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Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 127 records · Page 7Linked to original sources

Control of spatial orientation of the angular vestibuloocular reflex by the nodulus and uvula.

Spatial orientation of the angular vestibuloocular reflex (aVOR) was studied in rhesus monkeys after complete and partial ablation of the nodulus and ventral uvula. Horizontal, vertical, and torsional components of slow phases of nystagmus were analyzed to determine the axes of eye rotation, the time constants (Tcs) of velocity storage, and its orientation vectors. The gravito-inertial acceleration vector (GIA) was tilted relative to the head during optokinetic afternystagmus (OKAN), centrifugation, and reorientation of the head during postrotatory nystagmus. When the GIA was tilted relative to the head in normal animals, horizontal Tcs decreased, vertical and/or roll time constants (Tc(vert/roll)) lengthened according to the orientation of the GIA, and vertical and/or roll eye velocity components appeared (cross-coupling). This shifted the axis of eye rotation toward alignment with the tilted GIA. Horizontal and vertical/roll Tcs varied inversely, with T(chor) being longest and T(cvert/roll) shortest when monkeys were upright, and the reverse when stimuli were around the vertical or roll axes. Vertical or roll Tcs were longest when the axes of eye rotation were aligned with the spatial vertical, respectively. After complete nodulo-uvulectomy, T(chor) became longer, and periodic alternating nystagmus (PAN) developed in darkness. T(chor) could not be shortened in any of paradigms tested. In addition, yaw-to-vertical/roll cross-coupling was lost, and the axes of eye rotation remained fixed during nystagmus, regardless of the tilt of the GIA with respect to the head. After central portions of the nodulus and uvula were ablated, leaving lateral portions of the nodulus intact, yaw-to-vertical/roll cross-coupling and control of Tc(vert/roll) was lost or greatly reduced. However, control of Tchor was maintained, and T(chor) continued to vary as a function of the tilted GIA. Despite this, the eye velocity vector remained aligned with the head during yaw axis stimulation after partial nodulo-uvulectomy, regardless of GIA orientation to the head. The data were related to a three-dimensional model of the aVOR, which simulated the experimental results. The model provides a basis for understanding how the nodulus and uvula control processing within the vestibular nuclei responsible for spatial orientation of the aVOR. We conclude that the three-dimensional dynamics of the velocity storage system are determined in the nodulus and ventral uvula. We propose that the horizontal and vertical/roll Tcs are separately controlled in the nodulus and uvula with the dynamic characteristics of vertical/roll components modulated in central portions and the horizontal components laterally, presumably in a semicircular canal-based coordinate frame.

Animals↗

Dynamics and kinematics of the angular vestibulo-ocular reflex in monkey: effects of canal plugging.

Dynamics and kinematics of the angular vestibulo-ocular reflex in monkey: effects of canal plugging. J. Neurophysiol. 80: 3077-3099, 1998. Horizontal and roll components of the angular vestibulo-ocular reflex (aVOR) were elicited by sinusoidal rotation at frequencies from 0.2 Hz (60 degrees/s) to 4.0 Hz ( approximately 6 degrees/s) in cynomolgus monkeys. Animals had both lateral canals plugged (VC, vertical canals intact), both lateral canals and one pair of the vertical canals plugged (RALP, right anterior and left posterior canals intact; LARP, left anterior and right posterior canal intact), or all six semicircular canal plugged (NC, no canals). In normal animals, horizontal and roll eye velocity was in phase with head velocity and peak horizontal and roll gains were approximately 0.8 and 0.6 in upright and 90 degrees pitch, respectively. NC animals had small aVOR gains at 0.2 Hz, and the temporal phases were shifted approximately 90 degrees toward acceleration. As the frequency increased to 4 Hz, aVOR temporal gains and phases tended to normalize. Findings were similar for the LARP, RALP, and VC animals when they were rotated in the planes of the plugged canals. That is, they tended to normalize at higher frequencies. A model was developed incorporating the geometric organization of the canals and first order canal-endolymph dynamics. Canal plugging was modeled as an alteration in the low frequency 3-db roll-off and corresponding dominant time constant. The shift in the low-frequency 3-dB roll-off was seen in the temporal responses as a phase lead of the aVOR toward acceleration at higher frequencies. The phase shifted toward stimulus velocity as the frequency increased toward 4.0 Hz. By incorporating a dynamic model of the canals into the three-dimensional canal system, the spatial responses were predicted at all frequencies. Animals were also stimulated with steps of velocity in planes parallel to the plugged lateral canals. This induced a response with a short time constant and low peak velocity in each monkey. Gains were normalized for step rotation with respect to time constant as (steady state eye velocity)/(stimulus acceleration x time constant). Using this procedure, the gains were the same in canal plugged as in normal animals and corresponded to gains obtained in the frequency analysis. The study suggests that canal plugging does not block the afferent response to rotation, it merely shifts the dynamic response to higher frequencies.

