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Biomedical subjects

M Alexander

Publications and source records attributed to M Alexander.

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

Research on physical activity and health among people with disabilities: a consensus statement.

Research is required to advance the understanding of issues related to the effect of physical activity on health and disease prevention among people with disabilities. This report is the result of a consensus process using selected experts in health and exercise. The purpose of the consensus conference was to identify research priorities for physical activity and health among people with disabilities. Priorities were established by 30 participants, who were selected by the principal investigators to achieve balance in the areas of engineering, epidemiology, medicine, nutrition, exercise physiology, and psychology. Experts summarized relevant data from their research and from comprehensive review of the scientific literature on the topic areas chosen for the conference. Public commentary was provided by participants in the 1996 Paralympic Congress. Panel members discussed openly all material presented to them in executive session. Commentary from open discussion periods were recorded and transcribed. Selected panelists prepared first drafts of the consensus statements for each research priority question. All of these drafts were distributed to the panelists and pertinent experts. The documents were edited by the drafting committee to obtain consensus. This research priority setting process revealed that greater emphasis must be placed on determining the risks and benefits of exercise among people with disabilities. Exercise must be studied from the perspective of disease prevention while mitigating risk for injury. Five areas were identified as focal points for future work: epidemiological studies; effects of nutrition on health and ability to exercise; cardiovascular and pulmonary health; children with disabilities; and accessibility and safety of exercise programs. As people with disabilities live longer, the need for addressing long-term health issues and risk for secondary disability must receive greater attention. As a consequence of the consensus process, specific recommendations for future research regarding the impact of exercise on the health and quality of life of persons with disabilities were defined.

Cardiovascular Diseases↗
PubMed1998

Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity In vivo against human leukemia and lymphoma xenografts.

Flavopiridol is a novel semisynthetic flavone derivative of the alkaloid rohitukine. Flavopiridol is known to inhibit potently the activity of multiple cyclin-dependent kinases. We have assessed its effects on normal and malignant cells in preclinical animal models of localized and disseminated human hematopoietic neoplasms. Flavopiridol, when administered as daily bolus intravenous (IV) injections, produced selective apoptosis of cells in the thymus, spleen, and lymph nodes, resulting in atrophy of these organs. With the exception of the intestinal crypts, apoptosis or tissue damage was absent in all other organs investigated (kidneys, liver, lungs, bone/bone marrow, muscle, and heart). Flavopiridol had a marked apoptotic effect documented by DNA nick-end labeling, or DNA agarose gels in xenografts of human hematopoietic tumors HL-60, SUDHL-4, and Nalm/6. After treatment with 7.5 mg/kg flavopiridol bolus IV or intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage subcutaneous (s.c.) human HL-60 xenografts underwent complete regressions, and animals remained disease-free several months after one course of flavopiridol treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV for 5 days underwent either major (two out of eight mice) or complete (four out of eight mice) regression, with two animals remaining disease-free for more than 60 days. The overall growth delay was 73.2%. The acquired immunodeficiency syndrome-associated lymphoma AS283 showed no significant response when flavopiridol was used in advanced s.c. tumors, but when treatment was initiated in early stages, there was a complete regression of the early tumors, and a significant overall growth delay (>84%). When flavopiridol was used in severe combined immunodeficient mice bearing disseminated human acute lymphoblastic leukemia Nalm/6 cells, there was 15-day prolongation in survival (P = .0089). We conclude that flavopiridol greatly influences apoptosis in both normal and malignant hematopoietic tissues. This activity was manifested in our study as a potent antileukemia or antilymphoma effect in human tumor xenografts, which was dose and schedule dependent. These findings provide compelling evidence for the use of flavopiridol in human hematologic malignancies.

Animals↗
PubMed1998

Utilization of sorbed compounds by microorganisms specifically isolated for that purpose.

