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Biomedical subjects

O Shpilberg

Publications and source records attributed to O Shpilberg.

At least 19 recordsLinked to original sources

Extramedullary disease and targeted therapies for hematological malignancies--is the association real?

During the past years targeted therapies have gained a major role in the treatment of cancer patients, including those with hematological malignancies. Extramedullary involvement is a rare manifestation of acute and chronic leukemias and of multiple myeloma. Nevertheless, with the expanding use of targeted treatments there is an impression that the incidence of extramedullary relapses is increasing. We reviewed the reports on this phenomenon in patients treated with all-trans-retinoic acid and arsenic trioxide for acute promyelocytic leukemia, thalidomide and bortezomib for multiple myeloma and imatinib for chronic myeloid leukemia. The pathogenetic mechanisms suggested are: life prolongation by these treatments allowing for disease progression arising from dormant cells; poor penetration of the drugs to sanctuary sites like the central nervous system; the requirement of some of these drugs, especially thalidomide, for the marrow microenvironment to exert their action; and finally, a possible active role for some of the drugs, like all-trans-retinoic acid. Since the use of these targeted therapies is expanding we should be aware of this association.

Antineoplastic Agents↗

Relation of parental history of coronary heart disease to obesity in young adults.

OBJECTIVE: To assess the association between obesity and parental coronary heart disease (CHD) history. DESIGN: Analysis of data from an ongoing, large-scale survey on medical status, health behaviour and attitudes. SUBJECTS: Representative samples of Israeli military personnel upon discharge from compulsory service at age 20-22 y. Overall 14297 men and 11638 women were interviewed and examined upon release from military service between 1989 and 1999. MEASUREMENTS: Data on demographic characteristics, family history of CHD, lifestyle, weight and height were collected. Analysis of variance and logistic regression were used. RESULTS: Higher mean body mass index (BMI) and obesity (BMI>30 kg/m(2)) were associated with paternal CHD history in both sexes, and with maternal CHD history among men. Offspring of a parent with a positive CHD history had a higher mean BMI (23.22 vs 22.86 kg/m(2), P<0.001) and were more likely to be obese (5.4 vs 3.7%, P<0.001) than offspring of parents with no history of CHD. Multivariate adjustment for demographic and behavioural variables associated with obesity attenuated the association (adjusted odds ratio for obesity 1.37, 95% confidence interval: 1.15, 1.64). When stratified by sex, this association remained statistically significant only among males. CONCLUSION: Young adults with a parental history of CHD are more likely to be overweight. This high-risk group should be targeted for early preventive activities.

Adult↗

Patients with Glanzmann thrombasthenia lacking platelet glycoprotein alpha(IIb)beta(3) (GPIIb/IIIa) and alpha(v)beta(3) receptors are not protected from atherosclerosis.

BACKGROUND: Platelets have been suggested to play a role in the early development of atherosclerosis. As one test of this hypothesis, we assessed whether patients with Glanzmann thrombasthenia who lack platelet glycoprotein alpha(IIb)beta(3) (GPIIb/IIIa) complexes or both alpha(IIb)beta(3) and the more ubiquitous alpha(v)beta(3) cell membrane complexes are protected from development of atherosclerosis. METHODS AND RESULTS: Seven patients with Glanzmann thrombasthenia, 45 to 66 years of age, underwent bilateral carotid artery ultrasonography and screening for risk factors of atherosclerosis. Findings consistent with early atherosclerosis evaluated by measurement of intima-media thickness and presence of atherosclerotic plaques were observed in 6 of the 7 patients. Intima-media thickness values higher than the 75th and 90th percentiles of age- and sex-matched white control subjects of the Atherosclerosis Risk in Communities (ARIC) study were observed in 30 and 8 of 56 carotid artery measurements, respectively. Five of the 6 patients with signs consistent with early atherosclerosis lacked both alpha(IIb)beta(3) and alpha(v)beta(3) complexes and 1 only lacked alpha(IIb)beta(3). CONCLUSIONS: Glanzmann thrombasthenia does not protect affected individuals from development of atherosclerosis.

