Israel Medical Association Journal

Background: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.

Background: A high incidence of abnormal pulmonary function tests has been reported in cross-sectional studies among patients with rheumatoid arthritis. Few patients have been enrolled in longitudinal studies.

Objectives: To perform PFT[1] in rheumatoid arthritic patients without pulmonary involvement and to identify variables related to changes in PFT over 5 years of follow-up.

Methods: Consecutive RA[2] patients underwent PFT according to American Thoracic Society recommendations. All surviving patients were advised to repeat the examination 5 years later.

Results: PFT was performed in 82 patients (21 men, 61 women). Their mean age was 55.7 (15.9) years and the mean RA duration was 11.1 (10) years. Five years later 15 patients (18.3%) had died. Among the 67 surviving patients, 38 (56.7%) agreed to participate in a follow-up study. The initial PFT revealed normal PFT in only 30 patients (36.6%); an obstructive ventilatory defect in 2 (2.4%), a small airway defect in 12 (17%), a restrictive ventilatory defect in 21 (25.6%), and reduced DLco in 17 (20.7%). Among the 38 patients participating in the 5 year follow-up study, 8 developed respiratory symptoms, one patient had a new obstructive ventilatory defect, one patient developed a restrictive ventilatory defect, and 5 patients had a newly developed small airway defect. The DLco had improved in 7 of the 8 patients who initially had reduced DLco, reaching normal values in 5 patients. Over the study period a new reduction in DLco was observed in 7 patients. Linear regression analyses failed to identify any patient or disease-specific characteristics that could predict a worsening in PFT. The absolute yearly decline in forced expiratory volume in 1 sec among our RA patients was 47 ml/year, a decline similar to that seen among current smokers.

Conclusions: Serial PFT among patients with RA is indicated and allows for earlier identification of various ventilatory defects. Small airways disturbance was a common finding among our RA patients.

Background: Medication errors are a common cause of morbidity and mortality.

Objectives: To evaluate the rate of acknowledgment of medication errors as reported by physicians working in the community and in hospitals.

Methods: An anonymous questionnaire was sent to 9320 active physicians (about 48% community physicians, 17% hospital physicians and 35% working in both places), with questions on the rate and type of medication errors that they had encountered during their professional career. The questions specified errors in dosage, type of medicine (wrong indication), route of administration and drug interactions.

Results: Only 627 physicians (6.7%) responded. Of these, nearly 79% admitted having made an error in prescribing medication; the majority admitted to more than one error. Physicians with fewer years of experience admitted having made a mistake more than did physicians with more experience (P = 0.019). Pediatricians and geriatricians made more dosage mistakes (P = 0.02), while family physicians and psychiatrists made more mistakes in drug interactions (P = 0.001).

Conclusions: It is possible that indifference, fear of identification, or lack of awareness may have contributed to the low response rate despite the fact that the questionnaire was anonymous. Educational programs should be implemented in medical schools to encourage physicians to report errors before the onset of adverse reactions.
 

Background: Patients with non-inflamed appendix have been reported to have had more hospitalizations and emotional disorders before and after the operation than patients with acute appendicitis.

Objectives: To compare abdominal pain characteristics, as well as demographic and psychosocial data in children with histologically confirmed appendicitis compared to non-inflamed appendices.

Methods: Charts of children with suspected appendicitis who had undergone appendectomy were retrospectively reviewed for relevant clinical and laboratory data. The patients or their parents were then contacted by phone and were asked to respond to a detailed questionnaire on abdominal symptoms as well as demographic and psychosocial data.

Results: The study group comprised 156 children: 117 with histologically confirmed appendicitis and 39 with normal appendices. Eighty-two patients (53.2%) were located and interviewed: 62 (54%) with appendicitis and 20 (51%) with normal appendices. Of the 82 children, 16 reported recurrent episodes of abdominal pain before or after surgery: 11 (17.7%) in the appendicitis group and 5 (25%) in the normal appendix group. Only six patients fulfilled the formal criteria for the diagnosis of recurrent abdominal pain: 5 (8%) from the appendicitis group and 1 (5%) from the non-inflamed appendix group (not significant). In addition, no significant statistical differences were found between the groups regarding school performance, behavior and social interaction with peers.

Conclusions: We could not demonstrate an increased incidence of recurrent abdominal pain, nor could we identify significant psychosocial morbidity in those children undergoing a non-inflamed appendectomy.

Background: Spontaneous pneumomediastinum is a rare entity that usually occurs in young males without any apparent precipitating factor. Several case series have been published focusing on clinical features, workup and prognosis. Due to the rarity of this entity, there is no consensus on the most appropriate treatment.

Objectives: To describe the clinical characteristics and course of patients with spontaneous pneumomediastinum in our institution.

Methods: This is a retrospective descriptive study based on a review of the charts of all patients discharged from our hospital with a diagnosis of SPM during the period 2000 to 2007. Thirteen patients were identified and information on their clinical presentation, course, hospital stay, investigations and outcome was gathered.

