Israel Medical Association Journal

Background: Familial dysautonomia is a genetic disease that affects the sensory and autonomic nervous systems with varying severity. The deep breath test is one of several measures used to assess the severity of autonomic diseases, but its value in familial dysautonomia has not yet been investigated.

Objectives: To determine the diagnostic value of the DBT[1] in patients with familial dysautonomia.

Methods: Eight patients with familial dysautonomia and eight healthy volunteers were examined by electrocardiography for 1 minute at rest and during forced deep breathing. The following values were recorded: maximum expiratory and minimum inspiratory heart rate and the difference between them (ΔE/I), standard deviation of the heart rate values, interbeat intervals, and E/I[2] ratio. Spectral power analysis of heart rate variability was also performed.

Results: The patients with familial dysautonomia showed a lesser change in heart rate in response to the change in breathing pattern than the controls. Mean values in the study group were significantly higher for minimal inspiratory heart rate and significantly lower for ΔE/I, heart rate standard deviation and E/I ratio, indicating a non-flexible heart response and abnormal parasympathetic function. These findings were supported by power spectral analysis.

Conclusions: Patients with familial dysautonomia have a significantly disturbed response to physiological stimuli. The DBT may serve as a reliable means to quantify autonomic dysfunction in this patient population.

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.

Ten years ago we published a review updating current knowledge on heart failure. We summarized that heart failure is a neuro-humoral and inflammatory syndrome, and that pro-inflammatory cytokines are involved in cardiac depression and in the complex syndrome of heart failure. We suggested that understanding the involvement of these cytokines may enable us to reverse cardiac depression and heart failure. Now we know that there are several mechanisms involved in this syndrome, including inflammation, nitric oxide-dependent pathways, apoptosis, reactive oxygen species, and mitochondrial energy metabolism. This review will focus on the up-to-date mechanistic aspects of heart failure, including clinical trials that have contributed to our better understanding of this entity.

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: Erectile dysfunction is associated with treatable cardiovascular risk factors; therefore, screening for erectile dysfunction and its cardiovascular risk factors is of clinical importance.

Objectives: To detect erectile dysfunction cases and assess their severity among military personnel.

Methods: The Sexual Health Inventory for Men questionnaire was handed out to military personnel aged 25–55 years during routine examinations.

Results: A total of 19,131 men, with a mean age of 34.0 ± 7.1 years, participated in routine physical examinations during the years 2001–2005. More than half of them (n=9956, 52%) completed the SHIM[1] questionnaire. No significant differences were found between those who completed the SHIM questionnaire and those who did not, in terms of mean age, mean body mass index, and prevalence of cardiovascular risk factors. One out of every four men (25.2%) suffered from erectile dysfunction, which was mild in 18.9%, mild to moderate in 4.4%, moderate in 1.1% , and severe in 0.7%. Even though treatable cardiovascular risk factors were quite prevalent in the study group (45.2% of them suffered from dyslipidemia, 25.6% smoked, 4.2% suffered from essential hypertension, and 1.6% from diabetes mellitus), erectile dysfunction was significantly associated with age and diabetes mellitus alone (P < 0.0001).

Conclusions: There is a high prevalence of erectile dysfunction and associated treatable cardiovascular risk factors in Israeli men aged 25–55, especially those with diabetes. 

Background: Since surgical repair of tetralogy of Fallot was introduced, follow-up studies have shown that the majority of patients lead actives lives and have no subjective exercise limitation.

Objectives: To examine lung function, cardiopulmonary functional capacity and echo-Doppler assessment of pulmonary pressure in adult patients 20 years after repair of TOF.

Methods: Unselected consecutive patients performed full lung function testing, progressive cardiopulmonary exercise, and echo-Doppler assessments of pulmonary pressure.

Results: Fifty consecutive patients (33 men, 17 women) aged 29 ± 11 years who underwent surgical repair of TOF at age 10.1 ± 10.9 years were enrolled in this study. Patients after TOF showed no restriction (forced expiratory vital capacity 80%, total lung capacity 91%) and had normal oxygen saturation (97%) and 6 minute walking distance (600 meters). Echocardiography showed normal pulmonary pressure and left ventricular ejection function (62%). Cardiopulmonary exercise testing showed mild limitation of exercise capacity with oxygen uptake at maximal effort of 75–78% predicted.

Conclusions: After corrections of TOF the study patients had normal lung function and pulmonary arterial pressure but mild limitation in their exercise capacity.
 

Background: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs[1].

