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Biomedical subjects

Y Danon

Publications and source records attributed to Y Danon.

At least 19 recordsLinked to original sources

Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis leading to renal failure is the most severe complication in untreated patients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different ethnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a high frequency of carriers among Jews from the various ethnic groups. In North African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations among healthy individuals (M694V 29%, V726A 16%, M6801 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84.4%, V726A 9.0%, M6801 0% and E148Q 6.6%). Six healthy asymptomatic individuals were found to carry mutations in both alleles: two homozygotes for E148Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mutation E148Q is associated with a milder phenotype, which explains the lower prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises the question of the need for molecular screening for M694V homozygotes in the Israeli North African Jewish community.

Adult↗

Phenotype-genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis.

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent attacks of inflammation of serosal membranes. Amyloidosis is the most severe complication of the disease. The aim of this study was to investigate the genotype-phenotype correlation and specifically the association between amyloidosis and the four common mutations in exon 10 of the gene causing FMF (MEFV) in a total of 83 FMF families from three ethnic groups: North African Jews, Armenians and Turks. A significant association was found between amyloidosis and the specific mutation at the MEFV gene: Met694Val (RR = 1.41, P = 0.02). Amyloidosis was present in 18 out of 87 homozygous FMF patients (20.7%) and in only two out of the 41 compound heterozygous FMF patients (4.9%). No patients carrying other mutations had amyloidosis. There was no significant association between the various mutations and the type or severity of the FMF symptoms. This finding underscores the importance of performing molecular studies on all suspect FMF patients. In addition to providing accurate diagnosis, these tests allow identification of presymptomatic genetically affected individuals, detection of carriers and assessment of the risk for amyloidosis in later life.

Adolescent↗

Assessment of pyrin gene mutations in Turks with familial Mediterranean fever (FMF).

Familial Mediterranean fever (FMF) is an autosomal recessive disease clinically characterized by recurrent short self-limited attacks of fever accompanied by peritonitis, pleurisy, and arthritis and can lead to amyloidosis and renal failure in the longer term. It is prevalent mainly in non-Ashkenazi Jews, Armenians, Turks, and Arabs. Due to the lack of an accurate diagnostic test, patients often experience years of attacks and invasive diagnostic procedures before the correct diagnosis is made and adequate treatment is begun. Recently, the gene responsible for FMF, denoted pyrin, has been cloned, and three disease mutations have been described (French FMF Consortium, 1997; International FMF Consortium, 1997). In the current study we assessed the spectrum of mutations in this gene in 16 unrelated families of Turkish origin. The three previously reported missense mutations (Met-Ile at codon 680, Met-Val at codon 694, and Val-Ala at codon 726) accounted for 29 of the 34 disease alleles. In one patient in whom no disease mutation was identified, the clinical picture was atypical enough to raise questions regarding the diagnosis. These results imply that the origin of FMF in Turkey is heterogeneous, that molecular diagnosis of FMF is possible in the majority of cases and clinically helpful, and that delineation of the undiscovered disease mutation(s) in the remaining cases remains a high priority.

Armenia↗

Amyloidosis in familial mediterranean fever is associated with a specific ancestral haplotype in the MEFV locus.

Familial Mediterranean fever (FMF) is a recessive disease characterized by recurrent attacks of inflammation of serosal membranes, and the gene responsible, MEFV, has been recently identified. Amyloidosis is considered to be the most severe complication. Since colchicine is effective in preventing FMF amyloidosis and since this process can develop even prior to the FMF symptoms, lifelong colchicine treatment is recommended for all FMF patients. Identification of the factor which determines amyloidosis will allow treatment to be directed only to those at risk. In order to investigate the association between amyloidosis and MEFV haplotypes, we studied 56 families from three ethnic groups. We compared the haplotypes of FMF patients with and without amyloidosis in each ethnic group separately and identified 14 different MEFV core haplotypes. A significant association (P < 0.004) was found between amyloidosis and a specific core haplotype, 153bp:104bp at markers D16S3370 and D16S2617, respectively. Amyloidosis was present in 20 out of 70 homozygotes for this haplotype and in 6 out of 35 compound heterozygotes for this and other core haplotypes. None of the patients who did not carry this allele had amyloidosis. There was no association between the various haplotypes and severity of the FMF symptoms, age of onset, or age at commencement of colchicine. Further investigation of the MEFV haplotypes in additional patients is recommended as such an association may save many mildly affected or asymptomatic patients with non-amyloidotic genotypes from receiving unnecessary lifelong colchicine treatment.

Adolescent↗

Measles immunity and response to revaccination of a young adult population in Israel.

