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Biomedical subjects

D Fisher

Publications and source records attributed to D Fisher.

At least 19 recordsLinked to original sources
PubMed2006

Nicotine and smoker status moderate brain electric and mood activation induced by ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist.

As the increased smoking prevalence in schizophrenics may be interpreted as an adaptive response to an underlying biological defect, investigations into nicotine's actions within N-methyl-d-aspartate (NMDA) antagonist drug models of schizophrenia may improve our understanding of the role of glutamatergic neurotransmission in initiating and maintaining nicotine dependence in this disorder. In this double-blind, placebo-controlled, randomized study, the electroencephalographic (EEG) and subjective response to a sub-psychotomimetic intravenous dose of the NMDA antagonist ketamine was examined in 20 regular smokers and 20 non-smokers pretreated with placebo or nicotine gum. Although nicotine increased EEG arousal, ketamine produced electrocerebral signs of brain activation (decreased slow wave power) and sedation (decreased fast wave power and frequency), which were not affected by nicotine pretreatment and were evident only in non-smokers. Ketamine increased a number of self-report indices of subjective arousal, some of which were attenuated and potentiated by nicotine in smokers and non-smokers, respectively. These findings suggest that long-term (evidenced by smoker vs. non-smoker comparisons) and short-term (acute) nicotine exposure may alter NMDA receptor-mediated arousal and mood systems in a way that promotes nicotine dependence in smokers, and addresses neurobiological deficiencies in smokers with schizophrenia.

Adult↗
PubMed2006

An ultra-clean firn core from the Devon Island Ice Cap, Nunavut, Canada, retrieved using a titanium drill specially designed for trace element studies.

An electromechanical drill with titanium barrels was used to recover a 63.7 m long firn core from Devon Island Ice Cap, Nunavut, Canada, representing 155 years of precipitation. The core was processed and analysed at the Geological Survey of Canada by following strict clean procedures for measurements of Pb and Cd at concentrations at or below the pg g(-1) level. This paper describes the effectiveness of the titanium drill with respect to contamination during ice core retrieval and evaluates sample-processing procedures in laboratories. The results demonstrate that: (1) ice cores retrieved with this titanium drill are of excellent quality with metal contamination one to four orders of magnitude less than those retrieved with conventional drills; (2) the core cleaning and sampling protocols used were effective, contamination-free, and adequate for analysis of the metals (Pb and Cd) at low pg g(-1) levels; and (3) results from 489 firn core samples analysed in this study are comparable with published data from other sites in the Arctic, Greenland and the Antarctic.

Air Pollutants↗
PubMed2006

Molecular modeling studies of the binding characteristics of phosphates to sevelamer hydrochloride--assessing a novel technique to reduce phosphates contamination.

Recent advances in the use of polymeric materials for the remediation of phosphate from aqueous systems, including biological environments, have prompted the use of computational techniques to determine which methods are feasible to model such complex systems and to model the mechanism of binding action. In particular, Sevelamer Hydrochloride (Renagel) is used as our model polymer. A relatively simple system is constructed with a dimer of Sevelamer Hydrochloride and four phosphate ions used for capture. This work reports on molecular dynamics and Monte Carlo simulations used to determine average structure, and points of intermolecular interaction, and calculate changes in volume after the successful capture of phosphate in our model. Our resulting volume changes are of the order of 20-25%, in comparison to experimental swelling measurements on similar systems, which have an average swelling of 50-60% in aqueous media.

Models, Molecular↗
PubMed2006

[Treatment of pediatric femur fractures by immediate reduction and spica cast application--clinical and economical feasibility in the Israeli medical system].

