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Biomedical subjects

L White

Publications and source records attributed to L White.

At least 109 records · Page 6Linked to original sources
PubMed1995

Response of brain tumors to chemotherapy, evaluated in a clinically relevant xenograft model.

Chemotherapy for brain tumors remains unsatisfactory. Despite increasing participation in clinical trials, there is a clear need for pre-clinical models. Heterotransplantation of surgical specimens directly into the anterior chamber of the nude mouse eye has been demonstrated to produce evaluable xenografts. Drug access in this model is considered to mimic the blood-brain barrier. Five clinical specimens in 3 children with primitive neuroectodermal tumor/medulloblastoma were the sources of 293 intraocular xenografts (5 cohorts by source). Each tumor-bearing mouse received 1 of 5 drugs or normal saline, by intraperitoneal injection, weekly for 5 weeks. Response was monitored for up to 22 weeks, using a staging system which estimates the proportion of the anterior chamber filled by tumor. Results were analysed both as response rates (shrinkage in excess of 50%) at the conclusion of the treatment course and as time to tumor progression by the life table method. Comparison of response rates within cohorts by source of xenografts (exact chi-square test for overall and 2-sided Fisher's exact test for paired comparisons) indicated cyclophosphamide to be the most effective single agent. In logrank analyses cyclophosphamide achieved significantly longer delays to progression than all other drugs in one cohort and longer delays than all but diaziquone in 2 other cohorts. The intraocular xenograft model is a clinically relevant system for the study of therapeutic agents in brain tumors. The effectiveness of intensive dosage cyclophosphamide in a model dependent on access across the blood-aqueous barrier is important and consistent with recent clinical data.

Animals↗
PubMed1995

Breast implants, rheumatoid arthritis, and connective tissue diseases in a clinical practice.

This study was designed to assess the relationship between breast implants and certain rheumatologic diseases (rheumatoid arthritis and diffuse connective tissue diseases). The study base was a rheumatological practice in Atlanta, Georgia that started in 1982 and began computerizing its records in 1985. The computerized records through May 1992 included 4229 women patients, 150 with breast implants and 721 with a diagnosis of rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs). Of the 721 patients who had been diagnosed as having rheumatoid arthritis (RA) and/or one of the connective tissue diseases (CTDs), 392 had rheumatoid arthritis, 344 had connective tissue disease, 15 had both rheumatoid arthritis and a connective tissue disease, and 33 had more than one connective tissue disease. Of the patients with connective tissue disease, 179 had systemic lupus erythematosus, 64 had scleroderma, 49 had Sjögren's syndrome, 36 had dermatomyositis or polymyositis, and 49 had mixed connective tissue disease. Data were analyzed by univariate and multivariate techniques including logistic regression. Significant variables included age at first visit, income strata, and period of first visit. Analyses were performed for each clinical diagnosis, for all connective tissue diseases together (CTDs), and for those with rheumatoid arthritis and/or connective tissue disease (RA/CTD). Analyses were performed on the total data base and on the records of new patients (1986-1992). The adjusted odds ratio for breast implants among women who entered the practice in 1986-1992 and were diagnosed as having rheumatoid arthritis and/or one of the connective tissue diseases (RA/CTDs) was 0.45 (0.22-0.90), for those with rheumatoid arthritis was 0.61 (0.28-1.49), for those with any of these specific diffuse connective tissue diseases was 0.34 (0.11-1.06) compared to those without the disease. For systemic lupus erythematosus, the odds ratio of 0.24 (0.03-1.75) was based on a single case who had the disease 5 yr before the implant. For Sjögren's syndrome, the odds ratio was 1.67 (0.39-7.13) based on two cases, one of whom had the disease 5 yr before the implant. The calculated odds ratios for scleroderma, dermatomyositis/polymyositis, and mixed connective tissue disease were zero since no cases were diagnosed among the patients with breast implants. This study found no evidence that women with breast implants are at an increased risk for having rheumatoid arthritis or other diffuse connective tissue disease.

