Israel Medical Association Journal

Background: Cancer is a leading cause of mortality worldwide. The most effective way to combat cancer is by prevention and early detection.

Objectives: To evaluate the outcome of screening an asymptomatic population for the presence of benign and neoplastic lesions.

Methods: Routine screening tests for prevention and/or early detection of 11 common cancers were conducted in 300 consecutive asymptomatic, apparently healthy adults, aged 25–77 years. Other tests were performed as indicated.

Results: Malignant and benign lesions were found in 3.3% and 5% of the screenees, respectively, compared to 1.7% in the general population. The most common lesions were in the gastrointestinal tract followed by skin, urogenital tract and breast. Advanced age and a family history of a malignancy were associated with increased risk for cancer with an odds ratio of 9 and 3.5, respectively (95% confidence interval 1.1–71 and 0.9–13, respectively). Moreover, high serum C-reactive protein levels and polymorphisms in the APC and CD24 genes indicated high cancer risk. When two of the polymorphisms existed in an individual, the risk for a malignant lesion was extremely high (23.1%; OR[1] 14, 95% CI[2] 2.5–78).

Conclusions: Screening asymptomatic subjects identifies a significant number of neoplastic lesions at an early stage. Incorporating data on genetic polymorphisms in the APC and CD24 genes can further identify individuals who are at increased risk for cancer. Cancer can be prevented and/or diagnosed at an early stage using the screening facilities of a multidisciplinary outpatient clinic.

Background: Cow's milk allergy is the most prevalent food hypersensitivity, affecting 2–3% of infants, but it tends to resolve with age. Cow’s milk-specific immunoglobulin E in the serum is an important measure in the diagnosis and follow-up of infants and children with cow's milk allergy.

Objectives: To examine the relation between CmsIgE[1] and the probability of resolution of milk allergy.

Methods: CMsIgE was determined in the serum of 1800 infants and children referred for the evaluation of possible milk allergy. All children with CmsIgE of 1 kU/L or above were followed at the allergy clinic and, according to their condition, underwent milk challenge. The diagnosis of cow's milk allergy was made on the basis of a significant and specific history or a positive oral food challenge. Subsequently, oral tolerance was defined as an uneventful oral challenge.

Results: A total of 135 infants and children had milk-specific IgE greater than 1 kU/L. Forty-one percent of children still had clinical milk allergy after the age of 3 years. Sixty-eight percent of children older than 3 years with persistence of cow's milk allergy had milk-specific IgE > 3 IU/ml before the age of 1 year. Furthermore, 70% of children who at 3 years old had resolved their cow's milk allergy had milk-specific IgE that was lower than 3 IU/ml before the age of 1 year. The positive predictive value of CmsIgE > 3 IU/ml to persistent cow's milk allergy at age 3 years was 82.6% (P = 0.001), with a sensitivity of 67.9% and specificity of 70.4%.

Conclusions: Milk-specific IgE concentration in the first year of life can serve as a predictor of the persistence of milk allergy.

Background: Ocular hypotony is a common unexplained feature of myotonic dystrophy type 1. Spuriously low applanation tonometric readings can be caused by thin corneas, flat corneal curvature and corneal edema.

Objectives: To determine whether structure abnormalities of the cornea cause spuriously low readings in applanation tonometry.

Methods: We utilized a TMS-2N corneal topographer, a NonconRobo SP-6000 Specular microscope and a Corneo-Gage Plus 1A Pachymeter to examine seven patients with DM1[1] and eight healthy controls. Intraocular pressure, central corneal thickness, and endothelial cell density were measured, and simulated keratometry readings were made. Cornea guttata and irregularity of corneal topography patterns were also sought.

Results: The mean intraocular pressure was 9.86 ± 1.29 mmHg for all patients (intraocular operated and non‑operated eyes) and 12.88 ± 1.89 mmHg for the controls (P = 0.000021, two-tailed t-test). Central corneal thickness was 530.57 ± 35.30 micron for all patients and 535.00 ± 39.62 micron for the controls (P = 0.75, two-tailed t-test). Endothelial cell density was 3164 ± 761 cells/mm² for all patients and 3148 ± 395 cells/mm² for the controls (P = 0.94, two-tailed t-test). Simulated keratometry readings were similar in both groups when the operated eyes were excluded. Cornea guttata and irregularity of corneal topography patterns were also noted in the study group.

Conclusions: Corneal thickness, corneal curvature and corneal hydration were within normal limits and thus were not the cause for the low applanation tonometry reading in DM1. The presence of cornea guttata and irregularity of corneal topography patterns in DM1 warrants further investigation. 