BACKGROUND: Pediatric femur fractures are common injuries necessitating immediate application of spica cast or surgical stabilization. Currently, neither conservative nor operative fixation shows superior results; nevertheless, operative intervention has become more common lately. The current study retrospectively investigates short term results of immediate spica cast application, as well as the economic consequences of this treatment. METHODS: All cases of pediatric (6 months - 6 years) femur fractures treated in a single medium-sized hospital during 3 years were reviewed. Characteristics of fracture treatment and economical aspects were analyzed. RESULTS: Twenty four patients (17 boys and 7 girls, mean age 2.5 years, range 9 months to 5.5 years), were treated during the study period by immediate closed reduction and spica cast application. Eleven patients were also treated for medical reasons. All cases achieved acceptable alignment and shortening after cast removal. Two patients were re-admitted to the hospital Emergency Room but no changes in treatment were needed, one patient needed re-reduction. Mean hospital stay was 2.75 days. Calculated cost of such treatment is estimated to be almost equal to the compensation given by insurance companies (based on hospital stay in Israel). CONCLUSIONS: Immediate application of spica cast for pediatric femur fractures, achieves its goals of appropriate fracture-alignment and acceptable complication rates. The authors believe that the compensation should be procedure-based and not hospital-stay based, in a way that will encourage higher efficacy of medical treatment and shortened hospital stay.

Casts, Surgical↗
PubMed2005

The changing use of disease-modifying anti-rheumatic drugs in individuals with rheumatoid arthritis from the United Kingdom General Practice Research Database.

OBJECTIVES: To describe the use of disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA) and changing trends in their use. METHODS: We used the General Practice Research Database (GPRD) to describe DMARD use by patients with RA identified using ICD-9 codes. The GPRD is a UK national database containing records of more than 7 million individuals from 683 general practices. Subjects were studied between 1987 and 2002. The prevalence and duration of individual DMARD use and changing trends in DMARD use were investigated. RESULTS: Thirty-four thousand three hundred and sixty-four patients with RA were identified. Only 17,115 (50%) individuals were prescribed at least one DMARD during the study period. The most commonly prescribed DMARD over the study period was sulphasalazine (46.3%) and then methotrexate (31.4%). Use of methotrexate has increased 17-fold (1.8% of all DMARD prescriptions in 1988 to 30% in 2002) whereas use of gold has fallen (13.2% to 2.3%). Analysis of DMARD persistence using Kaplan-Meier survival curves showed the methotrexate use persisted significantly longer than other DMARDs with an estimated median of 8.1 yr. Prednisolone was used in up to 50% of RA patients in any one year and has remained fairly constant throughout the study period. CONCLUSIONS: Large numbers of individuals with a clinical diagnosis of RA identified from a large primary care database are not receiving DMARDs. This work suggests that many individuals with RA have not been treated appropriately and this may have major long-term consequences on joint damage and general health.

Aged↗
PubMed2004

Modified magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity.

Burkitt and Burkitt-like lymphomas are rapidly growing tumors which require specialized therapy. Although intensive, multi-agent regimens have been effective in children, results are more variable in adults. Magrath et al. previously described a regimen that was highly effective in children and young adults. This phase II study of a modified Magrath regimen was designed to assess its efficacy in older adults and reduce treatment-related toxicity. Fourteen patients with Burkitt/Burkitt-like lymphoma and median age of 47 years were stratified into two categories: low-risk (normal LDH and a single focus of disease measuring less than 10 cm, 3 patients) and high risk (all other, 11 patients). Low-risk patients received three cycles of modified CODOX-M (cyclophosphamide, doxorubicin, adriamycin, vincristine with intrathecal methotrexate and cytarabine followed by high-dose systemic methotrexate, regimen A). High-risk patients received four alternating cycles of regimens A and B (A-B-A-B). Regimen B consisted of ifosfamide, cytarabine, etoposide and intrathecal methotrexate (IVAC). The modified treatment regimen was associated with no grade 3/4 neuropathy and only one episode of grade 3/4 mucositis. All patients completed protocol therapy and there were no treatment-related deaths. Twelve patients (86%, 90% CI: 61 97%) achieved a complete response; 1 patient achieved a PR and 1 patient died of progressive disease. Nine patients (64%) are alive and disease free at a median follow-up of 29 months. This modified Magrath regimen is effective and well-tolerated in a representative group of older adult patients.

Adolescent↗
PubMed2004

Outpatient rehabilitative treatment of chronic fatigue syndrome (CFS/ME).

