Israel Medical Association Journal

A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren’s syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed. The pattern of beat-to-beat blood pressure associated with performance of the Valsalva maneuver, and a low plasma norepinephrine level that did not increase in response to standing, established that the orthostatic hypotension was neurogenic. Treatment with an alpha-adrenoceptor agonist and fludrocortisone yielded partial improvement. After systemic diseases involving autonomic failure were excluded, cardiac sympathetic neuroimaging was performed by ¹²³I-metaliodobenzylguanidine (MIBG) scanning. The normal uptake seen in the heart indicated intact post ganglionic sympathetic innervation. There were no signs of central neurodegeneration or peripheral neuropathy. Because of symptoms and signs of both parasympathetic and sympathetic failure without denervation, an autonomic ganglionopathy was considered. A high titer of antibody to the neuronal nicotinic receptor, which mediates ganglionic neurotransmission, was obtained. The diagnosis of autoimmune autonomic ganglionopathy (AAG) was made, and the management strategy shifted to first lowering the antibody burden by plasma exchanges and then instituting chronic anti-autoimmune treatment with rituximab and a low dose of cortiosteroid. The patient showed remarkable improvement.

Background: Pulmonary arterial hypertension (PAH) is a significant consequence of congenital heart disease (CHD). Its presence and severity is associated with increased morbidity and mortality. 

Objectives: To evaluate the clinical and demographic characteristics of adults with congenital heart diseases (ADCHD) and PAH at a single center. 

Methods: A prospective registry of all patients with PAH was conducted between 2009 and 2015. 

Results: Thirty-two patients were identified. The mean age at the last visit was 44 years (range 19–77 years). The prevalence of PAH among all ADCHD patients was 6% (95% confidence interval 4.3%–8.4%). A much higher prevalence (53%) was found in patients with Down syndrome. Most patients with PAH had moderate or severe disease. Fifteen patients (47%) were treated with pulmonary vasodilators and 6 (19%) with combination therapy. The average World Health Organization functional class was 2.6. Morbidity included cerebral vascular accident or transient ischemic attack in 22% (mostly in patients with right-to-left shunt) and arrhythmia in 37% of the patients. During a median follow-up of 3.5 years, 5 patients (15.6%) died. Of 13 women with no mental retardation, 11 were or had been married and all had children (between 1 and 13, mean 3.3). 

Conclusions: Patients with congenital heart disease and PAH have significant morbidity and mortality. PAH is more prevalent in patients with Down syndrome. While pulmonary pressure during the reproductive years was not always known, 27% of women with PAH at the time of the study were multiparous.

 

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: The optimal approach to the evaluation of asymptomatic bacteruria in stroke patients is uncertain. 

Objectives: To compare elderly patients after an acute stroke with and without asymptomatic bacteriuria for the development of symptomatic urinary tract infections (UTI).

Methods: We prospectively monitored patients over 65 years of age admitted to our rehabilitation hospital after an acute stroke, with and without asymptomatic bacteriuria, for the development of symptomatic UTIs. The prevalence of bacteriuria was determined by urine cultures obtained 2 and 4 weeks after admission. Patients with and without persistent bacteriuria were compared to identify variables associated with bacteriuria.

Results: Fifty-five patients were included in the study. The prevalence of asymptomatic bacteriuria at baseline was 20%. Of all 55 stroke patients, 13 (23.6%) developed a symptomatic UTI during the 30 day follow-up. Patients with stroke and asymptomatic bacteriuria at baseline had an increased risk of developing a symptomatic UTI (54.5% with asymptomatic bacteriuria vs. 15.9% without, P = 0.011). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that bacteruria remained a significant covariate for symptomatic UTI (hazard ratio 2.86, 95% confidence interval 0.71–10.46, P = 0.051). When subjects who experienced symptomatic urinary infection were included, the prevalence of bacteriuria in the study cohort declined to about 45.5% by 30 days. 

