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.     

Cytologic diagnosis of peritoneal fluids. Applicability to the laparoscopic diagnosis of endometriosis

OBJECTIVE: To determine the accuracy of cytologic examination of laparoscopically obtained peritoneal fluid in the diagnosis of endometriosis. STUDY DESIGN: This investigation analyzed 50 laparoscopic fluid specimens received over a three-year period. Retrospective cytologic findings were correlated with clinical history and laparoscopic diagnoses. Touch preparations were also collected from necropsies to develop cytologic criteria necessary to distinguish endometrial cells from mesothelial cells. RESULTS: The presence of hemosiderin-laden macrophages in peritoneal fluids was more specific but less sensitive than the presence of endometrial cells for the diagnosis of endometriosis. CONCLUSIONS: In women undergoing laparoscopy to detect endometriosis, the identification of endometrial cells alone in peritoneal fluids may not be sufficient to render a definitive diagnosis of endometriosis. However, the presence of hemosiderin-laden macrophages in this population should alert the cytologist to that possibility.     

A phase I study of letrazuril in AIDS-related cryptosporidiosis

OBJECTIVE: The intestinal parasite Cryptosporidium is a common cause of chronic diarrhoea in AIDS patients and is responsible for significant morbidity and mortality. No effective treatment is currently available for this condition. Here we aim to determine the safety, tolerance, and clinical effect of letrazuril in the treatment of AIDS-related Cryptosporidiosis. DESIGN: A prospective, open-label study of letrazuril was performed. SETTING: The study was conducted at the Immune Deficiency Treatment Centre (IDTC) of Montreal General Hospital, a tertiary-care centre with inpatient and outpatient facilities. PARTICIPANTS: All HIV-positive patients presenting to the IDTC between November 1991 and January 1993 who had symptomatic intestinal Cryptosporidiosis were enrolled in this protocol. Sixteen participants entered the study and 15 were available for evaluation, having completed at least 2 weeks on the study medication. INTERVENTIONS: Patients received letrazuril daily in escalating doses of 50 to 100 mg orally for 6 weeks. Clinical and laboratory evaluations were performed weekly during the treatment phase, with a follow-up evaluation 4 weeks after the end of this phase, for a total study period of 10 weeks. MAIN OUTCOME MEASURES: Response to letrazuril was assessed by eradication of Cryptosporidial oocysts from the stool and symptomatic improvement in diarrhoea and abdominal pain. Haematological, biochemical, and electrocardiographic parameters were also studied to evaluate potential toxicities of the treatment. RESULTS: Fourteen evaluable patients had baseline CD4 lymphocyte counts ranging from 3 to 99 x 10(6)/l cells (mean, 30 x 10(6)/l cells). (The fifteenth evaluable patient had a CD4 count 235 x 10(6)/l.) Of these 14 patients, five showed a major response (symptomatic improvement and eradication of Cryptosporidial oocysts from the stool), two had a minor response (symptomatic improvement with persistence of oocysts in stool), and seven had no response to therapy with letrazuril. Seven patients developed a transient drug-related rash. CONCLUSION: Fifty per cent of the AIDS patients in this study experienced an improvement in their Cryptosporidial disease while receiving letrazuril. No serious dose-related toxicities were observed. Larger Phase II trials are needed to evaluate the safety and efficacy of letrazuril in AIDS-associated intestinal Cryptosporidiosis.     

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.     

Effects of total replacement of atrial myosin light chain-2 with the ventricular isoform in atrial myocytes of transgenic mice

BACKGROUND: In contrast to their well-known and critical role in excitation-contraction coupling of vascular smooth muscle, the effects of the myosin light chains on cardiomyocyte mechanics are poorly understood. Accordingly, we designed the present experiment to define the cardiac chamber-specific functional effects of the ventricular isoform of the regulatory myosin light chain (MLC2v). METHODS AND RESULTS: Postnatal transgenic cardiac-specific overexpression of MLC2v was achieved by use of the alpha-myosin heavy chain promoter. Enzymatically disaggregated atrial and ventricular mouse myocytes were field-stimulated at multiple frequencies, and mechanical properties and calcium kinetics were studied by use of video edge detection and FURA 2-AM, respectively. MLC2v overexpression resulted in complete replacement of the atrial with the ventricular isoform of the regulatory myosin light chain at the steady-state mRNA and protein levels in the atria of transgenic mice. Mechanical properties of transgenic atrial myocytes were enhanced to the level of ventricular myocytes of control animals in association with modest decreases in the amplitude of the calcium transient. CONCLUSIONS: MLC2v modulates chamber-specific contractility by enhanced calcium sensitivity and/or improved cross-bridge cycling of the thin and thick filaments of the cardiomyocyte.     

Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-containing cells in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus)

We assessed forearm vascular and blood pressure responses to dynamic leg exercise in patients 7 and 28 days postmyocardial infarction. To determine a possible association between abnormal exercise vascular responses and baroreflex dysfunction, integrated and carotid baroreflex sensitivity and forearm vascular responses (during application of subhypotensive lower body negative pressure) were assessed. On day 7, 42 patients were compared with 21 age- and sex-matched controls. All subjects were assessed for (1) forearm vascular resistance during semierect exercise, (2) blood pressure measurements during erect treadmill exercise, and (3) integrated, cardiopulmonary, and carotid baroreceptor sensitivity. These studies were repeated in 13 patients on day 28. Forearm vascular resistance increased during exercise by 36% +/- 63% in patients versus 121% +/- 105% in controls (P = 0.0001), and fell in 15 patients, a response seen in none of the controls. Exercise hypotension was demonstrated in 5 patients, all of whom had abnormal vasodilator vascular responses. Those patients with vasodilator responses had a lower left ventricular ejection fraction (52% +/- 12% vs 62% +/- 9%; P = 0.007), and lower cardiopulmonary mechanoreceptor sensitivity (-6.6 +/- 3.9 units vs +6.4 +/- 10.4 units, P = 0.02) than those with constrictor responses, respectively. In the 13 patients studied on day 28, the change in forearm vascular resistance was similar to that observed on day 7 (36% +/- 63% vs 46% +/- 73%). Paradoxical vasodilation of forearm vessels during leg exercise is common in patients studied 7 and 28 days postmyocardial infarction, and is associated with lower left ventricular ejection fraction and abnormal vascular responses during subhypotensive lower body negative pressure.     

Genomic analysis reveals chromosomal variation in natural populations of the uncultured psychrophilic archaeon Cenarchaeum symbiosum

Molecular phylogenetic surveys have recently revealed an ecologically widespread crenarchaeal group that inhabits cold and temperate terrestrial and marine environments. To date these organisms have resisted isolation in pure culture, and so their phenotypic and genotypic characteristics remain largely unknown. To characterize these archaea, and to extend methodological approaches for characterizing uncultivated microorganisms, we initiated genomic analyses of the nonthermophilic crenarchaeote Cenarchaeum symbiosum found living in association with a marine sponge, Axinella mexicana. Complex DNA libraries derived from the host-symbiont population yielded several large clones containing the ribosomal operon from C. symbiosum. Unexpectedly, cloning and sequence analysis revealed the presence of two closely related variants that were consistently found in the majority of host individuals analyzed. Homologous regions from the two variants were sequenced and compared in detail. The variants exhibit >99.2% sequence identity in both small- and large-subunit rRNA genes and they contain homologous protein-encoding genes in identical order and orientation over a 28-kbp overlapping region. Our study not only indicates the potential for characterizing uncultivated prokaryotes by genome sequencing but also identifies the primary complication inherent in the approach: the widespread genomic microheterogeneity in naturally occurring prokaryotic populations.     

Updating accounts following a correction of misinformation

The research examined whether corrected misinformation influences anaphoric inferences people make during subsequent reading. Participants read a set of corrected-misinformation and no-misinformation stories and made judgments about probe words that were either appropriate or inappropriate anaphoric referents. At a short delay, the results showed less activation for appropriate referents that were corrections of misinformation. At longer delays, the activation of appropriate referents showed no significant difference, but misinformation probes were more quickly recognized than were inappropriate referents that were incidentally mentioned in control story versions. In all conditions, appropriate referents showed more activation than inappropriate ones. The results suggest that corrected misinformation can continue to influence on-line reading processes.     

Cellular mechanisms of epiboly in leech embryos

Gastrulation in leech embryos is dominated by the epibolic movements of two tissues: germinal bands, composed of segmental precursor cells, and an overlying epithelium that is part of a provisional integument. During gastrulation, the germinal bands move over the surface of the embryo and coalesce along the prospective ventral midline. Concurrently, the epithelium spreads to cover the embryo. We have begun to analyze the mechanisms involved in gastrulation in the leech by assessing the independent contributions of the epithelium and the germinal bands to these cell movements. Here we describe cellular events during epiboly in normal embryos and in embryos perturbed by either reducing the number of cells in the epithelium, or by preventing the formation of the germinal bands, or both. These experiments indicate that both the germinal bands and the epithelium are able to undergo epibolic movements independently, although each is required for the other to behave as in control embryos.