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Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 127 records · Page 7Linked to original sources
PubMed1999

Sea urchin fertilization during a KC-135 parabolic flight.

For long-term exposure to space it is crucial to understand the underlying mechanisms for altered physiological functions. We have chosen the sea urchin system to study the effects of microgravity on various cellular processes visible during fertilization and subsequent development. We report here on experiments performed on NASA's KC-135 during parabolic flight trajectories to validate procedures to be implemented as part of the first Aquatic Research Facility Space Shuttle experiment on STS-77.

Animals↗
PubMed1999

Utilization of the aquatic research facility and fertilization syringe unit to study sea urchin development in space.

Methods were developed for the investigation of the effects of microgravity on early development in sea urchins within the Canadian Space Agency's Aquatic Research Facility (ARF). The ARF payload provided light, temperature control, automated fixation capability, and a 1 G on-orbit centrifuge control. Eggs and embryos of either the sea urchin species Lytechinus pictus or Strongylocentrotus purpuratus were loaded into Standard Container Assemblies (SCAs) which comprised the experimental aquaria (33 mL volume) contained within the ARF. A newly developed Fertilization Syringe Unit (FSU) was used to achieve "in-flight" fertilization capability. Fixative solutions were preloaded into fixation blocks maintained adjacent to the SCAs and injected at pre-selected time points, resulting in final (diluted) concentrations of either 0.5% or 2% glutaraldehyde (depending upon embryonic stage). Light, scanning, and transmission electron microscopy determined that all desired embryonic and cell division stages (16-cell stage, blastula, gastrula, and pluteus) were preserved using the experimental protocols and fixation capability provided by the ARF/FSU system.

Animals↗
PubMed1998

Inhibition of elastase by N-sulfonylaryl beta-lactams: anatomy of a stable acyl-enzyme complex.

beta-Lactam inhibitors of transpeptidase enzymes involved in cell wall biosynthesis remain among the most important therapeutic agents in clinical use. beta-Lactams have more recently been developed as inhibitors of serine proteases including elastase. All therapeutically useful beta-lactam inhibitors operate via mechanisms resulting in the formation of hydrolytically stable acyl-enzyme complexes. Presently, it is difficult to predict which beta-lactams will form stable acyl-enzyme complexes with serine enzymes. Further, the factors that result in the seemingly special nature of beta-lactams versus other acylating agents are unclear-if indeed they exist. Here we present the 1.6 A resolution crystal structure of a stable acyl-enzyme complex formed between porcine pancreatic elastase and a representative monocyclic beta-lactam, which forms a simple acyl-enzyme. The structure shows that the ester carbonyl is not located within the oxyanion hole and the "hydrolytic" water is displaced. Combined with additional kinetic and mass spectrometric data, the structure allows the rationalization of the low degree of hydrolytic lability observed for the beta-lactam-derived acyl-enzyme complex.

Amino Acid Sequence↗
PubMed1998

Awkward moments in patient-physician communication about HIV risk.

BACKGROUND: Physicians frequently encounter patients who are at risk for HIV infection, but they often evaluate risk behaviors ineffectively. OBJECTIVE: To describe the barriers to and facilitators of comprehensive HIV risk evaluation in primary care office visits. DESIGN: Qualitative thematic and sequential analysis of videotaped patient-physician discussions about HIV risk. Tapes were reviewed independently by physician and patient and were coded by the research team. SETTING: Physicians' offices. PARTICIPANTS: Convenience sample of 17 family physicians and general internists. Twenty-six consenting patients 18 to 45 years of age who indicated concern about or risks for HIV infection on a 10-item questionnaire administered before the physician visit were included. MEASUREMENTS: A thematic coding scheme and a five-level description of the depth of HIV-related discussion. RESULTS: In 73% of the encounters, physicians did not elicit enough information to characterize patients' HIV risk status. The outcome of HIV-related discussions was substantially influenced by the manner in which the physician introduced the topic, handled awkward moments, and dealt with problematic language and the extent to which the physician sought the patient's perspective. Feelings of ineffectiveness and strong emotions interfered with some physicians' ability to assess HIV risk. Physicians easily recognized problematic communication during reviews of their own videotapes. CONCLUSIONS: Comprehensive HIV risk discussions included providing a rationale for discussion, effectively negotiating awkward moments, repairing problematic language, persevering with the topic, eliciting the patient's perspective, responding to fears and expectations, and being empathic. Educational programs should use videotape review and should concentrate on physicians' personal reactions to discussing emotionally charged topics.