A bacterium obtained by enrichment on nonsorbed phenanthrene was unable to degrade phenanthrene sorbed to polyacrylic beads and had little activity on phenanthrene sorbed to lake-bottom sediment. A bacterium obtained by enrichment on phenanthrene sorbed to polyacrylic beads readily mineralized the compound sorbed to the beads or the sediment. Degradation by the second bacterium of phenanthrene sorbed to beads 38-63 microns or 63-150 microns in diameter was more rapid than the rate of desorption of the hydrocarbon in the absence of the bacterium. Little degradation of sorbed, nonleachable phenanthrene in soil was effected by another isolate obtained by enrichment with the nonsorbed hydrocarbon, but a mixed culture and the bacterium obtained by enrichment on the sorbed compound extensively degraded phenanthrene. Because microorganisms specifically obtained for their capacity to degrade sorbed phenanthrene are more active than species not specialized for use of the bound compound, we suggest that microorganisms enriched on nonsorbed compounds may not be appropriate for evaluation of biodegradation and bioremediation of sorbed compounds.

Bacteria↗
PubMed1998

Microbial factors and gingival crevicular fluid aspartate aminotransferase levels. A cross-sectional study.

The aim of this cross-sectional study was to investigate the clinical application of chairside tests for gingival crevicular fluid (GCF) aspartate aminotransferase (AST) levels and plaque BANA hydrolysis activity with the presence of the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. The study comprised 100 periodontitis sites (pocket depths > or =4 mm, GI=3) from 10 patients with chronic adult periodontitis and 100 control sites (pocket depths <4 mm, GI<3) from 10 periodontally healthy patients comprising 55 healthy sites (pocket depths <4 mm, GI=0) and 45 gingivitis sites (pocket depths <4 mm, GI=1 or 2). The values for both BANA hydrolysis and AST levels were significantly higher in samples from periodontitis compared with gingivitis and healthy sites (p<0.001). A. actinomycetemcomitans was identified in 45% and P. gingivalis in 17% of periodontitis sites but neither pathogen was recovered from control sites and there was no significant correlation with the clinical parameters measured. There was no significant relationship between the presence of P. gingivalis and/or A. actinomycetemcomitans with BANA hydrolysis or AST levels. A significant correlation (p=0.0017) was observed between BANA hydrolysis and pocket depth and between AST hydrolysis and the GI (p=0.01). This study failed to demonstrate a positive association between chairside analysis of GCF metabolites for AST levels and/or BANA hydrolysis with P. gingivalis and A. actinomycetemcomitans. However, the GCF metabolites had a significant correlation with periodontally diseased sites in patients with chronic adult periodontitis and may help confirm clinical observations.

Adult↗
PubMed1998

MAP kinase pathways in the yeast Saccharomyces cerevisiae.

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Uneven distribution of desmosterol and docosahexaenoic acid in the heads and tails of monkey sperm.

Previously we demonstrated high concentrations of desmosterol and docosahexaenoic acid (DHA, 22:6 n-3) in monkey testes and sperm. Desmosterol, a cholesterol precursor, is not present elsewhere in the body. High concentrations of DHA are found elsewhere only in the retina and brain. To examine the distribution of these compounds in the heads and tails of sperm, we separated them and determined their sterol, fatty acid, and phospholipid molecular species composition. Desmosterol predominated in tails (134.4 vs. 1.7 microg/10(9) cells in heads). The cholesterol content was also greater in the tails (66.2 vs. 30.3 microg/10(9) cells in heads). Sperm tails had more polyunsaturated fatty acids than the heads (34.1 vs. 12.1% of total fatty acids) which resulted mainly from the higher contents of DHA (19.6 vs. 1.1%) and arachidonic acid (20:4 n-6) (6.4 vs. 1.6%) in the tails. These differences in fatty acid composition occurred mainly in phospholipids: phosphatidyl choline and phosphatidyl ethanolamine for n-3 fatty acids and phosphatidyl serine and cardiolipin for n-6 fatty acids. Fifteen phospholipid molecular species were identified. Sperm tails had more molecular species containing unsaturated fatty acids than the heads. Our results reveal the large differences in membrane lipid composition between the heads and tails of sperm. Most (99%) of the desmosterol and DHA in sperm is located in the tail. These differences may be responsible for the different functions of these two components of sperm. The large number of double bonds in DHA, six, and in desmosterol, two, may contribute to the membrane fluidity necessary for the motility of the sperm tails.

