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Biomedical subjects

A Koshy

Publications and source records attributed to A Koshy.

At least 19 recordsLinked to original sources

Leishmaniasis diagnosed by liver biopsy: management of two atypical cases.

Two patients presenting with pyrexia of unknown origin were diagnosed as having visceral leishmaniasis based on the presence of Leishmania donovani bodies in liver tissue. Of particular interest is that these two case reports suggest that in patients with pyrexia of unknown origin, a liver biopsy for L. donovani bodies should be considered even when several months have passed since leaving an endemic area, when splenomegaly is absent, when bone marrow examination and serology are not diagnostic, and even when abnormal coagulation necessitates a transjugular liver biopsy.

Adult↗

Improved response to ribavirin interferon combination compared with interferon alone in patients with type 4 chronic hepatitis C without cirrhosis.

UNLABELLED: Response to treatment with alpha interferon with or without concomitant ribavirin varies according to the viral genotype in patients with chronic hepatitis C. AIM: This study was undertaken in order to determine the response of genotype 4 chronic hepatitis C to interferon and ribavirin combination compared to interferon alone in patients without cirrhosis. METHODS: Fifty-two patients were given interferon alone at a dose of 5 million units, 3 times a week and another 60 patients were administered with interferon combined with ribavarin (1,000-1,200 mg/ day) for 24 weeks. Sustained biochemical response was defined as normal ALT, 6 months after end of therapy. Sustained virologic response was defined as negative HCV RNA, 6 months after the end of therapy. RESULTS: Only 10/52 (19%) patients showed sustained biochemical response after interferon alone, while 31/60 (52%) showed sustained biochemical response after interferon combined with ribavirin (p<0.01). Only 4/52 (8%) patients showed sustained virologic response after interferon alone, while 25/60 (42%) showed sustained virologic response after interferon combined with ribavirin (p<0.001). CONCLUSION: These results show that patients with chronic hepatitis due to hepatitis C virus type 4 show a poor response to interferon alone but a better response to interferon combined with ribavirin.

Adult↗

Crohn's disease presenting as pyogenic liver abscess with review of previous case reports.

A 40-yr-old male doctor from India presented with pyogenic liver abscesses as the first manifestation of Crohn's disease. The Crohn's disease itself was limited to the appendix and the adjacent cecum and could be diagnosed only 6 months after the presentation with liver abscess. This single case highlights three unusual features of Crohn's disease, and stresses the importance of meticulous search for a cause for pyogenic liver abscess when it occurs in an otherwise healthy adult.

Adult↗

Relationship between biochemical, virological, and histological response during interferon treatment of chronic hepatitis C.

The present study was conducted to evaluate the relationship between biochemical, virological, and histological response during the course of interferon therapy. Ninety consecutive patients with well-documented chronic hepatitis C virus (HCV) were treated with 5 MU of interferon alfa-2b three times weekly for 6 months. Liver biopsy was performed, and serum HCV RNA titer was measured before and at the completion of interferon treatment. Normalization of serum alanine transaminase (ALT) concentration (biochemical response) was observed in 50% of patients. In these patients, Knodell score declined significantly from 9.6 +/- 0.5 to 5.0 +/- 0.5 (P < .01), and 75% became HCV RNA negative. The remaining patients (50%) were biochemical nonresponders; mean Knodell score declined from 9.6 +/- 0.5 to 7.7 +/- 0.5 (P < .01), and 11% became HCV RNA negative. For both biochemical responders and nonresponders, the decline in Knodell score was confined to the components of hepatic inflammation (piecemeal necrosis + lobular + portal inflammation); no change in fibrosis was observed. Hepatic inflammation declined by 5 points or more in 69% of biochemical responders and 48% of biochemical nonresponders, and by at least 50% from pretreatment values in 74% and 38% of biochemical responders and biochemical nonresponders, respectively. For all patients (both biochemical responders and nonresponders) who remained viremic at the conclusion of interferon therapy, the reduction in hepatic inflammation was a linear function of the decline in HCV RNA titer. We conclude that more than one third of patients who had no biochemical response after 6 months of interferon therapy achieved a similar improvement in hepatic histology as was observed in patients with biochemical response. This improvement in hepatic histology appeared to correlate with a reduction in HCV RNA titer, especially in patients who remained viremic.

