Israel Medical Association Journal

Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Background: A mass influx of immigrants from the former Soviet Union to western countries and Israel followed the demise of the Soviet Bloc at the beginning of the 1990s. It was expected that these immigrants would have a higher morbidity and mortality rate similar to that in Russia.

Objectives: To measure and compare self-reported diseases, subjective health and health services utilization of a representative sample of veteran Israeli Jews and immigrants from the former USSR.

Methods: A cross-sectional survey of Israeli adults was performed by telephone interviews. The survey included 793 Israeli Jews, of whom 124 were immigrants from the former USSR who arrived in Israel after 1989 (response rate 52%).

Results: The immigrants reported a higher rate of diseases and sub-optimal health after adjustment for other variables. However, no excess in health services utilization was reported. A time trend of reporting sub-optimal subjective health was observed: the longer the immigrants spent in Israel the more their reporting patterns resembled those of immigrants who arrived in Israel before 1970. Those who arrived after 1994 more frequently reported having a chronic disease.

Conclusions: Acculturation seems to have been the main effect on the immigrants' health, together with a healthy migrant effect at the beginning of the 1990s. The immigrants' health was worse in the later years of the immigration wave, partially reflecting the poor state of health in Russia compared to Israel.
 

Background: Urinary incontinence in older women is common. Its characteristics and impact on quality of life is not well established since these women are usually reluctant to tell their healthcare providers about the problem.

Objective: To determine the characteristics of urinary incontinence in women and the manner in which it affects patients quality of life.

Methods: Twenty family physicians were requested to distribute a questionnaire to the first 25 consecutive women aged 30 to 75 years who visited their clinic for any reason. The questionnaire covered general health issues, symptoms of urinary incontinence, and quality of life.

Results: A total of 418 women, mean age 50.0 ± 11.8 years, completed the questionnaire (84% response rate). Of these, 148 (36%) reported having episodes of urinary incontinence. Urinary incontinence was found to be associated with older age, menopause, obesity and coexisting chronic disorders. Sixty percent of the women with urinary incon­tinence found it to be a disturbing symptom, and 44% reported that it had a detrimental effect on their quality of life. Only 32% of the affected women had sought medical advice, half of them from their family physician. Treatment was recommended to 66% of those who sought help, and in about two-thirds of these it brought some measure of relief.

Conclusions: Urinary incontinence is a common com­plaint among women attending primary care clinics, but it does not receive appropriate attention, Though it often adversely affects quality of life, only a small proportion of women seek medical advice. Family physicians should raise the issue as a part of the routine general health check-up.
 

Background: Israel lacks a systematic surveillance of sports injuries, and knowledge of risk factors and specific patterns of injury is inadequate. In order to promote prevention of sports-related injuries, the magnitude of the problem must first be identified and the incidence and severity of sports injuries described.

Objective: To conduct a survey on previous sports injuries among a sample of Israeli athletes.

Methods: A convenience sample of Israeli amateur athletes participating in the 1997 15th Maccabiah Games was randomly selected. The study group answered an anonymous self-administered questionnaire that included sociodemographic data, and information regarding their sports activity and sports-related injuries that had occurred during the previous 2 years.

Results: The study group, aged 12-3 years (median age 21), comprised 301 consenting athletes in 28 different sports. Of these athletes 56.1% reported having had at least one injury. Most injuries (75.6%) involved the upper and lower extremities, and 37.8% of the injured sportsmen had received medical attention from a physician. Half of the athletes participated in contact sports - both collision and limited impact. This group had a much greater proportion of reported injuries in all age groups.

Conclusion: Surveillance of sports injuries should be expanded in order to develop appropriate prevention programs in Israel.

Background: The frequent coexistence of two or more sexually transmitted diseases in one patient has been reported in non-dermatological literature, mostly in languages other than English. Identification of Ureaplasma urealyticum, Chlamydia trachomatis and Mycoplasma hominis in men with other STDs is important, since these bacteria have been implicated in a variety of diseases such as non-gonococcal urethritis, premature rupture of fetal membranes, and infertility in female sexual partners of these patients.

Objective: To assess the frequency of concomitant STD, particularly urethral colonization of U. urealyticum, C. trachomatis and M. hominis, in men consulting for suspected STD-related symptoms.