Conclusion: Elderly patients with stroke and asymptomatic bacteriuria have an increased risk of developing a symptomatic UTI compared to those without asymptomatic bacteriuria during a 30 day post-stroke follow-up.

 

The unique characteristics of the next generation of medical professionals in Israel and the current model of physician employment in the country may pose a real threat to the high quality of both public clinical care and medical education in the near future, and to the continued flourishing of clinical research. According to the Israel Medical Association’s general obligations for Israeli physicians, the doctor should place the patient's interests foremost in his or her mind, before any other issue. This has led many to believe that selflessness or altruism should be among a physician’s core values. Is the application and realization of these obligations compatible with the realities of 21st century medicine? Is altruism still a legitimate part of the modern medical world? The Y generation, those born in the 1980s and 1990s, now comprise the majority of the population of residents and young specialists. They have been characterized as ambitious, self-focused, entrepreneurial, lacking loyalty to their employer, and seeking immediate gratification. Under these circumstances, is it possible to encourage or even teach altruism in medical school? Demands on physicians' time are increasing. The shortage of doctors, the growth of the population, the way in which health care is consumed, and the increasing administrative burden have all gnawed away at the time available for individual patient care. This time needs to be protected. The altruism of physicians could become the guarantee of first-rate care in the public sector. The continued existence of clinical research and high level clinical teaching also depends on the allocation of protected time. In light of the emerging generation gap and the expected dominance of Y generation physicians in the medical workforce in the near future, for whom altruism may not be such an obvious value, solutions to these predicaments are discussed.

Background: Six medical disciplines are responsible for assessment, diagnosis and treatment of people with attention deficiency hyperactivity disorder (ADHD) in Israel: family doctors, pediatricians, adult and child neurologists, adult and child psychiatrists.  

Objectives: To investigate differences in ADHD diagnostic practices between three different pediatric subspecialties in the clinical setting in order to establish a common ground for a future unified approach.

Methods: An anonymous web-based questionnaire was administered to child psychiatrists, pediatric neurologists and general pediatricians who are actively involved in ADHD diagnosis (n=104).

Results: Neurologists and pediatricians rarely use the mental status examination, while psychiatrists rarely perform a neurological or physical examination (P < 0.0001). A general clinical impression of learning abilities and/or neurodevelopmental skills was implemented more often by pediatric neurologists (P < 0.04).

Conclusions: The significant differences found between the three medical specialties with regard to the clinical evaluation of ADHD could be attributed, at least in part, to the ambiguity of available guidelines concerning the clinical examination, and to the adherence of each specialty to its own "skills." Larger surveys in other countries should be considered and an effort made to create a common, "inter-disciplinary" ground on this important part of ADHD evaluation, differential diagnosis, and research.

 

Autoimmune diseases constitute a diverse group of disorders characterized by cellular and humoral responses against self. The humoral autoimmune responses are directed against various cellular and extracellular components. These responses are highly specific for each autoimmune disease and result in the production of autoantibodies that characterize certain disease entities, representing a valuable tool for the diagnosis of autoimmune diseases. Furthermore, certain autoantibodies are helpful in the prognosis of disease development, progression and severity, as well as in the classification of patients with distinct disease subtypes. Today, the value of autoantibodies in the follow-up of patients is limited, but preliminary data suggest that they may be useful in predicting response to treatment. 

Background: Studies in lung transplantation demonstrate that the ancestry and gender dissimilarities of donor–recipients lead to a decrease in survival of the recipient. 

Objectives: To evaluate the survival of lung transplant recipients in Israel based on whether the donors and recipients are of Jewish or Arab ancestry as well as survival based on gender match or mismatch.

Methods: We performed a retrospective observational cohort study of 345 lung transplant recipients at the Rabin Medical Center, Petah Tikva, Israel between January 1997 and January 2013. We compared the survival of lung transplant recipients in two ancestry categories: ancestry matched (Jewish donors to Jewish recipients or Arab donors to Arab recipients) and ancestry mismatched (Jewish donors to Arab recipients and vice versa). We also compared the survival among the four gender donor and recipient combinations (male to male, female to female, male to female, and female to male). 