Adult↗

Short-term IgM and IgG antibody responses to hepatitis E virus infection.

53 adult patients with acute hepatitis caused by hepatitis E virus were identified by the presence of IgM antibody to hepatitis E virus, and followed for 12 months to evaluate the kinetics of anti-HEV antibodies. All but 1 female Kuwaiti patient were expatriate workers from the Indian subcontinent, temporarily working in Kuwait. Follow-up samples obtained at 1, 3, 6 and 12 months were evaluated for IgM and IgG antibodies to hepatitis E virus. IgM-class antibodies to hepatitis E virus were detectable in 12/27 (44%) patients at 1 months, in 0/26 at 3 months, in 0/8 at 6 months and 0/6 at 12 months. IgG antibodies to hepatitis E virus were detectable in 46/47 (98%) at onset, 26/27 (96%) at 1 month, in 26/29 (90%) at 3 months, 16/16 (100%) at 6 months and 8/8 (100%) at 12 months of follow-up. This study suggests that IgM antibodies to hepatitis E virus decline rapidly after an acute infection but IgG antibodies to hepatitis E virus persists for at least 1 year in many patients.

Acute Disease↗

17 beta-estradiol treatment increases the levels of estrogen receptor and its mRNA in male rat liver.

This study examined estrogen receptor dynamics in the livers of male obese rats (SHHF/Mcc-cp) treated for two weeks with a continuous, low dose of 17 beta-estradiol compared with untreated controls. An increased binding capacity for tritiated 17 beta-estradiol in the cytosol, consistent with binding to the estrogen receptor, was demonstrated in treated males relative to control males (P < 0.01). These observations were confirmed using curve-peeling techniques with saturation analysis, ammonium sulfate precipitation/fractionation of cytosol protein, and chromatographic techniques to isolate the high-affinity binding from other interfering factors. Increased hepatic nuclear estrogen receptor levels in treated males (112.3 +/- 8.3 fmol/g liver) compared with controls (64.1 +/- 6.8 fmol/g liver) suggested that the liver was under estrogenic influences. This interpretation was supported by an increase in serum triglyceride levels, reflecting increased very low density lipoprotein secretion by the liver. Reductions in testosterone levels and in the weights of seminal vesicles and the testes in treated males indicated detrimental effects on reproduction. An interpretation of increased synthesis of estrogen receptor with 17 beta-estradiol treatment was supported by the observation of an increase in the mRNA for estrogen receptor. Taken together, these observations indicate that continuous, low-dose 17 beta-estradiol treatment induces estrogenic action in the livers of male rats and also increases hepatic estrogen receptor, probably indirectly, via an increase in its mRNA.

Animals↗

Characterization of a hepatic protein in nonhuman primates that binds mibolerone but not dihydrotestosterone or methyltrienolone.

During our studies of the hepatic androgen receptor in cynomolgus monkeys, tritiated mibolerone +/- a 200-fold excess of unlabeled mibolerone has been used to determine specific binding in cytosol. During time-course studies, high-capacity, unsaturable binding of [3H]mibolerone was noted after short-term incubations (4 h, 4 degrees C). When hepatic cytosol from male monkeys was incubated for 18 h at 4 degrees C, the high-capacity binding disappeared; saturable, high-affinity binding with characteristics consistent with the androgen receptor then could be identified. The characterization of [3H]mibolerone binding in molybdate-stabilized hepatic cytosol using sucrose density gradients and gel filtration yielded an unstable binding peak in addition to that of the androgen receptor. This lower molecular weight protein identified by gel filtration did not bind other androgens, including methyltrienolone, and did not have characteristics of other binding proteins that have been identified previously. This protein was not precipitated from 30% ammonium sulfate, which allowed it to be separated from the androgen receptor. Binding to this protein in ovariectomized female monkeys did not disappear with extended incubation at 4 degrees C, suggesting greater stability or a higher capacity. The function of this protein is not known, but both triamcinolone acetonide and contraceptive progestins appeared to displace tritiated mibolerone that was bound to it. This high-capacity binding of mibolerone interferes in the assessment of androgen receptor levels in these females unless it is eliminated. The synthetic androgen methyltrienolone does not bind to this protein and is a better choice for defining binding to the androgen receptor in these tissues.