Algorithms↗

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

BACKGROUND: Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. METHOD: A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. RESULTS: The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. CONCLUSIONS: Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

Adrenergic Uptake Inhibitors↗

Reactions of adult and teenaged smokers to the Massachusetts tobacco tax.

OBJECTIVES: This study assessed smokers' reactions to a 25 cents cigarette tax imposed in Massachusetts. METHODS: A statewide telephone survey of 1783 adult smokers and 216 teenaged smokers was conducted. RESULTS: Among adult smokers, 3.5% reported that they had stopped smoking, owing in part to the price increase; 35% had considered quitting and 19% had attempted to cut the cost of smoking by switching to cheaper brands or cutting down. Among teenagers, 21% had considered quitting and 26% had cut costs. Low-income smokers were more responsive to the price increase than more affluent smokers. CONCLUSIONS: A modest and temporary price increase promoted quitting among adult smokers and reduced cigarette consumption among low-income teenagers.

Adolescent↗

Trends in organ donation.

Renal and extrarenal transplant data were collected for seven geographical regions for the period 1989-1996. In Western Europe and North America the number of kidney donors increased by 926 and 2743, respectively. The total number of transplants also increased in both regions by 3756 and 6936, respectively. Renal transplants accounted for approximately 60% of the total number of transplants and, although the number of renal transplants did not alter in Western Europe, the number rose by 3055 in North America. Outside of these regions the number of extrarenal transplants was 3-18% of the total. The number of living kidney donors in North America increased each year and was higher than the number recruited in Western Europe (3389 vs 943 in 1996). With the exception of Eastern Europe, where virtually no renal transplants were carried out using organs from living donors, the number of living kidney donors rose in other regions: for example, in Latin America, the proportion of living kidney donors rose from 29% in 1970-88 to 51% in 1995, and, in Asia, 90% of kidneys were donated by living donors. As the quality of cadaveric donor organs is often sub-optimal, the use of living donors is likely to increase in both Western Europe and North America, but is unlikely to become the most important source of organs in these regions.

Humans↗

Mammalian type I interferon receptors consists of two subunits: IFNaR1 and IFNaR2.

The human type I interferon (IFN) receptor consists of two essential subunits, huIFNaR1 and huIFNaR2; however, so far only IFNaR1 has been identified in other species. Furthermore, it has been suggested that in some species the type I IFN receptor may consist of a single subunit, since expression of murine IFNaR1 in human cells rendered them responsive to several type I murine IFNs. To resolve this issue, we screened a mouse cDNA library with a probe derived from huIFNaR2 cDNA. A cDNA clone, coding for a transmembrane protein which has 49% identity with huIFNaR2 was isolated. This level of identity suggests that this cDNA codes for a muIFNaR2. In addition, several cDNA clones, coding for two distinct soluble variants of muIFNaR2 were identified. To test whether muIFNaR2 is a functional component of the receptor, we co-expressed it with muIFNaR1 in human cells and with an IFN-responsive luciferase reporter vector. Treatment of these cells with muIFN-beta induced high levels of luciferase, whereas no induction was obtained in cells expressing only one of the two subunits. We therefore conclude that the murine type I IFN receptor consists of two different subunits--a configuration shared by humans, and probably all other mammals.