AIMS: To assess the outcome of outpatient multidisciplinary rehabilitative treatment (graded activities/exercise programme, family sessions, and supportive care) compared with supportive care alone for children and adolescents with chronic fatigue syndrome (CFS/ME). METHODS: Fifty six young people (aged 9-17 years) with CFS/ME by standard criteria were followed up for 3-24 months. All subjects received supportive care. Families additionally opted to either enter the rehabilitation programme (supportive care plus graded activities/exercise programme and family sessions) or have no additional treatment. RESULTS: Twenty two (39%) subjects had supportive care alone and 26 (46%) entered the programme. Treatment groups were comparable at baseline in terms of age, severity and duration of illness, Wellness score, and school attendance. At end of follow up, those in the programme group had significantly higher Wellness score and school attendance than those having supportive care alone. The programme significantly reduced the overall severity of illness: after the programme, 43% had complete resolution of CFS/ME compared to only 4.5% of those having supportive care alone. The presence of depressed mood and family beliefs about the aetiology of CFS/ME were not significantly associated with outcomes. CONCLUSIONS: Outpatient rehabilitative treatment offers significant potential to improve the prognosis of CFS/ME in childhood and adolescence.

Adolescent↗
PubMed2003

Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect.

A total of 228 patients with multiple myeloma (MM), 166 patients receiving autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell-depleted allogeneic transplantation were analyzed to compare overall survival (OS), progression-free survival (PFS) and risk of relapse. Patients receiving autologous transplantation had a significantly improved OS (P=0.006) and PFS (P=0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%, respectively, compared with 51% and 28% for allogeneic transplantation. By 4 years after transplantation, outcome was similar with OS and PFS for autologous transplantation 41% and 23%, respectively, compared with 39% and 18% for allogeneic transplantation. The 4-year cumulative incidence of nonrelapse mortality was significantly higher in patients receiving allogeneic transplantation (24% vs 13%) (P=0.004). Relapse was the principle cause of treatment failure for both groups; however, there was a significantly reduced risk of relapse associated with allogeneic transplantation at 4 years: 46% for allograft vs 56% for autograft (P=0.02). Despite a lower risk of relapse after allogeneic transplantation, autologous transplantation is associated with improved OS and PFS compared with allogeneic transplantation in patients with MM. Strategies focused on reducing nonrelapse mortality in allogeneic transplantation may translate into an improved outcome for patients receiving allogeneic transplantation.

Adult↗
PubMed2002

Matrix metalloproteinase-like activity from hemocytes of the eastern oyster, Crassostrea virginica.

Investigation of oyster blood cell lysate revealed one prominent band of proteolytic activity when analyzed using gelatin and collagen impregnated polyacrylamide gel electrophoresis. The proteolytic activity was inhibited by 1,10 phenanthroline and EDTA, but not by other proteinase inhibitors. Maximal activity was shown at pH 8.2 and the molecular weight of the protein responsible for the activity was estimated to be 68 kDa. Proteolytic activity was also measured by fluorescence assays containing hemocyte lysate and fluorescein-labeled gelatin, type I or type IV collagen. Characteristics of this proteolytic activity suggest that an invertebrate matrix metalloproteinase is responsible.

Animals↗
PubMed2002

Effect of total body irradiation dose escalation on outcome following T-cell-depleted allogeneic bone marrow transplantation.

