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Biomedical subjects

J Sawyer

Publications and source records attributed to J Sawyer.

At least 37 records · Page 2Linked to original sources
PubMed1999

An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score.

BACKGROUND: The Migraine Disability Assessment (MIDAS) instrument is a five-item questionnaire developed to measure headache-related disability and improve doctor-patient communication about the functional consequences of migraine. OBJECTIVES: To examine the test-retest reliability and internal consistency of the five items and of the overall MIDAS score in population-based samples of migraine sufferers in two countries and to compare consistency across countries. METHODS: Using a clinically validated telephone interview, population-based samples of migraine-headache sufferers were identified in the United States (Baltimore, MD) and the United Kingdom (Merton and Sutton, Surrey). Eligible individuals completed the MIDAS questionnaire on two occasions an average of 3 weeks apart. The MIDAS score is derived from five questions about missed time from work and household work (one question each about missed days and days with at least 50% reduced productivity) and missed days of nonwork activities. RESULTS: A total of 97 migraine-headache sufferers from the United States and 100 from the United Kingdom completed the MIDAS questionnaire twice. Mean and median item values and overall MIDAS scores were similar between the United States and the United Kingdom. Test-retest Spearman correlations of individual items ranged from 0.46 to 0.78. No significant differences in item-specific correlations were observed between the United States and United Kingdom. The test-retest Pearson correlation of the MIDAS score (i.e., sum of lost days and reduced-effectiveness days in each domain) was 0.80 in the United States and 0.83 in the United Kingdom. The Cronbach alpha, a measure of internal consistency, was 0.76 in the United States and 0.73 in the United Kingdom. CONCLUSIONS: This is the first international population-based study to assess the reliability of a disability-related illness severity score for migraine. The reliability and internal consistency of the Migraine Disability Assessment score are similar to that of a previous questionnaire (Headache Impact Questionnaire). However, the Migraine Disability Assessment score requires fewer questions, is easier to score, and provides intuitively meaningful information on lost days of activity in three domains.

Adolescent↗
PubMed1999

Total therapy with tandem transplants for newly diagnosed multiple myeloma.

Between August 1990 and August 1995, 231 patients (median age 51, 53% Durie-Salmon stage III, median serum beta-2-microglobulin 3.1 g/L, median C-reactive protein 4 g/L) with symptomatic multiple myeloma were enrolled in a program that used a series of induction regimens and two cycles of high-dose therapy ("Total Therapy"). Remission induction utilized non-cross-resistant regimens (vincristine-doxorubicin-dexamethasone [VAD], high-dose cyclophosphamide and granulocyte-macrophage colony-stimulating factor with peripheral blood stem cell collection, and etoposide-dexamethasone-cytarabine-cisplatin). The first high-dose treatment comprised melphalan 200 mg/m2 and was repeated if complete (CR) or partial (PR) remission was maintained after the first transplant; in case of less than PR, total body irradiation or cyclophosphamide was added. Interferon--2b maintenance was used after the second autotransplant. Fourteen patients with HLA-compatible donors underwent an allograft as their second high-dose therapy cycle. Eighty-eight percent completed induction therapy whereas first and second transplants were performed in 84% and 71% (the majority within 8 and 15 months, respectively). Eight patients (3%) died of toxicity during induction, and 2 (1%) and 6 (4%) during the two transplants. True CR and at least a PR (PR plus CR) were obtained in 5% (34%) after VAD, 15% (65%) at the end of induction, and 26% (75%) after the first and 41% (83%) after the second transplants (intent-to-treat). Median overall (OS) and event-free (EFS) survival durations were 68 and 43 months, respectively. Actuarial 5-year OS and EFS rates were 58% and 42%, respectively. The median time to disease progression or relapse was 52 months. Among the 94 patients achieving CR, the median CR duration was 50 months. On multivariate analysis, superior EFS and OS were observed in the absence of unfavorable karyotypes (11q breakpoint abnormalities, -13 or 13-q) and with low beta-2-microglobulin at diagnosis. CR duration was significantly longer with early onset of CR and favorable karyotypes. Time-dependent covariate analysis suggested that timely application of a second transplant extended both EFS and OS significantly, independent of cytogenetics and beta-2-microglobulin. Total Therapy represents a comprehensive treatment approach for newly diagnosed myeloma patients, using multi-regimen induction and tandem transplantation followed by interferon maintenance. As a result, the proportion of patients attaining CR increased progressively with continuing therapy. This observation is particularly important because CR is a sine qua non for long-term disease control and, eventually, cure.

