Israel Medical Association Journal

Background: Adhesive capsulitis, also termed “frozen shoulder,” is controversial by definition and diagnostic criteria that are not sufficiently understood. The clinical course of this condition is considered as self-limiting and is divided into three clinical phases. Several treatment methods for adhesive capsulitis have been reported in the literature, none of which has proven superior to others.

Objectives: To evaluate the long-term follow-up of patients with idiopathic adhesive capsulitis who were treated conservatively.

Methods: We conducted a long-term follow-up (range 5.5–16 years, mean 9.2 years) of 54 patients suffering from idiopathic adhesive capsulitis. All patients were treated with physical therapy and non-steroidal anti-inflammatory drugs.

Results: An increased statistically significant improvement (P < 0.00001) was found between the first and last visits to the polyclinic in all measured movement directions: elevation and external and internal rotation.

Conclusions: Conservative treatment (physical therapy and NSAIDs[1]) is a good long-term treatment regimen for idiopathic adhesive capsulitis.

Background: Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF[1] patients with end-stage lung disease.

Objectives: To determine the role of NIPPV[2] in CF patients awaiting lung transplantation.

Methods: Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode.

Results: The patients' mean age at initiation of BiPAP[3] was 15 years (range 13–40 years) and the mean duration of BiPAP usage was 8 months (range 3–16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P < 0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m²). Blood pH, p_aCO₂, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P < 0.003). There were no major complications during BiPAP usage.

Conclusions: We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.

Mortality rates have been falling at all ages, even for very old cohorts, in most western countries as well as in Israel. The question remains open as to whether morbidity rates are also decreasing, especially for Israel’s elderly. While health is improving in almost all industrialized countries, the situation in Israel is not yet resolved. While the more recent cohorts of the young-old (65–74 years) are healthier than their predecessors, Israel’s old-old (75+) may still be lagging behind other countries with regard to improvements in health status. This phenomenon is not well understood but could be explained in part by the more severe formative experiences of many of Israel’s very elderly cohort.

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

Background: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living-donor segmental liver transplantation may be the only alternative.

Objectives: To report our initial experience with urgent lifesaving LDLT[1] in this unique scenario.

Methods: Three adult patients with FHF[2] (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography.

Results: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications.

Conclusions: Urgent adult-to-adult living-donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

Classic anticoagulant drugs, such as heparin and warfarin, are very effective. Although in use for more than 50 years, they have some clinical drawbacks. Heparin, now better termed unfractionated heparin, can only be used intravenously and its laboratory control is complicated. Warfarin is orally administered, but its therapeutic window is very narrow and patients need repeated laboratory tests. Moreover, both drugs are non-specific, as they inhibit the coagulation cascade at several steps. Pharmaceutic research has developed new drugs, some of which are already on the market, such as fondaparinux, a pentasaccharide that can interact with antithrombin, thus inhibiting factor Xa. This pentasaccharide is part of the parent heparin molecule and can be chemically synthesized, with the advantage of avoiding extractive compounds. Fondaparinux has a half-life compatible with once-a-day administration; modification of its structure (idraparinux) has led to more stable binding with antithrombin and to an increase in its half-life to allow once-a-week administration. Alternatives to oral anticoagulants have been developed following the study of some compounds like hirudin, which directly binds thrombin and blocks its catalytic site. One of these molecules, ximelagatran, is in advanced clinical development. Ximelagatran is converted into its active form, melagatran, in the circulation, and thrombin activity can be blocked by oral administration twice daily. There is no need for laboratory control and phase II and phase III studies are encouraging. The next few years should bring great changes in the treatment of patients with thromboembolic disorders.

Microscopic colitis is an idiopathic chronic inflammatory bowel disease presenting with watery diarrhea. While colonoscopy and radiology findings are normal, the colon shows striking pathologic findings, including lymphocytic colitis and collagenous colitis. The clinical course is usually benign with sustained remission. Recent medical evidence shows that bismuth and budesonide are effective treatments.

The painting Mona Lisa in the Louvre, Paris, by Leonardo da Vinci (1503–1506), shows skin alterations at the inner end of the left upper eyelid similar to xanthelasma, and a swelling of the dorsum of the right hand suggestive of a subcutaneous lipoma. These findings in a 25–30 year old woman, who died at the age of 37, may be indicative of essential hyperlipidemia, a strong risk factor for ischemic heart disease in middle age. As far as is known, this portrait of Mona Lisa painted in 1506 is the first evidence that xanthelasma and lipoma were prevalent in the sixteenth century, long before the first description by Addison and Gall in 1851.

Background: A major psychological sequel of terrorist attacks is post-traumatic stress disorder. The relation between certain psychological factors specific to terrorist attacks (e.g., perceived control attributed to oneself/to the military, anticipated duration of terrorism) and PTSD[1] symptoms have not been examined.

Objective: To examine the prevalence, correlates and moderators of PTSD-like symptoms following terrorist attacks in Israel.