Adult↗
PubMed1995

Cognitive functioning in chronically hospitalized schizophrenic patients: age-related changes and age disorientation as a predictor of impairment.

Although schizophrenic patients manifest cognitive impairments, there is considerable variability across patients in the severity of this impairment. Very chronic patients with a poor outcome, particularly geriatric patients, manifest the most severe impairments, which have often been characterized as resembling dementia. This study examined age-related changes in cognitive functioning in a sample of schizophrenic patients (n = 393) ranging from 25 to 95 years of age, with a specific focus on identifying aspects of performance that were impaired in the youngest patients and preserved in the oldest patients. Age disorientation was examined in detail because it was previously found to predict global intellectual impairment in chronic patients. All 22 test items changed linearly over time (with age), with aspects of orientation, concentration, and delayed recall most impaired in young patients and naming and sentence repetition most preserved in the oldest patients. Age disoriented patients had more severe cognitive impairments at each age and the age-related changes in global impairment were more severe for these patients. The prevalence of age disorientation was consistent with previous reports and a one-year retest of the sample found that age disorientation was extremely stable over time within patients. The types of functions that are preserved in the oldest patients underscore previous findings of differences between geriatric schizophrenic patients and patients with degenerative diseases and the stability of age disorientation suggests that it is a trait of a subset of schizophrenic patients, those who appear to have the most severely declining course of illness.

Adult↗
PubMed1995

Inaccuracy of self-reported weights and heights among American Indian adolescents.

To determine the accuracy of self-reported weights and heights and of relative weight status in a sample of American Indian adolescents, a survey was conducted in middle and high schools on or near three Indian reservations-Navajo, Choctaw, and Blackfeet. Self-reported weights and heights were compared with measured weights and heights. Participants were 12 through 19 years old. (N = 806, 47.4% male). Overall, both boys and girls underreported weight (mean difference = self-reported - measured mean values)(-3.4 +/- 13.1 and -4.6 +/- 13.0 lb, respectively) and overreported height (0.6 +/- 2.1 and 0.2 +/- 2.6 in, respectively) However, underweight boys and girls overreported weight (normal: -1.6 +/- 7.9 and -1.4 +/- 6.3; overweight: -7.5 +/- 17.9 and -11.6 +/- 19.0 lb, respectively). Although correlations between measured and reported weight, height, and body mass index (BMI) were high, the sensitivity of relative weight categories based on BMI using self-reported weight and height compared with measured weight and height was poor: 66.7% for underweight (BMI < 15th percentile, based on a national reference population), 88.9% for normal weight, and 73.6% for overweight (> 85th percentile). These results call into question the accuracy of self-reported weight and height measurements among American Indian youth and are similar to findings among non-American Indian adolescents. Therefore, their use in prevalence studies should be avoided, and they should be used cautiously in other types of epidemiologic studies.

Adolescent↗
PubMed1995

Metered-dose inhalers: do emergency health care providers know what to teach?

STUDY OBJECTIVE: To evaluate the ability of emergency health care providers and patients to demonstrate the proper use of metered-dose inhalers (MDIs). DESIGN: Prospective cross-sectional survey. SETTING: Five Midwestern community teaching hospitals. PARTICIPANTS: One hundred eighty-five health care providers, comprising emergency medicine house staff (n = 60), attending emergency physicians (n = 50), and ED nurses (n = 75). Also recruited were 100 consecutive ED patients with clinical history of asthma being treated with at least one MDI for more than 3 months. INTERVENTIONS: We surveyed patients and health care providers to assess their knowledge of and ability to use a conventional MDI. The subject's technique of using a placebo inhaler was graded by a trained observer using a checklist of six essential steps. RESULTS: Forty-one percent (76 of 185) of health care providers and 49% (49 of 100) of ED asthma patients performed at least five steps correctly (P = .24). There were no significant differences in performance scores among the emergency medicine house staff (42%), attending emergency physicians (34%), and ED nurses (45%). Only 15% of all health care providers and 17% of asthma patients were able to describe how to estimate the amount of medicine left in the canister. CONCLUSION: These results suggest that many patients use MDIs improperly. Emergency physicians, house staff, and nurses responsible for instructing patients in optimal inhaler use may lack even rudimentary skills with these devices.