Adult↗
PubMed1999

Reliability of the migraine disability assessment score in a population-based sample of headache sufferers.

BACKGROUND: The Migraine Disability Assessment (MIDAS) score is used to quantify headache-related disability. In a previous study, we showed that the MIDAS score was highly reliable in population-based samples of migraine headache sufferers in two countries. OBJECTIVES: To examine the test-retest reliability and internal consistency of the five items comprising the MIDAS score and the overall MIDAS score in a population-based sample of both migraine and nonmigraine headache sufferers. METHODS: Using a clinically validated telephone interview, a population-based sample of migraine and nonmigraine headache sufferers was identified in Baltimore, Maryland, USA. A total of 97 migraine cases and 80 nonmigraine subjects completed the MIDAS questionnaire on two occasions an average of 3 weeks apart. The MIDAS score is derived from five questions about missed time from work (or school) and household work (one question each about missed days and days with at least 50% reduced productivity) and missed days of nonwork activities. RESULTS: Among all headache sufferers the test-retest Spearman's correlations of individual MIDAS questions ranged from 0.67 to 0.73. The Spearman's correlation for the MIDAS score (i.e., sum of lost days and reduced effectiveness days in each domain) was 0.84. Cronbach's alpha, a measure of internal consistency, was 0.83. Mean and median item values and the overall MIDAS scores differed between migraine and nonmigraine cases. Even after adjusting for differences in headache frequency, the mean MIDAS scores differed substantially (i.e., 10.3 points) between migraine cases and nonmigraine cases. CONCLUSIONS: The reliability and internal consistency of the MIDAS score are high, as tested in a population-based sample of headache sufferers. MIDAS scores are substantially higher in migraine cases than in non-migraine cases, supporting the validity of the measure.

Adolescent↗
PubMed1998

Urinary basic fibroblast growth factor. A biochemical marker for preosseous fibroproliferative lesions in patients with fibrodysplasia ossificans progressiva.

Angiogenesis is a prominent histopathologic feature of preosseous fibroproliferative lesions in patients who have fibrodysplasia ossificans progressiva. Basic fibroblast growth factor is an extremely potent in vivo stimulator of angiogenesis, and has been implicated in the growth of solid tumors. An enzyme linked immunosorbent assay for basic fibroblast growth factor was performed on urine samples from patients who had active (n = 28) and inactive (n = 39) fibrodysplasia ossificans progressiva, and compared with urine samples from normal age and gender matched control subjects (n = 54). Median basic fibroblast growth factor levels were 2705 pg/g of creatinine in the normal control group, 5058 pg/g of creatinine in patients with inactive fibrodysplasia ossificans progressiva (no significant difference), and 8793 pg/g of creatinine in patients with active fibrodysplasia ossificans progressiva. Female subjects, both normal and with fibrodysplasia ossificans progressiva, had higher levels of urinary basic fibroblast growth factor than did male subjects. There was no correlation of urinary basic fibroblast growth factor levels with age or severity of preexisting disability. These data document an elevation of urinary basic fibroblast growth factor during acute flareups of fibrodysplasia ossificans progressiva and provide a biochemical basis for considering antiangiogenic therapy for inhibiting endochondral osteogenesis in this disorder.

Adolescent↗
PubMed1997

Cytogenetics and molecular genetics in multiple myeloma.

Specific cytogenetic abnormalities have been identified in multiple myeloma that confer a poor prognosis, even with intensive chemotherapy and autotransplants. The identification and characterization of potential genes involved in these different chromosomal changes and their interplay with oncogenes and tumor suppressor genes controlling cellular growth and apoptosis is the major focus of this review.

Chromosome Aberrations↗
PubMed1997

Zolmitriptan (Zomig, 311C90), a novel dual central and peripheral 5HT1B/1D agonist: an overview of efficacy.

The efficacy of zolmitriptan (Zomig, 311C90), a 5-hydroxytryptamine (5HT)1B/1D receptor agonist, in the acute oral treatment of migraine was evaluated in an extensive clinical trial program. Four randomized, placebo-controlled studies (total 2480 patients) were performed; data from two of these trials established that a 2.5 mg dose was on the shoulder of the dose-response curve (2-h headache response rate 64%), showing similar efficacy to the 5 mg dose (67%). In this program, the efficacy of zolmitriptan was not influenced by the pretreatment headache duration; the presence of aura preceding the headache, migraine associated with menses or migraine upon awakening; or by concomitant use of oral contraceptives or antidepressants. In addition, zolmitriptan 5 mg proved consistently effective in the treatment of multiple migraine attacks for up to 1 year. Zolmitriptan reduced the incidence of nausea, photophobia and phonophobia, reduced impairment of normal activity and demonstrated positive effects on patients' quality of life. Thus, zolmitriptan is a highly effective acute oral antimigraine therapy, with 2.5 mg providing the optimal balance between efficacy and tolerability.