Adolescent↗
PubMed1998

Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B.

Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4, 5-trisphosphate [PtdIns(3,4,5)P3] and PtdIns(3,4)P2 in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr308-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P3 and associated with lipid vesicles containing it. These kinases contain an NH2-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed1998

Endogenous BDNF protein is increased in adult rat hippocampus after a kainic acid induced excitotoxic insult but exogenous BDNF is not neuroprotective.

Systemic administration of the excitotoxin kainic acid to adult rats results in a well defined pattern of loss of the CA1 and CA3 pyramidal neurons of the hippocampus. Prior to this neuronal loss, brain-derived neurotrophic factor (BDNF) mRNA is substantially increased. We show here that BDNF protein is increased after excitotoxic insult in specific areas of the hippocampus, reaching maximal levels 24 h after the insult. BDNF protein levels in the hippocampus increase in direct relation to the severity of seizure. Up to 7 days after injection of kainic acid, levels of full-length TrkB protein were unchanged, whereas levels of truncated TrkB protein were significantly increased by 12 h. To determine whether elevations in BDNF protein levels are potentially beneficial to hippocampal neurons exposed to an excitotoxic stress, we infused exogenous BDNF prior to and during the period of neuronal death caused by kainic acid. We find that administration of high levels of exogenous BDNF does not affect severity of seizure, but does in fact, exacerbate the injury caused by kainic acid, specifically to CA3 pyramidal neurons. Although there was a trend toward sparing of CA1 pyramidal neurons on the side infused with BDNF, this was not significant. In the same paradigm, infusion of exogenous NT-3 had no effect.

Animals↗
PubMed1998

Serum S-100 protein levels after pediatric cardiac operations: a possible new marker for postperfusion cerebral injury.

BACKGROUND: The release of neuron-specific astroglial S-100 protein to the cerebrospinal fluid is a marker of cerebral damage. The aim of this study was to determine the pattern of release of S-100 protein to serum after pediatric cardiac operations and extracorporeal circulation. METHODS: Sequential blood samples from 97 children (up to 16 years) were taken after induction of anesthesia, immediately after the discontinuation of extracorporeal circulation, and 5 and 15 hours after extracorporeal circulation. The children were divided into five groups including three age groups, children with Mb Down syndrome, and children undergoing circulatory arrest. RESULTS: The serum concentrations of S-100 protein before the cardiac operation were found to be highest in neonates. Children with Down syndrome, regardless of age, had basal levels comparable to those in neonates. There was an increase in S-100 protein concentration immediately after extracorporeal circulation and a multivariate regression analysis showed this difference in S-100 protein concentration to be significant with respect to age (p = 0.002), perfusion time (p < 0.001), and circulatory arrest (p < 0.001), but the difference was not significant with respect to weight, Down syndrome, and core temperature (p > 0.8). In children younger than 1 month old and after circulatory arrest, levels of S-100 protein remained high at 5 hours after extracorporeal circulation. CONCLUSION: These findings emphasize the necessity of using age-matched reference values and taking perfusion time into consideration when S-100 protein levels are evaluated with respect to cerebral postperfusion injuries in pediatric patients undergoing cardiac operations.

Adolescent↗
PubMed1998

Statistical methods in epidemiology: a comparison of statistical methods to analyze dose-response and trend analysis in epidemiologic studies.

Evaluation of various statistical methods to describe accurately associations between exposures and disease are constantly being explored. Spline regression has been suggested as an alternative to using categorized variables in studies of disease etiology, as it uses all data points to estimate the shape of the association between a given exposure and disease outcome. It has been proposed that this method is especially beneficial when associations are concentrated in a small range of the overall distribution of the exposure. In this study, we use data from a large case-control study of colon cancer to evaluate associations obtained from logistic regression models that use spline regression for main exposure and confounder effects with those that use categorized variables for main exposure. Our results show that for variables for which the association appears to be linear, such as body size and dietary intake of calcium, fiber, and cholesterol, associations are similar when estimates are generated from spline or categorized variable models. For other variables, such as total energy intake, for which associations appear to be strongest in the upper end of the distribution, estimates of association appear to be conservative when using categorized variables. The data also suggest that selection of cut points for the categorized variables may have an impact on the associations observed. Spline regression appears to be useful to estimate the shape of the association between a given exposure and disease and may provide guidance as to the appropriateness of using categorized variables. The risk estimates from spline regression appear to be similar to those from traditional categorical methods. When effects are large or rapidly changing, spline models may more appropriately describe the association.

