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Biomedical subjects

J Schulman

Publications and source records attributed to J Schulman.

At least 19 recordsLinked to original sources
PubMed2003

Neuropsychiatric thalamocortical dysrhythmia: surgical implications.

Clearly, more clinical experience must be amassed to define in detail the possibilities of this surgical approach in disabling neuropsychiatric disorders. We propose, however, that the evidence for benign and efficient surgical intervention against the neuropsychiatric TCD syndrome is already compelling. The potential appearance of strong postoperative reactive manifestations requires a close association between surgery and psychotherapy, with the latter providing support for the integration of the new situation as well as the resolution of old unresolved issues.

Adult↗
PubMed2002

Second-generation microstimulator.

The first-generation injectable microstimulator was glass encased with an external tantalum capacitor electrode. This second-generation device uses a hermetically sealed ceramic case with platinum electrodes. Zener diodes protect the electronics from defibrillation shocks and from electrostatic discharge. The capacitor is sealed inside the case so that it cannot be inadvertently damaged by surgical instruments. This microstimulator, referred to as BION, is the main component of a 255-channel wireless stimulating system. BION devices have been implanted in rats for periods of up to 5 months. Results show benign tissue reactions resulting in identical encapsulation around BION and controls. Stimulation threshold levels did not change significantly over time and ranged between 0.81 to 1.35 mA for all the animals at a 60 micros pulse width. All of the tests performed to date indicate that the BION is safe and effective for long-term human implant. We have elected to develop BION applications by seeking collaboration with the research community through our BION Technology Partnership.

Animals↗
PubMed2002

State level estimates of the incidence and economic burden of head injuries stemming from non-universal use of bicycle helmets.

OBJECTIVE: To develop national and state level estimates for preventable bicycle related head injuries (BRHIs) and associated direct and indirect health costs from the failure to use bicycle helmets. METHODS: Information on the effectiveness and prevalence of use of bicycle helmets was combined to estimate the avoidable fraction, that is, the proportion of BRHIs that could be prevented through the use of bicycle helmets. The avoidable fraction multiplied by the expected number of BRHIs gives an estimate of the number of preventable cases. Direct and indirect health costs are estimated from a social perspective for the number of preventable BRHIs to assess potential cost savings that would be achieved if all riders wore helmets. RESULTS: Approximately 107,000 BRHIs could have been prevented in 1997 in the United States. These preventable injuries and deaths represent an estimated $81 million in direct and $2.3 billion in indirect health costs. Estimates range from 200 preventable BRHIs and $3 million in health costs in Wyoming (population 480,000) to 13,700 preventable BRHIs and $320 million in health costs in California (population 32.3 million). CONCLUSIONS: A number of successful approaches to increasing bicycle helmet use exist, including mandatory use laws and community based programs. The limited use of these strategies may be related to the fact that too little information is available to state agencies about the public health and economic burden of these preventable injuries. In conjunction with information on program costs, our estimates can assist state planners in better quantifying the number of preventable BRHIs and the costs and benefits of helmet promotion programs.

Bicycling↗
PubMed2001

Early-stage breast cancer treatment among medically underserved women diagnosed in a national screening program, 1992-1995.

BACKGROUND: Little research has been conducted on the breast cancer treatment of low income, underserved women. This study was designed to describe initial treatment of breast cancer among low-income women diagnosed through federally funded screening programs in Detroit, Michigan, and the states of New Mexico and California; and to compare the treatment received by program women with early-stage breast cancer with that of all women diagnosed in those regions. METHODS: Data from the three screening programs were linked with cancer registry data from the corresponding geographic areas. All women diagnosed between 1992 and 1995 through the state-based screening programs and all women contemporaneously diagnosed with breast cancer in the three regions were studied. Descriptive analyses were done of the proportion of women with breast cancer receiving treatment; the proportion of early-stage breast cancer (stage I or II) cases treated with breast-conserving surgery, and the proportion treated with mastectomy; and among women with breast-conserving surgery, the proportion receiving radiation therapy. Logistic regression models controlled for age and stage at diagnosis, race or ethnicity and geographic region. RESULTS: Less than 2% of program women diagnosed with breast cancer received no treatment. More than two of five women with early-stage breast cancer underwent breast-conserving surgery, with 72% of these women receiving radiation therapy. Multivariate regression analysis revealed that women with stage IIA or IIB breast cancer had lower odds of undergoing breast-conserving surgery than women with stage I (0.51 [95% CI = 0.30-0.87] and 0.36 [95% CI = 0.19-0.70], respectively). Women over age 65 and those with incompletely staged cancer had the lowest odds for receiving radiation therapy after breast-conserving surgery (0.29 [95% CI = 0.09-0.99] and 0.14 [95% CI = 0.03-0.72], respectively). Women diagnosed through the screening programs had odds of undergoing breast-conserving surgery similar to those of all women in the regions (1.11 [95% CI= 0.89-1.39]). CONCLUSIONS: Treatment patterns for women diagnosed with early-stage breast cancer through three state-based screening programs appear to have been similar to those reported in the literature. In addition, their treatment appears to have been similar to that of other women during the same time period.

