Israel Medical Association Journal

Background: Patients with end-stage renal disease are at high risk of mycobacterial infection.

Objectives: To analyze the difficulties in reaching an accurate diagnosis of tuberculosis in dialysis patients.

Methods: We conducted a retrospective follow-up of patients who attended our peritoneal and hemodialysis units during the 10 year period 1995–2005.

Results: Our dialysis unit diagnosed 10 cases of tuberculosis caused by Mycobacterium tuberculosis and 9 cases of Mycobacterium other than tuberculosis. In the former group, five patients had mycobacterium in the sputum, which was diagnosed by intraabdominal mass biopsy in one, culture of the gastric juices in one, and pleural fluid culture or pleural biopsy in three. One of these patients was suffering from pleural TB[1] as well as Potts disease. Of the patients with Mycobacterium other than tuberculosis, five were diagnosed by sputum cultures, three by urine cultures and one in peritoneal fluid. Differences in treatment and outcome were also reviewed.

Conclusions: The diagnosis of TB in dialysis patients should be approached with a high index of suspicion. It is clear that extensive diagnostic procedures are required to ensure an accurate diagnosis of the disease. Tuberculosis incurs a significant added burden due to the need for isolation of infected patients within the dialysis unit. Treatment of patients with Mycobacterium other than tuberculosis should be addressed individually.

Background: Asthma control and treatment compliance are widely investigated issues around the world. Studies have demonstrated relatively low asthma compliance and control in 40–90% of asthma patients in different countries. There are no available data on the Israeli adult asthmatic population

Objectives: To investigate the level of asthma control and compliance in adult asthmatic patients.

Methods: This cross-sectional study of consecutive adult asthmatic patients visiting the pulmonary clinic used a combined questionnaire that included demographics, data on asthma severity and management, and asthma control and compliance scores. Each patient was interviewed and questionnaires were filled out during a routine visit.

Results: The study group comprised 142 males (35.4%) and 259 females (64.6%). Compliance was found optimal in 8 patients (2%), fair in 146 (36%), partial in 156 (39%) and poor in 92 (23%) of the participating asthmatic patients. Asthma control was found optimal in 26 (7%), fair in 124 (31%), partial in 122 (30%) and poor in 129 (32%) patients. Sephardic and Ashkenazi Jewish origin, higher level of education, and treatment protocol including either single fixed-dose inhalers or short-acting beta-agonist bronchodilators significantly improved compliance in our cohort. Socioeconomic status and compliance were found to positively affect asthma control, whereas active smoking negatively affected asthma control in the study patients.

Conclusions: The figures of optimal asthma control and compliance to treatment in Israeli adult asthmatics are low and worse than reported in other studies abroad.
 

Background: The patient package insert, an information leaflet included by law in the packaging of prescription drugs, contains information for the user on the specific medication.

Objectives: To explore how patient information leaflets influence patient anxiety and adherence.

Methods: A prospective cohort study was conducted in the practices of 15 family physicians. All patients receiving a new prescription for antibiotics, analgesics or antihypertensives were included. Physicians completed a questionnaire containing demographic data, assessment of the patient’s anxiety, a prediction about adherence to the treatment, and response to the information leaflet. Patients were contacted by telephone for a follow-up structured interview. Patients' reactions to the information leaflet, adherence to treatment, and use of other sources of information on medication were assessed.

Results: The study group comprised 200 patients. The patient information leaflet was read by 103 of them (51.5%). A higher educational level and a chronic medication were associated with reading the leaflet (P = 0.02 and 0.01 respectively). In 36 (34.9%), an increase in anxiety was reported after reading the leaflet. Among those who read the leaflet, 9.7% had decreased adherence. Patients who stated that reading the leaflet caused anxiety were more likely to reduce their use of the medication – 7/36 (19.5%) vs. 3/67 (4.5%), P = 0.01.

Conclusions: The proportion of patients reading the drug information leaflet is about 50%, lower than that found in previous studies. Reading the leaflet did not greatly affect adherence but aroused anxiety and decreased adherence in some patients.
 

Background: Endothelial dysfunction is recognized as a major factor in the development of atherosclerosis and it has a prognostic value.

Objectives: To detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects and patients with cardiovascular disease.

Methods: We prospectively assessed brachial artery flow-mediated dilation in 110 consecutive subjects (46 CVD[1] patients and 64 healthy controls), mean age 57 ± 11 years; 68 were men. After an overnight fast and discontinuation of all medications for ≥ 12 hours, percent improvement in FMD and nitroglycerin-mediated vasodilatation were assessed using high resolution ultrasound.