Aged↗

Decline in immunity to polio among young adults.

A serologic survey was conducted on a population-based representative sample of 521 18-year-old soldiers recruited to the Israel Defence Forces in 1997. The prevalence of neutralizing antibodies and geometric mean titers (GMTs) against the three types of poliovirus (Mahoney, MEF and Saukett strains) were found to be 98.7% (GMT--169.95), 99.6% (GMT--297.14) and 96.4% (GMT - 59.48), respectively. These GMTs are markedly lower than those recorded 4 years after booster vaccination carried out during a 1988 polio outbreak, and suggest a decline in immunity against polio among young adults. These findings support the policy of routine revaccination of children and adolescents in countries at risk of imported polioviruses and of revaccination of adults traveling to areas to which polio is endemic.

Adolescent↗

Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary heart disease among men in the Multiple Risk Factor Intervention Trial.

In this nested case-control study, lipoprotein (a) [Lp(a)] concentrations and apo(a) isoform size were measured in serum samples obtained from men participating in the prospective Multiple Risk Factor Intervention Trial (MRFIT). Serum from men aged 35 to 57 years and stored for up to 20 years were analyzed for Lp(a) levels (n=736) and isoform size (n=487), respectively. Cases involved nonfatal myocardial infarctions (MI; n=98), documented during the active phase of the study that ended on February 28, 1982 and coronary heart disease (CHD) deaths (n=148) monitored through 1990. Median Lp(a) levels did not differ between cases and controls and mean apo(a) size did not vary between cases and controls in the entire study population. When adjusted for age and Lp(a) concentration, logistic regression analysis indicated that small apo(a) isoforms were associated with CHD deaths among smokers (OR 3.31; 95% CI 1.07-10.28).

Adult↗

Engraftment-associated hypophosphatemia--the role of cytokine release and steep leukocyte rise post stem cell transplantation.

Hypophosphatemia associated with bone marrow transplantation has been infrequently reported. The suggested mechanism is phosphate uptake by the replicating cells. Various cytokines are associated with the development of hypophosphatemia. The present study evaluated the interrelationship between cytokine release, the rise in WBC and the development of hypophosphatemia during the engraftment period. Blood samples were obtained from 60 patients undergoing peripheral blood stem cell transplant, on the day of admission and then daily from the day of transplant until discharge. Hypophosphatemia developed in 62% of the patients. The median day of minimal phosphorus level was +8 and it antedated engraftment by 2 days. There was a significant correlation between the day of minimal phosphorus level and the day of maximal WBC and a significant correlation between the fall in phosphorus level and WBC rise. IL-6 and IL-8 showed similar kinetics. Higher IL-6 and IL-8 levels were directly associated with lower phosphorus levels. In conclusion, hypophosphatemia commonly occurs in the post-transplant period. We assume that both a direct effect of cytokine release and an increased consumption by the dividing WBCs contribute to its appearance. As its occurrence usually antedates engraftment it can be used as a forerunner for WBC recovery.

Adult↗

Secular trends in the epidemiology of pediculosis capitis and pubis among Israeli soldiers: a 27-year follow-up.

BACKGROUND: Pediculosis capitis and pubis are not mandatorily reported diseases in most countries. Thus, the reported rates of these diseases in large populations are usually inaccurate and based on estimations. OBJECTIVE: To describe the global epidemiology of pediculosis capitis and pubis in the Israeli Defense Force. METHODS: We analyzed the data obtained from the routine and mandatory reporting of every individual case of pediculosis capitis and pubis to the Army Health Branch Epidemiology Department since 1972 and 1973, respectively. RESULTS: During this period, epidemics of pediculosis capitis and pubis were observed between 1973 and 1985 and 1972 and 1987, with 17.7- and 3.9-fold increases in incidence, respectively. These two epidemics were followed by a sharp decline in morbidity (113.6- and 13.6-fold between 1981 and 1999 and 1984 and 1999, respectively) to the present. CONCLUSIONS: A number of factors could be responsible for the observed decline in morbidity, e.g. socioeconomic, pharmacologic, environmental, or prevention policy modifications. The rates of pediculosis capitis and pubis have continuously declined since the last epidemic of 1972-1987, indicating the influence of these and possibly other factors.

