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: Non-gonococcal urethritis is the most common clinical diagnosis for men seeking care at sexually transmitted disease clinics.

Objective: To identify the pathogens involved in NGU[1] among males attending an Israeli STD clinic.

Methods: During 19 months spanning September 1996 to July 1998 we investigated a cohort of 238 male patients attending the Bnai Zion Medical Center STD[2] clinic with a clinical presentation of urethritis. Intraurethral swab specimens were tested for Neisseria gonorrhea, Ureaplasma urealyticum, Mycoplasma hominis, and Trichomonas vaginalis by culture and for herpes simplex virus by antigen detection. First voiding urine for Chlamydia trachomatis was done by polymerase chain reaction. The specific seropositivities of HSV[3] types 1 and 2 were tested by enzyme-linked immunosorbent assay.

Results: From among 238 males with dysuria or urethral discharge an etiology for urethritis was found for 71 (29.8%). N. gonorrhea was recovered in only three men (4.2%). In the remaining 68 NGU patients C. trachomatis (35/68, 51.5%) and U. urealyticum (31/68, 45.6%) were the most common infecting and co-infecting pathogens (P < 0.0001). M. hominis and T. vaginalis were found in 9/68 (13.2%), and 1 patient, respectively. HSV was recovered from the urethra in 7/68 males (10.3%) – 3 with HSV-1, 2 with HSV-2, and 2 were seronegative for HSV. None of these males had genital lesions. Although a single etiologic agent was identified in 45/68 infected men (66.2%), co-infection was common: 2 organisms in 15 (22%) and 3 organisms in 8 (11.8%).

Conclusion: C. trachomatis and U. urealyticum were the most common infecting and co-infecting pathogens in this cohort of men with NGU. Unrecognized genital HSV infections are common in males attending our STD clinic and symptomatic shedding of HSV occurs without genital lesions. Still, the microbial etiology in this group remains unclear in many patients despite careful microbiologic evaluation.

Background: Familial multiple lipomatosis is an extremely rare disease. The disease usually does not affect the daily life of FML victims, but they may experience difficulty in performing everyday physical tasks if the lipomas are multiple and large. Inheritance is frequently by autosomal dominant transmission, although cases with recessive inheritance have also been reported.

Objectives: To determine the pattern of inheritance of the disease in a family with 83 members spanning three generations.

Methods: A complete family analysis was performed and all surviving members of the family were examined. Laboratory investiga-tions were conducted in those with FML, including serum lipid, cholesterol and glucose levels, white blood cell count, hemoglobin, erythrocyte sedimentation rate, and renal and hepatic function tests.

Results: There were no consanguineous relationships between spouses in the family. The disease was first seen on the neck of the (male) index patient. This patient had 4 sons, 8 daughters and 60 grandchildren. The disease was established in four of his daughters and two of his sons. One of the female grandchildren whose mother has the disease was also affected. The laboratory findings were normal for all patients.

Conclusion: Our findings showed that a) the disease is transmitted by the autosomal dominant route of inheritance; and b) lipomas observed at an early age may be numerous and large, may diffuse, and sometimes have to be excised surgically.
 

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: Elevated fibrinogen, considered an independent risk factor for coronary disease, stratifies an individual as high risk for coronary disease. A risk marker requires little intra-individual variability during a long period.

Objectives: To establish intra-individual variability of fibrinogen levels in patients with coronary disease.

Methods: We investigated fibrinogen levels prospectively in four blood samples drawn from 267 patients with a history of arterial disease (arterial group) and from 264 patients with cardiac valve replacements (valvular group). The samples were taken during the course of 78.7 and 78.8 days from the arterial and valvular groups respectively.

Results: Marked intra-individual dispersion with a reliability coefficient of 0.541 was found in the arterial group and 0.547 in the valvular group. The Bland-Altman test showed low probability to obtain similar results in different samples from the same individual. These results show large intra-individual variability, with similarities in the arterial as well as in the valvular group.

Conclusions: It is not possible to stratify a patient by a specific fibrinogen dosage.

Systemic infection or inflammation causes a decrease in intestinal iron absorption and impairs the release of recycled iron from macrophages. Decreased availability of iron may deny this essential element to invading pathogens and may inhibit their multiplication and other metabolic processes but also results in anemia of chronic disease. This article reviews recent discoveries that shed light on the regulation of iron metabolism during infection and iron overload, and point to the central role of a newly discovered peptide, hepcidin. Evidence to date indicates that hepcidin is a negative regulator of intestinal iron absorption, placental iron transport, and the release of iron from macrophages that recycle iron from senescent red cells. It may also be the central mediator of iron sequestration during infections and inflammatory states and the mediator of anemia of chronic disease. Rapid progress in this area is a good example of the beneficial effects of improvements in peptide analysis and chemistry, advances in genomics, and the increasing use of transgenic mice to determine the function of newly discovered genes and proteins.

The etiology of inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided limited insight into disease pathogenesis. There is ample evidence that these diseases are in part the result of genetic predisposition. The early search for candidate genes focused on genes involved in the regulation of immune function.

Recent genome wide searches reported several susceptibility loci for Crohn’s disease and ulcerative colitis. The recent identification of the IBD1 gene (NOD2) with mutations that are associated with susceptibility to Crohn’s disease will have a major impact on the understanding of the genetics of this disease.