Adult↗
PubMed1998

Dosimetric considerations of water-based bolus for irradiation of extremities.

The dosimetry of high-energy photon beams in the treatment of superficial lesions occurring in extremities was examined. Large parallel-opposed fields with different photon beam energies were used. The extremity was immersed in water contained in a commercially available plastic wastebasket. The water bolus serves to even out the surface irregularities of the extremities and to remove the skin sparing effect. A polystyrene block was placed at the floor of the wastebasket to ensure that the extremity was encompassed in the radiation fields. The photon beam energies considered were 4 MV, 6 MV, 10 MV, and 24 MV. The results show that the dose distributions are more homogeneous with higher photon beam energies. The isodose lines are more constricted at mid-plane for low energy photon beams. Higher energy photon beams, 10 MV and up would be preferable for the treatment of superficial lesions of the extremities immersed in water bolus contained in a typical wastebasket size.

Extremities↗
PubMed1998

Kidney transplants from living donors: how donation affects family dynamics.

Living donors continue to provide the optimum outcome for kidney transplant recipients, yet information is limited on how donation can affect the donor and his or her family. Questionnaires returned by 524 donors whose donor nephrectomies took place between August 1, 1985 and December 31, 1996 at the University of Minnesota were analyzed to determine if perioperative complications influence their quality of life, among other emotional and lifestyle areas. Results showed that donors have a higher quality of life than the general population, confirming they have an increased self-worth and positive self-esteem. An overwhelming 96% would donate again. However, donation was self-reported as more stressful when complications were experienced (P = .003) and when donors were female (P = .041). Relatives other than immediate family members (extended relatives) were more likely to be among the 4% who said they would not donate again. Available support, financial impact, and relationship changes as a result of donation also were revealed. Relevant results from this larger study are discussed as they relate to how the renal donor and transplant family are affected.

Adolescent↗
PubMed1998

Protein deposition from dry powder inhalers: fine particle multiplets as performance modifiers.

PURPOSE: To evaluate the use of carrier-based dry powder aerosols for inhalation delivery of proteins and examine the effect of fine particle excipients as potential formulation performance modifiers. METHODS: Bovine serum albumin (BSA) was co-processed with maltodextrin by spray-drying to produce model protein particles. Aerosol formulations were prepared by tumble mixing protein powders with alpha-lactose monohydrate (63-90 microns) or modified lactoses containing between 2.5 and 10% w/w fine particle lactose (FPL) or micronised polyethylene glycol 6000. Powder blends were characterised in terms of particle size distribution, morphology and powder flow. Formulation performance in Diskhaler and Rotahaler devices was investigated using a twin stage impinger operating at 60.s51 min-1. RESULTS: Inhalation performance of binary ordered mixes prepared using BSA-maltodextrin and lactose (63-90 microns) was improved by addition of FPL and micronised PEG 6000. For the addition of 5% w/w FPL the protein fine particle fraction (0.5-6.4 microns) using the Diskhaler was increased from 31.7 +/- 2.4% to 47.4 +/- 2.2%. Inclusion of FPL and micronised PEG 6000 changed the bulk properties of inhalation powders and reduced powder flow but did not affect device emptying. Unexpectedly, improvements in performance were found to be independent of the order of addition of FPL to the ternary powder formulations. SEM studies revealed that this was probably the result of a redistribution of protein particles between the coarse carrier lactose component and added FPL during mixing. CONCLUSIONS: Fine particle excipients can be used to improve the performance of carrier-based protein dry powder aerosols. Mechanistically, enhancement of performance is proposed to result from a redistribution of protein particles from coarse carrier particles to the fine particle component in the ternary mix.

Aerosols↗
PubMed1998

Vitamin E and colon cancer: is there an association?

The role of vitamin E in the etiology and prevention of colon cancer is not clear. It is possible that various forms of vitamin E may act differently in colon tissue and may be effective chemopreventive agents. Previous reports of vitamin E and colon cancer have focused on alpha-tocopherol and have not considered other dietary forms of vitamin E. Data from a study of 1,993 cases and 2,410 controls were used to evaluate the associations between the four most common forms of dietary vitamin E and supplemental vitamin E and colon cancer. After adjusting for other health and life-style factors, we did not observe a statistically significant association between dietary tocopherols and colon cancer. There were, however, suggestions of an inverse association between total alpha-tocopherol equivalents and colon cancer among women diagnosed with colon cancer before the median age of the control population, 67 years [odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.36-1.22] and a direct association between gamma-tocopherol and colon cancer among these women (OR = 1.44, 95% CI = 0.92-1.93). Women diagnosed with colon cancer when > or = 67 years of age appeared to have some protection from use of vitamin E supplements (OR = 0.80, 95% CI = 0.56-1.15). These data offer only limited support for a protective effect of vitamin E and colon cancer after adjustment for other health and life-style factors.