Methods: All patients attending our dermatology clinic for STD-related symptoms during a 12 month period in 1996–97 underwent systematic clinical and laboratory screening for syphilis, gonorrhea, NGU, prostatitis, genital herpes simplex infection, Condyloma acuminatum, urethral carriage of U. urealyticum, C. trachomatis and M. hominis, as well as serological screening for HIV, and hepatitis B and C infections.

Results: A total of 169 men with STD-related symptoms were enrolled in the study. The following clinical diagnoses were established: NGU in 109 men, C. acuminatum in 40, genital herpes simplex in 10, prostatitis in 7, latent syphilis in 6, primary syphilis in 1, and Behcet’s disease in 1. No clinical evidence of STD was found in 13 patients. Of the 169 patients, 39 (23%) had two or more concomitant STDs, of whom 27 (69%) had C. acuminatum associated with one or more of the urethral pathogens. A positive U. urealyticum culture was found in 67.5% (27/40) of the men with C. acuminatum as compared to 42% (40/96) among the patients with NGU who did not have C. acuminatum (P=0.004, X² test). Conversely, the prevalence of C. acuminatum among patients positive for U. urealyticum was significantly higher than the prevalence among those who were negative – 27/75 (36%) vs. 13/94 (14%), P<0.0009, X² test. About half of the U. urealyticum-positive patients with C. acuminatum had no clinical signs or symptoms of urethritis.

Conclusion: Our findings suggest that patients with C. acuminatum should be assessed for U. urealyticum carriage and, when identified, their sexual contacts should be actively sought and treated.

__________________________________

* Dr. Zvulunov is now with the Department of Pediatrics, Joseftal Hospital, Eilat, Israel.

STDs = sexually transmitted diseases

NGU = non-gonococcal urethritis

Background: In simultaneous pancreas-kidney transplantation, with both organs coming from the same donor, the addition of a pancreas to the kidney transplant does not jeopardize the kidney allograft outcome despite higher postoperative SPK morbidity. Pancreas allograft outcome has recently improved due to better organ selection and more accurate surgical techniques.

Objective: To demonstrate the positive impact of SPK on kidney allograft outcome versus kidney transplantation alone in insulin-dependent diabetes mellitus patients with end-stage renal failure.

Methods: We performed 39 consecutive SPKs in 14 female and 25 male IDDM patients with renal failure after an average waiting time of 9 months. Multi-organ donor age was 30 years (range 12-53). The kidneys were transplanted in the left retroperitoneal iliac fossa following completion of the pancreas transplantation; kidney cold ischemia time was 16±4 hours. Induction anti-rejection therapy was achieved with polyclonal antithymocytic globulin and methylprednisolone, and maintenance immunosuppression by triple drug therapy (prednisone, cyclosporine or tacrolimus, and azathioprine or mycophenolate mofetil). Infection and rejection were closely monitored.

Results: All kidney allografts produced immediate urinary output following SPK. Two renal grafts had mild function impairment due to acute tubular damage but recovered after a short delay. Three patients died from myocardial infarction, cerebrovascular event and abdominal sepsis on days 1, 32 and 45 respectively (1 year patient survival 92%). An additional kidney allograft was lost due to a renal artery pseudo-aneurysm requiring nephrectomy on day 26. Nineteen patients (49%) had an early rejection of the kidney that was resistant to pulse-steroid therapy in 6. No kidney graft was lost due to rejection. Patients with acute kidney-pancreas rejection episodes suffered from severe infection, which was the main cause of morbidity with a 55% re-admission rate. Complications of the pancreas allograft included graft pancreatitis and sepsis, leading to a poor kidney outcome with sub-optimal kidney function at 1 year. Kidney graft survival at one year was 89% or 95% after censoring the data for patients who died with functioning grafts.

Conclusions: Eligible IDDM patients with advanced diabetic nephropathy should choose SPK over kidney transplantation alone from either a cadaver or a living source.

__________________________________

SPK= simutaneous pancreas-kidney transplatation

IDDM= insulin-dependent diabetes mellitus

Background: Articular cartilage is incapable of undergoing self-repair since chondrocytes lose their mitotic ability as early as the first year of life. Defects in articular cartilage, especially in weight-bearing joints, will predictably deteriorate toward osteoarthritis.  No method has been found to prevent this deterioration. Drilling of the subchondral bone can lead to fibrocartilage formation and temporary repair that slowly degrades. Animal experiments indicate that introducing proliferating chondrocytes such as cultured articular chondrocytes can reliably reconstruct joint defects.