Adolescent↗
PubMed1995

Antisense gene suppression against human ICAM-1, ELAM-1, and VCAM-1 in cultured human umbilical vein endothelial cells.

Antisense gene suppression has been carried out for human ICAM-1, ELAM-1, and VCAM-1 in cultured human umbilical vein endothelial cells (HUVEC) stimulated by lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1 beta. A panel of antisense phosphorothioate oligodeoxyribonucleotides (PS-ODN), complementary to mRNA or pre-mRNA of these molecules, were tested for their gene suppression activity monitored by radioimmunoassay of the respective cell surface adhesion molecules. Sequences targeted by effective antisense PS-ODNs were located throughout the mRNA and pre-mRNA. "Hot spots" of gene suppression sites for each region were observed. Shift of the PS-ODN hybridizing site upstream or downstream by a few bases resulted in drastic change of gene suppression efficiency. In addition to translation arrest and RNase H activity, a third mechanism was proposed for antisense gene suppression, involving multiple binding sites for PS-ODN and the activities of RNase H and RNases other than RNase H. Suppression of ICAM-1, ELAM-1, or VCAM-1 in HUVEC by their antisense PS-ODNs resulted in the reduction of adhesion of monocytes and U937 to HUVEC. This may suggest cooperativity among the adhesion molecule pairs in endothelial-leukocyte adhesion, since decrease of a single adhesion molecule on EC surface significantly reduced cell-cell adherence.

Base Sequence↗
PubMed1995

Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration.

AIMS: This study was designed to assess the relative corneal penetration of topical drops of three antibiotics and to relate those levels to minimum inhibitory concentrations for organisms associated with bacterial keratitis. METHODS: Four drops of each of ciprofloxacin, norfloxacin, and ofloxacin (0.3% topical ophthalmic preparations) were given to 12 patients undergoing corneal transplantation. After the recipient tissue was removed, corneal drug penetration was measured using high performance liquid chromatography. RESULTS: Intracorneal concentrations of ofloxacin (geometric mean 0.81 mg kg-1) were significantly higher than both ciprofloxacin (0.60 mg kg-1; p = 0.048) and norfloxacin (0.54 mg kg-1; p = 0.012). Ciprofloxacin and norfloxacin concentrations did not differ significantly (p = 0.33). CONCLUSIONS: Review of the minimum inhibitory concentrations of the fluoroquinolones against ocular pathogens reveals that ciprofloxacin is more potent than ofloxacin against many bacteria; ofloxacin is in turn more potent than norfloxacin. These data favour the selection of ciprofloxacin and ofloxacin rather than norfloxacin for the empirical treatment of corneal infection. The greater potency of ciprofloxacin offsets the superior penetration of ofloxacin. There is a need for improved clinical trial data concerning the use of fluoroquinolone eyedrops in ulcerative keratitis; some encouraging data are available for ciprofloxacin but not (in humans) for norfloxacin or ofloxacin.

Adolescent↗
PubMed1995

Severity of symptoms in chronically institutionalized geriatric schizophrenic patients.

OBJECTIVE: The goal of this study was to characterize the symptoms of geriatric, chronically ill, institutionalized schizophrenic patients and investigate age-related differences in schizophrenic symptoms and cognitive performance from early adulthood to late senescence. METHOD: The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitive performance, respectively, of 393 institutionalized schizophrenic patients stratified into seven groups designated by 10-year age intervals from 25 years to over 85 years. RESULTS: In the comparisons of the seven age groups, significant differences between groups in positive and negative subscale scores on the Positive and Negative Syndrome Scale and in Mini-Mental State scores were revealed. Significant correlations between Mini-Mental State scores and Positive and Negative Syndrome Scale negative symptom scores, but not positive symptom scores, were found for all age groups, except for the youngest patients studied. Current treatment with neuroleptics and prior treatment with ECT, insulin coma, or leukotomy could not account for the poor cognitive performance of the older schizophrenic patients. CONCLUSIONS: The older schizophrenic patients continued to experience psychotic and nonpsychotic symptoms in senescence. Their positive symptoms were moderately less severe and their negative symptoms and cognitive impairment were significantly more severe than those of the younger patients. Somatic treatment appeared not to be responsible for the severe cognitive impairment and negative symptoms of the older patients. These data are relevant to chronically hospitalized geriatric schizophrenic patients but not necessarily to all geriatric schizophrenic patients.