In order to evaluate the true immune status and the effect of revaccination on a young adult population, we collected serum samples from 289 military recruits who were vaccinated during an outbreak in 1991. Most vaccinees, age 18-25 years, had apparently been immunized once before as infants. Sera collected just prior to the vaccination and 14 and 28 days afterwards were tested for measles antibodies by hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA)-IgM. Before vaccination, 46 (15.9%) of the subjects had no HI antibodies, (< 1:4) and 48 (16.6%) had borderline (1:4) HI titer. Following vaccination, only ten (3.5%) remained negative and 19 (6.6%) had borderline titer. The increase in HI antibody titer was inversely proportional to the prevaccination titer, and 159 subjects (55.0%) showed no increase at all. The geometric mean titer (GMT) rose from 9.14 to 21.47. Among the prevaccination-negative subjects (HI < 1:4) 28 (60.9%) reached a postvaccination titer of > or = 1:8, and eight (17.4%) reached a titer of 1:4. Twelve (26.1%) of the negative subjects seroconverted and developed IgM, 16 (35%) seroconverted without IgM, and 18 (39%) remained negative and did not develop IgM. A group of eight vaccinees with prevaccination titer of > or = 1:4 developed IgM. Some were probably infected by the circulating wild-type virus prior to the vaccination. Thus, a total number of 20 of the 289 subjects studied (6.9%) had true negative preimmune status as judged by the IgM test. However, the vaccination campaign prevented further measles cases, apparently by increasing the population's immunity, particularly in individuals with very low titers or without measles antibodies.

Adolescent↗

The factor structure and criterion validity of the short form of the Eating Attitudes Test.

One of the more frequently used measures of eating disorders is the 40-item Eating Attitudes Test (EAT) developed by Garner and Garfinkel (1979). Although originally designed to diagnose anorexia nervosa, the test has recently been applied to nonclinical populations also. In this study, we examined psychometric and validity data for a short version of the scale, the EAT-26. Using a sample of 809 female soldiers in their late teens, results showed that the EAT-26 is reliable, the factor structure is different from that obtained in clinical groups, and the EAT-26 is significantly correlated with body image, weight, and diet.

Adolescent↗

The gene for familial Mediterranean fever in both Armenians and non-Ashkenazi Jews is linked to the alpha-globin complex on 16p: evidence for locus homogeneity.

Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder characterized by short episodes of fever, peritonitis, pleuritis, and arthritis. While FMF has been shown to be inherited in an autosomal recessive fashion in both non-Ashkenazi Jews and Armenian families, clinical differences have raised the possibility of genetic heterogeneity. As its pathogenesis is unknown, mapping of the gene for FMF may provide the first objective method for early and accurate diagnosis of this disease. After excluding 45% of the entire human genome, we studied 14 Armenian and 9 non-Ashkenazi Jewish families with FMF and tested linkage with the alpha-globin locus on chromosome 16. Analysis of the PvuII length polymorphism of the 3' HVR (hypervariable region) probe showed significant linkage with the FMF gene (maximum lod score [lodmax] = 9.76 at maximum recombination fraction [theta] = .076). In the Armenians, the lodmax = 3.61 at theta = .10; and for the non-Ashkenazi Jews, lodmax = 6.28 at theta = .06. There was no evidence for genetic heterogeneity between the Armenians and the non-Ashkenazi Jews (chi 2 = 1.28; P = .26) or within either ethnic group (chi 2 = .00; P = .50). Thus, the gene for FMF is linked to the alpha-globin complex on chromosome 16p in both non-Ashkenazi Jews and Armenians.

Armenia↗

Prevalence and correlates of diphtheria toxin antibodies among young adults in Israel.

The paucity of information about immunity against diphtheria of young adults in Israel prompted us to analyse sera from a random sample of 480 recruits (263 males and 217 females) aged 18-19 years. Antitoxin antibody levels were determined by means of ELISA. Of the recruits 58.1% had antibody values greater than 0.1 IU/ml; 38.5% had amounts between 0.01 and 0.1 IU/ml, which is considered low when using the ELISA method, and 3.3% had less than 0.01 IU/ml. The results of this study suggest that a booster dose of antidiphtheria vaccine should be given to adults in Israel in order to ensure adequate antibody levels.

Adolescent↗

Analysis of historical epidemiological data to guide intervention policy in the face of an infectious disease outbreak: poliomyelitis in Israel in 1988.

During the 1988 outbreak of 15 cases of Type 1 poliomyelitis mainly among previously vaccinated young adults in Israel, there were conflicting views on the need for and timing of mass vaccination. Since there was a possibility that the initially localized outbreak may spread more widely, it was felt that an early decision on vaccination policy should be made. Public health officials were faced with varied interpretations of the existing data on the extent of the immune status of the population; some indicating that as many as 15% of young adults lacked immunity to the Type 1 virus. Two major questions posed were whether or not the outbreak was a purely localized event in a single subdistrict, and whether the seasonality of the disease would limit its spread. Based on historical data, probability analysis of three cases occurring outside the subdistrict at the time of the outbreak suggested more widespread dispersion of the virus. Further analysis indicated very limited seasonality of the disease in this region, suggesting that the onset of colder weather would have little impact on the spread of the virus. Careful analysis of the local epidemiology of the disease is an important tool for guiding urgent decisions on mass intervention policy in outbreak situations.

