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Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 109 records · Page 6Linked to original sources
PubMed1999

Spatial orientation of the angular vestibulo-ocular reflex.

During vestibular nystagmus, optokinetic nystagmus (OKN), and optokinetic afternystagmus (OKAN), the axis of eye rotation tends to align with the vector sum of linear accelerations acting on the head. This includes gravitational acceleration and the linear accelerations generated by translation and centrifugation. We define the summed vector of gravitational and linear accelerations as gravito-inertial acceleration (GIA) and designate the phenomenon of alignment as spatial orientation of the angular vestibuloocular reflex (aVOR). On the basis of studies in the monkey, we postulated that the spatial orientation of the aVOR is dependent on the slow (velocity storage) component of the aVOR, not on the short latency, compensatory aVOR component, which is in head-fixed coordinates. Experiments in which velocity storage was abolished by midline medullary section support this postulate. The velocity storage component of the aVOR is likely to be generated in the vestibular nuclei, and its spatial orientation was shown to be controlled through the nodulus and uvula of the vestibulocerebellum. Separate regions of the nodulus/uvula appear to affect the horizontal and vertical/torsional components of the response differently. Velocity storage is weaker in humans than in monkeys, but responds in a similar fashion in both species. We postulate that spatial orientation of the aVOR plays an important role in aligning gaze with the GIA and in maintaining balance during angular locomotion.

Humans↗
PubMed1999

Model-based study of the human cupular time constant.

The time constant of the angular vestibulo-ocular reflex (aVOR), measured from the response to steps of rotation about a yaw axis, has frequently been estimated as a single exponential. However, the slow phase velocity envelope during per- or post-rotatory nystagmus is more accurately represented by two exponential modes. One represents activity in the vestibular nerve induced by deflection of the cupula, the other by activation that the input from the canals produces in the central velocity storage integrator. The sum of the cupula and the integrator responses describes the overall response of slow phase eye velocity and can be approximated by a double exponential. Frequently, there is a plateau in the initial portion of eye velocity response, but this may be masked by habituation, making the cupula contribution unobservable and impossible to estimate. Using a model-based technique to analyze responses with a clear plateau, we estimated peripheral and central vestibular time constants by double exponential fits to slow phase eye velocity. Cupular time constants were varied from 1 to 10 s to identify values that gave optimal fits of the data according to a Chi-square criterion. The mean cupular time constant for 10 human subjects was 4.2 +/- 0.6 s. Fits of the data were also good for time constants between 3.5 to 7 s, but not for 1 to 3 or 7.5 to 10 s. The estimated cupular time constants also fit responses where there was no plateau. In 8 monkeys, cupular time constants were estimated as 3.9 +/- 0.5 s, which agreed with those derived from activity in the vestibular nerve. There was no difference between monkey and human cupular time constants from these estimates. It is likely that the human cupular time constant is similar to that of the monkey and shorter than previously thought.

Adult↗
PubMed1999

Neutralising antibody responses to two doses of measles vaccine at 5 and 13 months of age in the United Kingdom.

Fifty-three children born in the United Kingdom between April 1993 and July 1994 were given two doses of measles vaccine, at 5 and 13 months of age, and their neutralising antibody reports were studied to assess the feasibility of protecting infants (aged 1 to 11 months) in the event of an outbreak or who were due to travel abroad. Sixteen infants responded at 5 months, an additional 35 responded at 13 months and two did not respond. The responses were inversely related to the levels of maternal antibodies (p < 0.0001). Infants who responded at 5 months also produced higher responses at 13 months than those who did not respond initially (p = 0.0001). No serious side effects were encountered. These data suggest that measles vaccine protects 30% of infants at 5 months and that a second dose at 13 months results in almost universal seroconversion.

Analysis of Variance↗
PubMed1999

In saliva veritas.

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Antibodies, Viral↗
PubMed1998

The giant, O'Brien

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Journal Article↗
PubMed1998

Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation.

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.

Activities of Daily Living↗
PubMed1998

Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha/ARNT.

Hypoxic stress induces the expression of genes associated with increased energy flux, including the glucose transporters Glut1 and Glut3, several glycolytic enzymes, nitric oxide synthase, tyrosine hydroxylase, erythropoietin and vascular endothelial growth factor (VEGF). Induction of these genes is mediated by a common basic helix-loop-helix-PAS transcription complex, the hypoxia-inducible factor-1alpha (HIF-1alpha)/aryl hydrocarbon nuclear translocator (ARNT). Insulin also induces some of these genes; however, the underlying mechanism is unestablished. We report here that insulin shares with hypoxia the ability to induce the HIF-1alpha/ARNT transcription complex in various cell types. This induction was demonstrated by electrophoretic mobility shift of the hypoxia response element (HRE), and abolished by specific antisera to HIF-1alpha and ARNT, and by transcription activation of HRE reporter vectors. Furthermore, basal and insulin-induced expression of Glut1, Glut3, aldolase A, phosphoglycerate kinase and VEGF was reduced in cells having a defective ARNT. Similarly, the insulin-induced activation of HRE reporter vectors and VEGF was impaired in these cells and was rescued by re-introduction of ARNT. Finally, insulin-like growth factor-I (IGF-I) also induced the HIF-1alpha/ARNT transcription complex. These observations establish a novel signal transduction pathway of insulin and IGF-I and broaden considerably the scope of activity of HIF-1alpha/ARNT.

