Israel Medical Association Journal

Background: Carbohydrate malabsorption of lactose, fructose and sorbitol has already been described in normal volunteers and in patients with functional bowel complaints including irritable bowel syndrome. Elimination of the offending sugar(s) should result in clinical improvement.

Objective: To examine the importance of carbohydrate malabsorption in outpatients previously diagnosed as having functional bowel disorders, and to estimate the degree of clinical improvement following dietary restriction of the malabsorbed sugar(s).

Methods: A cohort of 239 patients defined as functional bowel complaints was divided into a group of 94 patients who met the Rome criteria for irritable bowel syndrome and a second group of 145 patients who did not fulfill these criteria and were defined as functional complaints. Lactose (18 g), fructose (25 g) and a mixture of fructose (25 g) plus sorbitol (5 g) solutions were administered at weekly intervals. End-expiratory hydrogen and methane breath samples were collected at 30 minute intervals for 4 hours. Incomplete absorption was defined as an increment in breath hydrogen of at least 20 ppm, or its equivalent in methane of at least 5 ppm. All patients received a diet without the offending sugar(s) for one month.

Results: Only 7% of patients with IBS and 8% of patients with FC absorbed all three sugars normally. The frequency of isolated lactose malabsorption was 16% and 12% respectively. The association of lactose and fructose-sorbitol malabsorption occurred in 61% of both patient groups. The frequency of sugar malabsorption among patients in both groups was 78% for lactose malabsorption (IBS 82%, FC 75%), 44% for fructose malabsorption and 73% for fructose-sorbitol malabsorption (IBS 70%, FC 75%). A marked improvement occurred in 56% of IBS and 60% of FC patients following dietary restriction. The number of symptoms decreased significantly in both groups (P<0.01) and correlated with the improvement index (IBS P<0.05, FC P<0.025).

Conclusions: Combined sugar malabsorption patterns are common in functional bowel disorders and may contribute to symptomatology in most patients. Dietary restriction of the offending sugar(s) should be implemented before the institution of drug therapy.

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IBS = irritable bowel syndrome

FC = functional complaints

Background: About one-third of patients with severe ulcerative colitis do not respond to conventional therapy and require urgent colectomy. It was recently shown that cyclosporin is effective in some of these patients.

Objectives: To review the current experience of six hospitals in central Israel that used cyc-losporin in patients with severe ulcerative colitis.

Methods: The files of all 32 patients treated with cyclosporin for corticosteroid-resistant ulcerative colitis were reviewed. Activity of disease was measured by a clinical activity, index colonoscopy and laboratory tests.

Results: The average duration of treatment with intravenous cyclosporin was 12.7 days (range 9–28) after which the disease activity index dropped from an average of 14.22 to 4.74. The mean time for response was 7.5 days (4–14). Twelve patients (40%) required surgery within 6 months and another 6 patients (18.8%) were operated on after more than 6 months. Twelve patients (37%) maintained remission for at least 6 months and did not require surgery. In one patient treatment was stopped because of non-compliance and one was lost to follow-up. There were numerous side effects, but in only one case with neurotoxicity was treatment withdrawn.

Conclusions: Cyclosporin is a relatively safe and effective treatment for severe ulcerative colitis. It induced long-term remission in 37% of the patients, and in those who required surgery the treatment resulted in an improved clinical condition before the operation.

Background: Ulcerative colitis begins in early childhood in 4% of cases. Medical therapy is non-specific, and as many as 70% of children will ultimately require surgery. The dynamic growth, physical and psychological changes that characterize childhood are severely compromised by the complications of ulcerative colitis and its therapy.

Objective: To review the outcome of children undergoing early surgery for ulcerative colitis at a tertiary medical center in Israel.

Methods: A retrospective review was conducted of all children operated on following failure of medical therapy for ulcerative colitis during a 5 year period.

Results: Eleven children underwent a J-pouch procedure with ileo-anal anastomosis in one to three stages. Postoperative complications included recurrent pouchitis in 5 patients, intestinal obstruction in 3, fistula with incontinence in one, stricture in one, and wound infection in 4. Follow-up revealed that most of the patients have three to four soft bowel movements daily. All currently enjoy normal physical activities and a rich social life.

Conclusions: The quality of life in children with ulcerative colitis was markedly improved following J-pouch surgery. This procedure was not associated with major complications. We recommend early surgery as an alternative to aggressive medical therapy in children with this disease.

Background: Concomitant bacterial and viral infection is a well-known phenomenon, however only very rarely has a bacterial infection been reported during hepatitis A virus infection.

Objective: To evaluate retrospectively the clinical records of children hospitalized with HAV infection for a concomitant infection proved or presumed to be bacterial.

Method: A retrospective study was conducted on all the children hospitalized with hepatitis A infection from 1988–96 in our center. The records were evaluated for a concomitant infection.

Results: Of 40 children hospitalized with HAV infection, 13 were found to have a concomitant infection: these included 6 with pneumonia, 4 with pyelonephritis and 1 case each of purulent otitis media, osteomyelitis and staphylococcal bacteremia.

