Israel Medical Association Journal

Background: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.

Background: A high total plasma homocysteine level is an independent risk factor for cardiovascular and cerebrovascular disease, but the evidence connecting plasma tHcy level with hypertension is inconsistent.

Objective: To determine the association between plasma tHcy level and some common risk factors for cerebrovascular disease (recurrent  stroke, diabetes mellitus, hypertension, ischemic heart disease and hyperlipidemia) in patients presenting with primary or recurrent acute ischemic strokes.

Methods: This retrospective cross-sectional chart analysis was conducted in a university-affiliated referral hospital. During an 18 month period we identified 113 acute ischemic stroke patients (mean age 71.2), 25 of whom had a recurrent stroke. Plasma tHcy[1] level, obtained 2–10 days after stroke onset, was determined by the high performance liquid chromatography method with fluorescence detection. A multivariate logistic regression model was used to determine the independent relationship between each potential risk factor and tHcy level above or below the 75th percentile.

Results:  Hypertension was more frequent among patients with plasma tHcy level above than below the 75th percentile (51.7% vs. 80.8%, respectively, P = 0.012). After adjusting for demographic and clinical variables, the odds ratio for recurrent stroke and hypertension, with tHcy above or below the 75th percentile, was 3.4 (95% confidence interval 1.01–10.4, P = 0.037) and 4.02 (95% CI[2] 1.2–13.9, P = 0.028), respectively.

Conclusions: A high plasma tHcy level is associated with history of hypertension and recurrent stroke among patients presenting with acute ischemic stroke. These results were independent of other risk factors such as atrial fibrillation, diabetes and hyperlipidemia. Hypertensive stroke patients with hyperhomocysteinemia should be identified as high risk patients as compared to non-hypertensive stroke patients, and may warrant more vigorous measures for secondary prevention.

Background: Cystic fibrosis is no longer a terminal illness of childhood and mean survival is now over 30 years. Adult patients with atypical CF[1] are increasingly being diagnosed. In Israel, all patients are still followed in pediatric centers.

Objectives: To describe our experience with adult CF, stressing the importance of adult-related health and psychosocial issues.

Methods: Twenty-five CF patients aged 20–50 years, constituting 44% of the 57 patients followed at our center, were analyzed for pulmonary and extrapulmonary features and management.

Results: Nineteen were diagnosed as children and 6 as adults. Nineteen were pancreatic-insufficient and 6 were pancreatic-sufficient, including 5 diagnosed as adults. Pulmonary status was usually stable, with forced expiratory volume in 1 second 66.3 ± 21% (mean ± SD) and no difference between pancreatic-sufficient and insufficent patients. The latter had more hemoptysis, Pseudomonas infection, intestinal obstruction, liver disease and diabetes. Two patients died of malignancy and two of advanced lung disease. A majority received continuous inhaled and oral antibiotics, bronchodilators, Dnase, physiotherapy and periodic home intravenous antibiotics. Psychosocial functioning was excellent: 60% were employed, 36% were married and 40% had children (none with CF). Patients diagnosed as adults had mild multisystem disease or isolated severe lung disease.

Conclusions: CF adults generally have a good quality of life. Advances in understanding the CF defect and a plethora of new treatment modalities bode well for the future. Patients must be maintained in optimal condition to reap the benefits, and there is an urgent necessity for adult physicians to develop expertise in CF.

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Background: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel cystinuria is especially common among Libyan Jews who suffer from non-type I disease.

Objectives: To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.

Methods: Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.

Results: Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients’ urinary pH. Eleven of the unaffected Libyan Jewish controls were found heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584+3 del AAGT mutation was not found in any of the Libyan Jewish controls.

Conclusion: Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.
 

Background: The mainstay of therapy for acute cholecystitis is cholecystectomy, which has a mortality of 14–30% in high risk patients. An alternative approach in patients suffering from acute cholecystitis with contraindications to emergency surgery is percutaneous cholecystostomy.

Objective: To evaluate the efficacy and safety of percutaneous cholecystostomy as the initial treatment of acute cholecystitis in high risk patients.

Methods: Eighty consecutive patients (42 men, 38 women) underwent ultrasound-guided percutaneous cholecystostomy over a 5 year period. Sixty-five patients suffered from acute calculous cholecystitis, 4 patients had acalculous cholecystitis, and 11 patients had sepsis of unknown origin.

