Israel Medical Association Journal

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.

Background: Prior studies have suggested that women are at higher risk for morbidity and mortality during coronary angioplasty, although long-term prognosis is similar after successful procedures.

Objectives: To examine the role of gender in coronary stenting, including immediate procedural success as well as early and late outcomes.

Methods: The study group comprised 560 consecutive patients (119 women and 441 men) who had undergone stenting over a 3 year period.

Results: The indications for coronary stenting were similar among women and men, and stents were successfully deployed at similar rates without complications (92 vs. 90% respectively). Cardiac death or myocardial infarction within 30 days of the procedure was observed in 5% of women and men, whereas none of the women, compared to 1.4% of men, had early revascularization. Bleeding complications occurred in 4% of women and 2% of men. During 10 ± 2.8 months of follow-up, 58% of women and men underwent repeat cardiac catheterization, revealing similar rates of restenosis, 36 vs. 32% respectively. During the study period, 3.3% of women as compared to 0.9% of men had a cardiac death (not significant). Cardiac death or myocardial infarction was observed in 7% of women and 8% of men, and the combined endpoint of death, myocardial infarction or revascularization, was noted in 24% and 26% respectively. Multivariate Cox analyses of the clinical, angiographic and procedural characteristics revealed that multiple stent deployment was the only predictor of major adverse cardiac event among men, whereas none of these characteristics predicted outcome in women.

Conclusion: Coronary stenting is performed with similar success rates among women and men, with similar restenosis rates, as well as early and late major adverse cardiac events.
 

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

Background: Despite the high incidence of pemphigus in the Jewish population, data on the epidemiology and etiology of the disease in Israel are sparse.

Objective: This study was conducted to identify clinical and epidemiologic features of pemphigus patients in Israel, while searching for risk factors that induce or exacerbate the disease.

Methods: Demographic and clinical information was recorded from the charts of 55 pemphigus patients treated over a 5 year period. A sample of 22 patients was compared to 22 age and gender-matched controls by means of a questionnaire querying details on lifestyle, including occupation, diet, sun exposure, and smoking.

Results: The findings show that the typical Israeli pemphigus patient is middle-aged, married, and of East European or Middle Eastern origin. The most common diagnosed clinical variant was pemphigus vulgaris, followed by pemphigus erythematosus. Some 70% of patients were treated with two or more immunosuppressive drugs and 62% entered long-lasting remission. Twenty-three percent of patients were exposed through their work to chemical substances, mainly pesticides, at the beginning of the disease and 18% of patients were continually exposed to ultraviolet radiation 5 years prior to onset of the disease.

Conclusions: There is a possible correlation between occupational exposure to pesticides and UV[1] radiation, and pemphigus induction.

Background: Acute pharyngitis in children is one of the most frequent illnesses for which primary care physicians are consulted. It is caused more frequently by viruses than by bacteria, but it is difficult to differentiate the causative agent by clinical signs alone. Group A Streptococcus accounts for 30% of children with a sore throat, and only in these cases is antibiotic therapy definitely indicated. However, the frequency and symptomatology of streptococcal pharyngitis in adults is not well established.

Objectives: To examine the clinical features that could distinguish sore throat caused by b-hemolytic group A Streptococcus in adults.

Methods: Patients aged over 16 years old (n=207) who presented with a sore throat to community clinics were examined and throat cultures were taken. The microbiologic confirmation of Group A Streptococcus was correlated with symptoms and clinical signs by univariate analysis.

Results: About 24% of the patients with positive cultures were younger individuals. Chills, absence of cough, pain in swallowing, absence of rhinitis, headache, vomiting, tonsillar exudate, oral malodor, fever >38°C and sweats had high sensitivity but low specificity for streptococcal pharyngitis. Univariate analysis suggested that chills and pharyngeal exudate had the greatest predictive value for streptococcal pharyngitis (P = 0.044, odds ratio 2.45; P = 0.001, OR[1] 5.49, respectively). When compared with a published scoring method (Centor criteria), large inconsistencies were found.

Conclusion: Our adult population had a relatively high prevalence of group A Streptococcus, and their presentation differed from that of pediatric patients. In primary care, a throat swab culture is not necessary in adults with a low score (0–1 points).

Background: Infant mortality in Israel is twofold higher among non-Jews than Jews.

Objectives: To determine the impact of congenital malformations and Mendelian diseases on infant mortality.

Methods: We compared the causes of infant mortality in a 4 year period among Jewish and non-Jewish Israeli citizens. Classification was done by analyzing all the death reports according to whether or not the child had any known major malformation, Mendelian disease and/or a syndrome, irrespective of the immediate cause of death.

Results: The infant mortality among non-Jews was double that among Jews (9 versus 4.4 per 1,000 live births). The rate of children with malformations/genetic syndromes was 3.1 times higher among non-Jews than among Jews (2.94 vs. 1.25 per 1,000 live births). The most significant difference was in the rate of Mendelian diseases, which were 8.3 times more frequent in non-Jewish children (0.16 vs. 1.33 per 1,000 live births respectively). A Mendelian disease was diagnosed in almost 15% of the non-Jewish infants and in less than 5% of the Jewish infants.

Conclusions: The most striking difference between the Jewish and non-Jewish infants was the incidence of congenital malformations and Mendelian diseases parallel to the differences in the consanguinity rates between the two populations.
 

Background: The osteoporosis-pseudoglioma syndrome is a rare autosomal recessive disorder characterized by severe juvenile-onset osteoporosis and congenital or early-onset blindness. Other manifestations include muscular hypotonia, ligamentous laxity, mild mental retardation and seizures. The gene responsible was recently identified to be the low density lipoprotein receptor-related family member LRP5 on chromosome 11q11-12.

Objective: To measure bone density in two siblings with the OPPG[1] syndrome as well as in their family members (parents and siblings).

Methods: Bone mineral density was determined in the lumbar spine (antero-posterior), femoral neck, two-thirds distal forearm (>95% cortical bone) and ultradistal forearm (predominantly trabecular bone) by dual-energy X-ray absorptiometry.

Results: The studies revealed osteoporotic changes both in the patients and the carriers.

Conclusion: The findings demonstrate that OPPG carriers have reduced bone mass, which is a risk factor for development of early osteoporotic changes.

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