Background: Persistent creatine kinase elevation is occasionally encountered in subjects without any clinical manifestation of a neuromuscular disorder or any condition known to be associated with increased serum CK[1] levels. It is still unresolved whether extensive investigations and specifically a muscle biopsy should be performed in clinically normal individuals with elevated CK levels.

Objective: To study the muscle pathology of patients with asymptomatic or minimally symptomatic hyperCKemia.

Methods: The clinical and laboratory data of patients with persistent hyperCKemia and normal neurologic examination were reviewed and their muscle biopsies evaluated.

Results: The study group included 40 patients aged 7–67 years; the male to female ratio was 3:1. Nineteen patients were completely asymptomatic, 20 had mild non-specific myalgia, and 1 had muscle cramps. Electromyography was performed in 27 patients and showed myopathic changes in 7 (26%). Abnormal muscle biopsy findings (e.g., increased variation in fiber size, increased number of central nuclei and occasional degenerating fibers) were detected in 22 of the 40 patients (55%). No fat or glycogen accumulation was detected. Immunohistochemistry demonstrated abnormal dystrophin staining in 3 patients (8%), resembling the pathologic changes of Becker muscular dystrophy. No abnormal findings were detected on immunohistochemical staining for merosin, dysferlin, caveolin 3, or alpha and gamma sarcoglycans. The EMG[2] findings did not correlate with the pathologic findings.

Conclusions: Abnormal muscle biopsies were found in 55% of patients with asymptomatic or minimally symptomatic hyperCKemia. Specific diagnosis of muscular dystrophy, however, was possible in only 8% of the patients.

Chronic periaortitis is a rare disease affecting the abdominal aorta, usually below the level of the renal arteries.

Background: In the last decade there has been an increase in asthma morbidity. Hospital admission rates for childhood asthma are influenced by the prevalence of asthma and the quality of asthma care.

Objective: To assess trends in hospital admission and readmission rates for childhood asthma in the Jezreel Valley in Israel in the last decade, and to evaluate the possible effect of changes in asthma treatment upon hospitalization for acute asthma during this period.

Methods: All records from pediatric patients from the central hospital in the Jezreel Valley in northeastern Israel over a 10 year period from 1990 through 1999 who were diagnosed as having asthma were thoroughly reviewed and analyzed for admissions, re-admissions, and treatment before and during admissions

Results: There were 1584 admissions, 1208 were first-time admissions and 374 were re-admissions. The number of first-time admissions increased significantly over time (P < 0.0001), with a significant decrease of re-admissions (P < 0.005); this finding was more significant in children under the age of 8 years (P < 0.005). The length of hospital stay decreased significantly from 3.3 days to 2.7 days (P < 0.002). Significant changes in the use of medications included an increase in inhalant glucocorticoids and a decrease in the use of sodium cromoglycate and theophylline. Controller medication use was concomitant with a significant decrease in the re-admission rates.

Conclusions: The increase in the admission rate and the decrease in the rate of re-admissions and the length of hospital stay probably reflect the increase in the prevalence of asthma and changes in its treatment, respectively. It is essential that asthma be recognized as a significant cause of morbidity and that controller medications be administered to decrease the asthma's severity, morbidity, and resultant hospital admissions.
 

Objectives: To describe the role of wireless capsule endoscopy in diagnosing isolated small intestinal Crohn’s disease in two adolescents.

Methods: Wireless capsule endoscopy was performed in two adolescents with severe protein-losing enteropathy and negative standard diagnostic workup.

Results: Wireless capsule endoscopy successfully diagnosed Crohn’s disease with uncharacteristic presentations and negative radiographic and endoscopic findings in both patients.

Conclusions: The non-invasiveness and ease in performance of capsule endoscopy on an ambulatory basis make this diagnostic modality especially advantageous for children.

Objectives: To evaluate the diagnostic accuracy and outcome of coccygectomy.

Methods: We retrospectively reviewed the operative results in nine patients (seven females and two males) who underwent coccygectomy for coccygodynia in the last 5 years following conservative treatment failure.

Results: The outcome of the procedure was excellent in five patients, good in one patient and poor in two patients.

Conclusions: It is mandatory to perform bone scanning in every patient with coccygodynia and before coccygectomy in order to rule out the presence of malignancy. Coccygectomy is recommended for patients with isolated coccygodynia.

Background: Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH[1] receptor gene.

Objective: To characterize the molecular defects of the GH-R[2] in Laron syndrome patients followed in our clinic.

Methods: Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.

Results: Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.

Conclusions: This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.

Background: The role of prostatic fossa radiation as salvage therapy in the setting of a rising prostate-specific antigen following radical prostatectomy is not well defined.