Results: Sixty-eight patients improved after the percutaneous gallbladder drainage, 10 patients died from co-morbid disease and 2 patients died from biliary peritonitis. During a 1 year follow-up, 32 of the patients underwent interval cholecystectomy, 4 additional patients died from a co-morbid disease, 18 patients did not suffer from any gallbladder symptoms, and 14 were lost to follow-up.

Conclusions: Percutaneous cholecystostomy is an effective contribution to the treatment of acute cholecystitis in high risk patients.

Background: Obesity is among the well-established risk factors for cardiovascular morbidity and mortality. However, the exact mechanisms are not well understood. Low concentrations of vitamins (fat soluble antioxidants and B vitamins) are linked to accelerated atherosclerosis through increased oxidative stress and homocysteine.

Objective: To compare plasma antioxidant vitamins (carotenoids and vitamin E), B vitamins (folic acid and B12) and homocysteine – all linked to increased cardiovascular morbidity – between patients with severe obesity and lean control subjects.

Methods: We investigated plasma carotenoids, vitamin E, folic acid, B12, and homocysteine in 25 obese patients and their age-matched controls (body mass index 38 ± 3 vs. 21 ± 2 kg/m²), respectively), related to BMI[1] and plasma insulin.

Results: Patients with obesity had normal B vitamins and a non-significant decrease in plasma homocysteine as compared to controls (9.4 ± 2.6 vs. 11.4 ± 4.8 mmol/L, P = 0.07). There was a significant decrease in both plasma carotenoids and vitamin E (0.69 ± 0.32 vs. 1.25 ± 0.72 and 24 ± 10 vs. 33 ± 14 mg/ml, respectively; P < 0.01). Both vitamins were inversely related to BMI and plasma insulin, which was significantly increased in patients with obesity (22 ± 21 vs. 6 ± 2 mU/ml, P < 0.01).

Conclusions: Obese patients with BMI above 35 kg/m² show low plasma antioxidants (carotenoids and vitamin E). This may result in increased oxidative stress and consequently enhanced atherosclerosis in these patients.

Background: The mortality rate for cholecystectomy for acute cholecystitis in the elderly is 10% in low risk patients and increases threefold in high risk patients. Ultrasound-guided percutaneous transhepatic cholecystostomy may serve as a rapid and relatively safe tool to relieve symptoms of sepsis and decrease gallbladder distension.

Objective: To determine the safety and effectiveness of PTC[1] in the treatment of acute cholecystitis in elderly debilitated high risk patients.

Methods: The study sample included 10 patients aged 63–88 (mean 77.6 years) with clinical and sonographic signs of acute cholecystitis for more than 48 hours (fever, white blood cells > 12,000/mm³, positive Murphy sign and distended gallbladder) who underwent ultrasound guided PTC. All had severe underlying disease (coronary heart disease, renal failure, chronic obstructive pulmonary disease, and others) that places them at high risk for surgical intervention.

Results: Eight patients showed rapid regression of the clinical symptoms following PTC drainage. One patient, with bacterial endocarditis, was febrile for 5 days after catheter insertion, but with rapid resolution of the biliary colic and sepsis. One patient died from perforation of the gallbladder and small bowel. PTC catheters were withdrawn 3–25 days after the procedure, and the patients remained free of biliary symptoms. Two patients underwent successful elective cholecystectomy 3 weeks later.

Conclusion: PTC may be a safe and effective treatment for high risk elderly patients with acute cholecystitis. It can be followed by elective cholecystectomy if the underlying condition improves, as soon as the patient stabilizes and no sepsis is present, or by conservative management in high surgical-risk patients.

Background: Carcinoma of the gallbladder is diagnosed in 0.3–1.5% of all cholecystectomy specimens.

Objectives: To establish the overall rate of gallbladder carcinoma and unexpected gallbladder carcinoma based on our experience.

Methods: We retrospectively evaluated all consecutive cholecystectomies performed in our ward during a 6 year period in order to determine the incidence of gallbladder carcinoma and to identify common characteristics of this particular group of patients.

Results: Of the 1,697 cholecystectomies performed in our ward during the 6 years, gallbladder carcinoma was diagnosed in six patients (0.35%), but was not suspected prior to surgery in any of them. In accordance with the literature, the occurrence in women (5/6) was higher than in men (1/6). The mean age was 70 years (range 55–90). The most common symptom was abdominal pain; the majority (5/6) had cholelithiasis, and the pathologic report confirmed the diagnosis of adenocarcinoma in all six patients.

Conclusions: The overall incidence of unsuspected gallbladder carcinoma in our series was 0.35%. We could not find any common characteristics for this particular group of patients when compared to patients with non-malignant pathology.