Israel Medical Association Journal

Background: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known.

Objectives: To evlauate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters.

Methods: Jewish Israeli prostate cancer patients (n=224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters.

Results: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner.

Conclusions: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.

Background: We treated two patients diagnosed with legionellosis and simultaneous Rickettsia conorii co-infection.

Objectives: To report the clinical and laboratory characteristics of this unusual combination, and to describe the execution and results of our environmental and epidemiologic investigations.

Methods: Serial serologic testing was conducted 1, 4 and 7 weeks after initial presentation. Water samples from the patients’ residence were cultured for Legionella. Follow-up cultures were taken from identical points at 2 weeks and at 3 months after the initial survey.

Results: Both patients initially expressed a non-specific rise in anti-Legionella immunoglobulin M titers to multiple serotypes. By week 4 a definite pattern of specifically elevated IgG[1] titers became apparent, with patient 1 demonstrating a rise in specific anti-L. pneumophila 12 IgG titer, and patient 2 an identical response to L. jordanis. At 4 weeks both patients were positive for both IgM and IgG anti-R. conorii antibodies at a titer ³ 1:100. Heavy growth of Legionella was found in water sampled from the shower heads in the rooms of both patients. Indirect immunofluorescence of water cultures was positive for L. pneumophila 12 and for L. jordanis.

Conclusions: Although most cases of community-acquired Legionella pneumonia in our region appear simultaneously with at least one other causative agent, co-infection with R. conorii is unusual and has not been reported to date. This report illustrates the importance of cooperation between clinicians and public health practitioners.

Background: Understanding discharge instructions is crucial to optimal healing but may be compromised in the hectic environment of the emergency department.

Objectives: To determine parents’ understanding of ED[1] discharge instructions and factors that may affect it.

Methods: A convenience sample of parents of children discharged home from the ED of an urban tertiary care pediatric facility (n=287) and a suburban level II general hospital (n=195) completed a 13-item questionnaire covering demographics, level of anxiety, and quality of physician’s explanation. Parents also described their child’s diagnosis and treatment instructions and indicated preferred auxiliary methods of delivery of information. Data were analyzed using the BMPD statistical package.

Results: Full understanding was found in 72% and 78% of the parents at the respective centers for the diagnosis, and in 82% and 87% for the treatment instructions (P  = NS between centers). There was no statistical correlation between level of understanding and parental age, gender, education, level of anxiety before or after the ED visit, or time of day. The most contributory factor to lack of understanding was staff use of medical terminology. Parents suggested further explanations by a special discharge nurse and written information as auxiliary methods.

Conclusions: Overall, parental understanding of ED discharge instructions is good. However, there remains a considerable number (about 20%) who fail to fully comprehend the diagnosis or treatment directives. This subset might benefit from the use of lay terminology by the staff, institution of a special discharge nurse, or use of diagnosis-specific information sheets.

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent attacks of fever and serositis. The disease is caused by mutations in the MEFV gene, presumed to act as a down-regulator of inflammation within the polymorphonuclear cells.

Objectives: To present the results of 412 FMF patients genotyped for three MEFV mutations, M694V, V726A and E148Q.

Results: The most frequent mutation, M694V, was detected in 47% of the carrier chromosomes. This mutation, especially common among North African Jewish FMF[1] patients, was not found in any of the Ashkenazi (East European origin) patients. Overall, one of the three mutations was detected in 70% of the carrier chromosomes. M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. Only one patient with the E148Q/E148Q genotype was detected despite a high carrier rate for this mutation in the Jewish population, a finding consistent with a low penetrance of this genotype. The M694V/M694V genotype was observed in 15 patients with amyloidosis compared to 4 amyloidosis patients with other genotypes (P < 0.0001).

Conclusions: Because of low penetrance and as yet other undetermined reasons, mutation analysis of the most common MEFV mutations supports a clinical diagnosis in only about 60% of patients with definite FMF.

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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.

