Biomedical subjects

E Sobel

Publications and source records attributed to E Sobel.

At least 19 recordsLinked to original sources

PubMed2006

Trait components provide tools to dissect the genetic susceptibility of migraine.

The commonly used "end diagnosis" phenotype that is adopted in linkage and association studies of complex traits is likely to represent an oversimplified model of the genetic background of a disease. This is also likely to be the case for common types of migraine, for which no convincingly associated genetic variants have been reported. In headache disorders, most genetic studies have used end diagnoses of the International Headache Society (IHS) classification as phenotypes. Here, we introduce an alternative strategy; we use trait components--individual clinical symptoms of migraine--to determine affection status in genomewide linkage analyses of migraine-affected families. We identified linkage between several traits and markers on chromosome 4q24 (highest LOD score under locus heterogeneity [HLOD] 4.52), a locus we previously reported to be linked to the end diagnosis migraine with aura. The pulsation trait identified a novel locus on 17p13 (HLOD 4.65). Additionally, a trait combination phenotype (IHS full criteria) revealed a locus on 18q12 (HLOD 3.29), and the age at onset trait revealed a locus on 4q28 (HLOD 2.99). Furthermore, suggestive or nearly suggestive evidence of linkage to four additional loci was observed with the traits phonophobia (10q22) and aggravation by physical exercise (12q21, 15q14, and Xp21), and, interestingly, these loci have been linked to migraine in previous studies. Our findings suggest that the use of symptom components of migraine instead of the end diagnosis provides a useful tool in stratifying the sample for genetic studies.

Chromosome Mapping↗

PubMed2003

The prevalence of coeliac disease antibodies in patients with the antiphospholipid syndrome.

High prevalence of coeliac disease (CD) has been reported in various autoimmune disorders, buthas not been studied in the antiphospholipid syndrome (APS). We aimed to establish the prevalence of CD antibodies in a cohort of APS patients, and to examine whether CD may be responsible for some of the manifestations of APS. Fifty-seven patients (47 females, 10 males) with APS were studied for clinical manifestations and serological markers of the disease, as well as the presence of anti-endomysial antibodies using an ELISA assay (EMA-ELISA). Control subjects were 171 healthy individuals, age- and sex-matched (141 females). Eight patients with APS (14%, six females) were found to have EMA-ELISA antibodies, compared with 2/141 (1.1%) of controls (P = 0.0003). Antibodies against beta2-glycoprotein-I (beta2GPI) epitopes (GRTCPKPDDLP) were more prevalent in EMA-positive patients than in EMA-negative patients (P = 0.006). Vasculitic skin lesions were significantly more common in EMA-ELISA-positive compared with EMA-ELISA-negative patients(62.5 versus 16.3%, P = 0.01). Among the skin manifestations, superficial cutaneous necrosis (37.5 versus 2%, P = 0.007) was more prevalent in EMA-ELISA-positive than in EMA-ELISA-negative patients. EMA-ELISA antibodies are common in APS, and their presence is associated with high prevalence of antibodies recognizing certain beta2-glycoprotein epitopes, and with cutaneous manifestations of APS.

Adult↗

PubMed2001

Chromosome 1 loci in Finnish schizophrenia families.

We have earlier reported evidence for linkage to two regions on chromosome 1q32--q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.

Adult↗

PubMed2001

Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.

Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.

Acanthosis Nigricans↗

PubMed2001

Multipoint estimation of identity-by-descent probabilities at arbitrary positions among marker loci on general pedigrees.

OBJECTIVES: To describe, implement, and test an efficient algorithm to obtain multipoint identity-by-descent (IBD) probabilities at arbitrary positions among marker loci for general pedigrees. Unlike existing programs, our algorithm can analyze data sets with large numbers of people and markers. The algorithm has been implemented in the SimWalk2 computer package. METHODS: Using a rigorous testing regimen containing five pedigrees of various sizes with realistic marker data, we compared several widely used IBD computation programs: Allegro, Aspex, GeneHunter, MapMaker/Sibs, Mendel, Sage, SimWalk2, and Solar. RESULTS: The testing revealed a few discrepancies, particularly on consanguineous pedigrees, but overall excellent results in the deterministic multipoint packages. SimWalk2 was also found to be in good agreement with the deterministic multipoint programs, usually matching to two decimal places the kinship coefficient that ranges from 0 to 1. However, the packages based on single-point IBD estimation, while consistent with each other, often showed poor results, disagreeing with the multipoint kinship results by as much as 0.5. CONCLUSIONS: Our testing has clearly shown that multipoint IBD estimation is much better than single-point estimation. In addition, our testing has validated our algorithm for estimating IBD probabilities at arbitrary positions on general pedigrees.