Animals↗
PubMed1997

Early detection of vasospasm after acute subarachnoid hemorrhage using continuous EEG ICU monitoring.

The neurologic morbidity of delayed ischemic deficits from vasospasm following aneurysmal subarachnoid hemorrhage (SAH) continues to be the most debilitating complication from this devastating illness. Neurologic critical care is focused on recognition and treatment of these secondary insults but often the treatment is withheld until an irreversible deficit becomes manifest. Continuous EEG (cEEG) monitoring provides a unique potential to recognize early secondary insults and offers an opportunity for early intervention. We studied 32 SAH patients using cEEG and trending of the quantitative measure, relative alpha (RA), to determine if reductions in RA variability occurred with documented vasospasm. In 19/19 patients with angiographically documented vasospasm, we found that RA variability was decreased by a mean of two grades and improved with resolution of vasospasm. In 10/19 this reduction in RA variability preceded the diagnosis of vasospasm by a mean of 2.9 days (SD 1.73). The positive predictive and negative predictive values are 76% and 100%, respectively. Non-diagnostic clinical signs at the time of RA variability reduction and vasospasm were present in 12/19 patients. Thus decreased RA variability is able to provide early detection of neurologic complications such as vasospasm in patients before clear clinical symptoms and signs occur.

Adult↗
PubMed1997

[Congenital sideroblastic anemia in an infant].

UNLABELLED: Sideroblastic anemia is rare in infants. When it occurs, it is generally hereditary and X-linked. CASE REPORT: A microcytic anemia without iron deficiency was diagnosed in a 2-month old infant with probable acquired cytomegalic infection. Bone marrow examination disclosed ringed sideroblasts without cytomegalic inclusions. Treatment with pyridoxine was tried without effect and no other therapeutic trial was attempted. The child, now aged 5 years, remains well without blood transfusion. CONCLUSION: Hereditary and acquired sideroblastic anemias may occur in infants and children. Whatever their cause might be, the evolution is unpredictable. The only successful treatment for the hereditary variant remains pyridoxine supplementation which brings relief in about one patient out of three. Efficiency and safety of other therapeutic regimens remain to be proven.

Anemia, Sideroblastic↗
PubMed1997

Albuterol via Turbuhaler versus albuterol via pressurized metered-dose inhaler in asthma.