Adult↗
PubMed1995

Validity and utility of the ADAS-L for measurement of cognitive and functional impairment in geriatric schizophrenic inpatients.

This study examined the usefulness of the Alzheimer's Disease Assessment Scale-Late Version (ADAS-L) for assessing cognitive and behavioral impairment in geriatric schizophrenic patients. Subjects were 339 geriatric schizophrenic inpatients. Discriminant function analyses compared the Mini-Mental State Examination (MMSE) with the ADAS-L as independent variables predicting the level of impairment on the criterion measure, the Clinical Dementia Rating. The ADAS-L surpassed the MMSE at correctly distinguishing severe to profound impairment; the MMSE was superior for identifying absent or questionable impairment. Findings provide evidence for the concurrent validity of the ADAS-L as an instrument for measuring impairment in geriatric schizophrenic inpatients.

Aged↗
PubMed1995

The longitudinal stability of cognitive impairment in schizophrenia. Mini-mental state scores at one- and two-year follow-ups in geriatric in-patients.

BACKGROUND: Severe cognitive impairment affects many patients with schizophrenia, especially geriatric in-patients. Little is known about the course of this impairment, however. METHOD: Two hundred and twenty-four geriatric schizophrenic in-patients were examined for changes in cognitive functioning over a one-year follow-up period, and 45 of them were assessed over a two-year period. In addition, the subset of 45 patients participated in a one-week and one-month test-retest reliability study of the instrument used to assess cognitive impairment, the Mini-Mental State Examination (MMSE). RESULTS: The average MMSE scores did not change over a one- or two-year follow-up period. The test-retest reliability of the scale was extremely good at both retest intervals. CONCLUSION: Among the implications of these data are that cognitive changes in geriatric schizophrenic patients are very slow and are more consistent with a neurodevelopmental process than a neurodegenerative course.

Aged↗
PubMed1995

A congenital heart defect in Drosophila caused by an action-potential mutation.

The mutation no action potential (nap) induces arrhythmia in the heartbeat of Drosophila melanogaster larvae at temperatures above 20 degrees C; heartbeat becomes normally rhythmic again after a shift back to 20 degrees C. For this phenotype, napa is almost completely recessive to the wild type, napa also reduces the temperature-sensitivity of heart rate over a wide range of temperature, for this phenotype, napa is dominant over the wild type, napa causes reversible paralysis in adults by epistatic effects on the expression of paralyrica, a gene encoding a voltage-dependent sodium channel. However, the paramutation, which induces paralysis in adults at 29 degrees C, has no effect on larval heartbeat at temperatures between 20 degrees and 37.5 degrees C. The period gene, contra earlier reports, has no effect on heartbeat.

Action Potentials↗
PubMed1995

A phase I study of ifosfamide and doxorubicin with recombinant human granulocyte colony-stimulating factor in stage IV breast cancer.

Our objective was to define the maximum tolerated dose of an escalating dose of ifosfamide in combination with a fixed dose of doxorubicin supported by granulocyte colony-stimulating factor (Neupogen). Eighteen women with stage IV breast cancer were enrolled in a Phase I study of an escalating dose of ifosfamide (1.2 g/m2/day for 5 days-2.75 g/m2/day for 5 days) with doxorubicin 20 mg/m2/day for 3 days. Granulocyte colony-stimulating factor was used at 5 microgram/kg on day 6 until hematological recovery. Prophylactic antibiotics were also used. The maximum tolerated dose of ifosfamide in combination with doxorubicin was 2.75 g/m2/day for 5 days. The objective response rate was 83% with a complete response rate of 33% (6/18 patients); the median time to treatment failure was 11.5 months. The median survival has not been reached and will exceed 18 months. We concluded that the recommended dose of ifosfamide in combination with doxorubicin is 2.5 g/m2/day for 5 days. This combination shows promise in stage IV breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Capillary electrophoresis: separation and quantitation of reverse transcriptase polymerase chain reaction products from polio virus.

