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Biomedical subjects

M Alexander

Publications and source records attributed to M Alexander.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

Optimizing biodegradation of phenanthrene dissolved in nonaqueous-phase liquids.

A study was conducted to optimize the biodegradation in soil slurries of phenanthrene initially dissolved in nonaqueous-phase liquids (NAPLs). The slow rate of degradation of phenanthrene in dibutyl phthalate was increased by addition of phenanthrene-degrading microorganisms to soil slurries containing the NAPL. The rate was further increased and the acclimation phase was shortened if the inoculum was grown in a medium containing the hydrocarbon and the phthalate before addition to the slurries. Composition of the growth medium only shortened the acclimation but had no effect on the rate. Vigorous agitation increased the rate and extent of mineralization of phenanthrene in dibutyl phthalate. The effect of temperature was affected by the presence and identity of the inoculum. Rapid and extensive mineralization of phenanthrene initially present in hexadecane and diesel oil were attained by use of intense agitation of the NAPL/soil slurry and inoculation with microorganisms grown in the presence of the NAPLs, but the influence of these variables was less with other NAPLs. Vigorous agitation and addition of an inoculum 24 h after introduction of a nonionic surfactant enhanced biodegradation of phenanthrene initially in 150 Bright stock oil and dibutyl phthalate. The results suggest improved means for the bioremediation of sites contaminated with NAPLs.

Biodegradation, Environmental↗

Mechanism of microbial utilization of biphenyl sorbed to polyacrylic beads.

A microbial consortium mineralized biphenyl sorbed to polyacrylic beads faster than the slow rate at which much of the compound was desorbed. Pure cultures of bacteria isolated from the consortium mineralized biphenyl in solution but not the sorbed compound. However, combinations of two strains did degrade biphenyl. The consortium did not reduce the surface tension in media containing sorbed biphenyl or biphenyl in solution, and addition of synthetic and microbially produced surfactants to pure cultures did not result in utilization of sorbed biphenyl by isolates able to use the soluble molecule. Cells from the consortium that were attached to continuously washed beads degraded the substrate. We suggest that bacteria may act on sorbed compounds without the necessity of an initial desorption and that the mechanism may involve cells attached to the particles rather than the excretion of a surfactant.

Bacteria↗

Pediatric pain practices: a national survey of health professionals.

The purpose of this study was to examine how health-care providers in U.S. teaching hospitals assess and manage children's pain. A 59-item questionnaire was sent to institutions with pediatric residency programs listed in the 1992 National Residency Matching Program. Two hundred and twenty-seven questionnaires were sent and 113 were returned. Two-thirds were from nurses, one-third from physicians. Sixty percent of the respondents stated that they had standards of care or protocols for pain in their institutions, but only one-quarter reported that the standards were followed 80% or more of the time. Use of formal pain-assessment tools was reported by 73% of the sample. Respondents reported that the effectiveness of pain assessment and management was lower for infants and younger children. Only 35% of the sample indicated it was "likely" or "very likely" that parents would be involved in planning prior to a painful event. Several obstacles to adequate pain management were identified by the respondents: knowledge deficit, attitudes, and resources.

Child↗

Generation of tumor-specific cytolytic T lymphocytes from peripheral blood of cervical cancer patients by in vitro stimulation with a synthetic human papillomavirus type 16 E7 epitope.

OBJECTIVE: Approximately 90% of squamous carcinomas of the cervix harbor the human papillomavirus and type 16 has been detected in nearly 50% of cases. Recent studies in mice have shown that the human papillomavirus type 16 E7 oncoprotein contains peptide epitopes that are processed and presented in association with a major histocompatibility antigen for recognition by cytolytic T lymphocytes. We investigated whether an epitope from human papillomavirus type 16 E7 could be used to generate specific human cytolytic T lymphocytes in patients with cervical carcinoma. STUDY DESIGN: After radiation therapy, three patients with antigen HLA-A2 and with locally advanced cervical cancer underwent leukapheresis. Epitope-specific cytolytic T lymphocytes were generated from the peripheral blood mononuclear cells by in vitro stimulation with autologous peripheral blood mononuclear cells pulsed with a human papillomavirus type 16 E7, HLA-A2-restricted, synthetic peptide, E7(11-20) (YMLDLQPETT). RESULTS: In two patients cytolytic T lymphocytes were capable of E7(11-20)-specific, HLA-A2-restricted cytolysis of the peptide-pulsed, HLA-matched, T2 target cell line. Cytolytic T lymphocytes from one of these patients also demonstrated specific cytolysis against the HLA-A2+, HPV-16+ CaSki cervical cancer cell line but did not lyse either HLA-A2+, HPV-16- MS-751 cells or HLA-A2-, HPV-16- HT-3 cells. CONCLUSIONS: These experiments demonstrate that novel cytolytic T lymphocytes that recognize a human papillomavirus type 16 E7 epitope can be generated by using the peripheral blood mononuclear cells from irradiated patients with cervical cancer. In addition, because CaSki cells were specifically lysed by the cytolytic T lymphocytes, these data indicate that the peptide E7(11-20) is endogenously processed and presented on the cell surface of the CaSki cells. The demonstration of epitope-specific lysis of cytolytic T lymphocytes of HPV-16+ cervical cancer cells supports further efforts to develop human papillomavirus peptide-based vaccines or antigen-specific adoptive immunotherapy for the prevention and treatment of cervical carcinoma.