BACKGROUND: Inhaled albuterol is most commonly self-administered by patients using a pressurized metered-dose inhaler (pMDI) but patients often have difficulty using the device. Dry powder devices such as the multi-dose, inspiratory flow driven inhaler (Turbuhaler) are often better handled by patients. OBJECTIVE: We sought to compare the efficacy and tolerability of 100 micrograms of albuterol delivered by a multi-dose, inspiratory flow driven inhaler (Turbuhaler) to a standard dose (200 micrograms) delivered by a pMDI (Ventolin) in chronic reversible obstructive airways disease. METHOD: In 6 centers, we studied 37 adults [19 men and 18 women, mean age 39 +/- 12 years; mean baseline forced expiratory volume in one second (FEV1) 72 +/- 13% (% predicted)] with stable but symptomatic reversible obstructive airways disease as demonstrated by 15% or greater increase in FEV1 following two puffs (200 micrograms) albuterol by pMDI. The crossover design comprised a 1-week run-in and two 2-week treatment periods separated by a 1-week washout. At the start and end of each treatment period, FEV1 was measured at the clinic. Patients self-administered albuterol 100 micrograms (2 x 50 micrograms) via Turbuhaler or 200 micrograms (2 x 100 micrograms) via pMDI in a double-blind fashion four times daily. Morning and evening peak expiratory flow (PEF) was noted daily. All non-study bronchodilators were withheld while open-label albuterol pMDI was offered for rescue. RESULTS: Of the 37 patients, 30 used inhaled steroids in constant doses throughout the study, one used inhaled cromoglycate and six used no anti-inflammatory therapy. There was no difference between treatment periods in morning PEF, diurnal fluctuation in PEF, increase in PEF following study drug, baseline FEV1 and FEV1 increase following study drug. Although there was no difference in symptom scores between treatments, the use of rescue beta 2-agonist was slightly but significantly higher during the Turbuhaler treatment period (1.34 versus 1.08 inhalations/ day, P = .04). Compliance with study drug was slightly but significantly lower during the Turbuhaler treatment period (87 versus 95%) such that the total number of beta 2-agonist puffs inhaled (scheduled plus rescue) was similar between treatments. With regard to adverse events, both treatments were well tolerated. CONCLUSIONS: These results suggest that the efficacy and tolerability of albuterol 100 micrograms qid inhaled via Turbuhaler is similar to albuterol 200 micrograms qid, inhaled via pMDI in stable reversible obstructive airways disease.

Adult↗
PubMed1997

Longitudinal assessment of quality of life in acute psychiatric inpatients: reliability and validity.

This study examined the reliability, validity, and responsiveness of Lehman's Quality of Life Interview (QOLI) as an outcome measure on 981 acutely ill psychiatric inpatients assessed longitudinally at admission and discharge. Patients were stratified into five diagnostic (DX) (depressed bipolar, depressed unipolar, schizophrenia, mania, and other diagnoses) and two substance use disorder (SA) strata (with and without concurrent substance abuse/dependence) based on DSM-III-R criteria. There was good replication of the factor structure, excellent internal consistency, overall and within DX and SA groups. Intercorrelations showed that the functional and satisfaction indices measure unique aspects of the quality of life. The construct consistency of the QOLI was dependent upon psychiatric diagnosis and life domain. Intercorrelations of functional and satisfaction indices for patients with depression were greater than for manic patients. We demonstrated strong consistency of construct validity for family and social relation domains, but not safety or leisure activities. Construct validity was shown to hold longitudinally. Analyses of DX and SA group differences on satisfaction and functional indices of the 8 life domains supported discriminative validity: Depressed patients reported the most dissatisfaction, followed by schizophrenic patients, and manic patients reported the greatest satisfaction in most life domains. Patients with concurrent substance abuse generally reported less satisfaction and lower quality of life than patients without a dual diagnosis. Examination of longitudinal changes in satisfaction indicated the QOLI is responsive to changes in global life, leisure activities, living situation, and social relations from hospital admission to discharge (an average of 2 weeks). This study supports the use of the QOLI as an outcome measure to assess quality of life in acutely ill hospitalized psychiatric patients.

Activities of Daily Living↗
PubMed1997

Adhesion molecule expression in normal skin and melanocytic lesions. Role of UV-irradiation and architectural characteristics in nevi.

Cell adhesion between surfaces of cells and to extracellular matrices represents a fundamental mechanism in tissue organization and influences the biological behaviour and the architecture of tumors. We investigated the expression of various adhesion molecules in normal skin (n=5), nevi (n=29), and malignant melanoma (n=10) by immunohistochemistry. Special attention was paid to the correlation between adhesion molecule expression and the respective architectural features, e.g. UV-induced morphological changes, and the arrangement of melanocytes in congenital nevi. In nevi, a single erythemagenic dose of UV-light did not influence the integrin expression of melanocytes, but results in an upregulation of alpha3 beta1- and alpha6 beta1-integrin within the suprabasal layers of the epidermis. This suprabasal labelling was associated with an increased number of suprabasal melanocytes in UV-irradiated nevi which were detected with HMB-45 antibody. Nine of 10 congenital nevi demonstrated a labelling of alpha4 beta1-integrin only in melanocytes of the deeper dermis. This integrin previously has been associated with high tumor thickness and the clinical outcome in melanomas. The integrin profile observed in melanomas differed in part from that seen in nevi with expression of beta2- and beta3-integrins in some cases. The results may indicate a correlation between adhesion molecule expression and histopathological findings in melanocytic lesions.