Algorithms↗

PubMed2001

Use of prostheses and footwear in 110 inner-city partial-foot amputees.

The number of partial-foot amputations performed is increasing, and many recommendations have been made regarding the use of prostheses and footwear designed to prevent higher-level amputations in this population. The present study investigated the use of prostheses and shoe inserts and the types of footwear worn by partial-foot amputees in the inner city to determine whether previous recommendations are being followed as well as whether new prosthetic styles are being used. The study surveyed 110 patients (73 men and 37 women) with a mean age of 58.6 years (range, 21 to 86 years) with partial-foot amputations of all levels. The results showed that about one-half of all patients wore a shoe-insert orthosis. Although 54% wore some form of special footwear to accommodate and protect the residual foot, no patient in this study wore a shoe with a rocker-bottom sole. Only one patient with a transmetatarsal amputation used a brace and only one patient in the entire study wore a modern cosmetic foot prosthesis.

Adult↗

PubMed2000

EMF exposure assessment in the Finnish garment industry: evaluation of proposed EMF exposure metrics.

Recently published studies indicate that having worked in occupations that involve moderate to high electromagnetic field (EMF) exposure is a risk factor for neurodegenerative diseases, including Alzheimer's disease. In these studies, the occupational groups most over-represented for EMF exposure comprised seamstresses, dressmakers, and tailors. Future epidemiologic studies designed to evaluate the possibility of a causal relationship between exposure to EMF and a neuro degenerative disease endpoint such as incidence of Alzheimer's disease, will benefit from the measurement of electromagnetic field metrics with potential biological relevance. Data collection methodology in such studies would be highly dependent upon how the metrics are defined. In this research the authors developed and demonstrated (1) protocols for collecting EMF exposure data suitable for estimating a variety of exposure metrics that may have biological relevance, and (2) analytical methods for calculation of these metrics. The authors show how exposure might be estimated under each of the three prominent EMF health-effects mechanism theories and evaluate the assertion that relative exposure ranking is dependent on which mechanism is assumed. The authors also performed AC RMS magnetic flux density measurements, confirming previously reported findings. The results indicate that seamstresses, as an occupational group, should be considered for study of the possible health effects of long-term EMF exposure.

Algorithms↗

PubMed2000

Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields.

The objective of this study was to determine whether daytime occupational exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal melatonin production. Sixty female volunteers were recruited. Thirty-nine worked in a garment factory, and 21 office workers served as a reference group. Exposure assessment was based on the type of sewing machine used and MF measurements around each type of machine. Eye-level MF flux density was used to classify the operators to higher (>1 microT) and lower (0.3-1 microT) exposure categories. A third group of factory workers had diverse MF exposures from other sources. The reference group had average exposure of about 0.15 microT. Urine samples were collected on Friday and Monday for three consecutive weeks. Melatonin production was assessed as urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion. The ratio of Friday morning/Monday morning 6-OHMS was used to test the hypothesis that melatonin production is suppressed after 4 days of occupational MF exposure with significant recovery during the weekend. Possible chronic suppression of melatonin production was evaluated by studying exposure-related differences in the Friday values by multivariate regression analysis. The Monday/Friday ratios were close to 1.0, suggesting that there is no increase in melatonin production over the weekend. The average 6-OHMS excretion on Friday was lower among the factory workers than in the reference group, but no monotonous dose-response was observed. Multivariate regression analysis identified MF exposure, smoking, and age as significant explanatory variables associated with decreased 6-OHMS excretion.

Adult↗

PubMed2000

Modulation of human leukocyte antigen and intracellular adhesion molecule-1 surface expression in malignant and nonmalignant human thyroid cells by cytokines in the context of extracellular matrix.