Adult↗
PubMed2000

Methodological issues in estimating smoking-attributable mortality in the United States.

The authors explored two methodological issues in the estimation of smoking-attributable mortality for the United States. First, age-specific and age-adjusted relative risk, attributable fraction, and smoking-attributable mortality estimates obtained using data from the American Cancer Society's second Cancer Prevention Study (CPS II), a cohort study of 1.2 million participants (1982-1988), were compared with those obtained using a combination of data from the National Mortality Follow-back Survey (NMFS), a representative sample of US decedents in which information was collected from informants (1986), and the National Health Interview Survey (NHIS), a nationally representative household survey (1987). Second, the potential for residual confounding of the disease-specific age-adjusted smoking-attributable mortality estimates was addressed with a model-based approach. The estimated smoking-attributable mortality based on the CPS II for the four most common smoking-related diseases-lung cancer, chronic obstructive pulmonary disease, coronary heart disease, and cerebrovascular disease-was 19% larger than the estimated smoking-attributable mortality based on the NMFS/NHIS, yet the two data sources yielded essentially the same smoking-attributable mortality estimate for lung cancer alone. Further adjustment of smoking-attributable mortality for disease-appropriate confounding factors (education, alcohol intake, hypertension status, and diabetes status) indicated little residual confounding once age was taken into account.

Adult↗
PubMed2000

U.S. Air force recruit injury and health study.

OBJECTIVES: To assess the types, rates, and risks of injury for male and female USAF recruits. DESIGN: Outpatient visits for female (5250) and male recruits (8656) were collected and analyzed for rate of injury, types of injuries, and risk of injury throughout a 6-week training period. RESULTS: One third of female recruits and one sixth of male recruits were injured at least once during recruit training. The overall rate for injuries in women and men was 63.0 and 27.8 per 1000 person-weeks, respectively. The adjusted relative risk for women versus men for all injuries was 2.22, and was consistent (1.67 to 3.27) across injury sites. Despite declining absolute rates of injury by week (106.1-13.4 for women and 53.7-13.2 for men), relative risk of injury for women versus men remained fairly constant throughout each training week. The relative risk for injury serious enough to result in medical hold was 1.69 for women vis-a-vis men. Approximately half of all medical discharges for women and men were for injuries. CONCLUSIONS: Female recruits were injured twice as often as male recruits, and were 1.5 times more likely to be removed from their training cohort for injury. Relative risk for injuries to specific body areas remained fairly consistent, indicating that no gender-specific injuries were occurring. Further efforts to determine the cause of injuries should be undertaken, and interventions aimed at reducing the disparate risk of injuries in women should be developed and evaluated.

Adolescent↗
PubMed1999

Preimplantation genetic diagnosis for spinal muscular atrophy type I.

OBJECTIVE: Couples with children who have spinal muscular atrophy type I (SMA) face a 25% risk of having affected offspring with spontaneous conception. Preimplantation genetic testing (PGT) is possible for the deletions in the survival motor neuron (SMN) gene that have been identified in 98% of SMA type I cases. PGT would provide new reproductive options for families at risk for SMA. METHODS: Three couples with previously affected children confirmed by DNA testing each underwent in vitro fertilization (IVF) and PGT of the resulting embryos. One or two blastomeres were biopsied from each embryo and analyzed for deletions in exons 7 and 8 of the SMN gene. RESULTS: Nine embryos were predicted to be unaffected, three to be affected, and one embryo could not be interpreted. One of three patients receiving transfer of unaffected embryos became pregnant with twins. CONCLUSIONS: Preimplantation genetic testing provides a means for couples at risk for spinal muscular atrophy type I to reduce their chance of initiating an affected pregnancy.

