Prospective, randomized trial of hypertonic glucose water and sodium tetradecyl sulfate for gastric variceal bleeding in patients with advanced liver cirrhosis

BACKGROUND AND STUDY AIMS: Information about the appropriate endoscopic treatment of gastric variceal bleeding is sparse. We therefore designed a prospective and randomized study to evaluate and compare efficacy and complication rates of two agents, hypertonic glucose water (50% GW) and sodium tetradecyl sulfate (STS), in treating acute gastric variceal bleeding after esophageal varix eradication. PATIENTS AND METHODS: Of 51 patients with advanced cirrhosis of the liver (Child's C), with acute gastric variceal bleeding initially evaluated, 25 patients were randomized to receive 1.5% STS and 26 to receive 50% glucose water. Treatment was aimed at achieving initial and permanent hemostasis by variceal eradication. RESULTS: Control of acute gastric variceal bleeding was achieved in 80% of the STS group and 92% of the GW group. The rebleeding rate in the STS group was 70%, while in the GW group it was 30% (P < 0.05). Overall, obliteration was achieved in only 32% of the STS group and 81% of the GW group during admission (P < 0.05). There was a trend toward a higher gastric ulcer rate in the STS group compared with the GW group (92% vs. 30%; P < 0.05). The rebleeding control rate and permanent hemostasis rate in the GW group (70%, 54%) were also significantly higher than in the STS group (21%, 12%; P < 0.05; P < 0.05). The hospital mortality for the STS group was 50%, and for the GW group 30%. CONCLUSION: Treatment with hypertonic glucose water in gastric vericeal bleeding was superior to treatment with STS in controlling bleeding and in achieving vericeal obliteration, less rebleeding, and a lower complication rate. The results of this study suggest that hypertonic glucose water is a clinically effective, easily available, and safe sclerosing agent.     

Lignocaine spray applicators are a potential source of cross-infection in the anaesthetic room

A 27 year old female with AIDS and disseminated histoplasmosis is presented. The clinical features include fever, weight loss, productive cough, splenomegaly and moderate pallor. The initial working diagnosis was pulmonary tuberculosis. The diagnosis of disseminated histoplasmosis was made terminally from bone marrow aspirate examination. Disseminated histoplasmosis with its varied clinical picture is likely to be missed in a patient with AIDS, and therefore a high index of suspicion is necessary for diagnosis.     

Choledochal cysts: a nine-year review

It has been suggested that asbestos might have an important role in the development of p53 mutations in mesotheliomas. The objective of this study was to examine asbestos-associated mesotheliomas and non-asbestos-associated mesotheliomas to establish whether the frequency of p53 immunostaining and, by implication, p53 gene mutation is related to asbestos exposure. Immunopositivity for p53 was found in seven (44%) of the 16 mesotheliomas examined. The frequency was approximately the same in both the asbestos-associated mesotheliomas and the non-asbestos-associated mesotheliomas. It is concluded that the frequency of p53 immunostaining in mesotheliomas and, by implication, the frequency of p53 gene mutation is probably not related to asbestos exposure.     

A comparison of clinical and structured interview diagnoses in a homeless mental health clinic

OBJECTIVE: This study compared psychiatric diagnoses ascertained by independent clinicians with structured research interviews of homeless psychiatric patients assessed in a mental health clinic and in the community. Problems of both overdiagnosis and underdiagnosis in structured research interviews compared to clinician assessment were predicted. METHOD: Over a period of a year, 97 patients referred to a mental health clinic for homeless people were assessed with the Diagnostic Interview Schedule (DIS) administered by a clinical social worker who then completed a full clinical psychiatric social work assessment. These same patients received a thorough and systematic clinical psychiatric evaluation by a psychiatrist or psychologist, both experienced with this population. These clinicians gathered data from multiple sources, often with extended observation over time. The DIS and clinician diagnoses were made blind to one another and then compared; the clinician was often made aware of some of the symptoms that the social worker had elicited, but not whether the elicited material was from the DIS or from the clinical assessment. Diagnoses of 33 clinic patients previously assessed by trained nonclinician DIS interviews in an epidemiologic study of the homeless population in the community were also compared to clinician diagnoses, and no information from these patients' survey DIS interviews was made available to the clinicians. RESULTS: Compared to clinician assessment, structured interviews underdiagnosed antisocial personality disorder (ASPD) and overdiagnosed major depression. Alcohol use disorder and schizophrenia showed only small discrepancies by assessment method. Drug use disorder revealed no bias according to method of ascertainment, but showed very discrepant kappa levels comparing DIS to clinician assessment in the two different comparison contexts. CONCLUSIONS: If structured research methods assessing the homeless population actually overestimate depression, underestimate ASPD, and misclassify drug abuse, then policies stemming from structured interview research recommendations may call for levels and types of services not optimally suited to the reality of this population's needs. Because mental illness and substance abuse are thought to be critical factors in the generation and perpetuation of homelessness, the issue of accurate diagnosis is tantamount to understanding and providing workable solutions to the problem of homelessness. Further research is needed to untangle potential confounders of the homeless situation to psychiatric diagnosis.     

