Israel Medical Association Journal

Background: Chronic heart failure is associated with excessive hospitalizations and poor prognosis.

Objectives: To summarize the 5 year experience of a single-center CHF[1] day care service, detect the cardiovascular and non-cardiovascular events, and evaluate the safety of the treatments provided.

Methods: We retrospectively studied all patients admitted to the CHF day care service of the Sheba Medical Center between September 2000 and September 2005.

Results: Advanced (New York Heart Association class III-IV) CHF patients (n=190), mean age 65 ± 12 years and left ventricular ejection fraction 25 ± 11%, were treated for 6 hourly biweekly visits; 77% had ischemic and 23% had non-ischemic cardiomyopathy. Treatment included: intravenous diuretic combinations (91%), intermittent low dose (≤ 5 mg/kg/min) dobutamine (87%), low dose (≤ 3 mg/kg/min) dopamine (38%), intravenous iron preparation and/or blood (47%), and intravenous nitropruside (36%). Follow-up of at least 1 year from initiation of therapy was completed in 158 of 190 patients (83%). Forty-six (29.3%) died: 23% due to CHF exacerbation, 5.7% from infection, 4.4% from sudden cardiac death, 3.8% from malignancy, 2.5% from malignant arrhythmias, 1.9% from renal failure, 1.3% from stroke, and 0.6% from myocardial infarction. There were only 0.68 rehospitalizations/patient/year; the most frequent cause being CHF exacerbation (16.5%).

Conclusions: Our study demonstrates the safety and potential benefits of a supportive day care service for advanced CHF patients. Multidrug intravenous treatment, accompanied by monitoring of electrolytes, hemoglobin and cardiac rhythm, along with education and psychological support, appear to reduce morbidity in advanced CHF patients and may have contributed to the lower than expected mortality/hospitalization rate.

Background: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

Hereditary angioedema is a rare genetic disorder, manifested by recurrent edema leading to disfigurement, organ dysfunction and life-threatening respiratory impairment that may become fatal. The hallmark of HAE is a C1 esterase inhibitor deficiency, but recent evidence points at bradykinin as the main mediator that causes hyperpermeability of small vasculature, leading to accumulation of edema fluid. Current therapeutic options for HAE[1] are limited, and consist of drugs, replacement therapy, and supportive treatment. In view of many disadvantages of the current therapeutic modalities new approaches to the treatment of HAE are now being offered. This review summarizes our experience with a new line of medications developed for the treatment of acute exacerbations and prophylaxis of HAE – icatibant: bradykinin receptor antagonist, ecallantide: kallikrein inhibitor, and two C1 INH[2] preparations: Berinert-P, human plasma-derived concentrate, and Rhucin: novel recombinant C1-INH produced in transgenic rabbits. Preliminary results of these studies are encouraging and may bring new hope to the patients with this distressing condition. The exact number of HAE patients in Israel is unknown and because patients are treated individually and comprehensive laboratory assessment is partial, many cases might be missed or not treated according to accepted guidelines. We offer a new specialty center for HAE patients, addressing the medical and psychosocial needs of patients and their families.

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Background: Reports of burn injuries in children are usually made by highly specialized burn units. Our facility admits children with burns < 20% total body surface area, while those with major burns are transferred to burn units at tertiary care facilities.

Objectives: To review our experience with thermal burns.

Methods: We conducted a retrospective review of all thermal burns admitted to our hospital during a 5 year period.

Results: Among 266 patients (69.2% boys) aged 3.5 ± 3.6 years, children < 3 years old were the most frequently injured (64.7%). Scalds (71.4%) were the most common type of burn. Partial thickness burns were sustained by 96.6% of children and TBSA[1] burned was 4.2 ± 3.6%. The mean hospital stay was 3.8 ± 4.5 days, and was significantly prolonged in girls (4.6 ± 4.8 vs. 3.5 ± 4.3 days, P = 0.01). Percent TBSA burned was correlated with patient age (r = 0.12, P = 0.04) and length of hospital stay (r = 0.6, P < 0.0001). Six patients (2.3%) (mean age 3.4 ± 2.3 years) were hospitalized in the Pediatric Intensive Care Unit due to toxin-mediated illness.

Conclusions: Children under the age of 3 years are at increased risk for burn injury, but older children sustain more extensive injuries. Prevention and awareness are needed for child safety.

Background: Iron deficiency and lead poisoning are common and are often associated. This association has been suggested previously, mainly by retrospective cross-sectional studies.

Objective: To assess the impact of short-term lead exposure at indoor firing ranges, and its relationship to iron, ferritin, lead, zinc protoporphyrin, and hemoglobin concentrations in young adults.

Methods: We conducted a clinical study in 30 young healthy soldiers serving in the Israel Defense Forces. Blood samples were drawn for lead, zinc protoporphyrin, iron, hemoglobin and ferritin prior to and after a 6 week period of intensive target practice in indoor firing ranges.