Adolescent↗

Active versus passive immunization against hepatitis A in the Israel defence forces: a cost-benefit analysis.

We compared cost-benefit and cost-effectiveness analyses of hepatitis A prevention with immune serum globulin (ISG) vs inactivated hepatitis A vaccine (iHAV) in the Israel Defence Forces. Personnel were grouped according to conditions and duration of service and analyses were performed based on maximum and minimum hepatitis A projected incidences for each group. For standing army soldiers in field units, iHAV is economically superior compared with ISG. For the five other groups studied, the reverse is true. Expected increases in production costs of ISG and expected decreases in costs of iHAV are likely to make iHAV more economical in the future.

Cost-Benefit Analysis↗

[Trends in epidemiology of hepatitis in the Israel Defense Forces-- direction over several years].

During the 50's and 60's there were large scale epidemics of hepatitis A every 3-4 years in the Israel Defense Forces. During these epidemics the annual incidence exceeded 10/1000 soldiers at risk. There has been a highly significant decrease in rates during the past 30 years. The average annual incidence of clinically identified viral hepatitis A decreased from an average of 6/1000 during the 60's to 2.5/1000 during the 70's. The decrease coincided with the introduction in the 1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG). The incidence was further significantly reduced to 0.5-1.0/1000 with the introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p < 0.001). Other factors probably played a role in accelerating the decline in morbidity, such as improvement in personal hygiene and sanitation facilities, and in waste disposal and other aspects of military environmental health. These improvements were probably more pronounced in the civilian sector, leading to decreased exposure of children to the virus and consequently a higher proportion of seronegatives at induction. Increase in the proportion of recruits without natural immunity to the virus poses greater risk, both in terms of personal morbidity as well as military operational ability. This risk, combined with problems of ISG use and availability, has propelled hepatitis A prevention policy towards the use of the new inactivated vaccines.

Female↗

[Development of molecular tests for rapid detection of enteropathogens].

Amplification of specific DNA sequences by polymerase chain reaction (PCR), enables rapid, sensitive and direct, specific identification of pathogens at very low concentrations in clinical samples. Studies in recent years have reported identification of several enteropathogens directly from stool samples by PCR. The amplification process includes the use of primers complementary to the DNA sequences specific to the pathogen, thus relying on the pathogen's genotype, rather than its phenotype on which identification by the methods of classical microbiology were based. We have developed PCR protocols for the differential identification of enteropathogens resembling the normal flora (enterotoxigenic E. coli (ETEC), E. coli O-157), Shigella spp, and the detection of enteropathogens that can not be grown on classic growth media (Norwalk virus). The amplification process is inhibited by several substrates present in fecal material (phenol, hemoglobin), limiting DNA extraction by phenol. The protocols we have developed for direct detection of Shigella spp and ETEC in stools circumvent inhibition of PCR by the use of a 4-hour pre-enrichment step in brain-heart infusion broth. Rapid and accurate identification of enteropathogens is important for prompt and focused intervention to stop the chain of transmission in outbreaks of gastroenteritis in military and civilian populations.

Dysentery, Bacillary↗

Adenomatous polyposis coli I1307K mutation in Jewish patients with different ethnicity: prevalence and phenotype.