Animals↗
PubMed1998

Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team.

BACKGROUND: Progressive multifocal leukoencephalopathy affects about 4 percent of patients with the acquired immunodeficiency syndrome (AIDS), and survival after the diagnosis of leukoencephalopathy averages only about three months. There have been anecdotal reports of improvement but no controlled trials of therapy with antiretroviral treatment plus intravenous or intrathecal cytarabine. METHODS: In this multicenter trial, 57 patients with human immunodeficiency virus (HIV) infection and biopsy-confirmed progressive multifocal leukoencephalopathy were randomly assigned to receive one of three treatments: antiretroviral therapy alone, antiretroviral therapy plus intravenous cytarabine, or antiretroviral therapy plus intrathecal cytarabine. After a lead-in period of 1 to 2 weeks, active treatment was given for 24 weeks. For most patients, antiretroviral therapy consisted of zidovudine plus either didanosine or stavudine. RESULTS: At the time of the last analysis, 14 patients in each treatment group had died, and there were no significant differences in survival among the three groups (P=0.85 by the log-rank test). The median survival times (11, 8, and 15 weeks, respectively) were similar to those in previous studies. Only seven patients completed the 24 weeks of treatment. Anemia and thrombocytopenia were more frequent in patients who received antiretroviral therapy in combination with intravenous cytarabine than in the other groups. CONCLUSIONS: Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Hospital attitudes: preliminary findings from donor action pilot projects.

PURPOSE: As part of the Donor Action collaboration (Eurotransplant Foundation, The Netherlands; Organización National de Transplantes, Spain; and The Partnership for Organ Donation, USA), a hospital survey was administered to gather baseline data on staff attitudes about organ donation and level of self-reported skills/confidence in performing a range of organ donation roles. METHODS: A standard survey instrument was administered in two hospitals in Spain, two in The Netherlands and one in the UK. In four hospitals the survey was administered to all ICU staff; in one hospital it was administered to a random sample of hospital staff. The instrument was created in English, and translated into Spanish and Dutch for the hospitals in each country. RESULTS: Data were analysed by country and showed consistently strong perceptions that organ donation saves lives (97%). Support for donation (95%) and willingness to donate one's own organs (82%) were high in all three country samples. Significant differences in belief were observed when respondents were asked whether they agreed that organ donation helps families with their grief. The UK respondents were more likely to agree (57%), with lower levels of agreement in Spain (47%) and The Netherlands (14%) (P < 0.0001). Average ratings of skills/confidence were highest for notifying the transplant coordinator (49%) and comforting the family (48%) with lower confidence reported regarding explaining brain death (34%), introducing organ donation (32%), and requesting organ donation (26%). Ratings varied widely across countries with UK respondents expressing the highest level of self-reported confidence, and Spanish respondents the lowest level. For example, 77% of UK respondents reported themselves skilled/confident explaining brain death, versus 47% of Dutch respondents and 11% of Spanish respondents (P < 0.0001). Similar results were seen regarding requesting organ donation: UK 53%; The Netherlands 30%; Spain 13% (P < 0.0001). CONCLUSIONS: There has been a lack of data about hospital staff attitudes and skills to allow for comparison across national systems, and to support the targeting of specific strategies to the needs within different countries. These results show the feasibility of collecting and comparing data across national systems. These pilot findings also suggest that there may be important differences in attitudes and self-perceived skills/confidence across countries. Work remains to correlate attitudes and self-perceived skills to actual performance. It is noteworthy that the sense of staff preparedness was lowest in Spain which has the highest donation rates. This may reflect the degree to which role specialization in donation has been successfully integrated into hospital practice. Expansion of the survey to additional hospitals will help to answer such questions.

Attitude↗
PubMed1998

Vestibular adaptation to space in monkeys.