Results: After a 6 week period of exposure to lead dust, a mean blood lead level increase (P < 0.0001) and a mean iron (P < 0.0005) and mean ferritin (P < 0.0625) decrease occurred simultaneously. We found a trend for inverse correlation between pre-exposure low ferritin levels and post-exposure high blood lead levels.

Conclusions: The decrease in iron and ferritin levels after short-term lead exposure can be attributed to competition between iron and lead absorption via divalent metal transport 1, suggesting that lead poisoning can cause iron depletion and that iron depletion can aggravate lead poisoning. This synergistic effect should come readily to every physician's mind when treating patients with a potential risk for each problem separately.
 

Background: Early detection of malignant melanoma of the skin is the most important factor in patient survival. Naked-eye diagnostic sensitivity and specificity are low. Patients with multiple nevi are at high risk to develop melanomas and the clinical follow-up of such patients is difficult, resulting in missed melanomas on the one hand and unnecessary biopsies on the other.

Objectives: To describe the set-up of a special clinic aimed at early detection of melanoma and follow-up of high risk patients and preliminary results from 20 months of operation.

Methods: We established a pigmented lesions clinic based on a digital photography studio enabling documentation and comparison over time of full body photography and dermoscopy.

Results: In the first 20 months of work, 895 patients were seen, 206 of them for follow-up visits. A total of 29,254 photos were taken. Altogether, 236 lesions were suspicious (either clinically or dermoscopically) and the patients were advised to excise them. Seven melanomas were found in this initial examination (which did not include long-term follow-up).

Conclusions: With multimode photographic cutaneous surveillance, early detection of melanoma in high risk patients has been reported. Our clinic utilizes the same techniques and diagnostic algorithm as other leading clinics throughout the world, thus enabling us to deliver better follow-up for those patients.
 

Background: Until three decades ago coronary heart disease and stroke were considered rare in the Israeli Bedouin population. Today, this population shows increasing high prevalence compared to the Jewish population.

Objectives: To evaluate the prevalence of diagnosed cardiovascular risk factors among the Bedouin (hypertension, diabetes mellitus, dyslipidemia), and to assess compliance with follow-up tests and drug treatment.

Methods: The study included all listed patients aged 20 years and older in eight clinics in major Bedouin towns, and in two large teaching clinics in Beer Sheva (Jewish population). Risk factor data were extracted from the clinics' computerized databases. For those diagnosed with hypertension, diabetes or dyslipidemia, drug purchasing data were collected from the pharmacy database to determine compliance with treatment, and from the central laboratory mainframe (HbA1c and low density lipoprotein-cholesterol) to evaluate follow-up and control.

Results: A significantly higher prevalence of diabetes in all age groups was found in the Bedouin population compared to the Jewish population; age-adjusted results show a prevalence of 12% vs. 8% respectively (P < 0.001). The prevalence of dyslipidemia and age-adjusted hypertension was lower among Bedouins (5.8% vs. 18.2%, P < 0.01 and 17% vs. 21%, P < 0.001 respectively). Two-thirds of hypertensive Bedouin patients and 72.9% of diabetic Bedouin patients were not compliant with treatment. For dyslipidemia only 10.4% of the Bedouins were compliant compared with 28.2% in the Jewish population (P < 0.001).

Conclusions: Compliance with drug therapy and follow-up tests was found to be a major problem in the Bedouin population.
 

Background: Burns are a major public health problem, with long hospitalization stay in both intensive care units and general wards. In Israel about 5% of all hospitalized injuries are burn injuries. There are no long-term epidemiological studies on burn injuries in adults in Israel.

Objectives: To identify risk factors for burn injuries and provide a starting point for the establishment of an effective prevention plan.

Methods: We analyzed the demographic, etiologic and clinical data of 5000 burn patients admitted to the five major hospitals with burn units in Israel during a 7 year period (1997–2003). Data were obtained from the records of the Israeli National Trauma Registry. The differences between various groups were evaluated using the chi-square test.

Results: Male gender was twice as frequent as female gender in burn patients (68.0% vs. 31.9%), and Jewish ethnicity was more common than non-Jewish (62.3% vs. 36.8%). Second and third-degree burns with body surface areas less than 10% constituted the largest group (around 50%). The largest age group was 0–1 years, constituting 22.2% of the cases. Inhalation injury was uncommon (1.9%). The most common etiologies were hot liquids (45.8%) and open fire (27.5%). Children less than 10 years old were burnt mainly by hot liquids while the main cause of burns for adults > 20 years old was an open flame. The majority of burns occurred at home (58%); around 15% were work related. The mean duration of hospitalization was 13.7 days (SD 17.7); 15.5% were in an intensive care unit with a mean duration of 12.1 days (SD 17.1). Surgical procedures became more common during the period of the study (from 13.4% in 1998 to 26.59% in 2002, average 19.8%). The mortality rate was 4.4%. We found a strong correlation between burn degree and total body surface area and mortality (0.25% mortality for 2nd to 3rd-degree burns with less than 10% TBSA[1], 5.4% for 2nd to 3rd-degree burns with 20–39% TBSA, and 96.6% for burns > 90% TBSA). The worst prognosis was for those over the age of 70 (mortality rate 35.3%) and the best prognosis was for the 0–1 year group (survival rate 99.6%).

