

Sixteen polycyclic aromatic hydrocarbons (PAHs) were screened for their ability to be directly cytotoxic to a cell line from the rainbow trout gill, RTgill-W1. Exposure times of 2 h or less were sufficient for direct cytotoxicity to be detected, which appeared to be caused by a common mechanism, the general perturbation of membranes. This was judged by the similarity of results obtained for three fluorescent indicator dyes, alamar Blue, 5-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM) and neutral red. Among the 16 PAHs tested, just two- and three-ring PAHs were found to be directly cytotoxic. These were naphthalene approximately = acenaphthylene approximately = acenaphthene > fluorene approximately = phenanthrene. The results suggest that water solubility and lipophilicity are the critical properties determining the direct cytotoxicity of PAHs and that they do so by influencing PAH accumulation in membranes. Only naphthalene was effective at concentrations well below its water solubility limit. Therefore, direct cytotoxicity is likely to be most environmentally relevant only with naphthalene.     

Immune and physiological responses of turkeys with green-liver osteomyelitis complex

A study of field turkeys was undertaken in order to determine the involvement of relative immunological differences in the etiology of turkey osteomyelitis complex (TOC). Lame and normal turkeys were sampled from commercial flocks just prior to processing in two separate trials. After testing for functions of both humoral and cellular immunity, the turkeys were necropsied and examined for lesions of TOC. There were significantly higher relative spleen and over weights and significantly lower body weights and relative bursal weights in birds with TOC. The birds with TOC had lower response to phytohemagglutinin-P in both in vivo and in vitro tests as well as lower circulating lymphocyte counts and higher monocyte, heterophil, and total white blood cell counts. There was a significantly higher antibody response to sheep red blood cells in turkeys with TOC, whereas antibody response to Salmonella pullorum antigen was not different. There were no significant differences in the percentages of mononuclear cells or heterophils able to phagocytize bacteria or latex particles, or kill bacteria; however, the heterophils from turkeys with TOC lesions did phagocytize significantly fewer latex particles per cell than did those of the healthy turkeys. Total serum protein, uric acid, and blood urea nitrogen levels were higher in birds with TOC, whereas hemoglobin, iron, alkaline phosphatase, and gamma-glutamyl-transferase levels were lower. Although many of the differences in birds with TOC could be caused by the normal host reaction to infection, further study may reveal innate differences that contribute to susceptibility to TOC.     

Depressive symptoms and self-concept in young people with spina bifida

Examined self-reported depressive symptoms in 72 young people with spina bifida, ages 9 to 18:11, and matched able-bodied comparison subjects, using the Dimensions of Depression Profile for Children and Adolescents (Harter & Nowakowski, 1987). Independent variables included gender, self-perceptions (including physical appearance), and perceived social support. Young people with spina bifida were at greater risk of depressive mood, low self-worth, and suicidal ideation. Girls, independent of disability, were at greater risk of depressive mood, low self-worth, and self-blame. Multiple regression analyses suggest that global self-worth serves as a mediating variable for the effect of physical appearance self-concept on depressed mood (particularly in young people with spina bifida), and that perceived parental social support has a direct effect on depressed mood (particularly in girls).     

A comparison of manual and controlled-force attachment-level measurements

This study compared the intra-examiner and inter-examiner error of 2 constant force probes to the reading of a conventional manual probe. 3 examiners made repeated examinations of attachment level using a modified Florida probe and a manual North Carolina probe (read to 1 mm or 0.5 mm); relative attachment level measurements were made using a Florida disk probe. One probe was used in each quadrant in 8 subjects with moderate to advanced periodontitis. Error was calculated as the mean of the absolute value of the difference between each examination, and the correlation between values at each examination calculated. Statistically-significant differences between probe type, examiners, and sites were detected using a repeated measures ANOVA accounting for the nesting within subjects. There was a significant difference in error by probe type (modified Florida probe 0.62 +/- 0.03 mm, r = 0.86; Florida stent probe 0.55 +/- 0.05 mm, r = 0.82; manual probe to 1 mm 0.39 +/- 0.02 mm, r = 0.88; manual probe to 0.5 mm 0.40 +/- 0.02 mm, r = 0.89; (p < 0.001). Significant differences were observed by examiners (p < 0.01). These data indicate that both manual and controlled-force probes can provide measurement within less than 1 mm of error; however, individual calibration of examiners remains important in the reduction of error.     

Immunohistochemical localization of novel CART peptides in rat hypothalamus, pituitary and adrenal gland

CART peptide specific polyclonal antisera were raised in rabbits. The antisera were raised to CART peptide fragments that span most of the predicted CART protein. The specificity of each antisera was demonstrated by blockade of immunostaining by the immunizing peptide but not by the other CART peptide fragments. In the hypothalamus and pituitary of colchicine and noncolchicine treated rats, immunostaining was observed in cell bodies, fibers and varicosities. Clusters of cells were also stained in the adrenal medulla. It is noteworthy that cellular immunostaining was only found in areas previously shown to express CART mRNA. These findings indicate the presence of CART peptide(s) in the hypothalamus, pituitary, and adrenal gland. Furthermore, we also present evidence for the possible processing of the CART pro-peptide into smaller peptide fragments. These neuroanatomical findings suggest a role of CART peptides in hypothalamic, pituitary and adrenal function.