Adolescent↗
PubMed1996

Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma.

Myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) have been reported after autologous transplantation (AT) for lymphoma. It is not clear whether myeloablative therapy used in conjunction with autologous transplantation contributes to the development of MDS/AML or whether the conventional chemotherapy preceding the transplant, and administered over a prolonged period, causes these secondary malignancies. To address this issue, we examined 188 patients with multiple myeloma (MM) who had received AT. 71 patients with no more than one cycle of standard chemotherapy were enrolled in our Total Therapy program, designed to avoid exposure to alkylating agents prior to peripheral blood stem cell mobilization (group 1). The median duration of pretransplant therapy in group 1 was 7.6 months and significantly shorter than the 24 months of 117 patients (group 2) with more prolonged conventional therapy (P = 0.0001). All seven patients developing MDS post-transplantation belonged to group 2 (P = 0.02); the median durations from initial therapy and first transplant were 66 months (range 38-86) and 24 months (range 9-39), respectively. Our findings provide evidence that prolonged standard-dose alkylating agent therapy prior to transplantation, rather than autotransplant-supported myeloablative treatment, is associated with development of MDS/AML. Stem cell damaging alkylator treatment should be avoided, not to compromise PBSC collection, but also to reduce the risk of treatment-related MDS/AML.

Aged↗
PubMed1994

Stimulus factors affecting the categorisation of faces and scrambled faces.

Three experiments are reported which investigate the categorisation of faces and scrambled faces in a face/scrambled face decision task. Three kinds of stimuli were presented in upright and inverted orientations; faces, highly scrambled faces (all features out of position) and moderately scrambled faces (two features out of position). Experiment 1 demonstrated that faces and highly scrambled faces are categorised equally quickly and both types of stimulus were categorised faster than moderately scrambled faces. These results held for both upright and inverted presentations. It is argued that for both upright and inverted presentations, faces are categorised by being matched in parallel to a stored mental representation of a face. In contrast scrambled faces are categorised following a serial search of facial features which is probably self-terminating. Experiment 2 demonstrates that the results of Experiment 1 hold when facial features are replaced by other objects which retain the same global shape as facial features and suggest that faces are categorised using a coarsely coded visual description. Experiment 3 demonstrates the importance of stimulus outline on the categorisation of both moderately and highly scrambled faces but not real faces. The results are discussed in terms of the stimulus information used, and the effect of inversion, on face categorisation.

Face↗
PubMed1992

Clinical phenotype and molecular analysis of a three-generation family with an interstitial deletion of the short arm of chromosome 5.

We report on a 3-generation family with an interstitial deletion of the short arm of chromosome 5. Varied manifestations were found among the affected individuals including microcephaly, hypertonia, and micrognathia; mental retardation was common to all affected individuals. High resolution chromosome analysis was interpreted as del(5) (pter- > p14.3::p13.3- > qter). Molecular comparison of the deletion in this family with individuals with other 5p deletions suggests that the clinical findings are due specifically to the chromosomal material deleted from 5p13.

Abnormalities, Multiple↗
PubMed1992

Misuse of ecstasy.

Explore the source record for details and available documents.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Is combination sulfonylurea and insulin therapy useful in NIDDM patients? A metaanalysis.