Conclusion: In areas where hepatitis A is endemic, a simultaneous infection with hepatitis A and other common bacterial infection during childhood may co-exist. A permissive role for HAV infection is suggested.

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HAV = hepatitis A virus

Background: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases.

Objectives: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel.

Methods: We examined the G380R mutation (G>A and G>C transition) and the mutation G375C (G>T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia.

Results: We found the G>A transition at codon 380 in 30 of our patients and the G>C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia.

Conclusions: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

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FGFR3 = fibroblast growth factor receptor 3

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.

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SPK= simutaneous pancreas-kidney transplatation

IDDM= insulin-dependent diabetes mellitus

Background: Israeli physicians are very familiar with the problem of interruptions during encounters with patients. However, a thorough search of the medical literature revealed only one report of this problem from Israel, and none from other countries.

Objectives: To characterize the phenomenon of interruptions to the patient-physician encounter in a clinic in Dimona and to assess the effect of an intervention program designed to reduce the magnitude of this problem.

Methods: During an 8 day work period in March 1997 all patient-physician encounters were recorded and characterized. An intervention program was then designed and implemented to reduce the number of interruptions. Data were again collected a year after the initial data collection.

Results: During the 8 day study period prior to the intervention program there were 528 interruptions to 379 encounters (mean of 1.39 per encounter). The main causes of interruptions were entrance of uninvited patients to the examination room (31%) and telephone calls (27%). Most of the interruptions occurred during the morning hours between 8 and 10 a.m. (45%) and at the beginning of the week (Sunday 30%). After the intervention program there were 402 interruptions to 355 encounters (mean of 1.13 per appointment, P=0.21).

Conclusions: There was no statistically significant improvement in the number of interruptions following the intervention program. This finding is either the result of a local cultural phenomenon, or it indicates a national primary care health system problem that may require a long-term educational program to resolve it. Further research is needed on the magnitude, causes and consequences of interruptions in family practice and, if warranted, methods will have to devised to cope with this serious problem.

Background: Trauma is the leading cause of death in children. In abdominal lesions the spleen is the most commonly involved organ. During the last two decades much effort has focused on spleen tissue conservation.

Objectives: To analyze the rationale of a multimodality management policy that includes autotransfusion and mesh wrapping.

Methods: Data gathered over 14 years illustrate the introduction of new techniques and their impact on cases of severe spleen rupture.

Results: A total of 122 children were treated during the 14 year period, 1985-98. In 16 children an absorbable mesh wrapping, alone or in combination with other techniques, was used to obtain hemostatis and save spleen tissue.

Conclusions: Mesh wrapping, partial splenectomy and autotransfusion can be used, alone or in combination, to preserve severely injured spleens. According to our records, all children survived with a functional spleen. There were no cases of rebleeding. In only one case of prolonged postoperative fever could the cause be traced to an infected spleen hematoma that was drained transcutaneously. Autotransfusion is performed simply and without the use of a "cell saver." Its use can be crucial in small or field hospitals or in a situation of mass casualty.

Background: Uterine rupture is a catastrophic obstetric complication, most often associated with a preexisting cesarean section scar. Although a vaginal birth after a cesarean is considered safe in modern obstetrics, it is not known whether repeated VBACs increase the risk of rupture, or whether the first VBAC proves the strength and durability of the scar, predicting further successful and less risky vaginal deliveries.

Objectives: To evaluate the effect of repeated vaginal deliveries on the risk of uterine rupture in women who have previously delivered by cesarean section.

Methods: In this retrospective study, 26 VBAC deliveries complicated by uterine rupture were matched for age, parity, and gravidity with 66 controls who achieved VBAC without rupture. The histories, demography, pregnancy, labor and delivery records, as well as neonatal outcome were compared.

Results: We found that the risk of rupture decreases dramatically in subsequent VBACs. Of the 40 cases of uterine rupture recorded during the 18 year study period, 26 occurred during VBAC deliveries. Of these, 21 were complicated first VBACs. We also found that the use of prostaglandin-estradiol, instrumental deliveries, and oxytocin had been used significantly more often during deliveries complicated with rupture than in VBAC controls.

Conclusions: Once a woman has achieved VBAC the risk of rupture falls dramatically. The use of oxytocin, PGE2 and instrumental deliveries are additional risk factors for rupture, therefore caution should be exerted regarding their application in the presence of a uterine scar, particularly in the first vaginal birth after cesarean.

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VBAC= vaginal birth after cesarean section

PGE2= prostaglandin-estradiol

Objective: To report a unique hereditary, juvenile onset, craniocervical predominant, generalized dystonia and parkinsonism affecting four members of one family.

Family Description: A father and three of his four daughters presented to us over the past 30 years with a similar picture of generalized dystonia, starting in the craniocervical region in the second or third decade of life. They later developed moderate parkinsonism, mainly manifesting bradykinesia, rigidity and abnormal postural reflexes. Biochemical and genetic tests excluded Wilson's disease, Huntington's disease and Oppenheim's dystonia.

Conclusion: This is a new type of familial dystonia-parkinsonism where the craniocervical dystonic symptoms are most prominent in the early stages while parkinsonism becomes the predominant problem later in life. A search for the genetic mutation in this family is underway.