Malignancy associated with hepatolithiasis

BACKGROUND/AIMS: Malignancy is known to be associated with hepatolithiasis. The present report summarizes the results of our management of patients with cholangiocarcinoma associated with hepatolithiasis. MATERIALS AND METHODS: Twenty patients with cholangiocarcinoma and associated hepatolithiasis were analyzed retrospectively. There were 12 males and 8 females, with a mean age of 59.3 years. The clinical records of these patients were reviewed to determine demographic characteristics, clinical features, laboratory findings, diagnostic tests, operative management and results of therapy. RESULTS: One patient was moribund on presentation and was treated conservatively. Fourteen patients underwent hepatic resection. Three of them had palliative resection. Hepatic resection was less likely to be performed in patients having right lobe disease (50%) as compared to patients having left lobe disease (90%) (p = NS). The overall operative morbidity and mortality rates after hepatic resection were 36% and 7%, respectively. Non-resective operations were performed in five patients. The overall operative morbidity and mortality rates after non-resective operations were 20% and 0%, respectively. After curative hepatic resection (11 patients), the 1- and 2-year survival rates were 81% and 51%, respectively. CONCLUSIONS: A suspicion of malignancy is necessary in managing patients with hepatolithiasis. Hepatic resection is the treatment of choice for cholangiocarcinoma when it is resectable.     

Thyroid peroxidase as toxicity target for dithiocarbamates

In vivo ethylenebisdithiocarbamates and ETU are toxic to the thyroid gland. Since the molecular target of these compounds is thought to be thyroid peroxidase (TPO) which catalyzes the transfer of iodine to thyroglobulin, we examined the effect of these compounds on peroxidative activity in Chinese hamster ovary (CHO) cells transfected with the human TPO gene. The activity was inhibited by 50 microM ETU, 5 microM ziram and 5 microM zineb, the last-mentioned effect being irreversible in the absence of iodide. Thiram had no effect. By contrast, the iodinating activity of TPO was blocked only by 5 microM ETU and 50 microM zineb but not by the other compounds. The effect on TPO-catalysed iodination could explain the differences in thyrotoxicity of these compounds in vivo.     

Prolonged survival in selected patients following surgical resection for pulmonary metastasis from hepatocellular carcinoma

BACKGROUND: Pulmonary metastasis is the commonest site of extrahepatic spread from hepatocellular carcinoma (HCC). The aim of the present study was to evaluate the efficacy of surgical management in patients with solitary pulmonary metastases from HCC. METHODS: This was a retrospective study of patients with HCC admitted for hepatectomy from July 1972 to June 1995. The records of patients who had a pulmonary resection for histologically proven pulmonary recurrence after curative hepatectomy were selected for analysis. RESULTS: In the study interval, 380 patients with HCC underwent hepatectomy. Some 48 patients (12.6 per cent) developed pulmonary metastases documented pathologically or radiologically. Nine (seven men and two women) were suitable for curative pulmonary resection. The median disease-free survival between hepatectomy and appearance of the lung metastasis was 21 months. The median survival after pulmonary resection was 42 months, and the 1-, 2- and 5-year survival rates were 100, 78 and 67 per cent respectively. CONCLUSION: Pulmonary resection for metastases from HCC resulted in long-term survival in these highly selected patients.     

Warfarin sodium (Coumadin) anticoagulant therapy for vascular access patency

The increase of geriatric and diabetic patients with poor vasculature brings about a corresponding increase in the use of synthetic vascular access grafts. Synthetic vascular accesses are plagued with numerous problems in maintaining patency. As a result, many practitioners use warfarin sodium. Coumadin, because of its predictability and bioavailability to interrupt the coagulation cascade to prevent thrombus formation. This article includes actions, interactions, monitoring, and adverse effects of this drug.     

Ligand-like effects induced by anti-c-erbB-2 antibodies do not correlate with and are not required for growth inhibition of human carcinoma cells

The c-erbB-2 gene encodes a M(r) 185,000 tyrosine kinase receptor (p185) with extensive homology to the epidermal growth factor receptor. We have conducted mechanistic studies with several anti-p185 monoclonal antibodies (TAb 250, -255, -257, -260, and -263) directed against the extracellular domain of p185 utilizing the SKBR-3, BT-474, and SKOV-3 cancer cell lines. Several of these antibodies exhibited ligand-mimicking properties: they induced tyrosine phosphorylation of p185; increased the catalytic activity of the receptor substrate phospholipase C-gamma 1; exhibited time- and pH-dependent internalization; induced receptor down-regulation; and increased the turnover of the p185 protein delta 3-fold. However, there was not a universal correlation between the antibody-mediated ligand-like effects and growth inhibition. TAb 250 inhibited BT-474 cells but did not alter p185 phosphotyrosine content or increase receptor turnover in these cells. TAb 260 increased p185 protein turnover but did not affect proliferation of the SKOV-3 cell line. Furthermore, blockade of TAb 250-induced receptor phosphorylation with the tyrosine kinase inhibitor tyrphostin 50864-2 did not abrogate TAb 250-mediated growth inhibition of SKBR-3 cells. These data suggest that ligand-like effects mediated by p185 antibodies are not critical for the growth inhibition of c-erbB-2-overexpressing carcinoma cells.     

Premorbid educational attainment in schizophrenia: association with symptoms, functioning, and neurobehavioral measures

The current adjustment of cochlear implant (CI) speech processors is based on a knowledge of the lower and upper limits (T- and C-levels) for electrical stimulus currents. These data are usually acquired from subjective classifications of individual patients. In cases with non-reliable patient responses, objective methods are necessary. Especially for the estimation of correct T-levels, auditory evoked potentials (AEP) can be applied, since they allow the determination of response thresholds in a frequency-specific manner. By determining the AEP of different latencies, late cortical responses can be registered almost without artifact contamination. These patients have been examined in 20 patients provided with 22- or 8-channel CI-systems (Nucleus or Med-EI implants). In all cases, clear responses and clearly discernible threshold transitions could be detected. By making use of acoustical stimulation in a free sound field, subjective hearing threshold and the T-levels of electrical stimulation could be verified. Since late responses are generated in the primary auditory cortex, their assessment permits a nearly integral functional control of the aided hearing system. To date, no problems have occurred from maturation or attentional effects in either pediatric or adult patients. The applicability in very young children remains to be explored.     

Temperature-sensitive neuromuscular transmission in Kv1.1 null mice: role of potassium channels under the myelin sheath in young nerves

In mammalian myelinated nerves, the internodal axon that is normally concealed by the myelin sheath expresses a rich repertoire of K channel subtypes thought to be important in modulating action potential propagation. The function of myelin-covered K channels at transition zones, however, has remained unexplored. Here we show that deleting the voltage-sensitive potassium channel Kv1.1 from mice confers a marked temperature-sensitivity to neuromuscular transmission in postnatal day 14 (P14)-P21 mice. Using immunofluorescence and electrophysiology, we examined contributions of four regions of the peripheral nervous system to the mutant phenotype: the nerve trunk, the myelinated segment preceding the terminal, the presynaptic terminal membrane itself, and the muscle. We conclude that the temperature-sensitive neuromuscular transmission is accounted for solely by a deficiency in Kv1.1 normally concealed in the myelinated segments just preceding the terminal. This paper demonstrates that under certain situations of physiological stress, the functional role of myelin-covered K channels is dramatically enhanced as the transition zone at the neuromuscular junction is approached.