Objectives: To study the efficacy and safety of pelvic and prostatic fossa radiation therapy following radical prostatectomy for adenocarcinoma.

Methods: A retrospective review of 1,050 patient charts treated at the Sheba Medical Center for prostate cancer between 1990 and 2002 identified 48 patients who received post-prostatectomy pelvic and prostatic fossa radiotherapy for biochemical failure. Two patients were classified as T-1, T2A-9, T2B-19, T3A-7 and T3B-11. Gleason score was 2–4 in 9 patients, 5–6 in 22 patients, 7 in 10 patients and 8–10 in 7 patients. Positive surgical margins were noted in 28 patients (58%) of whom 18 had single and 10 had multiple positive margins. Radiation was delivered with 6 mV photons using a four-field box to the pelvis followed by two lateral arcs to the prostatic fossa.

Results: At a median follow-up of 34.3 months (25th, 75th) (14.7, 51,3) since radiation therapy, 32 patients (66%) are free of disease or biochemical failure. Exploratory analysis revealed that a pre-radiation PSA[1] less than 2 ng/ml was associated with a failure rate of 24% compared with 66% in patients with a pre-radiation PSA greater than 2 ng/ml (chi-square P < 0.006).

Conclusions: For patients with biochemical failure following radical prostatectomy early salvage radiation therapy is an effective and safe treatment option.

Background: Pseudomembranous colitis is a well-recognized cause of diarrhea in patients receiving antibiotics and has significant consequences in terms of morbidity, mortality and cost. Clostridium difficile infection is the single most important infectious cause of PMC[1]. PMC is frequently nosocomial, with an increased risk of spread among institutionalized patients, both in hospitals and nursing homes.

Objective: To investigate the demographic, clinical and laboratory characteristics of PMC patients in an Israeli elderly population.

Methods: We studied 72 hospitalized patients with endoscopically proven PMC. The medical records of all patients including clinical history and laboratory data were reviewed, such as: age, pre-hospitalization status (dependency or not, in the community as compared to the nursing home), background medical history, presenting symptoms, antibiotic history, physical examination on admission, hematologic and biochemical parameters, treatment, duration of hospitalization, complications, mortality and recurrence of disease.

Results: Of the 72 patients (34 males and 38 females, mean age 77 years) 47% were nursing home residents. Pre-hospitalization antibiotic treatment was given to 91.4% for infections of the upper respiratory tract (45%) and urinary tract (45%). The most common antibiotics were cephalosporin (64%), penicillins (42%) and quinolones (28%). Sixty-four percent of the patients were treated with more than one antibiotic, 26% of patients received anti-acid therapy and 36% had been fed with a nasogastric tube. On admission, leukocytosis was found in 79% of patients, >20,000/mm³ in half of them; 60% were anemic, 60% had elevated erythrocyte sedimentation rate, and 78% had hypoalbuminemia. Treatment consisted of metronidazole (41%) or a combination of metronidazole and vancomycin (56%). Overall, 31% of patients recovered without complications, 29% died within 30 days of hospitalization, and 24% were re-hospitalized due to recurrence of PMC.

Conclusion: The most common antibiotics implicated in PMC are cephalosporin, penicillins and quinolones. The disease is associated with high mortality and recurrence rates.

Background: Atopic dermatitis is a common disease in infants and children and the incidence appears to be rising.

Objectives: To determine the presentation, allergies, and outcome among Israeli infants and children.

Methods: Children with atopic dermatitis referred to the allergy clinic at a regional pediatric center were evaluated for their medical history and their allergy. The allergic assessment was determined by utilizing skin prick tests and/or serum specific immunoglobulin E concentrations. The children were reexamined again for all parameters at the end of the follow-up period.

Results: Forty-six children with atopic dermatitis were studied, 27 males (58.7%) and 19 females (41.3%). A family history of allergy was found in 19 (41.3%). The median age at presentation was 17 months. Of the 46 children 33 (71.7%) revealed an allergy to one or more of the allergens. The most common combination was allergy to food and house-dust mites. The mean follow-up time was 64 months. By the age of 8 years full recovery was seen in 16 patients, half of whom recovered within 3.3 years from the date of presentation. The probability of complete remission was 58%, and for either complete or partial remission 76%. Upon reevaluation at the end of the follow-up period some patients lost their sensitivities, while others, who had been allergic to foods, became sensitive to house-dust mites and/or pollens.

Conclusions: Atopic dermatitis is an allergic problem in the northern region of Israel, as it is in other parts of the world. Food allergy and house-dust mites are major contributors to the evolution of eczema.