Results: %FMD[2] but not %NTG[3] was significantly lower in CVD patients (9.5 ± 8.0% vs. 13.5 ± 8.0%, P = 0.012) compared to healthy controls (13.4 ± 8.0% vs. 16.7 ± 11.0%, P = 0.084; respectively). In addition, an inverse correlation between %FMD and the number of traditional CVD risk factors was found among all study participants (r = -0.23, P = 0.015) and healthy controls (r = -0.23, P = 0.036). In a mean follow-up of 15 ± 2 months, the composite CVD endpoints (all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with FMD < 6% compared to subjects with FMD > 6% (33.3% vs. 12.1%, P < 0.03, respectively).
Conclusions: Thus, brachial artery %FMD provides important prognostic information in addition to that derived from traditional risk factor assessment

Rembrandt van Rijn (1606–1669) left behind the largest collection of self-portraits in the history of art. These portraits were painted over a period of 41 years, using a realistic technique. To evaluate Rembrandt's aging process we studied 25 uncontested Rembrandt oil self-portraits by means of objective and descriptive techniques. By measuring brow position changes through the years, we demonstrated that brow descent started in the second half of the third decade and began to level out in the fourth decade. Based on Rembrandts' aging physiognomy, from age 22 to 63, we believe that Rembrandt did not suffer from temporal arteritis, hypothyroidism, rosacea, or rhynophima and that no other facial signs of systemic diseases are evident, contrary to the opinions expressed by other medical professionals. We suggest that Rembrandt suffered from melancholia or mild depression, and propose the possibility of chronic lead poisoning as a theoretical illness that he might have had.

Background: When encountering complaints of pain in the area of Achilles tendon with a suspected lesion, the clinician seldom reaches a precise diagnosis based only on X-ray and clinical examination. Ultrasonography is useful for evaluating the pathology and treatment.

Objectives: To assess the relative contribution of real-time intraoperative ultrasound examination and immediate postoperative ultrasound in patients with acute rupture of the Achilles tendon treated by percutaneous suture method. The combination of both procedures provides a unique advantage that could facilitate better results.

Methods: Ultrasound examination was used in 20 patients with acute rupture of the Achilles tendon who were treated surgically. Intraoperative as well as postoperative ultrasound examinations were performed in 5 patients whereas 15 patients underwent an immediate postoperative ultrasound.

Results: Ultrasound pathologies were found in all patients. Percutaneous surgical correction of ruptured Achilles tendon with accurate positioning of the foot using real-time sonography was successful in all the patients.

Conclusion: As in many other soft tissue lesions, ultrasonography is a useful tool for evaluating the pathology and for planning the surgical correction of ruptures in the Achilles tendon.

In Israel, updating of the National List of Health Services is performed on a yearly basis in a systematic and structured mechanism for almost a decade. The existence of such a mechanism is vital for keeping medicine up to date, since many innovative and breakthrough medical technologies continuously and frequently evolve. The 2006 update is unique in several aspects, relating both to the mechanism and to the decision-making process. In this article we describe notable issues that arose during the current process: modifications to the update mechanism, the four-phase increase in allocated resources to fund the addition of new medical technologies (including the addition of finances at the expense of the 2007 planned budget), and public funding for high-cost therapies. Finally, we discuss the impact of medical advances on healthcare costs and a suggested constant annual addition to the budget.

Premature very low birth weight (< 1500 g) infants are one of the largest groups receiving parenteral nutrition. PN[1] should be optimized to answer their large nutritional requirements and suit their metabolic status, but should also be validated pharmaceutically. PN can be provided as a standard, usually commercial, formulation, representing the average needs of a large group of patients. Alternatively, an individualized PN compound adapted to the patient's needs can be prescribed and prepared, usually on a daily basis. The main advantage of individually prescribed PN is that it is tailored to suit a specific patient, thereby assuring the best possible nutrition and biochemical control. Batch-produced standardized PN bags can be readily available as ward stocks in neonatal intensive care units, enabling initiation of early PN immediately after the delivery of a premature infant. Moreover, standard PN solutions incorporate expert nutritional knowledge and support. A combination of standardized PN bags, prepared under strict standardization criteria, for most neonates, with a small number of specifically tailored individualized PN formulations for those in need for them, could reduce pharmacy workload and costs, and increase safety, while maintaining the desired clinical flexibility. For those in need of the individualized PN formulations, a computerized ordering system can save time, decrease prescription and compounding errors, and improve quality of nutritional care.

Objectives: To determine whether reliable data could be obtained at lower cost.

Methods: The study sample consisted of 50 patients with mild to severe stable COPD]1[. All underwent pulmonary function test and the cardiopulmonary exercise test, 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit. Functional capacity was graded according to each test separately and the functional capacities obtained were correlated.

Results: The results showed that most of the patients had severe COPD according to pulmonary function tests (mean forced expiratory volume in the first second 46.3 ± 19.9% of predicted value). There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test (r = 0.07, P = 0.64).

Conclusions: The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients.

Background: Poliovirus rapidly evolves by nucleic acid substitutions and genetic recombination with other polioviruses and non-polio enteroviruses. Evolving oral poliovirus (Sabin strains) can rapidly revert to neurovirulence and undergo antigenic alterations.

