Israel Medical Association Journal

The human papillomavirus family of viruses causes a variety of benign, premalignant and malignant lesions in men and women. All cervical cancers are caused by HPV[1]. It is the leading cause of death from cancer in women in developing countries; every year some 493,000 women develop cervical cancer and 230,000 women die every year of this disease. The vaccine against HPV includes virus-like particles, composed of the major viral capsid protein of HPV without the carcinogenic genetic core. Large-scale studies have shown that the vaccine is tolerated well, leads to high antibody levels in both men and women, and prevents chronic HPV infection and its associated diseases. To achieve effective coverage the vaccine should be given prior to sexual debut. Introduction of the vaccine into specific countries, particularly Israel, should take into account the local incidence of cervical cancer as well as the increasing incidence of precancerous cervical lesions and genital warts, which reduce quality of life and are associated with considerable costs.

This paper does not attempt to deal with the legitimate ethical or moral debate on abortion. Utilizing abortion as a subject I will show how science and medicine in general, and abortion in particular, were used as weapons of mass destruction by Nazi physicians in their zeal to comply with the political climate of the time. Nazi policy on abortion and childbirth was just one of the methods devised and designed to ensure the extermination of those whom the Nazis deemed had "lives not worth living." Physicians implemented these policies, not with the fate of their patients in mind, but rather in the name of the "state." When discussing pregnancy, abortion and childbirth during the Holocaust it is imperative to include an essay of how these issues affected the Jewish prisoner doctors in the ghettos and camps. Nazi policy dictated their actions too. From an extensive search of their testimonies, I conclude that for these doctors ethical discourse comprised a fundamental component of their functioning. I do not propose to judge them in any way and one should not, in my opinion, argue whether their behavior was or was not morally acceptable under such duress; nevertheless, unlike their Nazi counterparts, a key theme in their testimonies was to "keep their medical values."

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: Drug-induced thyrotoxicosis is not uncommon. It may worsen life-threatening arrhythmias and may be refractory to medical treatment. Near-total thyroidectomy presents a valid alternative to medical therapy and should be considered early in the management of the disease.

Objectives: To assess whether near-total thyroidectomy was a viable approach for our patients.

Methods: Twelve patients – 7 men and 5 women, aged 63 to 82 years – presented with drug-induced fulminant thyrotoxicosis following 1 to 12 months of amiodarone treatment (11 patients, mean 7 months) and after a 6 months course of interferon-alpha treatment (one patient). Medical therapy included propylthiouracil in doses up to 1200 mg/day in all patients and a beta-receptor antagonist in seven. Five patients had to stop amiodarone treatment and start high doses of steroids. A thyroid scan was performed in all patients using 5 mCi of Tc-99m pertechnetate. The thyroid scan showed absent uptake of the tracer in the thyroid bed in all patients, precluding the use of radioablation.

Results: Four patients (three with AIT[1] and one with interferon therapy) who did not respond to 3 months of medical therapy required surgical thyroidectomy due to severe unremitting thyrotoxicosis. A near-total thyroidectomy resulted in rapid correction of thyrotoxicosis, enabling continuation of the anti-arrhythmic drug. There were no intraoperative or postoperative arrhythmias. Subsequently, all patients recovered rapidly and remained well and euthyroid on thyroxine replacement therapy.

Conclusions: Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as a definitive treatment for resistant amiodarone or interferon-induced thyrotoxicosis.

Background: Decreased lacrimal gland output may cause dry eye syndrome. Using a rat model, we examined the feasibility of transplanting lacrimal gland cells from newborns.

Objectives: To restore lacrimal gland function in eyes with compromised tear production.

Methods: A model of dry eye in adult rats was developed by unilateral surgical removal of the main lacrimal gland. Tear secretion in both eyes was then assessed by masked Schirmer's test. Lacrimal gland tissue from newborn rats was transplanted into the fibrous connective tissue in which the lacrimal gland had been embedded. Masked Schirmer's test was repeated 4, 8 and 12 weeks after transplantation.

Results: Schirmer's test performed in 13 rats 10 days after unilateral lacrimal gland excision revealed significantly less wetting on the side with excised gland compared with the normal side (P < 0.003). The lack of secreting cells on the operated side was verified histologically. The reduction in tear secretion on the operated side remained significant for 8 weeks on average. In the six rats with transplanted lacrimal gland tissue however, there were no differences in tear reduction between the two eyes at 4, 8 or 12 weeks after the operation (P = 0.81, 0.56 and 0.8, respectively).

Conclusions: Transplantation of lacrimal gland tissue from newborn rats effectively restored eye wetting in this new model. Further research is needed to evaluate this new approach for treating lacrimal gland dysfunction. Using this model might also facilitate evaluation of potential clinical treatments for dry eyes.
 

Background: Measurement of function is an essential component of routine rehabilitation work (mainly for quantifying function at different phases in the rehabilitation process), rehabilitation policy (admission and discharge criteria, length of stay in rehabilitation), goal setting, and outcome measurement.

Objective: To explore the scope of the scales used for function assessment by the various disciplines of rehabilitation medicine in rehabilitation facilities.

