An Israeli national survey on ischemic colitis induced by pre-colonoscopy bowel preparation (R1).

Background and study aims: Ischemic colitis (IC) may occur as a complication of colonoscopy. The aim of this study was to characterize patients with IC that occurred after exposure to bowel preparation laxatives, prior to an elective colonoscopy. Patients and methods: A survey among Israeli gastroenterologists. Information was collected regarding individual cases. Results: Eight patients, who developed IC after bisacodyl ingestion that was taken as part of pre-colonoscopy bowel preparation protocol, were reported. In all patients, severe abdominal pain and/or hematochezia started shortly after the ingestion of the first dose of bisacodyl. IC was found in 7 patients during the planned colonoscopy and in 1 patient using computerized tomography. All patients received supportive treatment and recovered. Conclusions: IC induced by bisacodyl is a rare phenomenon. Regardless of being rare, we would advise withholding bisacodyl bowel preparation in elderly subjects with risk factors for IC that are scheduled for a colonoscopy.

Pulmonary valve stenosis and hemophilia A. Report of three cases and discussion of a possible genetic linkage.

We treated three unrelated patients with hemophilia A and congenital pulmonary valve stenosis. In two patients, the occurrence of the cardiac malformation was sporadic and in one familial. The coexistence of hemophilia A and pulmonary valve stenosis might suggest a genetic linkage for both disorders. Review of the literature supports the hypothesis that the inheritance of pulmonary valve stenosis is dominant and X-linked.

Quinidine-induced vasculitis.

Four patients developed nonthrombocytopenic purpura two to three weeks after initiation of quinidine therapy. The skin lesions disappeared and did not recur after cessation of quinidine therapy. Histologic examination revealed leukocytoclastic vasculitis with deposition of C3, IgA, and/or IgM in the small dermal vessels. Since quinidine purpura is usually associated with thrombocytopenia, the possibility of leukocytoclastic vasculitis as an additional cause of purpura is stressed.

Proposed mechanism of the inflammatory attacks in familial Mediterranean fever.

Peritoneal and synovial fluids of patients with familial Mediterranean fever lack a protein that inhibits neutrophil chemotaxis by antagonizing the complement-derived inflammatory mediator C5a. The C5a inhibitor activity was studied with the use of a C5a binding assay where peritoneal fluids were tested for their ability to inhibit recombinant C5a binding to dibutyryl cyclic adenosine monophosphate-induced U937 cells. In contrast to normal peritoneal fluids, those from patients with familial Mediterranean fever contained less than 1% C5a inhibitor activity. Gel filtration and ion exchange chromatography of peritoneal fluids from those patients did not yield any fraction that inhibited C5a binding. We suggest that the serosal tissue of patients with familial Mediterranean fever is devoid of C5a inhibitor activity and that this deficiency may explain in part the local inflammatory episodes characteristic of this disease.

Captopril-associated "pseudocholangitis'. A case report and review of the literature.

Captopril, a competitive inhibitor of angiotensin-converting enzyme, is widely used in the treatment of hypertension and heart failure. Captopril is known to be associated with dermatologic, hematologic, and pulmonary adverse effects. However, hepatotoxicity is extremely rare. A patient with severe cholestatic jaundice induced by captopril is presented. On admission to the hospital, the patient was diagnosed and treated as having cholangitis. Review of the literature showed similar occurrences in other patients. Patients treated with captopril who develop "atypical cholangitis" should be suspected of having captopril-associated liver damage.

Longitudinal prostaglandin E(2) generation in various organs during evolution of experimental portal hypertension.

It has been suggested that the arteriolar vasodilatation and hyperdynamic circulation observed in rats with partial portal vein ligation (PPVL) is caused by increased splanchnic and systemic delivery of vasodilator substances. The aims of our study were to determine organ-specific generation of prostaglandin E(2) (PGE(2)) in rats with PPVL during the evolution of portal hypertension. Rats with PPVL and sham-operated (S) rats were studied in the first, third, fourth and 14th postoperative days. They were anesthetized and splenic pulp pressure and blood pressure were measured. Spleen, colon and lungs were removed and the splenic, pulmonary and mucosal colonic PGE(2) were determined. All PPVL rats developed sequential hemodynamic changes compatible with evolving portal hypertension. Splenic pulp pressure was higher in PPVL rats compared with S rats during all days of the study. Within the group of PPVL the splenic pulp pressure was higher in the first postoperative day and decreased in the ensuing days. No changes in splenic and colonic PGE(2) generation were noted during the study period. Pulmonary PGE(2) generation increased significantly in the first postoperative day in PPVL rats compared with S rats. However, similar increase was observed on the third postoperative day in S rats. PGE(2) probably has no role in splanchnic hemodynamic changes during evolution of portal hypertension. Pulmonary PGE(2) generation may increase as a response to increased portal pressure, or to abdominal surgery.

