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Biomedical subjects

J Whitaker

Publications and source records attributed to J Whitaker.

At least 19 recordsLinked to original sources
PubMed2005

The use of botulinum toxin type-B in the treatment of patients who have become unresponsive to botulinum toxin type-A -- initial experiences.

The increasing use of botulinum toxin type-A, especially for focal dystonia and spasticity has highlighted the issue of secondary non-responsiveness. Within the last few years botulinum toxin type-B (Myobloc/Neurobloc) has become commercially available as an alternative to type-A. This paper discusses our initial experience of botulinum toxin type-B in a total of 63 individuals who attended our botulinum clinic. Thirty-six patients had cervical dystonia and a secondary non-response to type-A toxin. Thirteen of these patients (36%) had a reasonable clinical response to Neurobloc and continue to have injections. The other 23 patients either had no response, or a poor response, or had unacceptable side effects and ceased treatment. A small number of people with blepharospasm, hemifacial spasm and foot dystonia also had a disappointing response to injection. Twenty patients with spasticity were also type-A resistant. Seven of these show some continuing response to type-B, without unacceptable side effects. These findings demonstrate that botulinum toxin type-B has a place in the management of patients who have become non-responsive to type-A, but overall the responses to type-B toxin were disappointing.

Antibodies↗
PubMed2001

Botulinum toxin for people with dystonia treated by an outreach nurse practitioner: a comparative study between a home and a clinic treatment service.

OBJECTIVE: To study whether a trained outreach nurse practitioner could provide a service that is as good as, or better than, that provided at a hospital outpatient clinic for people who had been diagnosed with dystonia and required treatment with botulinum toxin. DESIGN: Randomized trial. SETTING: An outpatient department of a regional neurorehabilitation center and patients' homes in northern England. PATIENTS: Eighty-nine patients with a clinical diagnosis of spasmodic torticollis, blepharospasm, or hemifacial spasm who had ongoing treatment of dystonia with botulinum injections. INTERVENTIONS: Individuals were randomly allocated either to receive ongoing botulinum injections at home by the nurse practitioner or to continue attending the hospital outpatient clinic and be injected by medical staff. MAIN OUTCOME MEASURES: The following measures were recorded at each visit: demographic descriptors, dosage of botulinum toxin, treatment interval, side-effect profile, external referrals, and a questionnaire to determine qualitative opinion. RESULTS: Efficacy and duration of the botulinum was similar in both groups. Botulinum dosage and side-effect profiles were similar in both groups except for significantly less dysphagia (p < .018) in the home group (7 vs 24 occasions). Subjective opinion by the patients indicated statistically significant preference for home injections. Economic analysis indicated that the overall cost of the treatment was less in the home injection group (total cost per visit $36.90 [ pound 23.36] vs $79.00 [ pound 50.01]), but this difference was not statistically significant. CONCLUSION: A trained outreach nurse practitioner provided a service that was as good as, and in certain aspects better than, that provided by a hospital outpatient clinic. The nurse practitioner provided a more flexible, much appreciated, safe, and cost-effective service for this client group. Wider use of outreach nurse practitioners for dystonia should be encouraged.

Adult↗
PubMed2000

An investigation of the rigor of interpretation rules for STRs derived from less than 100 pg of DNA.

By increasing the PCR amplification regime to 34 cycles, we have demonstrated that it is possible routinely to analyse <100 pg DNA. The success rate was not improved (without impairing quality) by increasing cycle number further. Compared to amplification of 1 ng DNA at 28 cycles, it was shown that increased imbalance of heterozygotes occurred, along with an increase in the size (peak area) of stutters. The analysis of mixtures by peak area measurement becomes increasingly difficult as the sample size is reduced. Laboratory-based contamination cannot be completely avoided, even when analysis is carried out under stringent conditions of cleanliness. A set of guidelines that utilises duplication of results to interpret profiles originating from picogram levels of DNA is introduced. We demonstrate that the duplication guideline is robust by applying a statistical theory that models three key parameters - namely the incidence of allele drop-out, laboratory contamination and stutter. The advantage of the model is that the critical levels for each parameter can be calculated. This information may be used (for example) to determine levels of contamination that can be tolerated within the strategy employed. In addition we demonstrate that interpreting one banded loci, where allele dropout could have occurred, using LR=1/2f(a) was conservative provided that the band was low in peak area. Furthermore, we demonstrate that an apparent mis-match between crime-stain and a suspect DNA profile does not necessarily result in an exclusion. The method used is complex, yet can be converted into an expert system. We envisage this to be the next step.