Objectives: To evaluate the effect of 20 weeks of EPO[2]-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.

Methods: Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate.

Results: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC[3] and PMNL counts and ALP[4] activity following treatment. EPO retarded the deterioration in GFR[5]. The percent of PMNLs expressing EPO-R[6] was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.

Conclusions: These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Background: Rehabilitation camps can improve exercise tolerance and nutrition in cystic fibrosis patients.

Objectives: To assess weight gain, pulmonary function tests and daily symptoms in European CF[1] patients attending a rehabilitation camp at the Dead Sea, Israel.

Methods: We conducted a retrospective study assessing 94 CF patients who participated in winter camps held at the Dead Sea, Israel from 1997 to 2000. The camp program included daily physiotherapy, physical activities, and a high caloric diet. We assessed weight gain, pulmonary function tests, oxyhemoglobin saturation and daily symptoms before (pre), on departure (dep), and up to 3 months after the 3 week rehabilitation camp post). All data were analyzed by ANOVA for repetitive measurements. P < 0.05 was considered significant.

Results: Lung function tests and oxyhemoglobin saturation taken before, on departure and 3 months after camp were available for 35 patients. Forced expiratory volume in the first second (% predicted, average ± SD) improved by 8.2 ± 2.3% (pre, dep, post, P < 0.05). Oxyhemoglobin saturation mildly improved (1 ± 0.3%, pre, dep, post, P < 0.05). Forced vital capacity (% predicted) increased by 3.9 ± 1.2%, but was not significant (P = 0.19). Total body weight of 89 patients improved by 1.9 ± 0.9% during the camp time (P < 0.05, t-test), and in a group of 24 patients weight continuously increased up to 5.0 ± 1.7% at 3 months after the camp (P = 0.004, ANOVA).

Conclusions: In this attrition-limited retrospective study, European CF patients improved their pulmonary function and gained weight during and up to 3 months after a 3 week rehabilitation winter camp at the Dead Sea, Israel.

Background: Diabetes mellitus is associated with microvascular and macrovascular diseases, potentially manifested as endothelial dysfunction. In adults with type 2 diabetes the haptoglobin genotype 1-1 has been shown to have a protective role in inhibiting the development of complications. Although complications from type 1 diabetes are infrequent during childhood, endothelial dysfunction, which is an early marker of vascular complications, may occur.

Objectives: To evaluate endothelial function in adolescents with type 1 diabetes before the development of complications and to test for potential relationships between endothelial dysfunction and haptoglobin genotype.

Methods: The study group comprised 15 adolescents with type 1 diabetes. All underwent a general physical examination, diabetes control evaluation (including HbA1c levels), endothelial function assessment and haptoglobin genotype determination.

Results: There was a significant negative correlation between HbA1c levels and endothelial function (r = -0.48, P < 0.05), and HbA1c was significantly higher in patients with endothelial dysfunction than in those with normal endothelial function (9.9 ± 2.2 vs. 7.7 ± 1.0 mg/dl, P < 0.05). In addition, there was a tendency toward a positive correlation between high density lipoprotein and endothelial function (r = 0.4, P < 0.1). There was no correlation between the haptoglobin genotype and endothelial function.

Conclusions: These results show that even in patients without complications, uncontrolled type 1 diabetes is associated with endothelial dysfunction, which may lead to microvascular complications in the future.
 

Background: Seasickness is thought to result from conflicting inputs from the vestibular, visual and somatosensory systems. The otolithic organs, which are responsible for the sensation of linear acceleration and tilt, are important in the pathogenesis of seasickness. Vestibular evoked myogenic potentials test is an objective evaluation of saccular function.

Objective: To examine whether saccular function is related to the pathogenesis of seasickness.

Methods: VEMP1 was performed in 10 subjects susceptible to seasickness and in 14 non-susceptible subjects.

Results: Bilateral VEMP responses were obtained in 7 (50%) of the non-susceptible subjects and 1 (10%) of the susceptible subjects. No differences were found between the groups in P13 and N23 wave latencies, amplitudes, N13-P23 inter-peak latencies, and peak-to-peak asymmetry ratios. More subjects in the susceptible group had asymmetry ratios > 35%.   

Conclusions: The attenuated saccular response might be explained in the context of the neural-mismatch theory and/or the subjective vertical theory, as reflecting an adaptation effort to sea conditions. A larger study is necessary to determine whether a statistically significant difference in VEMP responses exists between seasickness-susceptible and non-susceptible subjects.