Cell Adhesion Molecules↗
PubMed1997

Charging for intensive care using direct nursing hours as the cost marker.

The hypothesis that direct nursing hours correlate with the cost of a patient stay in intensive care was tested. One hundred and thirty-nine patients were studied and the data collected included: (a) direct nursing hours applied to each patient; (b) a daily TISS score: (c) a detailed costing of each patient (all costs are shown in N.Z.$). There was a strong correlation between the direct nursing hours and the total cost per patient (r2 = 0.98) (total cost = 54 x direct nursing hours + 344). Also a strong correlation existed between the total TISS scores and the total costs per patient (r2 = 0.96) (total cost = 67.13 x TISS). Direct nursing hours offer a relatively simple and logical method of allocating costs per patient.

Direct Service Costs↗
PubMed1996

Maturity and fertility of rhesus monkey oocytes collected at different intervals after an ovulatory stimulus (human chorionic gonadotropin) in in vitro fertilization cycles.

In rhesus monkeys undergoing ovarian stimulation for in vitro fertilization (IVF), a midcycle injection of human chorionic gonadotropin (hCG) substitutes for the LH surge and induces preovulatory oocyte maturation. The time interval between injection and oocyte collection, ideally, allows for the completion of oocyte maturation without ovulation, which would reduce the number of oocytes available for harvest. To evaluate the influence of this time interval on oocyte parameters following hCG administration, we conducted a series of gonadotropin treatment protocols in 51 animals in which the interval from hCG administration to follicular aspiration was systematically varied from 27 to 36 hr. Follicle number and size, evaluated prior to hCG administration by sonography, did not vary significantly or consistently with preovulatory maturation time. Oocytes were harvested by laparotomy or laparoscopy, and scored for maturity before insemination. The percentage of mature, metaphase II (MII) oocytes at recovery increased significantly with increasing preovulatory time and was inversely proportional to that of metaphase I (MI) oocytes. However, oocyte yield tended toward a progressive decrease with increasing preovulatory maturation times from a high of 27 oocytes at 27 hr to a low of 17 oocytes/animal at the 36 hr time interval. Fertilization levels declined significantly from a high of 50% at 27 hr to a low of 30% at 36 hr. Thus, although higher percentages of mature oocytes were recovered at the longer time intervals, optimal oocytes/embryo harvests were realized after the shorter time intervals (27 and 32 hr) and are most compatible with the goal of achieving high yields of fertile oocytes and embryos following gonadotropin stimulation in rhesus monkeys.

Animals↗
PubMed1996

The foreign accent syndrome: a reconsideration.

This study compared the post-CVA speech of a patient presenting with the foreign accent syndrome (FAS) to both a premorbid baseline for that patient and to similarly analyzed data from an earlier reported case of FAS. The object of this research was to provide quantitative acoustic data to determine whether: (1) the constellation of phonetic features associated with FAS is the same across patients and (2) a common neural mechanism underlies FAS. Acoustic parameters investigated included features of consonant production (voicing, place and manner of articulation), vowel production (formant frequency and duration), and prosody. Results supported the characterization of FAS patients as having a "generic" foreign accent and the hypothesis that FAS deficits are qualitatively different from that of Broca's aphasia. However, comparison of this case with recent studies revealed the extent to which the constellation of phonetic features may vary among FAS patients, challenging the notion that a general prosodic disturbance is the sole underlying mechanism in FAS.

Brain↗