Israel Medical Association Journal

Background: The mortality rate associated with congenital heart surgery is apparently related to caseload.

Objective: To determine whether an increase in caseload over the long term at a single center affects management and outcome in children undergoing cardiac surgery.

Methods: Data were collected prospectively over a 4 year period from the computerized registry of the hospital’s pediatric intensive care unit. Five parameters were analyzed: age at surgery, type of surgery, preventive measures (open chest), surgery-related and other complications (diaphragm paralysis and acute renal failure, respectively), and mortality. The data of a single-type surgery (arterial switch) were analyzed for bypass time and mechanical ventilation on an annual basis.

Results: The age distribution changed over the years, with more children under 1 year of age (20% newborns) undergoing surgery by the fourth year of the study. The caseload increased from 216 in the first year to 330 in the fourth, with a concomitant decrease in mortality rate from 4.9% to 3.2%. The chest was left open in 3.2% of patients in the first year and in 9.2% in the fourth year. The rate of diaphragm paralysis decreased from 6% to 2.4%. Death due to acute renal failure in patients requiring dialysis decreased from more than 80% in the first 2 years to 36% in the last two. These changes show an improvement but failed to reach statistical significance. Regarding the arterial switch operation, there was a significant improvement in pump time and duration of mechanical ventilation.

Conclusions: The increase in caseload in pediatric cardiac surgery was accompanied by improved management, with a lower complications-related mortality rate. We suggest that for optimal care of children with congenital heart disorders, quality management resources should be concentrated in centers with high caseloads.
 

Background: Decreased elasticity of the aorta is associated with aging and several risk factors of atherosclerosis. The data regarding this phenomenon in patients with familial hypercholesterolemia are rather sparse.

Objectives: To evaluate non-invasively the elasticity of the proximal ascending aorta of 51 heterozygous FH[1] patients compared to 42 normal age and gender-matched controls.

Methods: Aortic elasticity was estimated by transthoracic echocardiography using the “pressure-strain” elastic modulus and aortic strain formulas.

Results: The elastic modulus score was higher in the FH group than in the controls (1.12 ± 0.91 10⁶ dynes/cm² vs. 0.65 ± 0.46 10⁶ dynes/cm² respectively, P = 0.01). This was consistent in both the pediatric (0.5 ± 0.2 10⁶ dynes/cm² vs. 0.4 ± 0.1 10⁶ dynes/cm² respectively, P = 0.009) and adult subgroups (1.3 ± 1.0 10⁶ dynes/cm² vs. 0.8 ± 0.5 10⁶ dynes/cm² respectively, P = 0.0004). Aortic strain was significantly lower in patients with FH than in controls (6 ± 4% vs. 9 ± 5% respectively, P = 0.0002). These findings reflected decreased elasticity of the proximal ascending aorta in the FH patients. In multivariate analysis, age, serum cholesterol level and serum triglycerides level were the independent predictors of the elastic modulus score, whereas age was the predictor of aortic strain.

Conclusions: The elasticity of the proximal ascending aorta is decreased in heterozygous FH patients.

Background: Onchocerciasis results from infestation by the nematode Onchocerca volvulus, and is characterized clinically by troublesome itching, skin lesions and eye manifestations. Since 1992, approximately 9,000 immigrants have arrived in Israel from the Kuwara province of northwest Ethiopia where the prevalence of onchocerciasis is particularly high.

Objectives: To determine whether onchocerciasis is the cause of cutaneous and ocular symptoms among recent immigrants from the Kuwara province in Ethiopia

Methods: We examined 1,200 recent immigrants from the Kuwara province residing at the Mevasseret Zion immigration center outside Jerusalem. Among them, patients with cutaneous signs suggestive of onchocerciasis underwent a skin-snip biopsy and a thorough eye examination.

Results: In the detailed skin examination performed in 83 patients, the most common skin finding was chronic papular onchodermatitis, found in more than 46 patients (55%);depigmentation and atrophy was found in 13 (15%) and 12 (14%), respectively. In 40 patients (48%), living microfilaria were detected in their skin snips. Of the 65 patients who underwent a thorough eye examination, 45 patients (66%) had ocular complaints. Corneal abnormalities were found in 55 of the 130 eyes (42%), active anterior segment intraocular inflammation and live microfilariae were found in 4 eyes (3%) and lens changes in 16 eyes (1 %). Eleven eyes (9%) showed retinal or choroidal changes.