Overload of iron in the skin of patients with varicose ulcers. Possible contributing role of iron accumulation in progression of the disease.

The brown pigmentation of the skin associated with venous ulceration is caused by increased local iron deposition. Diagnostic x-ray spectrometry, a method based on x-ray fluorescence analysis, was used for the noninvasive determination of iron levels in the skin of patients with venous ulceration. The mean (+/- SEM) iron concentration in the skin around the venous ulcer was elevated, compared with control values of nonulcerated skin (250 +/- 54 vs 128 +/- 39 micrograms) and compared with normal skin from the forearm (250 +/- 54 vs 14 +/- 2.5 micrograms). These data suggest that dermal iron deposition may not be an incidental by-product of increased venous pressure, but may actively perpetuate tissue damage in venous ulcerations.

The contraceptive choice for a Wilson's disease patient with chronic liver disease.

Preserved fertility status is frequently encountered in patients with Wilson's disease, and contraceptive counseling may, therefore, be a relevant issue. Yet, several contraceptive methods can adversely influence the hepatic function, and the efficacy of others may be affected by the liver disease. We describe a patient with Wilson's disease manifested by cirrhosis, portal hypertension, and bleeding esophageal varices who underwent termination of pregnancy at 9 weeks' gestation. Following the procedure, contraceptive advice was sought in order to postpone conception until portal hypertension was controlled and hepatic function improved. Intramuscular depot medroxyprogesterone acetate was administered and tolerated well by the patient. A detailed discussion of the contraceptive options for patients with chronic liver disease, in general, and Wilson's disease, in particular, follows the case report.

PIP: Although the fertility status of women with Wilson's disease may be preserved, contraceptive method choice is complicated by the tendency for some methods to have an adverse effect on hepatic function and, conversely, for liver disease to compromise the efficacy of some contraceptives. This paper presents the case of a 28-year-old woman diagnosed with Wilson's disease at 13 years of age. She presented to an Israeli hospital at 9 weeks' gestational age with bleeding esophageal varices, cirrhosis, and portal hypertension. Although the patient had been oligomenorrheic, with menses every 2-3 months, she had experienced 3 spontaneous first-trimester abortions. Due to the urgent need for a portal decompression shunt procedure and the risk of further bleeding, the patient opted to terminate the current pregnancy. To prevent conception until the patient's liver condition stabilized, she was injected with Depo-Provera and penicillamine treatment was resumed. Although IUDs and estrogen-containing oral contraceptives are relatively contraindicated in women with liver dysfunction, spermicide and barrier contraceptives are highly recommended and progesterone-only preparations can be safely prescribed.

Amiodarone-associated hypothyroidism--a possible cause of digoxin intoxication.

The problem of a possible interaction between amiodarone and digoxin is still unsettled. We have recently treated two patients with digoxin intoxication who had received amiodarone for eight and 36 months respectively. Both developed extreme bradycardia requiring temporary pacemakers. The presence of hypothyroidism was confirmed in both cases by laboratory data. Judging by present knowledge concerning the interaction between amiodarone, thyroid function, and digoxin, it is suggested that digoxin intoxication was not the result of its direct interaction with amiodarone. The possibility that amiodarone-induced hypothyroidism precipitated digoxin intoxication seems to be more plausible. Prevention of digitalis toxicity in amiodarone-treated patients would therefore require monitoring of thyroid function every three to six months. Frequent monitoring of digitalis blood levels is also indicated in patients with amiodarone associated hypothyroidism. Early detection of hypothyroidism and digitalis intoxication is necessary in view of the severity of the course of the disease.

Right ventricular infarction: unusual electrocardiographic and electrophysiological manifestations.