Adult↗
PubMed1996

Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (WAS), an X-linked immunodeficiency disease caused by mutation in the recently isolated gene encoding WAS protein (WASP), is known to be associated with extensive clinical heterogeneity. Cumulative mutation data have revealed that WASP genotypes are also highly variable among WAS patients, but the relationship of phenotype with genotype in this disease remains unclear. To address this issue we characterized WASP mutations in 24 unrelated WAS patients, including 18 boys with severe classical WAS and 6 boys expressing mild forms of the disease, and then examined the degree of correlation of these as well as all previously published WASP mutations with disease severity. By analysis of these compiled mutation data, we demonstrated clustering of WASP mutations within the four most N-terminal exons of the gene and also identified several sites within this region as hotspots for WASP mutation. These characteristics were observed, however, in both severe and mild cases of the disease. Similarly, while the cumulative data revealed a predominance of missense mutations among the WASP gene lesions observed in boys with isolated thrombocytopenia, missense mutations were not exclusively associated with milder WAS phenotypes, but also comprised a substantial portion (38%) of the WASP gene defects found in patients with severe disease. These findings, as well as the detection of identical WASP mutations in patients with disparate phenotypes, reveal a lack of phenotype concordance with genotype in WAS and thus imply that phenotypic outcome in this disease cannot be reliably predicted solely on the basis of WASP genotypes.

Child↗
PubMed1996

Cellular mechanisms involved in protection and recovery from influenza virus infection in immunodeficient mice.

We investigated the role of different lymphocyte subpopulations in the host defense reaction against influenza virus infection, taking advantage of various immunodeficient mouse strains. Whereas, following immunization, wild-type animals showed complete protection against challenge with a lethal dose of A/PR8/34 (PR8) virus, mice that lack both B and T cells but not NK cells (namely, scid and RAG2(-/-) mice) did not display any protective effect in similar conditions. By contrast, J(H)D(-/-) mice devoid of B cells and immunized with virus showed a protective response after challenge with a lethal dose. The immunized J(H)D(-/-) mice that survived completely recovered from the influenza virus infection. Immunized J(H)D(-/+) mice exhibited a more complete protection, suggesting the role of specific antibodies in resistance to infection. To assess the role of natural immunity in the host defense against influenza virus, we carried out experiments with scid mice challenged with lower but still lethal doses of PR8 virus. While an increased NK activity and an increased number of NK1.1+ cells in lungs of scid mice infected with PR8 virus were noted, in vivo depletion of the NK1.1+ cells did not affect the overall survival of the mice. Our results show that specific T cells mediate protection and recovery of J(H)D(-/-) mice immunized with live virus and challenged with lethal doses of influenza virus.

Animals↗
PubMed1995

Blood cardioplegia in the senescent heart.

As an increasingly aged population undergoes cardiac surgery, myocardial protective strategies must address the fundamental differences between adult and senescent myocardium. In a test of the hypothesis that senescent myocardium is less tolerant of cardioplegic arrest, adult (0.5 to 1.0 years) and senescent (6 to 9 years) sheep underwent 55 minutes of hypothermic blood cardioplegic arrest. A 5-minute dose of terminal warm blood cardioplegic solution was administered followed by 30 minutes of vented reperfusion. Left ventricular volume was monitored by means of sonomicrometric crystals in three orthogonal planes. Myocardial function was assessed with the preload recruitable stroke work relationship. Diastolic function was assessed with two techniques: the "stiffness" coefficient (beta), derived from the exponential end-diastolic pressure-volume relationship, and the time constant of isovolumic left ventricular pressure decay (tau). Data were acquired before arrest and after the reperfusion period. Contractility in the adult hearts was well preserved (preload recruitable stroke work: 63.7 +/- 6.1 versus 56.8 +/- 4.1 mJ/beat per milliliter per 100 gm, prearrest versus postarrest, p = not significant). In contrast, senescent heart contractility was poorly preserved (56.8 +/- 4.1 versus 35.4 +/- 4.2 mJ/beat per milliliter per 100 gm, p < 0.025). Early diastolic relaxation (tau) was prolonged in the adult hearts (42.5 +/- 3.3 versus 48.8 +/- 3.5 msec prearrest versus postarrest, p < 0.05), whereas the senescent hearts were essentially unchanged (49.3 +/- 3.1 versus 52.3 +/- 4.5 msec. p = 0.35). Myocardial stiffness (beta) was unchanged in both groups. When compared with adult hearts, contractility in senescent hearts is poorly preserved after cold blood cardioplegic arrest. Active diastolic relaxation, however, is more prolonged in adult hearts. Passive diastolic properties are unchanged in both groups. Because there are specific age-related differences in tolerance to cardioplegic arrest, extrapolation of myocardial protective strategies from studies in adult hearts to elderly patients may not be appropriate.