Blood Cells↗

Assessment of neglect reveals dissociable behavioral but not neuroanatomical subtypes.

In the current study, we investigated whether standard assessment techniques of visuospatial neglect are sensitive to detecting dissociable subtypes. We administered a battery of tasks commonly used to detect the presence of visuospatial neglect to 120 patients with unilateral right hemisphere infarcts and, in most cases, performed a systematic analysis of their lesions to quantify and localize brain damage. Using a factor analysis, we discovered seven relatively independent constructs, three of which were specifically related to the presence of left hemispatial neglect: Left Attentional Processing, Line Bisection, and Word Reading. Impairments in two of these factors, Left Attentional Processing and Line Bisection, occurred together in most cases but also occurred independently in 38 cases. There were no cases in whom Word Reading was present without concomitant deficits in one or the other two factors. These three factors could not be distinguished neuroanatomically; that is, lesions were equally likely in the temporal/parietal cortex, dorsolateral frontal cortex, or in deep frontal structures. These data confirm the notion that hemispatial neglect is a complex and multifaceted disorder composed of cognitively independent processes. These processes, however, cannot be dissociated neuroanatomically based on currently available assessment techniques.

Adult↗

A food-grade process for isolation and partial purification of bacteriocins of lactic acid bacteria that uses diatomite calcium silicate.

Bacteriocins, including nisin, pediocin PO2, brevicin 286, and piscicolin 126, were extracted from fermentation media by adsorption onto Micro-Cel (a food-grade diatomite calcium silicate anticaking agent) and subsequent desorption. The optimal conditions for desorption of piscicolin 126 were determined and applied to other bacteriocins, and the relative purities of the desorbed preparations were compared. Piscicolin was not successfully desorbed from Micro-Cel at pH 1.0 to 12.0, with organic solvents, or by increase of ionic strength up to 1 M NaCl. However, 25 and 75% of the bacteriocin activity was desorbed by using 1% sodium deoxycholate and 1% sodium dodecyl sulfate (SDS), respectively. Higher levels (up to 100%) of desorption were achieved by repeated elution or by an increase in surfactant concentration. Desorption of piscicolin with 1/10 volume of SDS solution resulted in a preparation with 10 times concentration in activity, equivalent to that of ammonium sulfate preparations (409,600 to 819,200 activity units/ml). Determination of organic nitrogen (N) content revealed that the desorbed piscicolin preparations were substantially free of proteinaceous substances (approximately 92 to 99%) compared with original culture supernatants and ammonium sulfate preparations. Nisin, pediocin, and brevicin were also desorbed with 1% SDS with a similar level of purification.

Bacteriocins↗

Telemedicine in Australia. 2: The Health Communication Network.

The Health Communication Network (HCN) in Australia is reviewed. Early interest from both the government and the medical community led to the establishment of a number of pilot services. Because of the community interest in privacy issues, determined efforts to understand and build structures to cope with privacy have been made. The first HCN services began to be tested in 1995, and progressive expansion is planned. The HCN, while supported by the government, is a separate, commercial entity, and much early work has thus focused on corporate governance, so that it will be able to do what it was designed for.

Australia↗

The importance of platelets in the expression of monocyte tissue factor antigen measured by a new whole blood flow cytometric assay.

Previous methods for the determination of monocyte tissue factor (TF) have been technically complex, difficult to standardize, prone to spuriously elevated results and difficult to implement in a clinical laboratory environment. We report the development of a two-color whole blood cytometric technique that overcomes many of these disadvantages. The assay uses small volumes of citrated blood (1.0 ml), can be performed in under one hour (if endotoxin stimulation is not performed), is reproducible (CV = 5%) and uses methodology commonly available in clinical laboratories. Baseline (mean +/- SD) expression of monocyte TF in normal subjects was very low (1.1 +/- 0.95%, Mean Fluorescence [Mean FL] 0.20 +/- 0.01) making relatively small increases easy to detect. Monocyte TF expression following endotoxin (LPS) stimulation for 1 h was 34.6 +/- 11.2% (Mean FL 0.32 +/- 0.04). LPS-stimulated activity varied between subjects (21-68%) but was remarkably consistent for individual subjects (CV = 5.4%). Stimulated monocyte TF expression was directly proportional to the platelet count and was reduced by platelet protective anticoagulants and by ingestion of aspirin. Non LPS-stimulated monocyte TF was markedly increased, in a dose-dependent manner, by adding collagen to whole blood. This was apparently associated with platelet-monocyte binding and could be abolished by anti-P-Selectin. We conclude that the whole blood flow cytometric assay of monocyte TF may be a valuable tool for clinical use and a useful model system for evaluating the humoral and cellular factors governing monocyte TF expression in a natural environment.