Conclusions: The groups at highest risk were children 0–1 years old, males and non-Jews (the incidence rate among non-Jews was 1.5 times higher than their share in the general population). Those with the highest mortality rate were victims of burns > 90% TBSA and patients older than 70. Most burns occurred at home.

Background: The measurement of maternal serum human chorionic gonadotropin as a predictor of fetuses with Down syndrome has been in use since 1987.

Objectives: To determine the correlation between extremely high levels of hCG[1] at mid-gestation and maternal and fetal complications.

Methods: The study group consisted of 75 pregnant women with isolated high levels of hCG (> 4 MOM) at mid-gestation, and the control group comprised 75 randomly selected women with normal hCG levels (as well as normal alpha-fetoprotein and unconjugated estriol levels). The data collected included demographic details, fetal anomalies, chromosomal aberrations, pregnancy complications, and results of neonatal tests.

Results: There was a significant increase in the frequency of fetal anomalies (detected by ultrasound), low birth weight and neonatal complications in the study group. We also found an increased rate of fetal/neonatal loss proportional to the increasing levels of hCG (up to 30% in levels exceeding 7 MOM).

Conclusion: Our study demonstrated an increased frequency of obstetric complications that was closely associated with raised hCG levels. The study also raises questions about the accuracy of the Down syndrome probability equation in the presence of extremely high levels of hCG where data on the frequency of Down syndrome is severely limited.

Background: Coronary heart disease and ischemic stroke are among the leading causes of morbidity and mortality in adults, and cerebrovascular disease is associated with the presence of symptomatic and asymptomatic CHD[1]. Several studies noted an association between coronary calcification and thoracic aorta calcification by several imaging techniques, but this association has not yet been examined in stable angina pectoris patients with the use of spiral computed tomography.

Objectives: To examine by spiral CT the association between the presence and severity of CC[2] and thoracic aorta calcification in patients with stable angina pectoris.

Methods: The patients were enrolled in ACTION (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS) in Israel. The 432 patients (371 men and 61 women aged 40–89 years) underwent chest CT and were evaluated for CC and aortic calcification.

Results: CC was documented in 90% of the patients (n=392) and aortic calcification in 70% (n=303). A significant association (P < 0.05) was found between severity of CC and severity of aortic calcification (as measured by area, volume and slices of calcification). We also found an association between the number of coronary vessels calcified and the presence of aortic calcification: 90% of patients with triple-vessel disease (n=157) were also positive for aortic calcification (P < 0.05). Age also had an effect: 87% of patients ≥ 65 years (n=219) were positive for both coronary and aortic calcification (P = 0.005) while only 57% ≤ 65 (n=209) were positive for both (P = 0.081).

Conclusions: Our study demonstrates a strong association between the presence and severity of CC and the presence and severity of calcification of thoracic aorta in patients with stable angina pectoris as detected by spiral CT.

Background: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia.

Objectives: To assess the added diagnostic value of a new cardiac performance index (dP/dt^ejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-nduced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia.

Methods: The study group comprised 40 patients undergoing Sestamibi-SPECT[1]/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dt^ejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dt^ejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dt^ejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone.

Results: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%.
Conclusions: If ECG alone is used for specificity, the combination with dP/dt^ejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise

Objectives: To estimate the influence of phlebotomies on large artery (C1) and small artery compliance (C2) in PV patients by using non-invasive methods.

Methods: Short-term hemodynamic effects of phlebotomy were studied by pulse wave analysis using the HDI-Pulse Wave CR2000 (Minneapolis, MN, USA) before and immediately after venesection (300–500 ml of blood). We repeated the evaluation after 1 month to measure the long-term effects.

Results: Seventeen PV patients were included in the study and 47 measurements of arterial compliance were performed: 37 for short-term effects and 10 for long-term effects. The mean large artery compliance (C1) before phlebotomy was 12.0 ml/mmHg x 10 (range 4.5–28.6), and 12.6 ml/mmHg x 10 (range 5.2–20.1) immediately after phlebotomy (NS). The mean small artery compliance (C2) before and immediately after phlebotomy were 4.4 mg/mmHg x 10 (range 1.2–14.3) and 5.5 mg/mmHg x 10 (range 1.2–15.6) respectively (delta C2–1.1, P < 0.001). No difference in these parameters could be demonstrated in the long-term arm.

Conclusions: Phlebotomy immediately improves arterial compliance in small vessels of PV patients, but this effect is short lived.