Conclusions: Skin and eye manifestations associated with onchocerciasis are prevalent among symptomatic Ethiopian immigrants to Israel from the Kuwara province.

Background: Multiple sclerosis is a chronic demyelinating disease of the central nervous system that presents with variable signs and symptoms. This variability in the clinical presentation may result in misdiagnosis, unnecessary referrals and misleading information to the patients.

Objectives: To identify the types of misdiagnoses made on the presentation of MS.

Methods: Fifty consecutive MS patients were questioned on their early symptoms, their mental status, the disease course until the diagnosis was confirmed, and the different diagnoses they received.

Results: The patients had been referred to 2.2 ± 1.3 specialists before seeing a neurologist, and learned about their disease 3.5 years after the onset of symptoms. Twenty-nine patients (58%) were initially given 41 wrong diagnoses. While the majority of women were misdiagnosed mentally, orthopedic work-up was offered to the men. Misdiagnosis of MS occurred most often in patients who presented with non-specific sensory symptoms that did not conform to a specific neurologic syndrome. The patients emphasized the fact that not knowing worsened their anxiety, whereas receiving the diagnosis enabled them to begin coping with their disease.

Conclusions: MS is often overlooked when patients present with non-specific sensory complaints. The difference in type of misdiagnosis between men and women may reflect a gender-dependent bias in the way physicians interpret sensory complaints.

Background: Cystic fibrosis is no longer a terminal illness of childhood and mean survival is now over 30 years. Adult patients with atypical CF[1] are increasingly being diagnosed. In Israel, all patients are still followed in pediatric centers.

Objectives: To describe our experience with adult CF, stressing the importance of adult-related health and psychosocial issues.

Methods: Twenty-five CF patients aged 20–50 years, constituting 44% of the 57 patients followed at our center, were analyzed for pulmonary and extrapulmonary features and management.

Results: Nineteen were diagnosed as children and 6 as adults. Nineteen were pancreatic-insufficient and 6 were pancreatic-sufficient, including 5 diagnosed as adults. Pulmonary status was usually stable, with forced expiratory volume in 1 second 66.3 ± 21% (mean ± SD) and no difference between pancreatic-sufficient and insufficent patients. The latter had more hemoptysis, Pseudomonas infection, intestinal obstruction, liver disease and diabetes. Two patients died of malignancy and two of advanced lung disease. A majority received continuous inhaled and oral antibiotics, bronchodilators, Dnase, physiotherapy and periodic home intravenous antibiotics. Psychosocial functioning was excellent: 60% were employed, 36% were married and 40% had children (none with CF). Patients diagnosed as adults had mild multisystem disease or isolated severe lung disease.

Conclusions: CF adults generally have a good quality of life. Advances in understanding the CF defect and a plethora of new treatment modalities bode well for the future. Patients must be maintained in optimal condition to reap the benefits, and there is an urgent necessity for adult physicians to develop expertise in CF.

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Background: Radiofrequency ablation has recently become a viable treatment option for unresectable primary or secondary lesions confined to the liver.

Objective: To study the local therapeutic efficacy, side effects and complications of radiofrequency ablation for the treatment of hepatocellular carcinoma and liver metastases This is the first reported experience of radiofrequency ablation for treating malignant hepatic tumors in Israel.

Methods: Fifteen consecutive patients, aged 53–73 years, with 23 lesions (8 patients with HCC[1] and 7 with secondary liver tumors) underwent radiofrequency ablation under general anesthesia. RITA nine-array 5 cm thermal ablation catheter and the model 1500 generator were used. The mean diameter of all tumors was 4.28 cm (range 1–10 cm). Three lesions were 1–3 cm in diameter (small), 17 lesions measured 3.1–5 cm (medium), and 3 measured 5.1–10 cm (large).

Results: Complete necrosis was found in 8 (66%) of 12 HCCs by computed tomography scan. Of the remainder, diffuse tumor recurrence was demonstrated in three lesions (25%) after lipiodol injection and there was one local tumor recurrence. In the metastases group complete necrosis was found in 5 of 11 lesions (45%). One major complication (peritonitis) was treated with antibiotics and four (26%) minor complications (right pleural effusion, small subcapsular hematoma) were monitored.

Conclusions: Radiofrequency ablation appears to be an effective, safe and relatively simple procedure for the treatment of liver tumors.

Background: Lower limb critical ischemia is a major problem in dialysed patients.

Objective: To evaluate the results of revascularization procedures, amputations and prosthetic rehabilitation in dialysed amputees.

