Eyal Leibovitz, MD, Dror Harats, MD and Dov Gavish, MD
Background: Hyperlipidemia is a major risk factor for coronary heart disease. Reducing low density lipoprotein-cholesterol can significantly reduce the risk of CHD, but many patients fail to reach the target LDL-C goals due to low doses of statins or low compliance.
Objectives: To treat high risk patients with atorvastatin in order to reach LDL-C goals (either primary or secondary prevention) of the Israel Atherosclerosis Society.
Methods: In this open-label study of 3,276 patients (1,698 of whom were males, 52%), atorvastatin 10 mg was given as a first dose, with follow-up and adjustment of the dose every 6 weeks. While 1,670 patients did not receive prior hypolipidemic treatment, 1,606 were treated with other statins, fibrates or the combination of both.
Results: After 6 weeks of treatment, 70% of the patients who did not receive prior hypolipidemic medications and who needed primary prevention reached target LDL-C levels. Interestingly, a similar number of patients on prior hypolipidemic treatment reached the LDL-C goals for primary prevention. The patients treated with other statins, fibrates or both did not reach the LDL-C treatment goals. Only 34% of all patients who needed secondary prevention reached the ISA LDL-C target of 100 mg/dl. Atorvastatin proved to be completely safe; only two patients had creatine kinase elevation above 500 U/L, and another six had mild CK elevation (<500 U/L). None of the patients had clinical myopathy, and only one had to be withdrawn from the study.
Conclusion: Atorvastatin is a safe and effective drug that enables most patients requiring primary prevention to reach LDL-C goal levels, even with a low dose of 10 mg. Patients in need of secondary prevention usually require higher doses of statins.
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Nurit Rosenberg, PhD, Ariella Zivelin, PhD, Angela Chetrit, PhD, Rima Dardik, PhD, Nurit Kornbrot, MSc, Dov Freimark, MD and Aida Inbal, MD
Background: Platelet adhesion and aggregation are mediated by specific platelet membrane glycoproteins GPIa/IIa, GPIba, and GPIIb/IIIa, and are essential steps in thrombus formation and development of acute myocardial infarction.
Objective: To evaluate the risks exerted by each of the following polymorphisms: HPA-1a/b in GPIIIa; 807C/T in GPIa; and HPA-2a/b, VNTR and Kozak C/T in GPIba in young males with AMI..
Methods: We conducted a case-control study of 100 young males with first AMI before the age of 53 and 119 healthy controls of similar age. All subjects were tested for the above polymorphisms.
Results: The allele frequencies of each of the platelet polymorphism were not significantly different between the young men with AMI and the controls. Smoking alone was associated with a 9.97-fold risk, and the presence of at least one metabolic risk factor resulted in a 2.57-fold risk of AMI.
Conclusion: These results indicate that platelet glycoproteins polymorphisms are not an independent risk factor for AMI.
Gabriel Izbicki, MD, David Shitrit, MD, Dan Aravot MD, Gershon Fink, MD, Milton Saute, MD, Leonid Idelman, MD, Ilana Bakal, BA, Jaqueline Sulkes, PhD and Mordechai R. Kramer, MD
Background: Historically, donor age above 55 years has been considered to be a relative contraindication for organ transplantation. The shortage of organs for transplantation has led to the expansion of the donor pool by accepting older donors.
Objectives: To compare the 1 year follow-up in patients after lung transplantation from older donors (>50 years old) and in patients after transplantation from younger donors (± 50 years).
Methods: The study group comprised all adult patients who underwent lung transplantation at the Rabin Medical Center between May 1997 and August 2001. Donors were classified into two groups according to their age: ≤ 50 years (n=20) and > 50 years (n=9). Survival, number and total days of hospitalization, development of bronchiolitis obliterans syndrome, and pulmonary function tests, were examined 1 year after transplantation.
Results: We performed 29 lung transplantations in our center during the observed period. Donor age had no statistically significant impact on 1 year survival after lung transplantation. There was no statistically significant effect on lung function parameters, the incidence of hospitalization or the incidence of bronchiolitis obliterans between both donor age groups at 1 year after transplantation.
Conclusions: Donor age did not influence survival or important secondary end-points 1 year after lung transplantation. By liberalizing donor criteria of age up to 65 years, we can expand the donor pool, while assessing other possible mechanisms to increase donor availability.