Aging↗
PubMed1994

Intact antiinfluenza virus immune response in targeted kappa-deficient mice.

Immunoglobulins are encoded by genes located in three different loci, the heavy chain (IgH), kappa light chain (Ig kappa), and lambda light chain (Ig lambda) loci. In mice, the kappa/lambda ratio of B cells is 95:5. In a previous study, we reported that kappa gene deletion causes the alternative usage of lambda 1 (93%) and lambda 2 (7%) light chains, and that the kappa anti-TNP repertoire is compensated for by the lambda repertoire even though the latter is clonally restricted in K-/- mice. To investigate the contribution of lambda antibodies to protection against virus, we compared K-/- mice with 129/Sv wild-type mice with respect to immune responses to influenza virus. PR8 virus immunized K-/- and 129/Sv mice showed no difference in the titer of anti-HA antibodies. Furthermore, the same immunized mice had sufficiently high neutralizing antibody titer to prevent infection when challenged with 7.5 x 10(4) TCID50 of PR8 virus. In addition, immunized K-/- mice were resistant to infection with 7.5 x 10(4) TCID50 and 7.5 x 10(5) TCID50 (10 and 100 LD50, respectively) of PR8 virus. Finally, K-/- mice are also capable of inducing cytotoxic T cells. These results suggest that the lambda repertoire can compensate for the kappa repertoire by generating a fully protective neutralizing antibody response.

Amino Acid Sequence↗
PubMed1993

Surveillance for and comparison of birth defect prevalences in two geographic areas--United States, 1983-88.

PROBLEM/CONDITION: CDC and a number of states have developed surveillance systems to monitor the birth prevalence of major defects. REPORTING PERIOD COVERED: This report covers birth defects surveillance in Metropolitan Atlanta, Georgia and selected jurisdictions in California for the years 1983-1988. DESCRIPTION OF SYSTEM: The California Birth Defects Monitoring Program and the Metropolitan Atlanta Congenital Defects Program are two population based surveillance systems that employ similar data collection methods. The prevalence estimates for 44 diagnostic categories are based on data from 1983 to 1988 for 639,837 births in California and 152,970 births in metropolitan Atlanta. The prevalences in the two areas are compared adjusting for race, sex and maternal age using Poisson regression. RESULTS: Regional differences in the prevalence of aortic stenosis, fetal alcohol syndrome, hip dislocation/dysplasia, microcephalus, obstruction of the kidney/ureter, and scoliosis/lordosis may be attributable to general diagnostic variability. However, differences in the prevalences of arm/hand limb reduction, encephalocele, spina bifida, or trisomy 21 (Down Syndrome) are probably not attributable to differences in ascertainment because these defects are relatively easy to diagnose. INTERPRETATION: Regional differences in prenatal diagnosis and pregnancy termination may affect prevalences of trisomy 21 and spina bifida. However, the reason for differences in arm/hand limb reduction is unknown, but may be related to variability in environmental exposure, heterogeneity in gene pool, or random variation. ACTIONS TAKEN: Because of the similarities of these data bases, several collaborative studies are being implemented. In particular, the differences in the birth prevalence of spina bifida and Down Syndrome will focus attention on the impact of prenatal diagnosis.

California↗
PubMed1993

Interpoint squared distance as a measure of spatial clustering.