Adult↗

Teaching smoking cessation to family practice residents: an experiential approach.

BACKGROUND AND OBJECTIVES: Smoking cessation is a complex process influenced by the smoker's motivation to quit and the effective use of external support measures. Understanding the complexities of smoking cessation can be difficult for physicians, many of whom have never smoked. This paper describes an experiential educational approach that exposes family practice residents to the process of smoking cessation through active participation in an American Lung Association (ALA) Freedom From Smoking group. METHODS: We designed and observed a 1-month educational program in which residents co-led a modified ALA group. Ethnography, a qualitative research technique, was used to discover what residents learned. RESULTS: We identified five themes that describe what residents learned through their experience in the ALA Group: 1) the power of nicotine addiction, 2) the power of the smoking cessation group, 3) skills, tips, tools, and tricks to help the smoker quit, 4) the process of redefining success, and 5) the ability to understand the smoker. Residents' recall of their experience remained vivid, even 9 months after the training concluded. CONCLUSIONS: This experiential approach provided a rich, lasting learning experience for the residents we studied.

Adult↗

Role of telemetry monitoring in the non-intensive care unit.

To determine the outcomes of patients admitted to a non-intensive care telemetry unit and to assess the role of telemetry for guiding patient management decisions, data from 2,240 patients admitted to a telemetry unit were collected prospectively during 7 months. Physicians recorded the outcomes (intensive care unit transfer and mortality) and assessed whether telemetry assisted in guiding patient management. Indications for admission to the telemetry unit included chest pain syndromes (55%), arrhythmias (14%), heart failure (12%), and syncope (10%). Telemetry led to direct modifications in management in 156 patients (7%; 95% confidence interval [CI] 5.9% to 8%). Telemetry was perceived as useful but did not alter management for 127 patients (5.7%; 95% CI 4.7% to 6.6%). Two hundred forty-one patients were transferred to an intensive care unit from the telemetry unit (10.8%; 95% CI 9.5% to 12%). Nineteen patients (0.8% of all admissions; 95% CI 0.5% to 1.2%) were transferred because of an arrhythmia identified by telemetry. Routine transfer after cardiac revascularization or surgery accounted for 134 transfers; clinical deterioration accounted for 88 transfers. There were 20 deaths in the unit (0.9%; 95% CI 0.5% to 1.3%): 4 of the 20 deaths occurred while patients were being monitored. The role of telemetry in guiding patient management may be overestimated by physicians, since it detected significant arrhythmias that led to change in medications or urgent interventions in a small fraction of patients.

Aged↗

Hospitalization for congestive heart failure. Explaining racial differences.

OBJECTIVE: To determine whether the higher rate of hospitalization among African Americans for congestive heart failure (CHF) could be explained by racial differences in the prevalence of clinical risk factors for CHF. DESIGN: Retrospective cohort study. SETTING: A large health maintenance organization (HMO). PATIENTS: A sample of 64,877 enrollees (27% African American and 73% white) of the Northern California Kaiser Permanente Medical Care Program who took at least one multiphasic health checkup (MHC) at or after the age of 40 years and were free of CHF at that time. MAIN OUTCOME MEASURES: First hospitalization with a principal diagnosis of CHF. RESULTS: Among cohort members younger than 60 years at baseline MHC, the age-adjusted risk ratio (RR) (African American/white) for CHF hospitalization was 2.14 for men and 2.73 for women, while for persons 60 years of age and older at MHC, the age-adjusted RR was 1.48 for both sexes. Cox proportional hazards models were used to adjust for risk factors and length of follow-up. In persons aged 60 years and older, the race difference was explained by greater prevalence of hypertension and diabetes in African Americans (RR = 1.12; 95% confidence interval [CI], 0.94 to 1.34 after adjustment for hypertension and diabetes). In those younger than 60 years, findings differed by sex. For men, African-American race was no longer a significant predictor of CHF after adjusting for hypertension, diabetes, left ventricular hypertrophy on electrocardiogram, and body mass index (adjusted RR = 1.16; 95% CI, 0.86 to 1.56). However, among younger women, African Americans continued at increased risk despite adjustment for these variables as well as smoking, plasma cholesterol, renal function, alcohol use, and myocardial infarction (adjusted RR = 1.49; 95% CI, 1.00 to 2.21). CONCLUSIONS: In this HMO population, the race differences in first hospitalization for CHF are largely explained by known clinical and behavioral risk factors, although in younger women these risk factors do not completely explain the excess risk among African Americans. These findings highlight the role of hypertension and diabetes in the development of CHF, particularly among African Americans.

Black People↗