Interactions between malignant cells and their environment are achieved via cell-surface receptors and adhesion molecules. The extracellular matrix (ECM) and ECM-bound cytokines modulate the expression of cell-surface molecules on target malignant cells, which may lead to changes in their susceptibility to cytolysis, in their ability to present antigens, and in the induction of local immune-cell activation and patrol. Eventually, these alterations may culminate in either the destruction, or escape and proliferation, of the tumor. We studied the effects of the ECM and its components in a "naive" form or following binding of the inflammatory cytokines interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) on the surface expression of human leukocyte antigen (HLA) class-I, HLA class-II (HLA-DR), and intracellular adhesion molecule-1 (ICAM-1), on nonmalignant and malignant thyroid cells. The basal expression of HLA class-I molecules was not significantly changed either by naive ECM and its components or by ECM-bound cytokines. ECM synergized with IFNgamma and TNFalpha in inducing HLA-DR molecules on nonmalignant and malignant thyrocytes, with higher HLA-DR levels on the malignant cells. The laminin component, in particular, synergized with IFNgamma. Basal ICAM-1 expression on nonneoplastic cells was not significantly affected by the cytokines when grown in the absence of ECM, but was significantly upregulated when cells were cultured on ECM. In contrast, in malignant thyrocyte cultures, ECM significantly attenuated IFNgamma- and TNFalpha-mediated enhancement of ICAM-1 expression. We concluded that signals derived from ECM-embedded cytokines participate in the regulation of key thyroid cell surface molecules and, thus, may affect the final outcome of human thyroid malignancies.

Animals↗

PubMed2000

Progressive pedal macrodactyly surgical history with 15 year follow-up.

Macrodactyly can affect the fingers and/or toes1. Histopathologic examination will distinguish macrodactylia fibrolipomatosis or neural fibrolipoma with macrodactyly, from macrodactylia as a part of neurofibromatosis. Surgical repair is aimed at decreasing the size of the affected foot so it is as near in size and shape to the normal foot as possible. Surgical approaches have included reconstructive surgery (usually staged debulking procedures), epiphyseal plate arrest and amputation. Repeated reconstructive surgical procedures, as illustrated in this report covering patient care over a 15 year period, are usually necessary due to recurring soft tissue and boney enlargement.

Adult↗

PubMed1999

Stroke survival after discharge from an acute-care hospital.

BACKGROUND AND PURPOSE: Survival after a stroke is likely to be best for patients well enough to be sent home but the relative risk of dying if patients do not qualify for a home discharge has not been well studied. We investigated the survival prognosis after an initial stroke depending on the facility to which the patient was discharged after an acute initial stroke. METHODS: All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed up to 4 years (mean of 24 months) until death, second stroke, or the end of the study. RESULTS: Among 662 patients who were discharged alive after hospitalization with an initial stroke, 128 (19%) went to a nursing home, 17(3%) to a short-term hospital, 140 (21%) to a rehabilitation facility, and 375 (57%) went home (discharge destination unknown for 2 patients). Compared to patients sent home after taking age, sex, selected baseline comorbidities, length of hospital stay, and neurological deficits into consideration, results from Cox proportional hazards model indicated that patients sent to a nursing home had 2.6 times greater risk of dying (95% CI = 1.81-4. 15) while those who were discharged to a rehabilitation facility had a death hazards ratio of 1.1. CONCLUSIONS: Mortality was greatest in the early months after discharge and decreased thereafter. Since the analysis was adjusted for age, sex, comorbidity, length of hospital stay, and number of neurological deficits, quality of care in a nursing home setting may account for the mortality difference but other factors such as social support network and living will instructions also need to be investigated.

Aged↗

PubMed1999

Natural history of the rearfoot angle: preliminary values in 150 children.

The degree of valgus in the heel during weightbearing (the rearfoot angle) is commonly used as an angular criterion in the evaluation and treatment of flatfoot in children and adults. The rearfoot angle has been frequently reported to reduce with age to a vertical heel position attained at approximately 7 years old. The present study evaluated the rearfoot angle in 150 healthy children (age range, 6-16 years). The average rearfoot angle for all children in this study was 4 degrees of valgus (SD, 1.1 degrees; range, 0 degree - 9 degrees of valgus). There was no significant difference in the rearfoot angle in children of different ages. The rearfoot angle did not reduce to the vertical heel position by age 7 as had been reported previously.

