Israel Medical Association Journal

Background: It is a challenge to diagnosis Clostridium difficile colitis.

Objectives: To determine, among patients who developed nosocomial diarrhea, whether serum procalcitonin (PCT) can distinguish between C. difficile toxin (CDT)-positive and CDT-negative patients.

Methods: This prospective study included 50 adults (>18 years) who developed diarrhea during hospitalization, 25 with a positive fecal test for CDT (study group) and 25 CDT negative (control group).

Results: Baseline demographic and underlying illnesses were similar in both groups. Duration of diarrhea was 6 ± 4 days and 3 ± 1 in the study and control groups, respectively (P = 0.001). Mean blood count was 20 ± 15 and 9.9 ± 4, respectively (P = 0.04). CRP level was higher in the study than in the control group (10.9 ± 7.4 and 6.6 ± 4.8, P = 0.028). PCT level was higher in the study group (4.4 ± 4.9) than the control group (0.3 ± 0.5, P = 0.102). A PCT level > 2 ng/ml was found in 7/25 patients (28%) and 1/25 (4%), respectively [odds ratio 9.33, 95% confidence interval (0.98 to 220), P = 0.049]. Multivariate analysis showed that only duration of diarrhea and left shift of peripheral leucocytes were significant indicators of CDT (P = 0.014 and P = 0.019, respectively). The mortality rate was 12/25 (48%) vs. 5/25 (20%), respectively (P = 0.04).

Conclusions: We found a non-significant tendency to higher PCT levels in patients with CDT-positive vs. CDT-negative nosocomial diarrhea. However, a PCT level > 2 ng/ml may help distinguish between these patients.

Background: Osler taught that splenic infarction presents with left upper abdominal quadrant pain, tenderness and swelling accompanied by a peritoneal friction rub. Splenic infarction is classically associated with bacterial endocarditis and sickle cell disease.

Objectives: To describe the contemporary experience of splenic infarction.

Methods: We conducted a chart review of inpatients diagnosed with splenic infarction in a Jerusalem hospital between 1990 and 2003.

Results: We identified 26 cases with a mean age of 52 years. Common causes were hematologic malignancy (six cases) and intracardiac thrombus (five cases). Only three cases were associated with bacterial endocarditis. In 21 cases the splenic infarction brought a previously undiagnosed underlying disease to attention. Only half the subjects complained of localized left-sided abdominal pain, 36% had left-sided abdominal tenderness 31% had no signs or symptoms localized to the splenic area, 36% had fever, 56% had leukocytosis and 71% had elevated lactate dehydrogenase levels. One splenectomy was performed and all patients survived to discharge. A post hoc analysis demonstrated that single infarcts were more likely to be associated with fever (20% vs. 63%, p < 0.05) and leukocytosis (75% vs. 33%, p = 0.06)

Conclusions: The clinical presentation of splenic infarction in the modern era differs greatly from the classical teaching, regarding etiology, signs and symptoms. In patients with unexplained splenic infarction, investigation frequently uncovers a new underlying diagnosis. 

Background: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense pre­clinical and clinical research in recent years. Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cell population. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma. However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothetial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer.

Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature.

Methods: As a model for this approach we delivered concentrated retroviral vectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir). was evaluated.

Results: No acute or long-term toxicity was observed after intraarterial infusion of the vector. Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature. This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain.

Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising new gene therapy strategies for the treatment of brain tumors.

Background: Familial dysautonomia is a genetic disease in which there is a defect in the autonomic and sensory nervous systems. These systems have a major role in the reproductive system.

Objective: To study the inter-relationship of autonomic and sensory dysfunction and gynecological function.

Methods: The gynecological histories of 48 women with familial dysautonomia were analyzed retrospectively. Their mean age was 22.25 years (range 12-47). Thirty-three women (65%) were available for further questioning and investigation of hormonal status.

Results: Menarche had occurred in 32 of the 48 (66.7%). Their average age of menarche was significantly delayed as compared to their unaffected mothers (15.5 vs. 13.6 years respectively, P=0.002). The most prominent finding was the very high prevalence, 81.2%, of premenstrual symptoms. Seven of 26 had premenstrual syndrome symptoms of dysautonomic crisis. Blood sex hormone levels were normal in 27 of the 33 patients studied. None reached natural menopause. One patient had adenomyosis, and another, dysgerminoma. Three patients became pregnant and delivered healthy infants.

Conclusion: Menarche is delayed in women with FD, and the physiological monthly hormonal fluctuations may disturb autonomic homeostasis sufficiently to precipitate dysautonomic crisis.