The expectation and variance for the mean interpoint squared distance are presented. In order to evaluate these expressions it is necessary to calculate the moments of a bivariate uniform distribution defined over an arbitrary polygon. Expressions for these moments are presented, allowing the mean interpoint squared distance to be used as a measure of spatial clustering. The distribution and power of this test statistic is explored on the unit square, and the spatial distribution of 11 cases of non-Hodgkin's lymphoma is investigated to illustrate an application of the approach.

Cluster Analysis↗
PubMed1993

Induction of antihemagglutinin antibodies by polyclonal antiidiotype antibodies.

Antiidiotypic antibodies can be envisioned as an alternative approach in the development of vaccines against influenza virus, which exhibits natural antigenic variations. In our work, we obtained two polyclonal cross-reactive anti-Id antibodies against PY102, VM113, and VM202 mAbs, which in turn are specific respectively for PR8 virus and laboratory-induced virus variants (PY102-V1 and VM113-V1). With these cross-reactive anti-Id antibodies, we were able to elicit anti-HA antibodies in mice. In comparing the anti-HA antibody response in animals injected with anti-Id antibodies to those immunized with PR8 influenza virus, we demonstrated that the HI titer was higher after virus immunization and that the PR8 virus boost was more efficient in this group. Our results showed that the polyclonal cross-reactive anti-Id antibodies were more efficient than the individual anti-Ids at eliciting responses. At the same time, we demonstrated that PR8-primed T cells, cultured with B cells from animals immunized with anti-Id antibodies, were able to produce anti-PR8 antibodies subsequent to stimulation with influenza virus.

Animals↗
PubMed1993

Glycosylation of neuraminidase determines the neurovirulence of influenza A/WSN/33 virus.

The neuraminidase (NA) gene of influenza A/WSN/33 (WSN) virus has previously been shown to be associated with neurovirulence in mice and growth in Madin-Darby bovine kidney (MDBK) cells. Nucleotide sequence analysis has indicated that the NA of WSN virus lacks a conserved glycosylation site at position 130 (corresponding to position 146 in the N2 subtype). To investigate the role of this carbohydrate in viral pathogenicity, we used reverse genetics methods to generate a Glyc+ mutant virus, in which the glycosylation site Asn-130 was introduced into the WSN virus NA. Unlike the wild-type WSN virus, the Glyc+ mutant virus did not undergo multicycle replication in MDBK cells in the absence of trypsin, presumably because of lack of cleavage activation of infectivity. In contrast, revertant viruses derived from the Glyc+ mutant were able to replicate in MDBK cells without exogenous protease. Nucleotide sequence analysis revealed that the NAs of the revertant viruses had lost the introduced glycosylation site. In contrast to wild-type and revertant viruses, the Glyc+ mutant virus was not able to multiply in mouse brain. These results suggest that the absence of a glycosylation site at position 130 of the NA plays a key role in the neurovirulence of WSN virus in mice.

Animals↗
PubMed1992

Cells expressing an H chain Ig gene carrying a viral T cell epitope are lysed by specific cytolytic T cells.

The epitope corresponding to amino acid residues 147-161 of the nucleoprotein (NP) of influenza A virus is recognized by CTL in association with H-2Kd class I Ag. Herein, we engineered an Ig molecule carrying this CTL epitope by replacing the diversity gene segment of the H chain V region of an anti-arsonate antibody with an oligonucleotide that encodes the CTL epitope. The chimeric H chain gene was expressed either alone or together with the parental L chain in the nonsecreting BALB/c myeloma B cell line, SP2/0. The Ig produced by cells transfected with both the chimeric H chain and parental L chains genes expressed the NP epitope but lost the original arsonate binding activity. In addition, SP2/0 cells expressing the chimeric H chain either alone or together with the parental L chain were lysed by class I restricted NP-epitope specific CTL. By contrast, SP2/0 cells pulsed with soluble chimeric Ig molecules were not lysed by the specific CTL. These observations indicate that: 1) this particular CTL epitope can be expressed on Ig molecules without altering the H and L chain pairing; 2) this CTL epitope can be generated from this chimeric Ig in which it is surrounded by flanking regions distinct from those of the viral NP; and 3) the generation of this CTL epitope from the Ig molecule requires the endogenous pathway as do viral proteins.

Amino Acid Sequence↗