Achilles Tendon↗

PubMed1999

Problems and management of the rearfoot in neuromuscular disease. A report of ten cases.

Neuromuscular disease commonly affects the rearfoot as equinus, equinovarus, and equinovalgus deformity. Spastic hemiplegia caused by stroke, head injury, and cerebral palsy results in equinovarus deformity of the rearfoot. Spastic diplegia, most frequently caused by cerebral palsy, results in equinovalgus rearfoot deformity. Problems in ambulation, footwear, and bracing, as well as their orthopedic management, in patients with neuromuscular disease are discussed in a case-report format.

Adolescent↗

PubMed1999

Calcaneal gait. Etiology and clinical presentation.

Equinus deformities are common in neuromuscular and trauma patients. In contrast, calcaneal gait disorders tend to be overlooked, and few reports characterize and review calcaneal gait problems and disabilities. In the past 3 years, the authors treated 17 patients with calcaneal gait. Six of these cases are reviewed; in addition, the general clinical characteristics of the patient with calcaneal gait pattern are described.

Adult↗

PubMed1999

Long-term follow-up of heel spur surgery. A 10-year retrospective study.

A comparative retrospective study of 48 open heel spur surgeries and 20 endoscopic plantar fasciotomies was conducted involving 59 patients over a 10-year period. There was a significant reduction in heel pain at the time of follow-up (average, 3 years) for both groups. Overall, 85% of procedures were associated with patient satisfaction with the results, and patients said that they would recommend heel spur surgery for relief of severe heel pain in 94% of cases. Factors influencing the postoperative outcome, such as duration of preoperative symptoms, extent of conservative care, and obesity, are discussed.

Calcaneus↗

PubMed1999

Orthoses in the treatment of rearfoot problems.

Orthotic management is helpful in the treatment of most orthopedic conditions involving the rearfoot, including plantar fasciitis, Achilles tendon disorders, posterior tibial tendon dysfunction, flatfoot, ankle sprains, and problems associated with diabetes, arthritis, and equinus disorders. A review of the effectiveness of orthoses in the treatment of these conditions is presented here. An in-depth analysis of the orthotic management of plantar fasciitis and a critical review of foot orthoses for the pronated foot are presented. Also discussed are the rationale and effectiveness of the tension night splint in the treatment of plantar fasciitis, orthotic devices for the different stages of posterior tibial tendon dysfunction, and the various categories of orthoses for off-loading the diabetic foot. The modern ankle brace, the effectiveness of prefabricated versus prescription foot orthoses, and recent developments in the ankle-foot orthosis are also reviewed.

Arthritis↗

PubMed1999

Reevaluation of the relaxed calcaneal stance position. Reliability and normal values in children and adults.

Reliability and normal values for the relaxed calcaneal stance position were determined in a nonclinic population of healthy adults and children (88 adults and 124 children) ranging in age from 5 to 36 years. The mean relaxed calcaneal stance position for adults was 6.07 degrees valgus (SD 2.71 degrees) (range, 1 degree varus to 14 degrees valgus). The mean relaxed calcaneal stance position for children was 5.6 degrees valgus (SD 2.9 degrees) (range, 6 degrees varus to 12 degrees valgus). There was no significant difference between the relaxed calcaneal stance positions of adults and children. In children the relaxed calcaneal stance position did not correlate with age, height, or weight and did not decrease with age to the theoretical normal value of 0 degree +/- 2 degrees as postulated by Root et al. The relaxed calcaneal stance position was found to be a reliable measurement; however, the theoretical normal value of 0 degree +/- 2 degrees was not found. The values reported in the present study correspond with the results of other empirical studies; thus the theoretical normal value for the relaxed calcaneal stance position of 0 degree +/- 2 degrees may be invalid.

Adolescent↗

PubMed1998

Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.

BACKGROUND: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. OBJECTIVE: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. PATIENTS AND METHODS: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. RESULTS: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). CONCLUSIONS: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).

AIDS Dementia Complex↗