Methods: Major amputation was carried out in 48 patients (4.5% of the dialysis population), and 24 patients entered the rehabilitation program. Widespread arterial calcification was common and led to falsely elevated ankle-brachial pressure indices in 9 of 14 limbs. Eight patients underwent revascularization. Subsequent major amputation was carried out 4 ± 4.5 months after the revascularization (above knee in 5 patients and below knee in 3). Of the 16 patients who underwent primary amputation, only 2 were above-knee amputees. Seven patients with toe or metatarsal amputation went on to a major amputation 1.8 ± 1.2 months after the distal amputation.

Results: No differences were found between diabetic and non-diabetic patients regarding the number of revascularization operations performed, the level of major amputation, or overall survival. Prosthetic rehabilitation was considered successful in 12 patients, partially successful in 8, and failed in 4 patients. Patient survival time was shortest in those patients with failed rehabilitation. A younger age confirmed favorable rehabilitation results, while long-standing diabetics and bilateral amputees were poor rehabilitation candidates. Patients who underwent primary amputation had more successful rehabilitation. A comparison between 24 dialysed amputees and 138 non-uremic amputees revealed similar rehabilitation results, although hospitalization time was longer in the dialysed patients.

Conclusions: Early definitive therapy is essential when dealing with critical ischemia. After diagnostic angiography, proximal revascularization should be performed where feasible. Primary amputation is indicated in patients with extensive foot infection or gangrene. Prosthetic rehabilitation is warranted in most dialysed amputees.
 

Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30–50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Activated protein C, an endogenous vitamin K-dependent anticoagulant, plays a major role in the down-regulation of the procoagulant arm. It also possesses anti-inflammatory properties. Endothelial damage during sepsis impairs the endothelium-dependent activation of protein C, thus shifting the balance towards thrombosis. This shift may contribute to the development of sepsis-related multi-organ failure. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients. Indeed, a recent randomized controlled trial demonstrated a reduction in overall mortality in patients with severe sepsis treated with APC[1]. In this review we discuss the pathogenesis of the coagulopathy of sepsis, as well as the new therapeutic approaches aimed at correcting the defects in the coagulation system.

The induced sputum technique allows sampling of the airways in a non-invasive manner and thus offers a unique opportunity to identify biomarkers of potential clinical utility in respiratory medicine. Sputum cells were originally examined in stained smears and the procedure was applied in both research and clinical settings from the 1950s through the 1970s. The cells, recovered from spontaneous coughing, were used to study lung cancer and respiratory infections and, later on, to diagnose Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus. The method was largely improved by the induction of sputum with aerosol of hypertonic saline and was extended to become part of the assessment of airway inflammation in bronchial asthma and chronic obstructive pulmonary disease. It was recently shown that induced sputum can be used to study interstitial lung diseases and, more specifically, sarcoidosis, non-granulomatous ILD[1], occupational lung diseases and other systemic diseases with lung involvement.

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Background: Several in vitro studies have reported on the efficacy of combined liposomal encapsulated doxorubicin (Doxil® or Caelyx®, MedEquip, UK) and hyperthermia over Doxil alone.

Objectives: To document the beneficial effect of Doxil-HT over Doxil alone in mice and to investigate the length of time HT[1] should be delivered.

Methods: M/109 lung tumor cells were injected into both leg pads of Balb/c female mice at age of 6–7 weeks. Two weeks later i.v. Doxil in a dose of 8 mg/kg (20–25 µg per mouse) was given and 4 HT sessions (2–3 days apart) were delivered during the subsequent 2 weeks at 2–3 days apart. HT was given to the left pad only for either 5 or 30 minutes (HT5 and HT30 respectively). Five weeks after tumor injection the mice were sacrificed and tumor volume and weight in both pads were measured. Internal comparisons between mice in the same treatment group and comparisons between different treatment cohorts were performed.

Results: In the combined Doxil-HT5 and Doxil-HT30 cohorts the tumor volume and weight in both pads were similar and did not differ from those achieved by Doxil alone. In the Doxil-HT30 cohort the tumor weight, but not the tumor volume, were smaller than those in Doxil-HT5 and Doxil alone (P = 0.006 and 0.01 respectively).

Conclusions: The combined Doxil-HT30 treatment is more effective then Doxil-HT5 or Doxil alone. Additional studies with different time scheduling and different temperatures are warranted.

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[1] HT = hyperthermia