Amino Acid Sequence↗

Randomized, blinded, placebo-controlled phase I trial of pegylated recombinant human megakaryocyte growth and development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer.

Thrombocytopenia caused by chemotherapy is an important cause of morbidity and mortality in the treatment of malignant disease. Recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is a potent stimulator of megakaryocytopoiesis and prevents chemotherapy-induced thrombocytopenia in preclinical studies. We administered PEG-rHuMGDF with filgrastim after dose-intensive chemotherapy to 41 patients with advanced cancers to determine its safety and effects on hematologic recovery. Carboplatin 600 mg/m2 and cyclophosphamide 1,200 mg/m2 were administered to patients with advanced cancer. Patients were randomly assigned to receive blinded study drug, either PEG-rHuMGDF or placebo (3-to-1 ratio), commencing the day after chemotherapy. PEG-rHuMGDF was given at doses of 0.03, 0.1, 0.3, 1.0, 3.0, and 5.0 microg per kilogram body weight by daily subcutaneous injection for between 7 and 20 days. All patients received concurrent filgrastim 5 microg per kilogram body weight per day until neutrophil recovery. Fifteen patients had received PEG-rHuMGDF alone in a previous phase I study. Platelet function and peripheral blood progenitor cells (PBPC) were assessed. PEG-rHuMGDF enhanced platelet recovery in a dose-related manner when compared with placebo. The platelet nadir occurred earlier in patients given PEG-rHuMGDF (P = .002) but there was no difference in the depth of the nadir. Recovery to baseline platelet count was achieved significantly earlier following PEG-rHuMGDF administration compared with placebo (median, 17 days for PEG-rHuMGDF 0.3 to 5.0 microg/kg versus 22 days for placebo, P = .014). In addition, platelet recovery was faster in patients who had previously received PEG-rHuMGDF, suggesting that pretreatment might be beneficial. Platelet function did not change during or after administration of PEG-rHuMGDF. Levels of PBPC on day 15 after chemotherapy were significantly greater in patients administered PEG-rHuMGDF 0.3 to 5.0 microg/kg and filgrastim compared with those given placebo plus filgrastim. PEG-rHuMGDF was well tolerated at all doses. Two patients given PEG-rHuMGDF had a thrombotic episode. PEG-rHuMGDF accelerates platelet recovery after moderately dose-intensive carboplatin and cyclophosphamide, and is likely to be clinically useful in treatment of chemotherapy-induced thrombocytopenia. Because it enhances mobilization of PBPC by filgrastim, PEG-rHuMGDF might also allow more efficient collection of stem cells for autologous or allogeneic transplantation.

Adult↗

The epidemiology of measles in England and Wales since the 1994 vaccination campaign.

The incidence of measles in England and Wales has fallen since the national vaccination campaign in November 1994, in which 92% of children aged 5 to 16 years were vaccinated. A total of 148 confirmed cases with onsets in the 18 months from January 1995 to June 1996 have been ascertained. Notified cases did not provide a reliable measure of incidence: 11,343 suspected cases were notified in the same period, 6426 (57%) of whom were tested for salivary antibody. Only 90 (1.4%) of cases tested were confirmed. Many confirmed cases occurred in small clusters; 12 imported cases were identified. The pattern of small, local clusters is what would be expected from the introduction of imported cases into a population with herd immunity. Serological surveillance showed that the campaign produced a significant fall in the proportion of 5 to 16 year old children with low levels of measles antibody: the proportion with levels < 50 mIU/ml fell from 8.4% to 2.1%; the proportion with levels < 100 mIU/ml fell from 15.7% to 6.6%. About 15% of 2 to 4 year old children had antibody levels < 100 mIU/ml before and after the campaign. The addition of a routine second dose of measles vaccine (as measles, mumps, and rubella vaccine) to the vaccination schedule will provide another opportunity to immunise these children before they start school. The two dose vaccination programme should maintain the herd immunity of the population and the elimination of endemic measles transmission.