Alleles↗
PubMed1999

Developing a managed care delivery system in New York State for Medicaid recipients with HIV.

In the state of New York, models of care known as HIV Special Needs Plans (HIV SNPs) are being developed to meet the unique health and medical needs of Medicaid recipients with HIV. Establishing managed care plans for the 80,000 to 100,000 HIV-infected Medicaid recipients residing in the state has required considerable effort, including distributing planning grants to solicit information and recommendations regarding program and fiscal policy; convening a workgroup to facilitate discussions between the state and the provider and consumer communities; conducting a longitudinal survey to assess the impact of managed care on persons with HIV; and developing a longitudinal, person-based, encounter-level database representing the clinical and service utilization histories of more than 100,000 patients for state fiscal years 1990 to 1996. The key fiscal issues identified and discussed were capitation rates, initial capitalization levels, and risk-adjustment mechanisms. Other pertinent issues included the importance of a benefits package supporting a comprehensive, integrated continuum of state-of-the-art services; marketing and enrollment; attention to provider and consumer training and education needs; and interdependence of financial reimbursement and benefits packages. From our experience in New York State, we conclude that a successful model of Medicaid managed care for persons with HIV should build on the existing infrastructure of services, using a collaborative process among government agencies, healthcare providers, and HIV/AIDS consumer communities. A future challenge lies in the implementation of the HIV SNP model and evaluation of its soundness and ability to ensure quality healthcare services.

Capitation Fee↗
PubMed1998

Interpreting simple STR mixtures using allele peak areas.

Although existing statistical models can interpret mixtures qualitatively based upon the alleles present, the use of automated sequencers opens the opportunity to take account of quantitative aspects embodied by the peak area. One step in understanding simple mixtures consisting of just two donors is to estimate the mixture ratio. This is relatively easy to do when four-allele mixtures are evident at a given locus. However, if the mixture consists of three or fewer alleles, the process it is not straightforward. We demonstrate that mixture estimates are consistent across all loci in a multiplex system. Once the mixture ratio is known, then the expected peak areas for any given combination of alleles can be estimated using a simple spreadsheet analysis.

Alleles↗
PubMed1998

Ventricular myxoma presenting as acute visual loss.

We report a case of left ventricular myxoma with embolization to the left posterior cerebral artery, causing acute visual loss. The tumor was successfully resected and a follow-up echocardiography after 21 months revealed no evidence of tumor recurrence. The patient also had a past history of testicular seminoma. We believe that this is the first case report of an association of cardiac myxoma and testicular seminoma.

Heart Neoplasms↗
PubMed1998

A topically applied quaternary ammonium compound exhibits analgesic effects for orthopedic pain.

OBJECTIVE: To investigate the effectiveness of a topically applied emulsion of an analgesic ammonium solution for the temporary treatment of pain associated with arthritis, tendinitis and bursitis. DESIGN: 100 subjects in a single center, presenting with chronic pain associated with arthritis, tendinitis, or bursitis trialed against placebo in a double-blind cross-over protocol. MAIN OUTCOME MEASURES: Measures of treatment success include reduction in pain, improvement in clinical and/or mechanical evaluations, and evaluation of local and systemic adverse effects. Analysis was conducted at two weeks, after one week's clearance, and again after two weeks. RESULTS: For chronic neuralgia associated with arthritis, tendinitis, and bursitis, the test material had a positive effect at temporary pain reduction. Several subjects also recorded improvements in mechanical evaluations from baseline. Withdrawals due to systemic or local adverse reactions were minimal. CONCLUSION: A topical emulsion of a strong ammonium solution utilizing quaternary ammonium, enhanced with certain penetration enhancers, is effective for temporary relief of pain associated with arthritis, tendinitis, and bursitis.

Administration, Topical↗
PubMed1997

Familial skewed X inactivation: a molecular trait associated with high spontaneous-abortion rate maps to Xq28.