Results: In 70% of patients the presenting complaint of SPM was pleuritic chest pain, while 30% of patients developed SPM in the course of another respiratory illness. Subcutaneous emphysema was the most common clinical finding (46%). Chest X-ray was diagnostic in 12 of 13 patients, and additional tests such as esophagogram and echocardiogram were unrevealing. Leukocytosis and electrocardiographic changes in inferior leads were seen in 30% of patients. Mean hospital stay was 48 hours, treatment was supportive, and symptomatic improvement was usually noted within 24 hours. No recurrences occurred.

Conclusions: SPM is a rare entity that should be considered in patients with pleuritic chest pain. Treatment is supportive, and if no clues for esophageal rupture are present investigations other than chest X-ray are probably not warranted. It is safe to discharge the patient within 24 hours provided that symptomatic improvement is achieved.
 

Background: Children report various types of fear in the context of hospitalization, such as fear of separation from the family, having injections and blood tests, having to stay in the hospital for a long time, and being told “bad news” about their health.

Objectives: To examine the effects of the “Teddy Bear Hospital” method on preschool children’s fear of future hospitalization.

Methods: The study group comprised 41 preschool children aged 3–6.5 years (mean 5.1 ± 0.7 years), and 50 preschool children, age matched and from a similar residential area, served as the control group. Assessment included a simple one-item visual analog scale of anxiety about hospitalization. This was assessed individually one day prior to the intervention and again a week after the intervention in both groups

Results: While baseline levels of anxiety were not different between groups [t(89) = .4, NS], children in the “Teddy Bear Hospital” group reported significantly lower levels of anxiety than the control group at follow-up

Conclusions: Our results indicate that by initiating a controlled pain-free encounter with the medical environment in the form of a “Teddy Bear Hospital,” we can reduce children’s anxiety about hospitalization.

Background: With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the sub-acute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the sub-acute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.

Objectives: To examine whether Arab ethnicity influences the Gaucher phenotype.

Methods: We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.

Results: There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.

Conclusions: For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.
 

Raynaud's phenomenon, fatigue and pain (myalgia and arthralgia) are important presenting symptoms of pediatric-onset mixed connective tissue disease. The difficulty is that many adolescent girls complain of pain along with fatigue without evidence for serious disease. However, in patients with Raynaud's phenomenon one should search for evidence of connective tissue diseases. Capillaroscopy could be helpful since capillary changes of the SD-type significantly correlate with future development of scleroderma spectrum disorders. Symptoms of MCTD[1] change in most patients during the disease course: in general the inflammatory features that are also seen in systemic lupus erythematosus and juvenile dermatomyositis have the tendency to disappear over years, but Raynaud's phenomenon is persistent and scleroderma symptoms become progressively prominent. Long-lasting remission occurs only in a minority of patients, while the majority has mild disease activity. Mortality in children with MCTD is lower than in adults. Since a change of symptoms is in the nature of the disease a thorough and frequent evaluation of children with (probable) MCTD is important to detect organ involvement which, if present, should be treated at an early (pre-symptomatic) stage. We present a diagnostic workup scheme for children and adolescents with propable MCTD.

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Background: Intrapartum risk is based mainly on obstetric history, which is lacking in primiparous women.

Objectives: To ascertain whether the traditional known risk of primiparity is an independent variable for both maternal and neonatal outcome.

Methods: All women admitted to labor during March-April 2002 were canvassed for eligibility for participation in the study based on an obstetric risk scoring system developed and validated for our population. During the study period, 1473 women presented for delivery. Of these, 298 women (20%) were eligible according to the exclusion criteria as "low risk" parturients: 135 (45%) were primiparous and 163 (55%) were multiparous (2–5 births).

Results: After correction for significant confounding factors, primiparity was revealed as an independent significant risk factor for instrumental delivery (odds ratio 15.5, 95%confidence interval 1.88–125) and for early postpartum hemorrhage (OR[1] 5.6, 95%CI[2] 1.9–16.6).

Conclusions: This study highlights early postpartum hemorrhage as a significant risk for primiparous women, independent of mode of delivery, and also confirms previous reports of maternal complications requiring transfer from birth centers/home deliveries to tertiary centers.

Background Drug-specific CD8+ TH1 lymphocytes have been found in the peripheral blood and involved skin of patients with drug-induced bullous exanthems.

Objectives To determine whether the interferon-gamma release test can identify culprit drugs in pemphigus patients.

Methods Clinical and laboratory workup for pemphigus was performed in 14 pemphigus vulgaris patients who had been exposed to drugs, and the IFNl[1] release test was conducted on their lymphocytes from heparinized venous blood cultured with medium, phytohemagglutinin and one of 32 drugs, or medium and phytohemagglutinin alone.

Results Ten of the patients and 13 of the 32 drugs exhibited a positive response to the test. Eight of the 10 patients with positive IFNl test results had a less severe course of the disease, with fast reduction in steroid dosage.

Conclusions The findings demonstrate both the ability of the IFNl release test to identify drugs that can induce pemphigus, and its usefulness in the diagnostic workup of pemphigus patients.