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Biomedical subjects

Sarah Brenner

Publications and source records attributed to Sarah Brenner.

At least 19 recordsLinked to original sources

Severe acne vulgaris and tobacco smoking in young men.

As the relationship between tobacco smoking and acne remains unclear, we examined the relationship between cigarette smoking and severe acne in a large cohort of young men. Trained nurses interviewed subjects upon discharge from compulsory military service, regarding family history, habits, and tobacco smoking habits. Data was correlated with severe acne status, as diagnosed and coded by board-certified dermatologists. In total, 27,083 male subjects participated in the study from 1983 to 2003, of which 237 (0.88%) had severe acne, 11,718 (43.27%) were active smokers, and 15,365 (56.73%) were nonsmokers at the time of interviews. Active smokers showed a significantly lower prevalence of severe acne (0.71%) than nonsmokers (1.01%) (P = 0.0078). An inverse dose-dependent relationship between severe acne prevalence and daily cigarette consumption became significant from 21 cigarettes a day (chi2 and trend test: P < 0.0001), odds ratio: 0.2 (95% CI: 0.06-0.63). The study did not aim to establish a temporal correlation, and passive smoking and acne treatments were not measured. Previous in vitro and clinical studies strongly support an association with nicotine. We suggest a trial with topical nicotine treatment for acne to further investigate this association.

Acne Vulgaris↗

Pemphigus vulgaris is associated with the transporter associated with antigen processing (TAP) system.

Pemphigus vulgaris (PV) is a human leukocute antigen (HLA) class II-associated autoimmune disease of the skin of unknown etiology. We recently described the association of pemphigus vulgaris with two clusters of microsatellite loci within the major histocompatibility complex region. One cluster includes the microsatellite marker TAP1CA, located in proximity to the transporter associated with antigen processing (TAP) genes. These genes are essential for class I antigen processing machinery and could be an additional set of genes involved in susceptibility to PV. The aim of this study was to investigate a possible association between TAP gene polymorphisms and PV. For this purpose we examined 37 unrelated Jewish Israeli patients with PV and compared them with 37 healthy Israeli Jewish HLA-matched controls. Significant differences were detected in TAP2 amino acid residues (p=0.001). Two PV TAP2 risk alleles were identified (TAP2*C and TAP2*D), the frequency of which was estimated to be 37.8% in the patients and 5.3 % in the controls. This association was found to be independent of HLA-DR. It is therefore likely that TAP2 genes are involved in susceptibility to development of PV.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Increased use of mental health services related to isotretinoin treatment: a 5-year analysis.

BACKGROUND: The association between exposure to Isotretinoin, the development of depression and suicide attempts is controversial. OBJECTIVE: To retrospectively assess pattern of utilization of mental health services in the Israeli Defense Forces (IDF) during a 5-year period for all subjects exposed to Isotretinoin in comparison to a control group consisting of army conscripts suffering from psoriasis. All subjects were young adults (18 to 21 years old) in compulsory military service. METHOD: Exposure to Isotretinoin mandates reporting and marking as a coded medical profile in the IDFs' computerized medical record of each conscript and soldier. Medical data, tracked by military medical profiles, were summarized from medical records of all subjects treated by Isotretinion during the years 1999-2003 and for the control group for the same period. Use of mental health services was the a-priori defined primary outcome measure. RESULTS: During the study period 1419 subjects were exposed to Isotretinoin and 1102 suffered from psoriasis. Utilization of mental health services was highest for the index group wherein 17.2% (245/1419) of subjects were evaluated or treated compared to 12.5% in the control group (psoriasis). The inter-group differences were statistically significant; Chi-square=15.9 (df=2), p=0.0003. CONCLUSIONS: We suggest that psychiatric evaluation be regularly undertaken prior to initiation of Isotretinion treatment in young adults at risk, as well as providing follow-up visits during and at completion of treatment.

Acne Vulgaris↗

Significance of autoimmunity to non-desmoglein targets in pemphigus.

The pathogenesis of pemphigus vulgaris (PV) is a highly controversial, "hot" topic that has received considerable enrichment in recent years by both clinical and basic researchers. On the one hand, the classical view of desmogleins (Dsg) as main targets of this autoimmune disease is supported by the characterization of pathogenic anti-Dsg3 antibodies from both patients and animal models. On the other hand, fundamental doubt has been raised towards this monopathogenic view by several independent factors: (1) pemphigus lesions can be induced in Dsg3-knockout (KO) mice; (2) pemphigus sera contain multiple autoantibodies against different adhesion molecules and also cholinergic receptors; (3) experimental inhibition of PV IgG induced acantholysis can be obtained by interference with different signaling cascades regulating both calcium homeostasis and apoptosis; and (4) cholinergic agonists exhibit anti-acantholytic activity both in vitro and in vivo. The field is open for controlled clinical trials and further basic research to unfold the true story of the pemphigus enigma and provide the basis for a better treatment of pemphigus patients.