In the present study reverse transcriptase (RT) polymerase chain reaction (PCR) products were generated from the RNA of polio virus. The products of the RT-PCR were analyzed by slab-gel electrophoresis (SGE) on 4% agarose gels, and capillary electrophoresis (CE). CE separations were performed in a coated capillary containing a linear polyacrylamide. Samples were injected hydrodynamically or electrokinetically. Detection of the RT-PCR products on CE was by UV absorbance at (254 nm) or by laser-induced fluorescence (LIF). While SGE resulted in adequate separation of 163 and 97 base pair RT-PCR products, separation of the 97, 71 and 53 base pair products was minimal. CE separations showed baseline resolution for all the above PCR products. Finally, it was possible to quantitate the amount of RT-PCR product by developing a standard curve showing a linear relationship between the amount of RNA used in the RT-PCR and the amount of product formed in the RT-PCR. These results suggest the greater resolution and enhanced sensitivity observed, together with the ease of quantitation, make CE a powerful alternative to SGE for the separation and quantitation of PCR products.

Electrophoresis↗
PubMed1994

Expression of platelet-derived growth factor and its receptors by two pre-B acute lymphocytic leukemia cell lines.

Platelet-derived growth factors (PDGF) are potent regulators of cell proliferation. The three isoforms of PDGF AA, AB, and BB are encoded by two genes: PDGF A and PDGF B. The v-sis oncogene is homologous to the PDGF-B gene. v-sis can transform cells that express the appropriate PDGF receptors. Two different types of receptors, PDGF-alpha and PDGF-beta, also encoded by two genes, have been identified. We show that two cell lines. SMS-SB and NALM-6, both derived from pre-B-cell acute lymphocytic leukemias, express the PDGF-A chain gene, and one of them, SMS-SB, releases PDGF-A chains into the media. The SMS-SB cells also express the PDGF-beta receptor, whereas NALM-6 cells express the PDGF-alpha receptor and bind PDGF. This extends the possible targets for PDGF to the B-cell lineage lymphocytes.

Humans↗
PubMed1994

Serological response to rotavirus infection in newborn infants.

We report the identification of rotavirus in stools of newborn infants at the "Hospital Materno Infantil de Caricuao" (HMIC) as well as the infants' serological responses to various rotavirus strains. The serological responses of another group of rotavirus-positive neonates studied previously at the "Maternidad Concepcion Palacios" (MCP) hospital was also evaluated. Fifty-four of 266 (20%) newborns examined at HMIC shed rotavirus. The infection rate was higher among infants admitted to the nursery (75%) than in those "rooming in" with their mothers (7%) (P < .01). Eleven of the 54 neonates (20%) had diarrhea; seven of them experienced mild, short-lived episodes, whereas five had frequent diarrhea bouts or diarrhea lasting for over 3 days; the remaining 43 infants were asymptomatic. Twenty-seven of 28 rotavirus specimens tested at HMIC had VP7 serotype 4 specificity and one belonged to VP7 serotype 1; VP4 typing performed on 24 of the viruses by RNA hybridization showed these viruses to be similar to the M37 strain, a rotavirus previously associated with asymptomatic infections in newborns at MCP. IgA seroresponses were detected in eight of 11 infants born at HMIC (73%), but most failed to developed neutralization responses to homologous or heterologous strains. Newborn infants who had shed the M37 rotavirus strain at MCP reacted similarly: 16 of 24 (67%) developed a rotavirus IgA rise, but only 29% developed a neutralization response.

Antibodies, Viral↗