We report a family ascertained for molecular diagnosis of muscular dystrophy in a young girl, in which preferential activation (> or = 95% of cells) of the paternal X chromosome was seen in both the proband and her mother. To determine the molecular basis for skewed X inactivation, we studied X-inactivation patterns in peripheral blood and/or oral mucosal cells from 50 members of this family and from a cohort of normal females. We found excellent concordance between X-inactivation patterns in blood and oral mucosal cell nuclei in all females. Of the 50 female pedigree members studied, 16 showed preferential use (> or = 95% cells) of the paternal X chromosome; none of 62 randomly selected females showed similarly skewed X inactivation was maternally inherited in this family. A linkage study using the molecular trait of skewed X inactivation as the scored phenotype localized this trait to Xq28 (DXS1108; maximum LOD score [Zmax] = 4.34, recombination fraction [theta] = 0). Both genotyping of additional markers and FISH of a YAC probe in Xq28 showed a deletion spanning from intron 22 of the factor VIII gene to DXS115-3. This deletion completely cosegregated with the trait (Zmax = 6.92, theta = 0). Comparison of clinical findings between affected and unaffected females in the 50-member pedigree showed a statistically significant increase in spontaneous-abortion rate in the females carrying the trait (P < .02). To our knowledge, this is the first gene-mapping study of abnormalities of X-inactivation patterns and is the first association of a specific locus for recurrent spontaneous abortion in a cytogenetically normal family. The involvement of this locus in cell lethality, cell-growth disadvantage, developmental abnormalities, or the X-inactivation process is discussed.

Abortion, Habitual↗
PubMed1995

The validation of a new vascular damage assay for photodynamic therapy agents.

The therapeutic effect of photodynamic therapy (PDT: photodynamic sensitizer + light) is partly due to vascular damage. This report describes a new vascular photodamage assay for PDT agents and a validation of the assay. The method described here quantitates changes in tissue blood perfusion based on the relative amount of injected fluorescein dye in treated and untreated tissues. A specially designed fluorometer uses chopped monochromatic light from an argon laser as a source for exciting fluorescein fluorescence. The fluorescent light emitted from the tissue is collected by a six element fiberoptic array, filtered and delivered to a photodiode detector coupled to a phase-locked amplifier for conversion to a voltage signal for recording. This arrangement permits a rather simple, inexpensive construction and allows for the simultaneous use of the argon laser by other investigators. The routine assay for characterizing a specific photosensitizer at a standard dose consists of the sequential allocation of eight mice to a set of different light doses designed to span the dose-response range of fluorescein fluorescence exclusion (measured 8-10 min after fluorescein injection). The assay validation experiment used an anionic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a at a dose of 0.4 mumol/kg. The parameter estimates (n = 34 mice) from fitting the standard Hill dose-response model to the data were: median fluorescence exclusion light dose FE50 = 275 +/- 8.3 J/cm2 and Hill sigmoidicity parameter m = -3.66 +/- 0.28. Subsets of the full data set randomly selected to simulate a standard eight mice experiment yielded similar parameter estimates. The new assay provides reliable estimates of PDT vascular damage with a frugal sequential experimental design.

Animals↗
PubMed1994

Multiparameter flow cytometric analysis of a pH sensitive formyl peptide with application to receptor structure and processing kinetics.

Environmentally sensitive molecules have many potential cellular applications. We have investigated the utility of a pH sensitive ligand for the formyl peptide receptor, CHO-Met-Leu-Phe-Phe-Lys (SNAFL)-OH (SNAFL-seminaphtho-fluorescein), because in previous studies (Fay et al.: Biochemistry 30:5066-5075, 1991) protonation has been used to explain the quenching when the fluoresceinated formyl pentapeptide ligand binds to this receptor. Moreover, acidification in intracellular compartments is a general mechanism occurring in cells during processing of ligand-receptor complexes. Because the protonated form of SNAFL is excited at 488 nm with emission at 530 nm and the unprotonated form is excited at 568 nm with emission at 650 nm, the ratio of protonated and unprotonated forms can be examined by multiparameter flow cytometry. We found that the receptor-bound ligand is sensitive to both the extracellular and intracellular pH. There is a small increase in the pKa of the ligand upon binding to the receptor consistent with protonation in the binding pocket. Once internalized, spectral changes in the probe consistent with acidification and ligand dissociation from the receptor are observed.