Animals↗

Multiple common naevi in Israeli adolescents.

The most prominent known phenotypic risk factor for the development of melanoma is a large number of common melanocytic naevi. The aims of this study were to determine the prevalence of multiple common naevi in a group of 17-year-olds and to identify possible associated risk factors. The study subjects were approximately 40,000 female and 60,000 male 17-year-old Jewish Israelis presenting to army recruitment centres for compulsory military service during a 1-year period from January 2003 to December 2003. Data were gathered on whole-body naevi count, years of education, place of residence and place of birth of the recruit, his/her parents and paternal grandparents. The count of whole-body naevi was carried out by military physicians. The multiple naevi phenotype was defined by the presence of more than 50 naevi. The prevalence of the phenotype was highest amongst recruits of American origin and lowest amongst those of Asian and African origin (P < 0.0001). The prevalence differed in different population centres, the highest being in the coastal cities of Haifa and Tel Aviv. This pattern corresponded to the geographical distribution of melanoma in Israel. Amongst male conscripts, the phenotype was more common in the better educated group (> or =12 years) than in the poorer educated conscripts (< or = 11 years) (P = 0.051). When adjusted for the factors studied, a significant correlation was found between a high multiple common naevi count and American and European origin and residence in coastal cities, reflecting the complex interplay between endogenous and exogenous factors of melanoma.

Adolescent↗

Allergic contact dermatitis among maintenance and clerical workers in a military population.

Contact dermatitis is one of the leading causes of occupational morbidity and absenteeism and has become an intolerable cause of missed workdays and health problems in the Israeli military. The aim of this study was to determine the rate of contact dermatitis in maintenance and clerical workers, the common allergens causing it, and the background of atopy in the subjects in order to design preventive measures. Medical records of all recruits to the Israel Defense Forces from 2000 to 2003 were reviewed for contact dermatitis. The 102 cases found were further assessed for job assignment, atopic background, and allergens. Of the 102 cases, 60 had irritant contact dermatitis and 42 had allergic contact dermatitis, of which 33 (78.6%) were maintenance workers, mainly mechanics. 13 soldiers in the maintenance job category (39%) and 2 soldiers in the clerical group (22.2%) had atopic background. There were 55 positive reactions in patch tests, 25 of them to oil and cooling fluids, with 14.5% attributed to methylchloroisothiazolinone/methylisothiazolinone) (Kathon CG). Atopy was found to be a risk factor for allergic contact dermatitis in our study and should be screened for in job assignment procedures in the military. Oil and greases contain significant allergens, especially their preservatives.

Adolescent↗

Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata.

Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type II papillary renal cell cancer (HLRCC). The genetic locus for MCL and HLRCC was recently mapped to chromosome 1q42.3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene ( FH ) were identified. Importantly, analysis of the FH gene in tumors of MCL patients revealed a second mutation inactivating the wild-type allele in some tumors. Based on these findings, it has been suggested that FH may function as a tumor suppressor gene in MCL. Here, we report the analysis of the FH gene in a group of 11 MCL families, with the identification of 8 different mutations accounting for the disease in all families. One of the mutations, 905-1G>A, has been identified in 4 families of Iranian origin. The analysis of highly polymorphic markers in the vicinity of the FH gene showed a shared haplotype in these 4 families, suggesting that 905-1G>A represents a founder mutation. Collectively, identification of 5 novel and 3 recurrent mutations further supports the role of FH in the pathogenesis of MCL.

Female↗

A novel system to diagnose cutaneous adverse drug reactions employing the cellscan--comparison with histamine releasing test and Inf-gamma Releasing Test.

BACKGROUND: There are several mechanisms to describe allergic drug reactions yet the methods to diagnose them are limited. OBJECTIVE: To compare several conventional clinical and laboratory methods to diagnose skin reactions to drugs to a new method of diagnosing drug reactions by the CellScan system. METHODS: The study entailed 21 patients who were diagnosed as suffering from drug eruptions, and 105 healthy controls with no history of drug allergy. The drugs were classified into two groups according to suspicion of causing drug allergy: high and low. Most of the patients were on more than one drug, leading to 41 patient-drug interactions (assays). Histamine releasing test (HRT), interferon (INF)-gamma releasing test and CellScan examination were performed on lymphocytes of the patients and controls. RESULTS: The HRTwas interpreted as positive in 9 out of 18 (50%) patients and in 13 out of 35 (37%) assays. Based on the INF-gamma releasing test, positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41 (59%) assays. In the CellScan test (CST), positive results were observed in 17 out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%) assays in the HRT, 20 out of 24 (83%) assays in the INF-gamma releasing test, and 21 out of 24 (87%) studies with the CellScan method. The rate of determining of the drug that caused the eruption in the low suspicion level drugs was 4 out of 13 (31 %) in the HRT, 4 out of 17 (24%) assays in the INF-gamma releasing test, and 8 out of 17 (47%) analyses in the CST. When examined in the CellScan, 99 out of 105 (94%) controls were interpreted as negative. CONCLUSION: This preliminary study indicates that the CellScan seems to be an easy and promising method for the detection of drugs responsible for adverse skin reactions. In contrast to the HRT and to the Interferon-gamma secretion test, the CellScan method is characterized by its ability to track and monitor the reaction of individual cells. By measuring the kinetic parameters of selected cells before and after adding the suspected drug, we were able to identify the culprit drug. The CellScan method had the highest sensitivity, and the interferon-gamma secretion test had the highest specificity for detection of the culprit drug. In contrast, the analysis of 105 normal control sera disclosed a high specificity of 94% for the CellScan method.