Objectives: To describe our clinical experience in culturing and transplanting autologous chondrocytes. 

Methods: Biopsies were obtained from 10 patients, aged 18–45, undergoing a routine arthroscopy in which a cartilage defect was identified with indications for cartilage transplantation. The biopsies were further processed to establish chondrocyte cultures. ACT was performed in 8 of the 10 patients because of persistent symptoms for at least 2 months post-arthroscopy. All patients (6 men and 2 women) had a grade IV cartilage defect in the medial or lateral femoral condyle, and three had a defect in the trochlear region as well. Biopsies were removed from the lateral rim of the superior aspect of the femur, and cells were cultured in a clean room. Following a 2 order of magnitude expansion, cells were implanted under a periosteal flap.

Results: The eight patients implanted with autologous cells were followed for 6 months to 5 years (average 1 year). Complaints of giving-way, effusion and joint locking resolved in all patients, and pain as assessed by the visual analogue score was reduced by an average of 50%. Follow-up magnetic resonance imaging studies in all patients revealed that the defects were filled with tissue having similar signal characteristics to cartilage.

Conclusions: Chondrocyte implantation is a procedure capable of restoring normal articular cartilage in cases with isolated joint defects. Pain can be predictably reduced, while joint locking and effusion are eliminated. The effect on osteoarthritis progression in humans has not yet been elucidated.

__________________________________

ACT = autologous chondrocyte transplantation

Background: Spectral analysis of heart rate variability has been shown to be a reliable non-invasive test for quantitative assessment of cardiovascular autonomic regulatory responses, providing a window reflecting the interaction of sympathetic and parasympathetic tone. Alterations in autonomic function are associated with a variety of physiologic and pathophysiologic processes and may contribute substantially to morbidity and mortality. Our previous study shows that patients with post-traumatic stress disorder have significantly lower HRV compared to controls, reflecting a basal autonomic state characterized by increased sympathetic and decreased parasympathetic tone.

Objectives: To apply this tool to PTSD patients treated with selective serotonin re-uptake inhibitors in order to assess the impact of such treatment on the autonomic dysregulation characterizing these patients.

Methods: Standardized heart rate analysis was carried out in nine PTSD patients treated with SSRI agents and compared to that in a matched control group of nine healthy volunteers and in nine untreated PTSD patients, based on a 15 minute resting electrocardiogram.

Results: Our preliminary results show that the HRV parameters indicating autonomic dysregulation, which characterize PTSD patients at rest, are normalized in responding patients by use of SSRIs. Neither the clinical implications of these findings nor their physiological mechanisms are clear at present, although we presume that they reflect a central effect, since the peripheral autonomic effects of SSRIs are relatively negligible.   

__________________________________

HRV = heart rate variability

PTSD = post-traumatic stress disorder

SSRI = selective serotonin re-uptake inhibitor

Background: Although the onset of fever in children often prompts parents to seek immediate treatment, the general level of parental knowledge on pediatric fever and administration of antipyretic medications is unknown. Parents without a basic understanding of treatment principles may give their children incorrect doses of medication. Overdosing may cause drug toxicity, while underdosing may lead to unnecessary, repeated clinic and/or emergency room visits.

Objectives: To assess parental decision-making with regard to treating fever in children, and its effectiveness, and to suggest methods for improving the level of treatment.

Methods: In this cross-sectional self-reported survey, questionnaires were completed by 650 parents who sought medical assistance for a child under the age of 10 years. Parents represented various socioeconomic levels, educational backgrounds and religious affiliations.

Results: Ninety-six percent of parents treated fevers that reached 38.5°C, and 77.6% treated fevers of only 38°C. Acetaminophen was the treatment of choice for 96% and dipyrone for 4%. Parental sources of information for managing and administering antipyretic drugs were medical personnel (40.7%), mother's or grandmother's experience (30%), and the enclosed leaflet or instructions on the bottle (29.3%). Forty-three percent of the parents administered the recommended dosage (10–20 mg/kg), whereas 24.3% used less and 32.7% used more; 11% exceeded a daily dosage of 120 mg/kg. 

Conclusions: A total of 57% of parents treated children with incorrect doses of antipyretic drugs. In 11% of the children treated, the daily dose was at a level that could cause severe toxicity. Parental knowledge of the treatment of fever must be improved.