BACKGROUND: A new mutation, I1307K, recently was reported in the adenomatous polyposis coli (APC) gene. This mutation was found to be predominant in Ashkenazi Jews, creating a hypermutable area and predisposing the development of carcinoma. The objective of the current study was to estimate the prevalence of this mutation in several of the ethnic groups that comprise the Israeli population and to elucidate the clinical features of the mutation carriers with colorectal carcinoma (CRC). METHODS: A total of 111 consecutive CRC patients were evaluated and their medical history and clinical data recorded. The general population (298 Ashkenazim and 189 Yemenites) also was tested for the presence of this mutation. Mutation screening was performed using both the polymerase chain reaction-based amplification refractory mutation system and a commercial APC kit. RESULTS: Of the total of 111 CRC patients, 15 (13.5%) carried the I1307K mutation and 26 of 487 subjects from the general population (5.3%) carried the I1307K mutation (P = 0.004). Among the 71 Ashkenazi CRC patients there were 12 carriers (16.9%) whereas 17 of the 298 Ashkenazi Jewish general population (5.7%) carried the mutation (P = 0.004). Of the 4 CRC patients of Yemenite origin, 3 carried the mutation and 9 carriers were found among 189 subjects in the general Yemenite population (4.7%) (P = 0.0007). None of the 34 Sepharadic or 2 Arab CRC patients carried the APC I1307K allele. Late age at diagnosis (64.6 years +/- 10.0, which is similar to that of the noncarriers), mostly right-sided tumors, and moderate to good differentiation constituted the phenotype of the mutation carriers. CONCLUSIONS: The authors believe the findings of the current study broaden the known spectrum of ethnic groups in which the APC I1307K mutation is prevalent. The phenotype of the mutation carrier CRC patients does not conform to the expected familial pattern of germline mutations. The phenotype and the differential incidence rate of CRC among APC I1307K carriers of various ethnic groups suggest low penetrance.

Adenomatous Polyposis Coli↗

Measles epidemic in Israel-successful containment in the military.

BACKGROUND: Measles vaccination at ages 12-15 months is a routine part of standard health care in developed countries. Nonetheless, the prevention and control of measles outbreaks remain a challenge, owing to incomplete or variable compliance with immunization programs and primary vaccine failure (approximately 5%). In Israel, vaccination coverage against measles is high, yet sero-epidemiological studies conducted in the early 1990s showed that 15% of 18-year-olds were unprotected. METHODS: 1994 there was a countrywide epidemic of measles, which spread to the military. The Israel Defense Forces Medical Corps immediately launched a wide-scale vaccination campaign, targeting primarily field units and training bases, where crowded living conditions are the rule. RESULTS: The immunization campaign led to an abrupt cessation of morbidity in the military. In the civilian sector, where no intervention was undertaken, the epidemic continued for another 4 months. CONCLUSIONS: Institutional measles outbreaks, especially in the presence of crowded conditions or high contact rates, may be effectively controlled by mass vaccination.

Incidence↗

A waterborne outbreak of gastroenteritis in the Golan Heights due to enterotoxigenic Escherichia coli.

BACKGROUND: Over a period of 4 days between May 18-21, 1998, a multifocal outbreak of diarrhea, involving 175 Israel Defence Force soldiers and at least 54 civilians, occurred in the Golan Heights. PATIENTS AND METHODS: Stool samples from 40 affected soldiers were collected for microbiological testing. In addition, a rapid PCR technique was employed for the direct detection of the heat-labile (LT) and heat-stable toxin (ST) genes of enterotoxigenic Escherichia coli (ETEC) in stool samples. RESULTS: All 40 stool specimens taken from patients with diarrhea was negative by culture. However, ETEC was detected in 16 stool specimens using the rapid PCR method. The epidemiological investigation found no association between the food items consumed prior to the onset of the outbreak and the attack rate of diarrhea. A review of the water distribution system revealed that all affected military posts and civilian communities were supplied by a common water pipeline. Water sampled from various points along the distribution system showed inadequate chlorination and high concentrations of E. coli. CONCLUSION: This report suggests that the involvement of ETEC in the etiology of waterborne diarrheal outbreaks may be underestimated, probably due to the difficulties involved in the laboratory identification of this enteropathogen. Adoption of our rapid method for the identification of ETEC, which is applicable to routine diagnostic laboratories, facilitates pathogen detection within hours, and allows early intervention in cases of widespread diarrheal epidemics.