Otolith-induced eye movements of rhesus monkeys were studied before and after the 1989 COSMOS 2044 and the 1992 to 1993 COSMOS 2229 flights. Two animals flew in each mission for approximately 2 weeks. After flight, spatial orientation of the angular vestibulo-ocular reflex was altered. In one animal the time constant of postrotatory nystagmus, which had been shortened by head tilts with regard to gravity before flight, was unaffected by the same head tilts after flight. In another animal, eye velocity, which tended to align with a gravitational axis before flight, moved toward a body axis after flight. This shift of orientation disappeared by 7 days after landing. After flight, the magnitude of compensatory ocular counter-rolling was reduced by about 70% in both dynamic and static tilts. Modulation in vergence in response to naso-occipital linear acceleration during off-vertical axis rotation was reduced by more than 50%. These changes persisted for 11 days after recovery. An up and down asymmetry of vertical nystagmus was diminished for 7 days. Gains of the semicircular canal-induced horizontal and vertical angular vestibulo-ocular reflexes were unaffected in both flights, but the gain of the roll angular vestibulo-ocular reflex was decreased. These data indicate that there are short- and long-term changes in otolith-induced eye movements after adaptation to microgravity. These experiments also demonstrate the unique value of the monkey as a model for studying effects of vestibular adaptation in space. Eye movements can be measured in three dimensions in response to controlled vestibular and visual stimulation, and the results are directly applicable to human beings. Studies in monkeys to determine how otolith afferent input and central processing is altered by adaptation to microgravity should be an essential component of future space-related research.

Adaptation, Physiological↗
PubMed1998

Medicinal herb use and the renal patient.

Medicinal herb use, although a popular branch of alternative medicine, may be inappropriate for the renal patient. The pharmacological activity, chemical components, and microbial content of herbs, as well as their ability to interfere with prescription medications, make medicinal herbs potentially dangerous for the renal patient. The purpose of this report is to inform the medical professional of the implications of renal patients using medicinal herbs.

Complementary Therapies↗
PubMed1998

A molecular map of T cell development.

Using a sensitive molecular marker for positive selection, the appearance of a particular functional TCR alpha chain sequence in cells from mice bearing a transgenic beta chain, we address several aspects of intrathymic T cell development. First, by examining specific TCR prior to and after maturation, we demonstrate how a restricted TCR repertoire is positively selected from a highly diverse immature TCR repertoire. Second, since this molecular marker is enriched in cells progressing toward the CD4 lineage and depleted in cells progressing toward the CD8 lineage, a map of the developmental pathway of alphabeta thymocytes can be inferred. Third, the first cells that show clear signs of positive intrathymic selection are identified.

Amino Acid Sequence↗
PubMed1998

T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients.

Multiple sclerosis (MS) is a disease of the central nervous system characterized by immune-mediated destruction of myelin. In patients with progressive deterioration, we have intensified immunosuppression to the point of myeloablation. Subsequently, a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with clinical MS and a decline of their Kurtzke extended disability status scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC) transplantation using a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy). Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all immunosuppressive medications, functional improvements have occurred in all three patients. We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis. Stem cell transplantation has resulted in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time.

Adult↗
PubMed1998

The effect of hemodilution on cerebral blood flow velocity in anesthetized patients.

UNLABELLED: Transcranial Doppler is used to estimate changes in cerebral blood flow, but the effect of hemodilution on cerebral blood flow velocity (CBFV) in anesthetized patients has not been evaluated. The aim of this study was to measure the effect of isovolemic hemodilution on CBFV and lumbar cerebrospinal fluid pressure (P(CSF)) in anesthetized patients without change in other physiological variables that may affect CBFV. Patients undergoing hemodilution were compared with a control group undergoing no hemodilution. With hemodilution, hematocrit decreased from 38% +/- 3% to 30% +/- 2%, arterial oxygen content (Cao2) decreased from 17.5 +/- 1.3 to 13.9 +/- 0.9 mL/dL, and CBFV increased from 50 +/- 10 to 58 +/- 10 cm/s. An equivalent of cerebral arterial O2 transport calculated as Cao2 x CBFV did not significantly change. Over the same time interval, there were no changes in the control group. There was no statistically significant change in P(CSF), pulsatility index, Paco2, blood pressure, heart rate, or body temperature in either group. We conclude that CBFV reflects cerebral blood flow changes after hemodilution. IMPLICATIONS: Hemodilution increases cerebral blood flow but may change the cerebral artery diameter, which could confound perioperative measurement of cerebral blood flow velocity. This study found transcranial Doppler ultrasonography to accurately assess the effects of hemodilution on the cerebral circulation, but the hematocrit should be taken into account to fully understand perioperative cerebral blood flow velocity changes.

Adult↗
PubMed1998

A transversely isotropic biphasic model for unconfined compression of growth plate and chondroepiphysis.

Using the biphasic theory for hydrated soft tissues (Mow et al., 1980) and a transversely isotropic elastic model for the solid matrix, an analytical solution is presented for the unconfined compression of cylindrical disks of growth plate tissues compressed between two rigid platens with a frictionless interface. The axisymmetric case where the plane of transverse isotropy is perpendicular to the cylindrical axis is studied, and the stress-relaxation response to imposed step and ramp displacements is solved. This solution is then used to analyze experimental data from unconfined compression stress-relaxation tests performed on specimens from bovine distal ulnar growth plate and chondroepiphysis to determine the biphasic material parameters. The transversely isotropic biphasic model provides an excellent agreement between theory and experimental results, better than was previously achieved with an isotropic model, and can explain the observed experimental behavior in unconfined compression of these tissues.

Animals↗