Adult↗

Teledermatology: quality assessment by user satisfaction and clinical efficiency.

BACKGROUND: The Israel Defense Forces implemented a pilot teledermatology service in primary clinics. OBJECTIVES: To assess user satisfaction and clinical short-term effectiveness of a computerized store and forward teledermatology service in urban and rural units. METHODS: A multi-center prospective uncontrolled cohort pilot trial was conducted for a period of 6 months. Primary care physicians referred patients to a board-certified dermatologist using text email accompanied by digital photographs. Diagnosis, therapy and management were sent back to the referring PCP. Patients were asked to evaluate the level of the CSAFTD service, effect of the service on accessibility to dermatologists, respect for privacy, availability of drugs, health improvement and overall satisfaction. PCPs assessed the quality of the teledermatology consultations they received, the contribution to their knowledge, and their overall satisfaction. RESULTS: Tele-diagnosis alone was possible for 95% (n=413) of 435 CSAFTD referrals; 22% (n=95) of referrals also required face-to-face consultation, Satisfaction with CSAFTD was high among patients in both rural and urban clinics, with significantly higher scores in rural units. Rural patients rated the level of service, accessibility and overall satisfaction higher than did urban patients. PCPs were satisfied with the quality of the service and its contribution to their knowledge. Rural physicians rated level of service and overall satisfaction higher than did urban physicians. Tele-referrals were completed more efficiently than referral for face-to-face appointments. CONCLUSIONS: CSAFTD provided efficient, high quality medical service to rural and urban military clinics in the IDF.

Adult↗

Pemphigus vulgaris triggered by glibenclamide and cilazapril.

A case of pemphigus triggered by glibenclamide and cilazapril is described. The suspicion of drug induction was confirmed in a laboratory study in which a pemphigus-like effect was induced by glibenclamide in cultured human skin explants. Withdrawal of the drugs and their replacement by hydrochlorothiazide and metformin resulted in subsidence of the lesions and no appearance of new lesions. The laboratory study carried out to verify the suspicion of drug induced pemphigus and to confirm the diagnosis proved useful in the differential diagnosis in this case.

Aged↗

HLA-G is associated with pemphigus vulgaris in Jewish patients.

Pemphigus is a group of life-threatening autoimmune blistering diseases of the skin and mucous membranes. The etiology and pathogenesis of this destructive autoimmune process remains unknown, but significant association with human leukocyte antigen (HLA) factors have been described in pemphigus vulgaris (PV) patient cohorts worldwide. We have recently analyzed DNA samples obtained from pemphigus patients and matched controls with a set of microsatellite markers, and found that markers mapped to HLA class I region are significantly associated with the disease. In order to narrow the region that is associated with the disease single nucleotide polymorphism (SNP) technology was used. In this study, a set of 26 SNP markers, which span a chromosomal region of about 600,000 bp, were used to screen DNA samples of the patients and their matched controls. Of the 26 SNPs, four markers were found informative, all mapped to HLA-G. Typing patients and controls for HLA-G polymorphism revealed significant differences in the exon 8 deletion/insertion variant. The latter is probably associated with the efficiency of transcription of this gene. Taken together, the results suggest that HLA-G is associated with PV in Jewish patients.

Alleles↗

A systemic reaction to patch testing for the evaluation of acute generalized exanthematous pustulosis.

BACKGROUND: Patch tests are considered safe but adverse reactions have been reported. OBSERVATIONS: A case of acute generalized exanthematous pustulosis (AGEP) provoked by a patch test with acetaminophen is described. Of special interest are the negative patch test results obtained with the offending drug. The case is discussed against the background of the putative mechanisms of AGEP and the reported systemic reactions to patch testing for AGEP. CONCLUSIONS: To our knowledge, this is the first report in the English-language literature of a generalized AGEP-like reaction caused by patch tests carried out to determine the drug eliciting AGEP.

Acetaminophen↗