Relation of systemic arterial pulse pressure to coronary atherosclerosis in patients with mitral stenosis

The relation of a wide systemic arterial pulse pressure to coronary atherosclerosis has not been fully defined. One hundred fifty-nine patients > 40 years old with symptomatic mitral stenosis (MS) who received routine coronary angiography were classified into 2 groups according to the presence of > or = 50% diameter narrowing of > or = 1 coronary artery (n = 48) or no significant disease (n = 111). Pulse pressure was determined both by noninvasive sphygmomanometer and invasive catheterization methods. There were no significant differences in risk factors of coronary artery disease (CAD) or the severity of MS between the 2 groups. From multivariate logistic regression analysis, independent predictors of development of CAD in MS were age (standardized coefficient beta = 1.3437, p = 0.0025), gender (beta = 0.0107, p = 0.0105), mean blood pressure (beta = 1.1839, p = 0.0105), and pulse pressure (beta = 1.3157, p = 0.0008). A wide pulse pressure (> or = 60 mm Hg) correlated with the presence of angiographically significant CAD with a sensitivity and specificity of 88% and 77%. The negative predictive value was 93%. Pulse pressure assessed by sphygmomanometry provided important clinical information. A wide pulse pressure in patients with MS was associated with a high incidence of CAD.     

Cobalamin analogues modulate the growth of leukemia cells in vitro

Analogues of cyanocobalamin (CN-Cbl), with functional groups attached to either the various propionamide groups of the corrin ring or to the ribose-nucleotide linker arm, have been evaluated in a cobalamin (Cbl)-dependent in vitro cell growth assay. In this bioassay, CN-Cbl supported, in a dose-dependent manner, the growth of the murine lymphoma BW5147 and the Cbl carrier protein, human apo-transcobalamin II, reduced the required concentration of Cbl by 100-1000-fold. Any chemical modification of Cbl decreased its ability to support cellular viability and proliferation, with several of the modifications abrogating activity completely. All of the Cbl analogues that promoted growth required the presence of apo-transcobalamin II for the optimal support of cell growth. Generally, Cbl analogues modified at the d-position of the corrin ring and, to a lesser degree, analogues modified at the b- position supported cell growth, whereas analogues with modifications at the e-position did not support cell growth. Mixing experiments demonstrated an inverse order of potency of Cbl analogues to inhibit cell growth. Thus, Cbl analogues with modifications at the e-position were potent inhibitors, whereas b-analogues exhibited only partial inhibitory activity at high molar excess, and d-analogues had no inhibitory activity at all. These results indicate that modifications at the e-position of Cbl abolish the ability of Cbl to support cell growth and generate potent inhibitors of Cbl-dependent cell growth.     