Adolescent↗

Mumps surveillance in England and Wales supports introduction of two dose vaccination schedule.

Sentinel surveillance in general practice and laboratory reports to the PHLS Communicable Disease Surveillance Centre show that the incidence of mumps has fallen to very low levels since vaccination against measles, mumps, and rubella was introduced in 1988. Hospital admissions for mumps show a 92% decline compared with the prevaccination era, to a rate of 0.2 per 100,000 population per year. Serological surveillance has shown an increase in the proportion of school age children who have no detectable antibody to mumps, which is consistent with the reduction in mumps virus transmission. The proportion of children aged 11 to 15 years with no detectable antibody is expected to peak at 19% in 1997. Mathematical models suggest that this increase in susceptibility is unlikely to allow a large resurgence of mumps in the short term but that school outbreaks may become more common. Outbreaks in universities and military establishments are possible in the medium term. Analysis of efficacy data for mumps vaccine indicates that mumps is unlikely to be eliminated with a single dose of vaccine at current coverage rates. A second dose of vaccine, which is now being offered to preschool children, will reduce morbidity and should eventually eliminate mumps if coverage is high enough.

Adolescent↗

Report of a collaborative study to establish the international standard for parvovirus B19 serum IgG.

With the introduction of commercial test kits and the wider availability of parvovirus B19 antibody testing, greater standardization is required. Moreover, with a B19 vaccine in the early stages of development, there will be long-term need of accurate measurement of parvovirus B19 antibody levels following natural infection and vaccination. A collaborative study was carried out to assess the suitability of a freeze-dried preparation designated 93/724 to serve as the International Standard for parvovirus B19 serum IgG. The proposed standard, which is a pool of sera from six U.K. blood donors, was assayed along with three coded samples. One was the proposed standard (Preparation A), one a pool of three donor sera (Preparation B) and the third an individual donor serum (Preparation C). These preparations were sent to nine laboratories in seven countries who tested them in 10 different enzyme immunoassays. There were no differences in the antibody content expressed relative to that of the proposed standard in assays using native or recombinant antigen. However, antibody was not detected in serum from an individual blood donor (Preparation C) in assays performed using kits which contained recombinant VP1 but not VP2. This highlights the differences which may be obtained in commercial kits which contain different antigens. The results of this study demonstrated that the proposed standard coded 93/724 is suitable to serve as the International Standard for parvovirus B19 serum IgG and this material has been established as the International Standard for parvovirus B19 IgG by the World Health Organization with an assigned unitage of 100 lU per ampoule. The standard, which is a pool of what can be assumed to be convalescent sera, will be suitable for standardizing diagnostic tests for use in seroprevalence studies and for assessing immunity. An additional standard will be required to standardise tests specifically for the detection of IgM and the diagnosis of acute infection.

Antibodies, Viral↗

Does the anchorage form and depth influence the pull-out strength of screws from bone cement? An experimental study.

The pull-out strengths of cortical screws inserted into soft, unpolymerised Refobacin Palacos bone cement (procedure S) and into hardened polymerised cement into which a hole had been drilled and tapped (procedure P) were compared. Cortical screws 58 mm in length, outer diameter 4.5 mm and inner diameter 2.95 mm were used. Screws were inserted into cement cylinders at 5 mm incremental depths between 10 and 30 mm. At a screw depth of less than 25 mm, the screws pulled out, and at a depth of greater than 25 mm, the screws broke in both procedures. There was no statistically significant difference in pull-out strength leading to burst or break between the two procedures for screws inserted to comparable depths, but there was a statistically significant difference regarding the screwing depth regardless of the procedure of screw insertion chosen. The average material stability (sigma) of the cortical screws used was calculated to be 1191 N/mm2, and the elasticity limit was 5137 N. This study demonstrated that the material stability and not the depth of screw insertion was the limiting parameter in screw anchorage in bone cement while static testing. To avoid screw breakage due to fatigue during continuous alternate loading, the screws should not be loaded above this value.

