Israel Medical Association Journal

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: Leptin, a pleiotropic hormone, has been suggested to be part of an acute phase response during an inflammatory stimulus. Its correlation with other acute phase reactants during minor infection in children has not been investigated.

Objectives: To study the correlation between serum leptin levels to those of C-reactive protein, a well-documented acute-phase reactant, in a series of pediatric patients with acute minor infections.

Methods: Leptin and CRP[1] levels were measured in 62 blood samples of pediatric patients presenting with mild febrile illness who were admitted to Dana Children’s Hospital in Israel. All children were finally diagnosed as having minor infection based on the negative blood/urine cultures and favorable outcome.

Results: Serum leptin level was positively correlated with CRP (r² = 0.5), total white blood cells (r² = 0.33) and absolute neutrophil count (r² = 0.31). The regression coefficient was the highest between leptin and CRP.

Conclusions: Circulating leptin concentrations are positively correlated with CRP levels during acute minor infection in children visiting the emergency room for febrile illnesses. Our observation suggests that leptin is indeed a part of acute-phase proteins. The wide scattering showed that it is not a better marker in minor infections than CRP, but it may contribute to weight loss and anorexia seen in the minority of patients during mild infections.

Background: The association between antibiotic use in the community and antimicrobial resistance is known. Attention has recently focused on the type of agents being prescribed.

Objectives: To implement, evaluate and compare the efficacy of two community interventions programs – continuous versus seasonal medical education – oriented to primary care physicians with emphasis on appropriate use of antimicrobial drugs.

Methods: From October 2000 to April 2003 we conducted two interventions: a) a monthly educational campaign in selected clinics promoting appropriate diagnosis of common infectious diseases and prudent antibiotic use (continuous intervention group); and b) a massive educational campaign, conducted before two consecutive winters, promoting the judicious use of antibiotics for treating respiratory infections (continuous intervention group and seasonal intervention group). Sixteen similar clinics were randomized (8 to each group). The total antibiotic use was measured as defined daily dose/1000 patients/day, and compared between the groups. 

Results: The total use of antibiotics decreased between 1999-2000 and 2002-2003 in both groups, but slightly more significantly in the continuous intervention group. The DDD/1000 patients/day for the seasonal group in 1999-2000 was 27.8 vs. 23.2 in 2002-2003; and for the continuous group 28.7 in 1999-2000 vs. 22.9 in 2002-2003, a reduction of 16.5% and 20.0% respectively (p<0.0001). The main change in antibiotic use was noted for broad-spectrum antibiotics.

Conclusions: We present a successful community intervention program aimed to reduce unnecessary antibiotic use. Amplification of this type of intervention is imperative to stop the increase in antimicrobial resistance.
 

Background: Hip fracture rates are increasing worldwide, and the risk for a second hip fracture is high. The decision to administer antiresorptive treatment is based mainly on bone mineral density and/or a history of previous osteoporotic fractures.

Objectives: To evaluate the contribution of BMD[1], previous fractures, clinical and laboratory parameters to hip fracture risk assessment.

Methods: The study population included 113 consecutive hip fracture patients, aged 72.5 ± 9.4 years, discharged from the Department of Orthopedic Surgery113 consecutive patients, 87 women and 26 men, aged 50-90 years, mean ag. BMD was assessed at the lumbar spine, femoral neck and total hip. The results were expressed in standard deviation scores as T-scores – compared to young adults and Z-scores – compared to age-matched controls. Plasma or serum levels of parathyroid hormone, 25-hydroxyvitamin 3 and urinary deoxypyridinoline cross-links were evaluated.

Results: We observed T-scores ≤-2.5 in 43 patients (45.3%) at the lumbar spine, in 47 (52.2%) at the femoral neck and in 33 (38%) at the total hip. Twenty-eight patients (29.5%) had neither low BMD nor previous osteoporotic fractures. Using a T-score cutoff point of (-1.5) at any measurement site would put 25 (89%) of these patients into the high fracture risk group. Mean DPD level was 15.9 ± 5.8 ng/mg (normal 4–7.3 ng/mg creatinine). Vitamin D inadequacy was observed in 99% of patients.

Conclusions: Using current criteria, about one-third of elderly hip fracture patients might not have been diagnosed as being at risk. Lowering the BMD cutoff point for patients with additional risk factors may improve risk prediction yield.

Objectives: To estimate self-medication with antibiotics by a population in northern Israel.

Methods: We sent by post a questionnaire on antibiotic usage to 2,615 adults, both Jewish and Arab, living in northern Israel.

Results: The overall response rate was low (17.9%), particularly among the Arab population (9.4% of respondents). Among the 467 respondents, 169 (36.2%) reported 215 antibiotic courses within the last year. Amoxicillin was the antibiotic most commonly used (32.7% of courses); 89.4% of antibiotics were obtained via a physician’s prescription; 114 respondents (24.4%) stored leftover antibiotics at home and 81 (18.7%) would consider self-medication with antibiotics without a medical consultation.

Conclusions: Our results show that over-the counter acquisition of antibiotics is rare in Israel. However, the storage of leftover antibiotics in the home constitutes an alternative potential source of self-medication that can have untoward consequences, not only for the individual patient but also for the general population since inappropriate antibiotic usage contributes to the increasing rates of antimicrobial resistance.

Objective: To establish the frequency of A. haemolyticum in throat cultures in a northern Israeli population and to estimate the clinical significance of this pathogen in patients with sore throat.

Methods: We examined suspected colonies for A. haemolyticum by gram stain, catalase test and reverse CAMP test in 518 throat cultures sent to the microbiologic laboratory of HaEmek Medical Center.

Results: Of the throat cultures tested, A. haemolyticum was recovered from one patient (0.2%). In contrast, group A Streptococcus (Streptococcus pyogenes) was recovered from 135 patients (26%).

Conclusion: A. hemolyticum is an uncommon pathogen implicated in acute pharyngitis, therefore routine screening in throat swabs is not required.