Alexander Guber, MD, Eyal Morris, MD, Baruch Chen MD and Shaul Israeli, MD
Background: Ventilator-dependent patients represent an increasing clinical, logistic and economic burden. An alternative solution might be monitored home care with high-tech ventilatory support systems.
Objectives: To explore the implications of such home-care management, such as its impact on quality of life and its cost-effectiveness, and to assess the practical feasibility of this mode of home care in Israel.
Methods: We surveyed 25 partly or fully home-ventilated patients (17 males and 8 females), average age 37.6 years (range 1–72), who were treated through a home-care provider during a 2 year period.
Results: Most patients (n=18) had a neuromuscular respiratory disorder. The average hospital stay of these patients prior to entry into the home-care program was 181.2 days/per patient. The average home-care duration was 404.9 days/per patient (range 60–971) with a low hospitalization rate of 3.3 ± 6.5 days/per patient. The monthly expenditure for home care of these patients was one-third that of the hospital stay cost ($3,546.9 vs. $11,000, per patient respectively). The patients reported better quality of life in the home-care environment, as assessed by the Sickness Impact Profile questionnaire.
Conclusions: Home ventilation of patients in Israel by home-care providers is a practical and attractive treatment modality in terms of economic benefits and quality of life.
Shlomo Vinker, MD, Sasson Nakar, MD, Elliot Rosenberg, MD, MPH and Eliezer Kitai, MD
Background: Colorectal cancer is the second leading cause of cancer mortality in Israel. Unfortunately, compliance with annual fecal occult blood testing is very low.
Objective: To assess the effectiveness of interventions to increase FOBT screening in primary care clinics in Israel.
Methods: A prospective, randomized study included all 50–75 year old enrollees of six family physicians in two primary care clinics. The register of two physicians, one from each clinic, was allocated to one of three groups. Two FOBT reminder strategies were tested: a physician reminder (753 patients), and a patient reminder that was either a phone call (312 patients) or a letter (337 patients). The control group (913 patients) of physicians continued administering their regular level of care. The main outcome measure was the percentage of patients undergoing FOBT screening in each study arm at the conclusion of the one year study period.
Results: In the intervention groups 14.3% (201/1,402) were screened using the FOBT over the course of the study year. Using an intent-to-screen analysis, the screening rate in the physician and patient reminder groups was significantly higher than in the control group(16.5 and 11.9%,vs. 1.2% respectively, P < 0.0001). Phone reminders were significantly more efective as compared to letters (14.7 vs. 9.2%, P = 0.01).
Conclusions: Our study has shown the benefit of various FOBT reminder systems, especially those centered around the family physician. Further research should focus on this area, in conjunction with other novel approaches.
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FOBT = fecal occult blood testing
Eliezer Golan, MD, Bruria Tal, PhD, Yossef Dror, PhD, Ze’ev Korzets, MBBS, Yaffa Vered, PhD, Eliyahu Weiss, MSc and Jacques Bernheim, MD
Background: Multiple factors are involved in the pathogenesis of hypertension in the obese individual.
Objective: To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.
Methods: We evaluated three groups: 25 obese hypertensive patients (age 45.7±1.37 years, body mass index 34.2±1.35 kg/m2, systolic/diastolic blood pressure 155±2.9/105±1.3, mean arterial pressure 122±1.50 mmHg); 21 obese normotensive patients (age 39.6±1.72, BMI 31.3±0.76, SBP/DBP 124±2.1/85.4±1.8, MAP 98.2±1.80); and 17 lean normotensive subjects (age 38.1±2.16, BMI 22.1±0.28, SBP/DBP 117±1.7/76.8±1.5, MAP 90.1±1.50). We determined basal resting metabolic rates, plasma insulin (radioimmunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n=14) and 14 (n=10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.
Results: Obese hypertensive patients had significantly higher basal RMR and plasma NE levels. Insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than that of obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP5, RMR, and plasma NE and insulin .Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.
Conclusions: A reduction of sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.
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BMI = body mass index
SBP/DBP = systolic blood pressure/diastolic blood pressure
MAP = mean arterial pressure
UNOx = urinary nitric oxide
RMR – resting metabolic rate
NE = norepinephrine
Gregory Kouraklis, MD, Andromachi Glinavou, MD, Dimitrios Mantas, MD, Efstratios Kouskos, MD and Gabriel Karatzas, MD
Background: Small bowel diverticula are usually asymptomatic and rare. Their importance is based on the fact that they carry the risk of serious complications.