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: 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: Little information is available on the clinical practice and implementation of guidelines in treating acute myocardial infarction patients in Israel.

Objective: To assess patient characteristics, hospital course, management, and 30 day clinical outcome of all AMI[1] patients hospitalized in Israel during a 2 month period in 2000.

Method: We conducted a prospective 2 month survey of consecutive AMI patients admitted to 82 of 96 internal medicine departments and all 26 cardiac departments operating in Israel in 2000. Data were collected uniformly by means of a hospital and 30 day follow-up form.

Results: During the survey 1,683 consecutive patients with a discharge diagnosis of AMI were included. Their mean age was 66 years; 73% were male. The electrocardiographic pattern on admission revealed ST elevation, non-ST elevation and an undetermined ECG[2] in 63%, 34% and 4% of patients respectively. Aspirin and heparin were given to 95% of patients. Beta-blockers and angiotensin-converting enzyme inhibitors were given to 76% and 65% of patients respectively. Among hospital survivors, 45% received lipid-lowering drugs. Thrombolytic therapy was administered in 28% of patients, coronary angiography was used in 45%, and 7% of patients underwent primary percutaneous coronary intervention. The 7 and 30 day mortality rates were 7% and 11% respectively.

Conclusions: This nationwide survey shows that one-third of the AMI patients in Israel are elderly (≥ 75 years). The survey suggests that clinical guidelines for the management of patients with AMI are partially implemented in the community. Data from large surveys representing the "real world" practice are of utmost importance for the evaluation of clinical guidelines, research and educational purposes.

Background: Puncture wounds in the feet of children present a clinical dilemma.

Objectives: To evaluate our approach, we reviewed the charts and all available images of 80 children admitted to our institution because of plantar punctures from 1988 to 1999.

Methods: The charts of 80 children were reviewed retrospectively.

Results: Three groups of patients were found: 59 with superficial cellulitis, 11 with retained foreign bodies, and 10 with osteomyelitis and/or septic arthritis. There was a significant presentation delay in patients from the second and third groups. Most common organisms were Staphylococcus aureus or Group A Streptococcus. Of the 80 children, 34 were treated surgically and 46 were treated with antibiotic therapy alone. All patients with osteomyelitis and septic arthritis were re-examined; at follow-up, all but one were asymptomatic apart from residual radiologic sequelae in four.

Conclusions: Patients with an established infection 24–36 hours after a plantar puncture should be admitted to hospital for parenteral antibiotic therapy. Delayed presentation is a significant marker for deep-seated infection. Further infection or relapse after initial improvement suggests the presence of osteomyelitis or a retained foreign body. A bone scan is advisable in all patients with suspected osteomyelitis: a positive bone scan necessitates aggressive early debridement combined with appropriate antibiotics; while negative bone scan, X-ray and exploration suggest that the infection is due to a foreign body, which can be detected by computed tomography.
 

Background: The mainstay of therapy for acute cholecystitis is cholecystectomy, which has a mortality of 14–30% in high risk patients. An alternative approach in patients suffering from acute cholecystitis with contraindications to emergency surgery is percutaneous cholecystostomy.

Objective: To evaluate the efficacy and safety of percutaneous cholecystostomy as the initial treatment of acute cholecystitis in high risk patients.

Methods: Eighty consecutive patients (42 men, 38 women) underwent ultrasound-guided percutaneous cholecystostomy over a 5 year period. Sixty-five patients suffered from acute calculous cholecystitis, 4 patients had acalculous cholecystitis, and 11 patients had sepsis of unknown origin.

Results: Sixty-eight patients improved after the percutaneous gallbladder drainage, 10 patients died from co-morbid disease and 2 patients died from biliary peritonitis. During a 1 year follow-up, 32 of the patients underwent interval cholecystectomy, 4 additional patients died from a co-morbid disease, 18 patients did not suffer from any gallbladder symptoms, and 14 were lost to follow-up.

Conclusions: Percutaneous cholecystostomy is an effective contribution to the treatment of acute cholecystitis in high risk patients.