Methods: Soon after a long wave of terrorist attacks in Israel in 2002, a convenience sample of 149 Israelis from five cities was assessed for terrorist attack exposure, perceived control, control attributed to the government/military, anticipated duration of the terrorism wave (predictability), and frequency of listening to the news. PTSD-like symptoms were assessed with a brief self-report scale.

Results: We found that 15.4% of the sample was directly exposed to a terrorist attack and 36.5% knew someone close who had been exposed to an attack. “Clinically significant” PTSD-like symptoms were reported by 10.1% of the sample. Correlates of PTSD-like symptoms were: perceived control in men, government control, and education in women (all inversely correlated to PTSD symptoms), and news-listening frequency in women (positively correlated to PTSD symptoms). PTSD-like symptoms were attenuated by the ability to predict the duration of the terrorism wave only in citizens exposed to an attack, and by perceived government control only among citizens listening infrequently to the news.

Conclusions: This study revealed that approximately 10% of Israelis in our sample had relatively frequent PTSD-like symptoms. Correlates of PTSD-like symptoms differed between men and women, and moderator effects were found. These findings reveal additional moderators that may have implications for treating PTSD following terrorist attacks.

Background: Splanchnic nerve stimulation evokes adrenomedullary catecholamine secretion via acetylcholine release and occupation of nicotinic cholinergic receptors on chromaffin cells.

Objectives: To assess whether among cultured adrenomedullary cells there exists a population that tonically secretes acetylcholine. If so, then blockade of enzymatic breakdown of acetylcholine by addition of a cholinesterase inhibitor to the medium would increase occupation of nicotinic receptors by endogenous acetylcholine and thereby induce catecholamine release.

Methods: Primary cultures of bovine adrenomedullary cells in 24-well plates (1 million cells per well) were incubated after 48–72 hours with fresh incubation medium (control), medium with added secretagogues (nicotine, angiotensin II, or K+) or the acetylcholinesterase inhibitor, edrophonium (10-7 to 10-³ M), for 1–20 minutes. Fractional release rates of epinephrine, norepinephrine and dopamine were compared to a control. We also examined whether co-incubation with edrophonium enhanced the effects of the secretagogues. All experiments were performed in quadruplicate and repeated three times.

Results: Nicotine, angiotensin II, and K+ each elicited time-related release of epinephrine, norepinephrine and dopamine by up to fourfold compared to the control. At all tested concentrations, edrophonium had no such effect. Co-incubation with edrophonium also failed to augment the secretory responses to nicotine, angiotensin II, or K+.

Conclusion: Bovine adrenomedullary cells in primary culture do not include a population of tonically active cholinergic cells.

Background: The indication for aortic valve replacement in patients with significant aortic stenosis is symptomatology. Aortic stenosis may be associated with bleeding from colonic angiodysplasia, resulting in anemia. Persistent anemia in such patients, despite lack of an identifiable source of bleeding, is not considered an indication for valve replacement.

Objectives: To report our experience with two elderly female patients who suffered from severe asymptomatic aortic stenosis, low levels of large von Willebrand factor multimer (10% and 5% respectively) and persistent anemia requiring multiple blood transfusions.

Methods: Both patients underwent an intensive work-up, but a source of bleeding could not be identified. Aortic valve replacement was performed in both patients.

Results: Aortic valve replacement abolished the need for further blood transfusions during a follow-up period of 20 months with normalization of the vWF[1] multimer level (20% and 30% respectively).

Conclusion: We suggest that aortic valve replacement be considered in selected patients with severe, otherwise asymptomatic aortic stenosis, who suffer from persistent anemia requiring multiple blood transfusions, lack an identifiable source of bleeding and have low levels of large vWF multimers.

Background: The infant mortality rate is a health status indicator.

Objectives: To analyze the differences in infant mortality rates between Jews and Arabs in Israel between 1975 and 2000.

Methods: Data were used from the Central Bureau of Statistics and the Department of Mother, Child and Adolescent Health in the Ministry of Health.

Results: The IMR[1] in 2000 was 8.6 per 1,000 live births in the Israeli Arab population as compared to 4.0 in the Jewish population. Between 1970 and 2000 the IMR decreased by 78% among Moslems, 82% among Druze, and 88% among Christians, as compared to 79% in the Jewish population. In 2000, in the Arab population, 40% of all infant deaths were caused by congenital malformations and 29% by prematurity, compared to 23% and 53%, respectively, in the Jewish population. Between 1970 and 2000 the rate of congenital malformations declined in both the Arab and Jewish populations. In the 1970s the rate was 1.4 times higher in the Arab community than in the Jewish community, and in 2000 it was 3.7 times higher.

Conclusion: As in the Jewish population, the IMR in the Arab community has decreased over the years, although it is still much higher than that in the Jewish community. Much remains to be done to reduce the incidence of congenital malformations among Arabs, since this is the main cause of the high IMR in this population.