Right ventricular infarction occurs in 19-43% of patients with acute inferior wall infarction (Lorell et al., 1979). Its clinical, hemodynamic, and anatomic features are well known and include associated inferior wall infarction, distended neck veins, clear lung fields, hypotension, and heart block (Cintron et al., 1981; Coma-Canella et al., 1979; Lloyd et al., 1981; Lopez-Sendon et al., 1981; Raabe and Chester, 1978; Rotman et al., 1974). Isolated right ventricular infarction is less frequent and occurs in 2.5-4.6% of autopsy studies of myocardial infarction (Cohn et al., 1974; Erhardt et al., 1976; Wartman and Hellerstein, 1948). This report describes a patient with isolated right ventricular infarction with unusual electrophysiological findings. Her initial electrocardiogram showed atrial escape rhythm with incomplete right bundle-branch block and left posterior hemiblock. Later, she developed atrioventricular (AV) block with supra- and infra-Hisian, "phase 4," conduction defects. The sinus malfunction and high degree AV block persisted over 2 weeks and an atrioventricular sequential pacemaker was implanted. Hymodynamic study showed that her cardiac output was highly dependent on the heart rate and properly timed AV interval, and the pacemaker was programmed accordingly.

[Does incidence of hepatitis A increase during shmitah (the Sabbatical year)?].

In Israel the biblical injunction of the sabbatical year (shmitah) prevails, whereby all Jewish-owned land should lie fallow during every seventh year. Consequently, it is customary for members of the orthodox Jewish community to eat only produce grown by non-Jews (Arabs). Many Arab farmers use sewage water for irrigation and since such water could be infected with hepatitis A virus (HAV), there is concern about the possibility of HAV epidemics during the sabbatical year. We therefore we examined the data of the Israeli Center for Disease Control (ICDC). We found no obvious increase in incidence of viral hepatitis during, nor in the year immediately after, all sabbatical years since 1951. However, the data was not comprehensive as it included only partial information on morbidity from HAV in our Jewish inhabitants. Also, there was no data specific for the orthodox Jewish community, which is especially at risk for HAV from sewage-irrigated vegetables. Irrespective of shmitah, there should be constant effort to prevent HAV infection in Israel.

[Cyclosporin for severe ulcerative colitis].

In recent years there have been numerous reports of successful treatment of resistant ulcerative colitis with cyclosporin. A series of 9 patients with moderate to severe active ulcerative colitis was treated with cyclosporin between September 1993 and October 1994. All 9 had failed to respond to conventional therapy, including salazopyrine and intravenous corticosteroids. They underwent colonoscopy and after contraindications to therapy were ruled out, received intravenous cyclosporin, 4 mg/kg/day for 7-10 days. They were discharged on oral cyclosporin with average serum levels maintained at 200 ng/ml. Response was assessed using the clinical score system of Schroeder et al. 2 out of 9 patients (22%) responded with full clinical remissions lasting more than 6 months. 6 patients had partial responses to the intravenous therapy, but symptoms resumed shortly after its cessation. Factors predicting favorable response to cyclosporin therapy were a shorter duration of disease with a fulminant clinical course. The success rate was less than that reported in the literature, possibly because of comparatively low serum cyclosporin levels. Potential complications of therapy and high cost preclude the routine use of cyclosporin in ulcerative colitis. Larger controlled studies are required to assess its efficacy and safety. Until such studies are available, cyclosporin may be tried in poor surgical risks or those not yet ready psychologically for total colectomy.

Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation.

BACKGROUND AND PURPOSE: We aimed to demonstrate the involvement of 5-HT(1A) receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice. EXPERIMENTAL APPROACH: Cannabidiol (5 mg x kg(-1); i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight-arm maze and the open field tests respectively. Hippocampi were analysed by RT-PCR for expression of the genes for tumour necrosis factor-alpha receptor 1, brain-derived neurotrophic factor (BDNF) and 5-HT(1A) receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist (0.5 mg x kg(-1)), was co-administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and bilirubin. KEY RESULTS: Cannabidiol improved cognition and locomotion, which were impaired by BDL, and restored hippocampal expression of the tumour necrosis factor-alpha receptor 1 and the BDNF genes, which increased and decreased, respectively, following BDL. It did not affect reduced 5-HT(1A) expression in BDL mice. All the effects of cannabidiol, except for that on BDNF expression, were blocked by WAY-100635, indicating 5-HT(1A) receptor involvement in cannabidiol's effects. Cannabidiol did not affect the impaired liver function in BDL. CONCLUSIONS AND IMPLICATIONS: The behavioural outcomes of BDL result from both 5-HT(1A) receptor down-regulation and neuroinflammation. Cannabidiol reverses these effects through a combination of anti-inflammatory activity and activation of this receptor, leading to improvement of the neurological deficits without affecting 5-HT(1A) receptor expression or liver function. BDNF up-regulation by cannabidiol does not seem to account for the cognitive improvement.

The clinical spectrum of cytomegalovirus colitis in adults.

