Israel Medical Association Journal

Background: Iatrogenic illness, defined as a disease that results from a diagnostic procedure or from any form of therapy, is a well-recognized phenomenon in clinical practice.

Objectives: To study and evaluate major car-diac iatrogenic disease as the cause of admission to the intensive cardiac care unit in the modern era.

Methods: We assessed 64 critically ill patients suffering from major cardiac iatrogenic problems among a total of 2,559 patients admitted to the intensive cardiac care unit during 3 years. Iatro-genic illness was defined as any problem that resulted from therapy. Only cardiac problems were included in the study. Complications of interventional cardiovascular procedures, suicide attempts or accidental intoxications were ex-cluded.

Results: There was evidence of a major cardiac iatrogenic problem as the cause for admission in 64 patients (2.5%): 58 (91%) suffered from ar-rhythmias (mainly bradyarrhythmias) secondary to beta-blockers, amiodarone, calcium antago-nists, electrolyte imbalance or a combination, and 6 (9%) had non-arrhythmic events (hypotension, syncope or acute heart failure). In 41 patients (64%) the iatrogenic event was considered pre-ventable

Conclusions: Major cardiac iatrogenic compli-cations are an important factor among patients admitted to the intensive cardiac care unit. Most of the events are bradyarrhythmias related to anti-arrhythmic agents. Almost two-thirds of events are preventable.

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: 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.

__________________________________

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: Many medications used for children have not undergone evaluation to assure acceptable standards for optimal dose, safety and efficacy. As a result, the majority of children admitted to hospital wards receive medications outside the terms of their license (off-label) or medications that are not specifically licensed for use in children (unlicensed). The extent of unlicensed and off-label medication use in ambulatory children is unknown.

Objective: To determine the extent of unlicensed and off-label medication use in a general pediatrics ambulatory hospital unit in Israel.

Patients and Methods: We conducted a retrospective analysis of the medical records of 132 outpatient children treated in the General Pediatrics Ambulatory Unit of the Soroka Medical Center, Beer Sheva, in November–December 1998.

Results: The children’s ages ranged from 1 month to 18 years (mean ± SD 50±58 months). Of the 222 prescriptions given to these children, one-third were unlicensed (8%) or unlabeled (26%). Different dose and age were the most common categories of off-label medication use. All 18 cases of unlicensed use were due to modifica-tion of licensed drugs (tablets were crushed to prepare suspensions). Altogether, 42% of children received medicines that were off-label and/or unlicensed.

Conclusions: More off-label than unlicensed medications were used. Further investigations are required to establish the extent of unproved drug use in both hospitalized and ambulatory pediatric patients in Israel. Recommendations recently issued by the Ministry of Health’s National Council for Child Health and Pediatrics constitute a first step in the Israeli contribution to the international effort demanding testing of medications for children.

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.

__________________________________

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.

_________________________________

FGFR3 = fibroblast growth factor receptor 3