Bacterial Toxins↗

Does immune serum globulin confer protection against skin diseases?

BACKGROUND: Following a case of serologically proven hepatitis A in a food-handling worker serving several military bases in the same vicinity, the entire military population was vaccinated with immune serum globulin (ISG). OBJECTIVE: To evaluate the effectiveness of ISG in preventing skin disease. METHODS: The data for this study were drawn from the military archives of the Medical Corps. The population of the bases was followed for a period of 3 months after immunization. Rates of selected skin diseases were compared with those of a nearby base during the same period, and with those in the population of the same bases a year earlier. RESULTS: The rates of several skin diseases (bacterial skin infections, dermatitis and eczema, fungal infections, acne, warts, nail disorders, and nonspecific skin diseases) among the vaccinated population were significantly lower when compared to the historical control group and to the contemporary control group of the nearby base. CONCLUSIONS: ISG provides a protecting effect for skin diseases, especially those of infectious origin.

Adolescent↗

Helicobacter pylori infection and subsequent peptic duodenal disease among young adults.

BACKGROUND: Evidence for a causal relationship between presence of Helicobacter pylori (H. pylori) in gastric mucosa and development of peptic disease is based largely on intervention studies in which eradication of H. pylori led to healing of the lesion. The aim of this study was to assess the importance of H. pylori seropositivity for subsequent development of peptic disease in a prospective study design in young Israelis. METHODS: A nested case-control serum bank study based on a systematic sample of male and female inductees to the Israel Defense Force. Twenty-nine cases of duodenal ulcer or duodenitis of moderate or higher severity, diagnosed between 1986 and 1995, were individually matched for age, sex, ethnicity, education and year of induction, with five healthy controls each. Presence of anti-H. pylori antibodies in the frozen stored sera was determined by ELISA. RESULTS: The geometric mean titre of anti-H. pylori antibodies at baseline was significantly higher in cases (18. 3 U/ml) than controls (6.9 U/ml; P = 0.009). The matched odds ratio for peptic ulcer disease by seropositivity was 3.8 (95% CI : 1.4-10. 2). A stronger association was evident for subjects diagnosed > or =2 years after induction than those diagnosed earlier. The population attributable fraction was 56.6% (95% CI : 15.7-81.1). CONCLUSIONS: Pre-existing infection with H. pylori, as determined by seropositivity, is an important determinant of development of duodenal ulcer or duodenitis in young Israelis, supporting the generalizability of an apparent causal association to diverse populations.

Adolescent↗

[High-dose chemotherapy and autologous stem cell transplantation for refractory and relapsing Hodgkin's disease as first-line therapy-- studies at Sheba Medical Center--Tel Hashomer].

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males. All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively. The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics. We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.

Adult↗

[Treatment of adults with acute lymphoblastic leukemia--results at the Sheba Medical Center, Tel-Hashomer, 1977-1988].

Acute lymphoblastic leukemia (ALL) is a malignant disease whose incidence is relatively low among adults, unlike in children. Adults with ALL have a lower rate of long-term disease-free survival. During the last 20 years, a German multicenter group has shown that their protocols have achieved good results in adults ALL. We reviewed the medical records of 35 ALL patients, aged 19-63 years, whom we treated with these protocols (1988-1997). The remission rate was 94%. At a median follow-up of 46 months the 2-year overall survival was 54% and the disease-free survival was 94%. Although 2 patients died of bone marrow transplant complications, no death was directly associated with drug toxicity. The main grade 3 or 4 side effects (WHO classification) were neutropenia (91%), thrombocytopenia (71%) and anemia (71%). With there protocols we achieved high overall and disease-free survival rates, especially in comparison with other reports. Despite the high rate of severe treatment toxicity, there were no fatalities directly related to treatment. These results emphasize the need to concentrate treatment of adult ALL patients in large medical centers with expertise in the use of the complicated treatment protocols required.

Adult↗