Prior studies of non-T-cell-depleted (TCD) transplantation have demonstrated a reduction in relapse in patients receiving escalated doses of TBI; however, overall survival in these studies was not significantly improved due to increased treatment-related toxicity seen at the higher doses of irradiation. Toxicity was in part related to an increased incidence of GVHD. Because T-cell depletion of donor bone marrow reduces the incidence of GVHD and other treatment-related complications after allogeneic bone marrow transplantation, it was postulated that TBI dose may be safely escalated in this setting and may decrease the risk of relapse following TCD BMT. Herein, we report the results of a trial assessing the safety and impact of escalated doses of TBI after TCD BMT. Two hundred adults with hematologic malignancies were treated in consecutive cohorts defined by increasing doses of TBI (1400, 1480, and 1560 cGy) in combination with cyclophosphamide. In vitro T-cell depletion using anti-CD6 monoclonal antibody was used for GVHD prophylaxis. The incidence of grade II or greater acute GVHD in patients receiving 1560 cGy (36%) was significantly higher than in patients receiving 1400 cGy (18%) (P = .04) or 1480 cGy (13%) (P = .01). Two-year treatment-related mortality was significantly higher in patients who received 1560 cGy of TBI (33%) than in those who received 1400 cGy (20%) (P = .04) or 1480 cGy (19%) (P = .05). The increased dose of TBI did not reduce the rates of relapse, with the estimated 2-year risk of relapse being 24% (1400 cGy), 24% (1480 cGy), and 31% (1560 cGy) for the 3 cohorts of patients. Overall survival at 2 years was inferior for patients receiving 1560 cGy of TBI (36%) compared with those who received 1400 cGy (55%) or 1480 cGy (58%) (P = .01). We conclude that dose escalation of TBI is associated with increased GVHD and inferior survival following TCD BMT. Future efforts to reduce the risk of relapse after TCD BMT should focus on immunologic methods to induce the graft-versus-leukemia effect after BMT rather than intensification of the ablative regimen by escalation of irradiation dose.

Adolescent↗
PubMed2002

Long-term follow-up of untreated patients with sleep apnoea syndrome.

Obstructive sleep apnoea (OSA) is a common disorder with numerous potential sequelae. Although the majority of these consequences can be reduced with appropriate treatment, only limited data exist regarding the natural progression ofthis disorder in untreated individuals. We hereby report a long-term follow-up of all untreated patients (n = 40) followed-up in the Technion Sleep Clinic, using both subjective and objective measurements. In addition, we report a long-term follow-up of 11 patients who attempted dietary weight loss. The average time interval between the first and second polysomnographies for the untreated group was 5.0 +/- 2.8 yrs, and 2.5 +/- 2.3 yrs for the weight reduction group. There was no significant change in Body Mass Index (BMI) or Respiratory Disturbance Index (RDI) between the two Polysomnographic (PSG) evaluations in the untreated patients. However, eight patients developed hypertension (n=5) or ischaemic heart disease (IHD) (n=3) between the two evaluations. RDI, age and BMI at the time ofthe initial evaluation were not predictive of changes in RDI, snoring intensity or minimal oxygen saturation. However, the patients who developed hypertension/IHD had significantly higher RDI than the patients who did not (46 +/- 27 vs. 23 +/- 17 h(-1), P < 0.005). In the weight-loss group, BMI decreased by a mean of 3.1 kg m(-2), and RDI decreased by 20events h(-1), P<0.05 for both. There was a significant correlation between the weight loss and improvement in RDI (R = 0.75, P = 0.005). We conclude that in untreated obstructive sleep apnoea patients RDI does not necessarily increase over time, but associated hypertension or ischaemic heart disease may develop. When weight loss is successfully achieved, sleep apnoea significantly improves with a high correlation between the extent of weight loss and the improvement in apnoea status.

Adult↗
PubMed2001

Interband and intraband (Drude) contributions to femtosecond laser absorption in aluminum.

Theoretical and experimental investigations of the absorption in metallic aluminum of femtosecond-laser radiation pulses with peak intensity I0 less similar 10(15) W/cm(2) are reported. Energy balance equations are solved for electron and phonon subsystems, together with Helmholtz equation for the laser radiation. Expressions for the relaxation times as functions of electron and phonon temperatures are obtained, with no free parameters. Contrary to the assumption made in published studies, we find that the interband rather than the intraband (Drude) absorption plays the dominant role in the near infrared and throughout the visible region at low and moderate intensities. For 50 fs, 800 nm laser pulses the absorption in interband transitions dominates for intensities up to few times 10(13) W/cm(2). For such pulses, broadening of the parallel-band interband absorption line with the increase in electron and phonon temperatures results, for I0 < or =5 x 10(13) W/cm(2), in the decrease of the absorption coefficient compared to the room-temperature value. In this paper, we present both the first theoretical prediction and the first experimental observation of this phenomenon. Dielectric permittivity gradients within the skin layer also contribute to the decrease in absorption. The mechanisms of the lattice disordering are considered quantitatively, and it is shown that for I0 < 10(14) W/cm(2) melting does not occur in the laser-pulse duration. Experimental results are presented for 800 and 400 nm wavelengths. The agreement between the theory and the experiment is very good.