Adolescent↗

A novel approach to military combat trauma education.

A heterogeneous group of 77 physicians on compulsory or reserve military service were exposed to a 5-day course in trauma management, specifically designed for military medical personnel. Cognitive knowledge of trauma care delivery of the medical officers was assessed by means of multiple-choice written tests, which were held before and upon completion of the course. The significantly improved (p less than 0.0001) scores of the post-course test demonstrate the value of a condensed trauma educational program. Analysis of the background variants (i.e., medical education, military, and residency training, and time since graduation) revealed that the relatively short but intensive course sufficed to surmount the difficulties inherent in instructing a student body composed of individuals with dissimilar professional experience. We advocate the institution of a compact course in trauma treatment, with the specific aim of enhancing the medical officer's knowledge in this critical field of medical care.

Analysis of Variance↗

Fatal accidental inhalation of bromochlorodifluoromethane (Halon 1211).

Bromochlorodifluoromethane (Halon 1211) is a widely used fire extinguishing agent. Several cases of sudden death in teenagers associated with BCF abuse have been reported. BCF is used as a fire extinguisher in battle tanks. Two young previously healthy male soldiers were accidentally exposed to BCF in a battle tank. The tank driver died, but the gunner survived the event with no medial complications. It is concluded that BCF should be used in confined chambers only after the evacuation of all personnel.

Accidents, Occupational↗

Risk factors for infection in fracture war wounds (1973 and 1982 wars, Israel)

The development of post-surgical wound infection was compared in two groups of soldiers who sustained fractures or amputations on the battlefield during the first month of the 1982 and 1973 wars. Risk factors for the development of post-surgical wound infection were sought. In the 1982 group, numbering 184, the four variables independently associated with infection were multiple operations during the follow-up period; drains inserted in the first operation; extensive tissue loss; and blood transfusion during the first operation. For the 1973 group, numbering 130, the significant variables were multiple operations; amputations (highly correlated with extensive tissue loss); injury involving other body systems in addition to the fracture; and open drains. The high risk associated with open drains in both wars raises doubt about their usefulness. The main distinction between injuries of the two wars was the high prevalence (72.3%) of multi-system injuries in 1973 versus low prevalence (29.2%) in 1982. Overall infection rates were similar (30.5% and 31.5%), but infections at the site of the fracture were twice as high in 1982. Pseudomonas was the most common single species of bacteria isolated from infected wounds (26% in 1982, 33.6% in 1973). It appeared in the wounds relatively late, 10-14 days after admission.

Adult↗

Effect of pyridostigmine on the exercise-heat response of man.

The effect of pyridostigmine on thermoregulatory responses was evaluated during exercise and heat stress. Eight heat acclimated, young adult male subjects received four doses of pyridostigmine (30 mg) or identical placebo tablets every 8 h, in a double blind, randomized, cross-over trial. A 30.3%, SD 4.6% inhibition of the circulating cholinesterase (ChE) activity was induced in the pyridostigmine-treated group. The subjects were exposed to 170-min exercise and heat-stress (dry bulb temperature, 33 degrees C; relative humidity 60%) consisting of 60 min in a sitting position and two bouts of 50-min walking (1.39 m.s-1, 5% gradient) which were separated by 10-min rest periods. No differences were found between treatments in the physiological responses and heat balance parameters at the end of exposure: heart rate (fc) was 141 beats.min-1, SD 16 and 150 beats.min-1, SD 12, rectal temperature (Tre) was 38.5 degrees C, SD 0.4 degrees and 38.6 degrees C, SD 0.3 degrees, heat storage was 60 W.m-2, SD 16 and 59 W.m-2, SD 15 and sweat rate was 678 g.h-1, SD 184 and 661 g.h-1, SD 133, in the pyridostigmine and placebo treatments, respectively. The changes in Tre and fc over the heat-exercise period were parallel in both study and control groups. Pyridostigmine caused a slight slowing of fc (5 beats.min-1) which was consistent throughout the entire exposure (P less than 0.001) but was of no clinical significance. The overall change in fc was similar for both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Sociodemographic correlates of neutralizing poliovirus and hepatitis A virus antibodies as markers of different modes of acquiring immunity.

The prevalence and sociodemographic correlates of antibodies against poliovirus and hepatitis A virus (HAV) were compared in a random sample of 457 military recruits in Israel inducted during 1987. Lower socioeconomic status (SES) was associated with a higher prevalence of anti-HAV antibodies (67.3 vs 32.5 percent), whereas the reverse was true for type 1 poliovirus (78.4 vs 89.5 percent). While the high prevalence of anti-HAV antibodies observed in the lower SES groups reflects considerable natural exposure to enteroviruses, immunity against poliovirus appears to be determined primarily by compliance with vaccination.

Antibodies, Viral↗