Results: Survival analysis revealed no significant differences between the two ancestry groups (P = 0.51) and among the four gender combinations (P = 0.58). On Cox multivariate analysis, younger donor age was the only significant parameter for longer survival (hazards ratio 1.025, 95% confidence interval 1.012–1.037).

Conclusions: Gender and ancestry mismatches in these two Israeli populations do not appear to alter the clinical outcomes following lung transplantation.

 

Background: Only a minority of patients with essential tremor (ET) and Parkinson’s disease (PD) undergo deep brain stimulation (DBS) surgery. Data on patient selection factors are useful.

Objectives: To compare the clinical characteristics of ET and PD patients who underwent DBS surgery with those of patients who had not undergone surgery.

Methods: We abstracted data from the electronic medical records of 121 PD and 34 ET patients who underwent DBS surgery at Columbia University Medical Center during the period 2009–2014. We compared this group with 100 randomly selected PD and 100 randomly selected ET patients at the Center who had not undergone DBS surgery. 

Results: Among other differences, age of onset in PD patients who had undergone surgery was younger than in those who did not: 14.9% vs. 3.0% with onset before age 40 (P = 0.003). They had also tried nearly double the number of medications (3.9 ± 1.7 vs. 2.3 ± 1.5, P < 0.001). Interestingly, there was no difference in the proportion of patients with tremor (81.0% vs. 88.0%, P = 0.16). Medical co-morbidities (heart and lungs) were less common in the PD patients who underwent DBS surgery. In the ET group, tremor causing impairment in activities of daily living occurred in all surgical patients compared to 73.0% of non-surgical patients (P < 0.001). The former had tried nearly double the number of medications compared to the latter (3.2 ± 1.7 vs. 1.3 ± 1.3, P < 0.001).

Conclusions: These data add to our understanding of the numerous clinical factors associated with patient referral to DBS surgery. 

 

Background: Despite the increased worldwide recognition of attention deficit/hyperactivity disorder (ADHD), there is a variability in the diagnostic rate of both ADHD and its co-morbidities. These diversities are probably related to the methodology and instruments used for the diagnosis of ADHD and to awareness and cultural interpretation of its existence. 

Objectives: To identify consistent differences in the clinical profile of Arab and Jewish children with ADHD in Israel who differ in their cultural, ethnic and socioeconomic background. 

Methods: We analyzed the data of 823 children and adolescents with ADHD (516 Jews and 307 Arabs) and compared the clinical characteristics between these two ethnic groups. All patients were evaluated in two neuropediatric and child development centers in northern Israel: one in Haifa and one in Hadera. Children with autism and intellectual disabilities were excluded. 

Results: The distribution of ADHD subtypes was similar in both populations. However, learning disorders and psychiatric co-morbidities (behavioral difficulties and anxiety) were reported more frequently in the Jewish population. The most commonly reported adverse effects to psychostimulants were mood changes, anorexia, headache, insomnia and rebound effect, and were more frequently reported in the Jewish population (42.0% vs.18.0%, P < 0.05).

Conclusions: We assume that these differences are related to cultural and socioeconomic factors. We suggest that the physician take cultural background into consideration when treating patients with ADHD.

 

In recent years, salivary gland ultrasonography (SGUS) has emerged as a promising tool for the diagnosis and prognostic stratification of patients with primary and secondary Sjögren’s syndrome. Several studies have emphasized that salivary ultrasonography could be a highly specific tool for the diagnosis of the disease. However, before it can be used in daily clinical practice the SGUS procedure needs standardization and validation in larger disease-control groups. In this review we provide an update on the role of SGUS in the diagnostic algorithm of primary Sjögren’s syndrome.