Effects of 4'-modified analogs of aristeromycin on the metabolism of S-adenosyl-L-homocysteine in murine L929 cells

(1'R,2'S,3')-9-(2',3'-Dihydroxycyclopentan-1'-yl)adenine (DHCaA), (1'R,2'S,3'R)-9-(2',3'-dihydroxycyclopentan-1'-yl)-3-deazaadenine (3-deaza-DHCaA), (4'R)-4'-methyl-DHCaA, and (4'R)-4'-vinyl-DHCaA, which are analogs of the carbocyclic nucleoside aristeromycin, were synthesized earlier by our laboratory and were shown to be potent inhibitors of purified bovine liver S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1). In the present study, these analogs were shown to produce rapid (within 15 min) and concentration-dependent (0.03-10 microM) inhibition of AdoHcy hydrolase in cultured murine L929 cells [relative order of inhibitory activity, DHCaA = 3-deaza-DHCaA > (4'R)-4'-vinyl-DHCaA = (4'R)-4'-methyl-DHCaA]. The relative potencies of these inhibitors on the L929 AdoHcy hydrolase were consistent with their inhibitory effects on the recombinant forms of rat liver and human placental enzymes. This inhibition of L929 cellular AdoHcy hydrolase persisted for up to 48 hr. The inhibition of the L929 AdoHcy hydrolase resulted in a significant increase in the cellular concentrations of AdoHcy, whereas the cellular S-adenosylmethionine (AdoMet) levels remained relatively constant, thereby elevating the AdoHcy/AdoMet ratios. Maximum increases in AdoHcy levels and AdoHcy/AdoMet ratios occurred within 6 hr of exposure to the inhibitors and persisted for at least 24 hr. At a concentration of 1 microM, DHCaA and 3-deaza-DHCaA increased AdoHcy/AdoMet ratios to approximately 0.8 (after 24 hr of exposure to the inhibitors), whereas (4'R)-4'-vinyl-DHCaA and (4'R)-4'-methyl-DHCaA elevated AdoHcy/AdoMet ratios to approximately 0.15, compared with control levels of 0.05. Treatment of L929 cells with concentrations of DHCaA, 3-deaza-DHCaA, (4'R)-4'-vinyl-DHCaA, and (4'R)-4'-methyl-DHCaA up to 10 microM did not result in changes in cellular levels of endogenous nucleotides (e.g., CTP, UTP, ATP, and GTP). In contrast, cells treated with 10 microM aristeromycin for 6 hr contained reduced cellular levels of CTP, ATP, and GTP and significant levels of aristeromycin triphosphate and a GTP metabolite of this carbocyclic nucleoside. These data clearly show that the 4'-modified analogs [DHCaA, 3-deaza-DHCaA, (4'R)-4'-vinyl-DHCaA, and (4'R)-4'-methyl-DHCaA] retain inhibitory activity toward cellular AdoHcy hydrolase, causing elevated levels of AdoHcy and elevated AdoHcy/AdoMet ratios. However, these analogs are devoid of substrate or inhibitory activity toward cellular adenosine kinase. In addition, aristeromycin is rapidly metabolized in murine L929 cell lysates, i.e., > 60% of the aristeromycin had been metabolized in 6 hr. In contrast, neither DHCaA nor 3-deaza-DHCaA showed any decrease in concentration after incubation with cell lysates for up to 6 hr.     

Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration

Oxysterols are biologically active molecules generated during oxidation of LDL. Several of these oxysterols were found in macrophage-derived foam cells from human atherosclerotic tissue (eg, 7-hydroxycholesterol, 7-ketocholesterol, 5-epoxycholesterol, and 25-hydroxycholesterol). A specific stimulation of interleukin-8 (IL-8) production by oxidized LDL (oxLDL) has been shown by other investigators. In foam cells from human atherosclerotic tissue, we found high levels of IL-8 (183.1 pg/10(6) cells) compared with monocytes (23.2 pg/10(6) cells) or monocyte-derived macrophages in culture (1.5 pg/10(6) cells). When monocytes and monocyte-derived macrophages, in vitro, were exposed to a series of different oxysterols, we found that all oxysterols tested had a tendency to stimulate IL-8 production but that 25-hydroxycholesterol was the most potent one. This stimulation of IL-8 production was time and dose dependent and could be blocked by cycloheximide. These results indicate that oxysterols in oxLDL may have a regulatory effect on IL-8 production. IL-8, a potent chemoattractant, may play a role in the recruitment of T lymphocytes and smooth muscle cells into the subendothelial space and may contribute to the formation of atherosclerotic lesions.