Objectives: To evaluate the threat of vaccine-derived poliovirus (1–15% divergence from the respective Sabin strain) for a poliomyelitis-free population in a country with a long-standing routine vaccination program.

Methods: We characterized genetic and antigenic changes in OPV[1] strains isolated from sewage in Israel and evaluated intestinal immunity by measuring fecal excretion after OPV challenge of vaccinated children.

Results: Characterization of poliovirus from sewage revealed eight type 2 and three type 3 vaccine polioviruses that had replicated and started to evolve (vaccine that replicated and diverged by 0.5 to ≤ 1.0%) and nine highly diverged type 2 vaccine-derived polioviruses (1–15% divergence from the respective Sabin strain) with 8–14% divergence between the years 1998 and 2005. Six of the eleven VRPV[2] uniquely recombined with OPV and/or NPEV[3]. The nine VDPV[4] were epidemically related, genotypically neurovirulent, and had 10–15 amino acid substitutions in antigenic sites altering their antigenicity, but shared a single recombination. Type 2 OPV was excreted by 23% and 17% of infants challenged with OPV 3 months after partial immunization (two doses each of OPV and enhanced inactivated poliovirus) or full immunization (three doses of each) respectively, despite high humoral antibody titers.

Conclusions: Our findings, which show that OPV is excreted for a significant period by children with high humoral immunity, emphasize the long-term potential threat from VDPV in highly vaccinated populations. An adequate immunization program, combined with environmental surveillance, is necessary to prevent poliomyelitis and community transmission of poliovirus. 

Background: Emergency room triage of patients presenting with chest pain syndromes may be difficult. Under-diagnosis may be dangerous, while over0diagnosis may be costly.

Objectives: To report our initial experience with an emergency room cardiologist-based chest pain unit in Israel.

Methods: During a 5 week pilot study, we examined resource utilization and ER [1] diagnosis in 124 patients with chest pain of uncertain etiology or non-high risk acute coronary syndrome. First assessment was performed by the ER physicians and was followed by a second assessment by the CPU[2] team. Assessment was based on the following parameters: medical history and examination, serial electrocardiography, hematology, biochemistry and biomarkers for ACS[3], exercise stress testing and/or 64-slice multi-detector cardiac computed tomography angiography. Changes in decision between initial assessment and final CPU assessment with regard to hospitalization and utilization of resources were recorded.

Results: All patients had at least two cardiac troponin T measurements, 19 underwent EST[4], 9 echocardiography and 29 cardiac MDCT[5]. Fourteen patients were referred for early cardiac catheterization (same/next day). Specific working diagnosis was reached in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124 patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and 35 (28%) to the Cardiology departments. CPU assessment and extended resources allowed discharge of 30/101 patients (30%) who were initially identified as candidates for hospitalization after ER assessment. Furthermore, 13/23 (56%) of patients who were candidates for discharge after initial ER assessment were eventually hospitalized. Use of non-invasive tests was significantly greater in patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001). The mean ER stay tended to be longer (14.9 ± 8.6 hours vs. 12.9 ± 11, P = NS) for patients discharged. At 30 days follow-up, there were no adverse events (myocardial infarction or death) in any of the 40 patients discharged from the ER after CPU assessment. One patient returned to the ER because of chest pain and was discharged after re-assessment. 

Conclusions: Our initial experience showed that an ER cardiologist-based chest pain unit improved assessment of patients presenting to the ER with chest pain, and enhanced appropriate use of diagnostic tests prior to decision regarding admission/discharge from the ER.

Polyubiquitylation of cellular proteins has long been recognized as a prelude to a degradative fate in proteasomes. In recent years, however, ubiquitin conjugation has emerged as a regulatory strategy of considerable versatility. Most notably, monoubiquitylation is attributed an intimate role in trafficking of membrane proteins between various cellular compartments. Diverse classes of transmembrane proteins from across the eukaryotic spectrum (e.g., epidermal growth factor-receptor and other receptor tyrosine kinases) become modified with monoubiquitin molecules. Monoubiquitylation of substrates, in turn, regulates both their endocytosis at the plasma membrane and sorting in endosomes for delivery to lysosomes or vacuoles. A mechanistic rationale lies in the identification of a growing list of ubiquitin-binding domains carried by a variety of endocytic adaptor proteins. Thus, ubiquitin-conjugated membrane proteins may form extensive contacts with the endocytic machinery. Further, ubiquitin-binding adaptors and other endocytic components are, likewise, often monoubiquitylated. In this case, ubiquitin conjugation may serve to enhance intermolecular avidity in cargo-bound endocytic complexes, or alternatively, to mediate timely inactivation of ubiquitin-binding adaptors. Interestingly, the ubiquitin/endocytosis interface is appropriated by pathogenic organisms, for instance, during budding of viruses from host-infected cells. Moreover, compromised ubiquitin-mediated transport of certain signaling receptors is associated with disease states, including oncogenic transformation.