Ammonium Sulfate↗

Extracellular glutamate: on-line monitoring using microdialysis coupled to enzyme-amperometric analysis.

An enzyme-amperometric detector cell is described for flow analysis of glutamate in dialysate emerging from an implanted microdialysis probe. Its small size allows it to be placed within a few centimetres of the animal preparation, reducing the delay for data acquisition to around 2 min. The selectivity is provided by glutamate oxidase, immobilised with glutaraldehyde on surfaces adjacent to the 3-electrode system. A film of 1,2-diaminobenzene, electropolymerized on the platinum working electrode, eliminates interference from ascorbic acid and other endogenous electroactive compounds. The high sensitivity (< 0.5 mumol/l) and fast response time of the cell (90% of maximum response in 30 s) make it particularly suitable for investigating conditions that produce rapid changes in brain extracellular glutamate. This is illustrated by monitoring changes in extracellular glutamate subsequent to cardiac arrest, and K(+)-induced local depolarization.

Amino Acid Oxidoreductases↗

Noradrenergic vasorelaxation of porcine coronary arteries is enhanced by direct, acute exposure to 17 beta-estradiol.

1. We tested whether responses of isolated coronary arteries to adrenergic agents are altered by overnight (18-22 hr) or acute exposure to physiological levels of 17 beta-estradiol. 2. Sensitivity to relaxation by norepinephrine (-log M ED50) was enhanced significantly in isolated arteries after acute exposure to 10(-9) M 17 beta-estradiol. Neither alpha-adrenergic contraction to norepinephrine, nor beta-adrenergic relaxation to isoproterenol was affected by acute exposure to 17 beta-estradiol. 3. Responses of coronary arteries to relaxation or contraction by norepinephrine, as well as relaxation by isoproterenol, were not altered by overnight incubation with 17 beta-estradiol or by removal of the endothelium. 4. We conclude that relaxation of coronary arteries by norepinephrine is enhanced by acute, direct exposure to physiological levels of 17 beta-estradiol. This enhancement does not result from effects of estradiol to suppress alpha-adrenergic contraction to norepinephrine or increase coronary beta-adrenergic receptor sensitivity.

Animals↗

Contribution of cerebrovascular parasympathetic and sensory innervation to the short-term control of blood flow in rat cerebral cortex.

In two groups of normotensive rats anaesthetised with halothane, either the nasociliary nerve (NCN) or the NCN and parasympathetic (PS) fibres together (NCN-PS) were functionally blocked at the right ethmoidal foramen. Blocking was achieved reversibly and repeatedly using a cooling probe. Cortical regional CBF (rCBF) was measured bilaterally using laser-Doppler probes. In Group 1, bilateral common carotid occlusion (CCO) was applied for 1 min both with and without block. In Group 2, CCO was applied permanently followed by stages of controlled haemorrhagic hypotension to deepen the ischaemia and the block applied at each stage. In Group 1, during CCO, rCBF was unaffected by blocking NCN-PS. However, during the transient postocclusive hyperaemia, blocking NCN-PS, but not NCN alone, significantly increased right side rCBF. In Group 2 and in Group 1 in the absence of CCO (normotension), rCBF was unaffected by blocking either set of fibres. We conclude that neither NCN nor PS fibres contribute to the tonic level of rCBF or to its autoregulatory control, but PS fibres conduct impulses tending to resolve postischaemic hyperaemia. We suggest that a subpopulation of PS fibres containing neuropeptide Y is activated under conditions of supernormal rCBF.

Afferent Pathways↗

Urinary schistosomiasis associated with hepatitis C virus infection.

We studied 26 adult patients referred for cystoscopy: 13 consecutive patients with schistosome ova on bladder biopsy and antibodies to Schistosoma species in serum were classified as having urinary schistosomiasis, while 13 consecutive patients without schistosome ova on bladder biopsy and who were negative for antibodies to Schistosoma species in serum served as controls. Nine of 13 patients (70%) and none of 13 controls (p < 0.0005) had antibodies to hepatitis C virus in serum (anti-hepatitis C virus). All controls and patients who were negative for anti-hepatitis C virus had normal serum alanine aminotransferase levels, while 2 of 9 (22%) positive for anti-hepatitis C virus had elevated levels. Our study shows that patients with urinary schistosomiasis are at high risk for anti-hepatitis C virus positivity and that some of them may have active liver disease. Therefore, it is imperative to screen patients with urinary schistosomiasis for associated hepatitis C virus infection and liver disease.