Objective: To study the implications and the therapeutic approach regarding small bowel diverticulosis.
Methods: The medical records of 54 patients with diverticular disease of the small bowel, including Meckel’s and duodenum diverticula, were retrospectively reviewed. The mean age of the 32 male and 22 female patients was 53.2 years.
Results: Diverticula were found in the duodenum in 11 cases, in the jejunum and ileum in 21 cases, and with Meckel’s diverticula in 22 cases. In 24% of the patients the diverticula were multiple. The most common clinical symptom was abdominal pain, in 44.4%. Most of the duodenum diverticula were asymptomatic; 47.6% of the patients with diverticular disease located in the jejunum and ileum presented with chronic symptoms. The overall diagnostic rate for symptomatic diverticula before surgery was 52.7%; in 33.3% diverticula were found incidentally during other diagnostic or therapeutic procedures. Forty-one patients were managed surgically: 15 patients were operated on urgently because of infection or rupture, 4 patients for bleeding, 5 patients for intestinal obstruction and one patient for jaundice.
Conclusions: The incidence of asymptomatic small bowel diverticula is difficult to ascertain. Patients with Meckel’s and duodenal diverticula are usually asymptomatic, while the majority of jejunal and ileal diverticula patients present with chronic symptoms. The preoperative diagnostic rate is higher for duodenal diverticula. Small bowel diverticula do not require surgical treatment unless refractory symptoms or complications occur.
Yoav Mattan, MD, Alice Dimant, MD, Rami Mosheiff, MD, Amos Peyser, MD, Steven Mendelson, MD and Meir Liebergall, MD
Background: Femoral hip fractures are a common occurrence in the elderly. Of the various fracture patterns, intertrochanteric injuries have the lowest rate of complications. Case reports of ensuing subcapital fracture have all been linked to incorrect placement of fixation devices or to osteomyelitis, while cases of avascular necrosis have only been reported rarely in the literature and are considered to occur at the rare rate of 0.8%.
Objectives: To check the incidence and outcome of AVN in intertrochanteric hip fractures.
Methods and Results: In a retrospective analysis of patients who had surgical treatment for intertrochanteric fractures, 10 patients (0.5%) underwent dynamic hip screw fixation for intertrochanteric fractures and subsequently developed painful AVN as their primary presentation. Three of these patients were also found to have subcapital fractures. On revision of the primary fixation no fault was found with nail placement.
Conclusions: The reported rate of AVN may be understated since many patients have limiting factors that prevent them from consulting a physician when in pain, and one-third of these patients die within 2 years. Therefore, we suggest that hip pain following fixation of an intertrochanteric fracture should prompt the clinician to consider the rare possibility of AVN or subcapital fracture.
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AV = avascular necrosis
Naomi B. Zak, PhD, Sagiv Shifman, MSc, Anne Shalom, PhD and Ariel Darvasi, PhD, MPH
The complex genetic nature of many common diseases makes the identification of the genes that predispose to these ailments a difficult task. In this review we discuss the elements that contribute to the complexity of polygenic diseases and describe an experimental strategy for disease-related gene discovery that attempts to overcome these factors. This strategy involves a population-based case-control paradigm and makes use of a highly informative, homogeneous founder population, many of whose members presently reside in Israel. The properties of single nucleotide polymorphisms, which are presently the markers of choice, are discussed, and the technologies that are currently available for SNP genotyping are briefly presented.
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SNP = single nucleotide polymorphism
Eduardo Garcua-Garcia, MD, Carlos A. Aguilar-Salinas, MD, Teresa Tusie-Luna, MD, PhD and Juan Antonio Rull-Rodrigo, MD
This review summarizes the clinical, metabolic and genetic characteristics of early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a clinical challenge and a public health problem. It is calculated that almost 300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large Mexican family structure and the high prevalence of the disease provide a unique opportunity to identify the genes and the metabolic abnormalities involved in this form of the disease. In a hospital-based population, our group found that insulin deficiency was the main defect in this form of diabetes. Mutations in the HNF-1α or HNF-4α genes or autoimmunity to the beta cell were found in a small proportion of cases, leaving unexplained the majority of cases. Also discussed are the epidemiologic and therapeutic implications of early-onset type 2 diabetes, and the possible role of genetic testing for prevention.