Method: A structured questionnaire was sent to 36 rehabilitation facilities. Respondents were asked to specify the scales they use for functional assessment for each of 15 selected pathologies. Also examined were satisfaction with the scales, as well as the existence of a computerized database of routine function assessment in the facility and the willingness to create a national agreed “common data set” of the assessments.

Results: The general response rate was 86.1% (31 of 36 questionnaires were returned). For the sake of data presentation, rehabilitation facilities were classified into four categories: general, geriatric, pediatric, and community. Most facilities performed function assessment using a total of 125 scales. Heterogeneity was found between facilities and between pathologies. The highest number of scales was found in the area of neurologic pathologies. For most pathologies, assessment of impairment was used more than assessment of disability. Most facilities in the survey did not have a computerized database of function assessments.

Conclusions: A “common data set” of function assessments in everyday clinical work would ensure standardization without necessarily limiting the use of additional scales and at the same time significantly minimize the current heterogeneity.
 

Background: Syndromic surveillance systems have been developed for early detection of bioterrorist attacks, but few validation studies exist for these systems and their efficacy has been questioned.

Objectives: To assess the capabilities of a syndromic surveillance system based on community clinics in conjunction with the WSARE[1] algorithm in identifying early signals of a localized unusual influenza outbreak.

Methods: This retrospective study used data on a documented influenza B outbreak in an elementary school in central Israel. The WSARE algorithm for anomalous pattern detection was applied to individual records of daily patient visits to clinics of one of the four health management organizations in the country.

Results: Two successive significant anomalies were detected in the HMO’s[2] data set that could signal the influenza outbreak. If data were available for analysis in real time, the first anomaly could be detected on day 3 of the outbreak, 1 day after the school principal reported the outbreak to the public health authorities.

Conclusions: Early detection is difficult in this type of fast-developing institutionalized outbreak. However, the information derived from WSARE could help define the outbreak in terms of time, place and the population at risk.

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: The significance of arrhythmia occurring after successful recanalization of an occluded artery during treatment following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction is controversial.

Objectives: To study the association of reperfusion arrhythmia with short and long-term survival.

Methods: We used a prospective registry of consecutive STEMI[1] patients undergoing PPCI[2]. Patients with an impaired epicardial flow (TIMI flow grade < 3) at the end of the procedure were excluded.

Results: Of the 688 patients in the study group, 22% were women. Mean (± SD) age of the cohort was 61 (± 14) years and frequent co-morbidities included diabetes mellitus (25%), dyslipidemia (55%), hypertension (43%) and smoking (41%). RA[3] was recorded in 200 patients (29%). Patients with RA had lower rates of diabetes (16% vs. 30%, P < 0.01) and hypertension (48% vs. 62%, P < 0.01), and a shorter median pain-to-balloon time (201 vs. 234 minutes, P < 0.01) than patients without RA. Thirty day mortality was 3.7% and 8.3% for patients with and without RA, respectively (P = 0.04). After controlling for age, gender and pain-to-balloon time the hazard ratio for mortality for patients with RA during a median follow-up period of 466 days was 0.46 (95% confidence interval 0.23–0.92).

Conclusions: The occurrence of RA immediately following PPCI for acute STEMI is associated with better clinical characteristics and identifies a subgroup with a particularly favorable prognosis.

Background: Necrotizing enterocolitis is a common progressive gastrointestinal disease affecting more than 5% of very low birth weight infants and associated with a high mortality rate.

Objectives: To determine whether excessive weight gain in preterm infants is an early sign of NEC[1].

Methods: Seventeen preterm infants with perforated NEC were identified and matched with 17 control subjects for birth weight and gestational age. The postnatal age (days) at diagnosis of NEC was identified, and weight changes as well as clinical and laboratory data were recorded and compared for 7 days prior through 7 days post-diagnosis.

Results: A significant difference in weight gain was noticed between D-1 and D 0. The NEC and control groups gained 5.1% and 1.2%, respectively (P = 0.002). None of the sick infants lost weight on days -1 to D 0.

Conclusions: Excessive weight gain was observed in premature infants who subsequently developed NEC. Daily evaluation of weight changes should be considered part of a strategy for early identification of infants at risk for developing NEC. Future studies are needed to confirm this finding in a prospective manner and to investigate its pathogenesis.

Background: Fractures of the femur in neonates are relatively uncommon. The infants feel pain and discomfort, causing parental distress, and the hospital stay is longer. Treatment of this specific fracture is problematic because of the small size of the baby.

Objectives: To review the results of the treatment of neonatal femoral fractures.

Methods: We retrospectively reviewed all neonatal fractures of the femur during a 12 year period. Thirteen fractures of the femur in 11 babies were treated with improvised Bryant skin traction of both legs. All the patients were re-examined after a mean follow-up period of 5.2 years.

Results: All fractures healed satisfactorily clinically and radiographically, with no residual deformity, no leg length discrepancy and no functional impairment.

Conclusions: Bryant’s traction for 2–3 weeks in hospital is a safe method for the treatment of femoral fractures in neonates, and the outcome is good.
 

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

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.