OBJECTIVE: To assess the efficacy of combination therapy with insulin and sulfonylurea in the treatment of NIDDM. RESEARCH DESIGN AND METHODS: Studies published between January 1966 and January 1991 were identified through a computerized Medline search and by hand searching the bibliographies of identified articles. We identified 17 eligible randomized, controlled trials of combination therapy in NIDDM. These trials had a minimum duration of 8 wk and at least one of three outcome measures (fasting glucose, HbA1, or C-peptide) with SD or SE of the mean reported to do metaanalysis. With standardized forms, three independent reviews abstracted measures of study quality and specific descriptive information about population, intervention, and outcome measurements. RESULTS: We calculated effect size and weighted mean changes of the three outcome measures for control and treatment groups. In the treatment group, the fasting plasma glucose decreased from a mean of 11.4 mM (206 mg/dl) at baseline to a mean of 9.16 mM (165 mg/dl) posttreatment, whereas the control group decreased from (11.3 to 10.8 mM) (204 to 194 mg/dl) (effect size 0.39, P less than 0.0001). For HbA1, the treatment group decreased from a baseline of 11.0 to 10.2% compared to 11.0 and 11.2% in the control group (effect size 0.43, P less than 0.0001). For fasting C-peptide, the treatment group increased from 0.49 to 0.58 nM (1.45 to 1.75 ng/ml) compared with 0.47 and 0.43 (1.42 and 1.30) for the control group (effect size 0.26, P less than 0.017). CONCLUSION: Combined insulin-sulfonylurea therapy leads to modest improvement in glycemic control compared with insulin therapy alone. With combined therapy, lower insulin doses may be used to achieve similar control. Obese patients with higher fasting C-peptides may be more likely to respond than others.

Blood Glucose↗
PubMed1992

Prevalence of human immunodeficiency virus infection in hospitalized adults at a teaching hospital in west Texas.

The prevalence of infection with human immunodeficiency virus (HIV) among hospitalized adults at a teaching hospital in West Texas was estimated by conducting a serological survey. Of the 2,458 patients tested, 12 (0.5%) were seropositive. All 12 were men of ages 28 through 50 years; 11 were white and 1 was Hispanic. Eleven were previously known to be HIV positive and were hospitalized for illnesses related to acquired immunodeficiency syndrome (AIDS). All seropositive patients were hospitalized on nonsurgical services of internal medicine, medical-surgical neurology, and family practice. These results indicated that the sampled population in West Texas showed a relatively low prevalence of HIV infection and that seropositive patients were predominantly white men hospitalized for AIDS-related illnesses.

Adolescent↗
PubMed1991

Intermolecular cross-links mediate aggregation of phospholipid vesicles by pulmonary surfactant protein SP-A.

As the most abundant glycoprotein component of pulmonary surfactant, SP-A (Mr = 30,000-36,000) plays a central role in the organization of phospholipid bilayers in the alveolar air space. SP-A, isolated from lung lavage, exists in oligomeric forms (N = 6, 12, 18, ...), mediated by collagen-like triple helices and intermolecular disulfide bonds. These protein-protein interactions, involving the amino-terminal domain of SP-A, are hypothesized to facilitate the alignment of surfactant lipid bilayers into unique tubular myelin structures. SP-A reorganization of surfactant lipid was assessed in vitro by quantitating the calcium-dependent light scattering properties of lipid vesicle suspensions induced by SP-A. Accelerated aggregation of unilamellar vesicles required SP-A and at least 3 mM free calcium. The initial rate of aggregation was proportional to the concentration of canine SP-A over lipid:protein molar ratios ranging from 200:1 to 5000:1. Digestion with bacterial collagenase or incubation with dithiothreitol (DTT) completely blocked lipid aggregation activity. Both treatments decreased the binding of SP-A to phospholipids. The conditions used in the DTT experiments (10 mM DTT, nondenaturing Tris buffer, 37 degrees C) resulted in the selective reduction and 14C-alkylation of the intermolecular disulfide bond involving residue 9Cys, whereas the four cysteines found in the noncollagenous domain of SP-A were inefficiently alkylated with [14C]-iodoacetate. HPLC analysis of tryptic SP-A peptides revealed that these four cysteine residues participate in intramolecular disulfide bond formation (138Cys-229Cys and 207Cys-221Cys). Our data demonstrate the importance of the quaternary structure (triple helix and intermolecular disulfide bond) of SP-A for the aggregation of unilamellar phospholipid vesicles.

Amino Acids↗
PubMed1991

Localization of the mouse thymidine kinase gene to the distal portion of chromosome 11.

We report the cytogenetic mapping of the thymidine kinase (tk-1) gene in the mouse using two complementary and independent analyses: (1) investigation of chromosome aberrations associated with tk-1 gene inactivation in the L5178Y TK+/- -3.7.2C cell line, and (2) fluorescence in situ molecular hybridization of cloned tk-1 cDNA probes to mitotic chromosomes of this cell line. The consensus location from both analyses is 11E1-E2. Consideration of the mouse tk-1 gene localization, along with evidence that the homologous human TK1 gene is located distally on the large arm of chromosome 17, appears to extend the region of homology between MMU11 and HSA17 to the distal end of both chromosomes.

Animals↗