Adult↗

Estrogen pretreatment directly potentiates endothelium-dependent vasorelaxation of porcine coronary arteries.

We tested whether vasorelaxation of coronary arteries is altered after overnight (18-22 h) exposure to physiological levels of 17 beta-estradiol. Ring segments of left circumflex coronary artery from six female and six castrated male pigs were incubated in vials of sterile Dulbecco's modified Eagle's medium with 1 nM 17 beta-estradiol, 1 nM 17 beta-estradiol + 10 nM tamoxifen, 1 nM 17 alpha-estradiol, or estrogen vehicle (ethanol) under normoxic conditions in an O2-CO2 incubator at 37 degrees C for 18-22 h. Coronary rings, with and without endothelium, were then suspended in vessel baths for measurement of isometric force. Vasorelaxation responses to the calcium ionophore A-23187, ADP, and nitroglycerin were examined in the rings after prostaglandin synthesis blockade and precontraction with U-46619. Sensitivity to A-23187 (-log M concentration required for 50% of maximal relaxation) was significantly enhanced in coronary rings with endothelium from females and castrated males when rings were incubated with 17 beta-estradiol but not when they were incubated with 17 alpha-estradiol or 17 beta-estradiol+tamoxifen. Acute (2h) exposure of coronary arteries to 1 nM 17 beta-estradiol did not alter responses to A-23187. 17 beta-Estradiol (1 nM) was not itself directly vasoactive in coronary arteries with or without prior incubation with the steroid. Vasorelaxation of rings with and without endothelium to ADP and nitroglycerin was not significantly different among the treatment groups. Relaxation to A-23187, but not ADP, was abolished by removal of the endothelium or exposure to 100 microM NO2-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Acute sporadic hepatitis E in Kuwait.

Fifty-seven adult patients with acute hepatitis and 34 comparison patients without liver disease were evaluated using a newly developed Western blot assay for IgM antibody to hepatitis E virus. The mean age of patients with hepatitis was 32 years (range, 18-55 years); 88% were male. Among patients with acute hepatitis, hepatitis A (anti-HAV IgM positive) was diagnosed in two (4%), hepatitis B (anti-HBc IgM positive) in three (5%), and hepatitis E (anti-HEV IgM positive) in 34 (60%). One hepatitis patient had CMV IgM, another had EBV IgM, and 16 others (28%) were negative for all serologic markers of acute viral hepatitis. No patient with acute hepatitis A or B and none of the comparison patients without acute hepatitis had anti-HEV IgM. All but one case of acute hepatitis E were found among expatriates of Asian origin, and acute hepatitis E was associated significantly with recent travel to the Indian subcontinent. These data suggest that acute hepatitis E is common among foreign workers in Kuwait but that little HEV transmission is occurring directly in Kuwait.

Acute Disease↗

Anti-HCV-positive cirrhosis associated with schistosomiasis.

Hepatosplenic schistosomiasis is occasionally associated with cirrhosis and progressive hepatic decompensation. The aim of the present study was to determine the prevalence of antibody to hepatitis C virus in patients with schistosomiasis and cirrhosis. The prevalence of anti-HCV was studied in 12 consecutive cases of schistosomiasis associated with biopsy proven cirrhosis. All patients had a past history of schistosomiasis and high titers of schistosomal antibodies in serum (1:32 to 1:4096). Five of the 12 patients had hepatic catheterization and were found to have sinusoidal involvement with corrected sinusoidal pressures ranging from 19 to 23 mm Hg. Four had ascites, six had pedal edema, and eight had peripheral signs of chronic liver disease in the form of palmar erythema, spider nevi, and/or gynecomastia. Ten of the 12 cases (83%) were repeatedly positive for anti-HCV/ELISA. These results suggest that when patients with schistosomiasis develop cirrhosis, associated hepatitis C virus infection should be suspected.

Adult↗