Analysis of Variance↗

Massive osteolysis of the skull base.

Gorham's vanishing bone disease is a rare disorder characterized by massive osteolysis. Its etiology is unknown. We report the case of a 14-year-old girl with an unusually aggressive course and extensive involvement originating within the skull base. To our knowledge this pattern has not been described previously. MR findings are discussed.

Adolescent↗

Pregnancy complicated by vesical calculus and vesicocutaneous fistula.

Bladder stones are a rare complication of pregnancy, with only 10 cases reported this century. This patient required a cesarean section for obstructed labor resulting from a 7 cm stone. Cystotomy with removal of the stone was performed with subsequent development of a vesicocutaneous fistula.

Adult↗

Antinociceptive effect of nifedipine and verapamil tested on rats chronically exposed to nicotine and after its withdrawal.

Antinociceptive effect of nifedipine (15 mg/kg i.p.) and verapamil (10 mg/kg s.c.) was examined in rats chronically exposed to nicotine (6 mg/kg/day via Alzet osmotic pump for 28 days) and after nicotine withdrawal. Sham operated rats served as control for testing DMSO (dimethylsulfoxide, a solvent for nifedipine), nifedipine and verapamil alone. Nociception was measured by the tail-flick technique. Nifedipine, but not verapamil, injected to control rats produced a ceiling tail-flick latency (20 sec) 30 min after the injection, lasting for 10 min. In rats exposed to chronic nicotine for 3 days, nifedipine treatment exhibited ceiling tail-flick latency within 10 min lasting for 80 min. Tested in rats exposed to nicotine for 3 weeks, nifedipine treatment produced this effect 25 min after the injection lasting for 60 min. Nicotine withdrawal abolished this effect. Verapamil did not exhibit any significant changes in tail-flick latencies. These data support our hypothesis that smoking patients treated with nifedipine could be at a potential risk in developing a high pain threshold and missing the first sign of heart attack--a chest pain.

Analgesics↗

Performance of the dipalmitoyl phosphatidylcholine test in predicting respiratory distress syndrome in contaminated samples of amniotic fluid.

OBJECTIVE: To evaluate the reliability of the dipalmitoyl phosphatidylcholine test in predicting respiratory distress syndrome (RDS) in the presence of common contaminants of amniotic fluid. METHODS: Forty specimens of amniotic fluid collected within 72 hours of delivery were divided in five 25 microL aliquots and diluted with either phosphate-buffered saline (control), meconium, blood, vaginal fluid, or semen. The concentration of dipalmitoyl phosphatidylcholine in all five groups of samples, as measured by the dipalmitoyl phosphatidylcholine test, was compared by paired t test, Dunnett test, and analysis of variance, and correlated with the neonatal respiratory status of the newborns. RESULTS: No significant differences in the concentration of dipalmitoyl phosphatidylcholine were found between control and the corresponding contaminated samples (P = .33). Of the 200 samples evaluated, 80 had dipalmitoyl phosphatidylcholine concentrations below 12 micrograms/mL and 120 had at least 12 micrograms/mL. Using a cutoff dipalmitoyl phosphatidylcholine concentration of 12 micrograms/mL, the presence of RDS was predicted accurately in all 15 control and in 61 of 65 contaminated samples. The absence of RDS, as predicted by a dipalmitoyl phosphatidylcholine value at least 12 micrograms/mL, was predicted accurately in 24 of 25 control samples and 96 of 100 contaminated samples. The overall accuracy of the dipalmitoyl phosphatidylcholine test in predicting RDS in contaminated samples was 98%. CONCLUSION: The dipalmitoyl phosphatidylcholine test is a reliable predictor of RDS in contaminated samples.

1,2-Dipalmitoylphosphatidylcholine↗