Israel Medical Association Journal

Background: Free bowel perforation is one of the indications for emergency surgery in Crohn’s disease. It is generally accepted that 1–3% of patients with Crohn’s disease will present with a free perforation initially or eventually in their disease course.

Objective: To evaluate the incidence and treatment results of free perforation in patients with Crohn’s disease and based on our experience to suggest recommendations.

Methods: Between 1987 and 1996, 160 patients with Crohn's disease were treated in our department and were followed for a mean period of 5 years.

Results: Of the 83 patients (52%) requiring surgical intervention, 13 (15.6%) were operated due to free perforation. The mean age of the perforated CD[1] was 33 ± 12 years and the mean duration of symptoms to surgery was 6 years. The location of the free perforation was the terminal ileum in 10 patients, the mid-ileum in 2 patients, and the left colon in 1 patient. Surgical treatment included 10 ileocecectomies, 2 segmental resections of small bowel, and resection of left colon with transverse colostomy and mucus fistula in one patient. There was no operative mortality. Postoperative hospital stay was 21 ± 12 days (range 8–55 days). All patients were followed for 10–120 months (mean 58.0 ± 36.7). Six patients (42%) required a second operation during the follow-up period.

Conclusion: The incidence of free perforation in Crohn’s disease in our experience was 15.6%. We raise the question whether surgery should be offered earlier to Crohn’s disease patients in order to lower the incidence of free perforation

Background: Fractures of the stemum may be associated with major injuries to thoracic organs, with serious consequences.

Objective: To assess the hospital course of patients diagnosed with isolated sternal fracture.

Methods: We reviewed 55 medical records of patients who were admitted with isolated sternal fracture to the emergency department during the period from January 1990 through August 1999.

Results: Fifty-one patients were involved in motor vehicle accidents, and the remainder sustained the injury as a result of a fall. Lateral chest X-ray upon admission was diagnostic in the majority of these patients (n=53). Electrocardiography (n=52) was abnormal in four patients – old myocardial infarction (n=1), non-specific ST-T changes (n=3). Cardiac enzymes (creatine-kinase-MB, n=42) were pathologically elevated in five patients. Echocardiography, performed in patients with ECG[1] abnormalities and/or elevated myocardial enzymes (n=7), was normal in these patients as well as in another 18 patients. There were no intensive care unit admissions or arrhythmias during the hospital stay, which ranged from 6 hours to 6 days (mean 2.3 ± 1.3 days, median 2 days).

Conclusion: Our findings support the view that patients with isolated sternal fracture, who have no abnormality in ECG and cardiac enzymes during the early hours after injury, are expected to have a benign course and can be discharged home from the emergency room within the first 24 hours.

Background: Complementary medicine is gaining popularity, yet medical school curricula usually ignore it.

Objectives: To determine whether senior medical students are interested in learning principles of complementary or alternative medicine, to check their degree of familiarity with it, and to suggest a format for such studies in the medical curriculum.

Methods: Senior medical students (n = 117) were surveyed by an anonymous questionnaire.

Results: Seventy-nine percent of the senior medical students were interested in studying complementary or alternative medicine in medical school, and 65% were interested in applying these techniques to treat patients. Eighty-seven percent of students were familiar with some techniques of complementary medicine.

Conclusions: Senior medical students are interested in studying complementary and alternative medicine in medical school and in applying these techniques in practice.
 

Background: Domestic violence is considered a major risk factor in pregnancy.

Objectives: To assess the prevalence of different kinds of abuse (physical, psychological, sexual) of pregnant as compared to non-pregnant women, and to identify demographic risk factors for physical abuse that characterize the woman and her partner.

Methods: A cross-sectional survey was conducted in 270 women seeking gynecologic care at women health centers in northern Israel. Information was collected by means of a standardized questionnaire administered via phone, and addressed demographic data, interaction with the partner, and reporting of physical abuse. All information was obtained from the respondents (including information about her partner).

Results: Four abuse scores were computed: severe physical attack, minor physical attack, psychological abuse, and sexual coercion. Psychological abuse was found to be the most prevalent (24%), followed by minor and severe physical attack (17% and 8.1%, respectively), and sexual coercion (5.6%). Physical attacks related to pregnancy (directed at the abdomen) occurred in 5.4% of the pregnant women. There was no significant difference in the prevalence of the different types of abuse between pregnant and non-pregnant women. Physical attack was associated with socioeconomic status, work status, and degree of religiosity.