Journal Article↗
PubMed2001

T-cell--depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect.

Previous trials of allogeneic bone marrow transplantation (BMT) in patients with multiple myeloma (MM) have demonstrated high response rates but also high transplantation-related mortality (TRM) and high relapse rates. Exploitation of this strategy remains of interest because donor lymphocyte infusions (DLIs) can induce a potent graft-versus-myeloma (GVM) effect. CD6 T-cell--depleted allogeneic BMT was combined with prophylactic CD4(+) DLI administered 6 to 9 months after BMT in an effort to reduce TRM and to induce a GVM response after BMT. Twenty-four patients with matched sibling donors and chemotherapy-sensitive disease underwent BMT. CD6 T-cell depletion of donor bone marrow was the sole method of graft-versus-host disease (GVHD) prophylaxis. GVHD after BMT was minimal, 1 (4%) grade III and 4 (17%) grade II GVHD. Fourteen patients received DLI, 3 in complete response and 11 with persistent disease after BMT. Significant GVM responses were noted after DLI in 10 patients with persistent disease, resulting in 6 complete responses and 4 partial responses. After DLI, 50% of patients developed acute (> or = II) or extensive chronic GVHD. Two-year estimated overall survival and current progression-free survival (PFS) for all 24 patients is 55% and 42%, respectively. The 14 patients receiving DLI had an improved 2-year current PFS (65%) when compared with a historical cohort of MM patients who underwent CD6-depleted BMT survived 6 months with no GVHD and did not receive DLI (41%) (P =.13). Although this study suggests that prophylactic DLI induces significant GVM responses after allogeneic BMT, only 58% of patients were able to receive DLI despite T-cell--depleted BMT. Therefore, less toxic transplantation strategies are needed to allow a higher proportion of patients to receive DLI and the benefit from the GVM effect after transplantation. (Blood. 2001;98:934-939)

Actuarial Analysis↗
PubMed2001

Detection of coronary artery stenosis with power Doppler imaging.

BACKGROUND: Power Doppler is a new imaging method for detecting microbubbles during myocardial contrast echocardiography (MCE) based on the registration of variance resulting from ultrasound-induced nonlinear bubble behavior. We tested the hypothesis that power Doppler imaging can be used to quantify coronary stenoses. METHODS AND RESULTS: Three left anterior descending (LAD) coronary stenoses of varying severity were created in each of 9 open-chest dogs. MCE was performed by continuous intravenous infusion of a nitrogen-filled bilayer shell microbubble, PB127, during triggered power Doppler imaging at incremental pulsing intervals. MCE and radiolabeled microsphere measurements were made at baseline and during each stenosis, with and without adenosine stress. Videointensities in the LAD and left circumflex (LCx) beds were plotted against pulsing interval and fit to a previously described exponential function modeling microbubble destruction and replenishment, which was used to derive parameters of bubble velocity (beta) and peak plateau videointensity (A). Contrast defects matching the location of radiolabeled microsphere hypoperfusion were clearly seen, without need for image processing. The product of beta and A was linearly related to LAD/LCx flow (r=0.90, P<0.0001) and inversely related to stenosis gradient (r=-0.70, P<0.0001). Endocardial/epicardial flow ratios were visualized and quantifiable. CONCLUSIONS: As with B-mode harmonics, a model of microbubble destruction/replenishment can be applied to power Doppler data as a means to detect a broad range of stenoses. Image clarity and the lack of attenuation or requirement for background subtraction are additional advantages of this imaging approach. Power Doppler MCE imaging holds promise for the detection of coronary artery disease.

Animals↗