Amino Acid Sequence↗
PubMed1992

Misplaced elderly patients in hospital: clarifying responsibilities.

In an attempt to assess the service provided by a geriatric department for the elderly population within its District, a census of the elderly patients occupying general medical beds in the same District was undertaken. These patients were assessed according to five criteria which identified patients as 'geriatric'. Sixty-one per cent of the patients occupying general medical beds were over the age of 65 years, and almost a half of these were geriatric according to the criteria used. The authors conclude that quantifying misplaced geriatric patients by screening for geriatric characteristics in a general medical population was a useful way of auditing the performance of a geriatric service.

Acute Disease↗
PubMed1991

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Adolescent↗
PubMed1990

Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals.

Myelin basic protein (MBP) is a candidate Ag for the autoimmune process believed to be involved in the pathogenesis of multiple sclerosis (MS). To investigate the fine specificity and HLA restriction of human MBP-specific CTL, long term T cell lines (TCL) were established from 22 MS patients and 16 healthy individuals by repeated antigenic restimulation. By using this approach, MBP-specific cytotoxic TCL were generated from 81% of the lines from MS patients and 69% of those from controls. TCL from both groups expressed the CD3+, CD4+, CD8- phenotype and secreted substantial amounts of IFN-gamma. By using large enzymatic and small synthetic peptides of MBP, TCL were primarily specific for the C-terminal part of the molecule and to a lesser extent for the N-terminal portion. Two regions of the molecule, MBP peptide 87-106 and MBP peptide 154-172, were recognized by the majority of the polyspecific lines and by four and three of 14 monospecific TCL, respectively. These highly immunogenic regions are of interest because they include sequences encephalitogenic in other species. The HLA restriction of each line was determined by using antibody blocking as well as various target cells including EBV-transformed B cells, homozygous typing cells, and fibroblasts transfected with cDNA for DR-alpha and DR-beta genes. All TCL were restricted by HLA-DR Ag. Several HLA-DR molecules restricted multiple cathepsin D-derived and synthetic MBP peptides, including the regions of peptides 87-106 and 154-172 which, respectively, were recognized in conjunction with four and three HLA-DR types. Three of these HLA-DR types are overrepresented in MS patients in different geographic regions. Together, these findings suggest that the MBP-specific cytotoxic T cell response, although not sufficient for disease, may be important for the pathogenesis of MS.

Amino Acid Sequence↗
PubMed1990

Activity of the multidrug transporter results in alkalinization of the cytosol: measurement of cytosolic pH by microinjection of a pH-sensitive dye.

Multidrug-resistant cells contain a plasma membrane efflux pump, the multidrug transporter, which actively expels certain hydrophobic drugs from the cytosol to the cell exterior. These drugs are usually positively charged at physiological pH. Because one might predict that this efflux of positively charged molecules might deplete the cytosol of protons, raising the cytosolic pH, we examined the cytosolic pH of multidrug-resistant cells directly using a pH-sensitive dye coupled to a membrane-impermeable molecule. The dye (SNARF), covalently coupled to 10,000 MW dextran, was mechanically microinjected into the cytosol of cultured multidrug-resistant mouse NIH3T3 cells which express the human multidrug transporter. The fluorescence emission of the dye in living cells was measured using epifluorescence microscopy at different wavelengths to provide a measure of the pH of the cytosolic environment. Multidrug-resistant cells had a higher cytosolic pH than drug-sensitive normal parental cells. As the pH of the culture medium was increased, normal cells maintained their cytosolic pH below 7.0, whereas the cytosolic pH of multidrug resistant cells rose. The difference in cytosolic pH between the two cell types was more than 0.2 pH units at an external culture medium pH of 8.2. Treatment with agents that inhibit multidrug transporter-mediated efflux, such as verapamil and vinblastine, essentially eliminated the elevation of cytosolic pH, presumably because they are good substrates for the pump which overwhelm its capacity to pump other materials. These results suggest that the multidrug transporter is indirectly a proton pump, and that cells may contain an endogenous substrate or substrates for this transporter in the absence of added drugs.

Alkalies↗