BACKGROUND: Colonic cytomegalovirus reactivation rarely occurs in adults without inflammatory bowel disease or a known immunosuppressive state. AIM: To describe our experience with such patients. METHODS: All consecutive admissions of patients with possible cytomegalovirus colitis, between 1995 and 2006, were reviewed retrospectively. RESULTS: Nineteen patients were studied. Most of the patients were elderly with multiple co-morbidities. Three main forms of disease presentation were recognized: acute diarrhoea, chronic diarrhoea and lower gastrointestinal bleeding. Colonic mucosal intranuclear inclusion bodies were found in 12 patients. Thirteen patients had cytomegalovirus viraemia (either by polymerase chain reaction and/or by white blood cell-cytomegalovirus antigenaemia test). Ganciclovir therapy was given to only eight patients; only five of these patients survived. The other subgroup of 11 patients received only supportive therapy. Most of the patients from this subgroup had a prolonged and complicated hospital course; only nine patients survived. Follow-up colonoscopies were performed only in five patients (out of the 14 patients who survived). In four of these patients, chronic mucosal inflammatory changes were noted. CONCLUSIONS: Cytomegalovirus colitis occurs rarely in adult individuals. The disease may have various and multiple acute and/or chronic clinical manifestations. Clinical awareness of this condition is needed.

Ascites in Nephrotic syndrome. Incidence, patients' characteristics, and complications.

The pathophysiology of ascites in patients with cirrhosis is complex and includes increases in hepatic sinusoidal pressure, the formation of hepatic and splanchnic lymph, renal sodium retention, and hypoalbuminemia. However, the role of hypoalbuminemia in ascites formation is controversial. Evaluating ascites in hypoalbuminemic patients with nephrotic syndrome could add to our understanding of the role of hypoalbuminemia in ascites development. We conducted a retrospective analysis of 52 adults and 21 children with nephrotic syndrome who were hospitalized in the Hadassah University Hospital on Mount Scopus during 1981-1994. There was a significant difference in the prevalence of ascites between pediatric (52%) and adult patients (23%) (p = 0.024). Pediatric patients had lower serum albumin levels than adults (1.70 +/- 0.08 g/dl vs. 2.10 +/- 0.07 g/dl, p = 0.001). Adult patients with ascites had lower serum albumin levels than adult patients without ascites (1.80 +/- 0.13 g/dl vs. 2.20 +/- 0.07 g/dl, p = 0.01). This difference was not found in pediatric patients. Temporary fluctuations in liver enzymes (up to four times the upper limit of normal for transaminases) were evident in five patients from the pediatric group with ascites, whereas all pediatric patients without ascites had completely normal liver enzymes (p = 0.035). Among the 12 adult patients with ascites, seven had liver disease (three with cirrhosis and four with amyloidosis), and two had right-sided congestive heart failure. Among the 40 adult patients without ascites, only four had liver disease (amyloidosis). The plasma albumin levels of the patients with amyloidosis without ascites were higher than patients with amyloidosis with ascites (1.90 +/- 0.10 g/dl vs. 1.50 +/- 0.07 g/dl, p = 0.03). Two patients with nephrotic syndrome and ascites (one without liver disease) had episodes of spontaneous bacterial peritonitis. Ascites in nephrotic syndrome is more common in children than in adults. Although in most pediatric patients ascites formation is probably a common manifestation of the general fluid retention, in most adult patients with nephrotic syndrome ascites can be attributed to both hypoalbuminemia and the presence of liver disease or congestive heart failure, with increased hepatic sinusoidal pressure.

Hypersensitivity reactions to drugs in acquired immunodeficiency syndrome.

We describe a patient with AIDS in whom recurrent drug eruption and fever following administration of various unrelated agents developed. Previous drug exposure was uneventful. A possible mechanism for this phenomenon is described.

AIDS and oropharyngeal candidiasis.

Oropharyngeal candidiasis occurred in a previously healthy young Israeli homosexual male. Additional symptoms included persistent diarrhea, weight loss, fever, generalized lymphadenopathy and peripheral neuropathy. Immunologic studies revealed lymphopenia with reversed T-helper/T-suppressor cells ratio and antibodies to human immunodeficiency virus, all compatible with the diagnosis of subclinical AIDS. Repeated courses of antimonilial treatment failed to eradicate the oropharyngeal lesions. The clinical picture of AIDS, particularly its oral manifestations, is described. The diagnostic and prognostic implications of oropharyngeal candidiasis as a presenting sign of the disease are discussed. In addition, precautionary measures that should be taken when treating persons infected with HIV are described.