Conclusion: Pregnant women were at a similar risk for abuse as non-pregnant women in all abuse categories. Predictors for abuse – socioeconomic status and religiosity – are reviewed primarily in a cultural context.

Background: Gaucher disease results from the accumulation of glucosylceramide (glucocerebroside) in tissues of affected persons. Patients sharing the same genotype present with widely varying degrees of lipid storage and of clinical manifestations.

Objectives: To determine whether variation in the glucosylceramide synthase (UDPGlucose ceramide glucosyltransferase) gene, which encodes the enzyme that regulates the synthesis of glucocerebroside, could account for the variability and clinical manifestations.

Methods: Patients homozygous for the 1226G (N370S) mutation, the most common in the Ashkenazi Jewish population, were investigated. The exons and flanking sequences of the gene were sequenced using DNA derived from five very mild Gaucher disease patients and four patients with relatively severe Gaucher disease. Results: One polymorphism was found in the coding region, but this did not change any amino acids. Seven other polymorphisms were found in introns and in the 5' untranslated region. Some of these were single nucleotide polymorphisms; others were insertions. The mutations appear to be in linkage equilibrium and none were found with a significantly higher frequency in either severe or mildly affected individuals.

Conclusions: Mutations in the glucosylceramide synthase gene do not appear to count for the variability in expression of the common Jewish Gaucher disease mutation.
 

Background: Decreased heparan sulfate proteoglycan content of the glomerular basement membrane has been described in proteinuric patients with diabetic nephropathy. Heparanase is an endo-b-D-glucuronidase that cleaves negatively charged heparan sulfate side chains in the basement membrane and extracellular matrix.

Objectives: To investigate whether urine from type I diabetic patients differs in heparanase activity from control subjects and whether resident glomerular cells could be the source of urinary heparanase.

Methods: Using soluble ³⁵S-HSPG[1] and sulfate-labeled extracellular matrix we assessed heparanase activity in human glomerular epithelial cells, rat mesangial cells, and urine from 73 type I diabetic patients. Heparanase activity resulted in the conversion of a high molecular weight sulfate-labeled HSPG into heparan sulfate degradation fragments as determined by gel filtration analysis.

Results: High heparanase activity was found in lysates of both epithelial and mesangial cells. Immunohistochemical staining localized the heparanase protein to both glomeruli capillaries and tubular epithelium. Heparanase activity was detected in the urine of 16% and 25% of the normoalbuminuric and microalbuminuric diabetic patients, respectively. Urine from 40 healthy individuals did not posses detectable heparanase. Urinary heparanase activity was associated with worse glycemic control.

Conclusion: We suggest that heparanase enzyme participates in the turnover of glomerular HSPG. Hyperglycemia enhances heparanase activity and/or secretion in some diabetic patients, resulting in the loss of albumin permselective properties of the GBM[2].

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[1] HSPG = heparan sulfate proteoglycan

[2] GBM = glomerular basement membrane

The leukocyte NADPH oxidase catalyzes the reduction of oxygen to O₂- (superoxide) at the expense of NADPH. The O₂- then dismutes to H₂O₂, which serves to oxidize Cl- to HOCl, a potent microbicidal agent that is used by leukocytes to kill invading microorganisms. This oxidation is catalyzed by myeloperoxidase. O₂ is also used to make other microbicidal oxidants, some in reactions with nitric oxide. The oxidase itself is highly complex, consisting of four unique subunits and Rac2. In the resting cell, two of the subunits, p22PHOX and gp91PHOX, are located in the membrane, and the other two, p47PHOX and p67PHOX, are in the cytosol. The electron-carrying components of the oxidase are

located in gp91PHOX; the NADPH binding site is generally regarded to be in gp91PHOX as well, but there is some evidence that it may be in p67PHOX. When the oxidase is activated, p47PHOX is phosphorylated at specific sites, and the cytosolic components plus Rac2 migrate to the membrane to assemble the active oxidase.

The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX[1] itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.

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