Adult↗
PubMed1998

Myopotential sensing by a dual chamber implantable cardioverter defibrillator: two case reports.

INTRODUCTION: Inappropriate discharges and/or improper inhibition of bradycardia pacing due to oversensing of extraneous signals in implantable cardioverter defibrillators (ICDs) have been described. With one exception, no previous report involving an intact lead system has cited myopotential oversensing as the cause. METHODS AND RESULTS: Two case reports of myopotential oversensing by a dual chamber ICD system are reported. In the first patient suffering from chronic pulmonary obstructive disease, intermittent myopotential sensing during labored respiration resulted in episodic inhibition of bradycardia pacing. In the second patient, oversensing of sustained myopotentials generated during strenuous isometric activity resulted in an inappropriate ICD discharge. For both, the ICD system consisted of a CPI model 1810 Ventak AV used in conjunction with a model 0125 Endotak lead, incorporating integrated bipolar sensing. CONCLUSION: Although modern ICDs have proven to be highly effective in detecting and terminating malignant tachyarrhythmias, the opportunity for improving their detection specificity remains.

Aged↗
PubMed1998

Angiotensin-converting enzyme inhibition attenuates proteinuria and renal TGF-beta 1 mRNA expression in rats with chronic renal disease.

Evidence suggests that transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine, induces renal extracellular matrix production and glomerular hypertrophy. The aim of the present study was to investigate the effect of captopril on the expression of TGF-beta 1 mRNA in a rat model of chronic renal failure: five-sixths nephrectomy. Chronic renal disease was induced by removal of the right kidney and ligation of three blood vessels supplying the left kidney. Sham-operated animals were used as controls. RNA was extracted from the viable remnant kidney of rats 1 day and 1 and 2 weeks following five-sixths nephrectomy and from the kidneys of rats who underwent sham surgery. TGF-beta 1 mRNA was induced within 24 h of partial nephrectomy, similar to that reported for early-onset genes. Subsequently, TGF-beta 1 mRNA expression continued to increase over the next 2-4 weeks. The upregulation of TGF-beta 1 correlated with the degree of proteinuria. Both the increase in TGF-beta 1 mRNA and proteinuria were abrogated by captopril treatment. In addition, no change in expression of ALK-5 or type II TGF-beta receptors following five-sixths nephrectomy was observed. These data suggest that captopril may protect against development of glomerulosclerosis and proteinuria by reducing TGF-beta 1 expression and hence matrix production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Cytotoxicity of xenobiotics and expression of glutathione-S-transferases in immortalised rat hepatocyte cell lines.

1. Immortalised rat hepatocyte cell lines are more sensitive to the cytotoxicity of 1-chloro-2,4-dinitrobenzene and ethacrynic acid than primary cultures of hepatocytes. 2. Class alpha glutathione S-transferases are not expressed in immortalised hepatocyte cell lines. Class pi glutathione S-transferase expression is elevated in the immortalised cell lines compared with freshly isolated hepatocytes, but it is not as high as in the HTC rat hepatoma cell line. 3. Immortalised hepatocyte cell lines may provide a sensitive model system for detecting cytotoxicity associated with xenobiotics which are detoxified by glutathione S-transferases.

Animals↗
PubMed1998

Development of an aromatherapy service at a Cancer Centre.

The aromatherapy service at the Cancer Support and Information Centre (CSIC) of this regional Cancer Centre has been continually assessed since its inception in 1993. New methods of assessing complementary therapies, based on the 'therapy-as-practised', have been explored. The present study evaluates the service following changes made after an initial pilot. The professional aromatherapist developed an evaluation tool, and formal questionnaires were limited to the Hospital Anxiety and Depression Scale (HADS). HADS was completed before and after a course of six aromatherapy sessions. Of 89 patients referred, 58 patients completed the six sessions. Referrals were made by health professionals working in the Cancer Centre and in the CSIC. The majority of patients were female with breast cancer and were receiving radical oncological treatment. Tension, stress and anxiety/fear were the most common reasons for referral, and this was reflected in high initial HADS scores. There were significant improvements in HADS scores in the 58 patients completing the course (mean anxiety, depression, and combined scores dropped from 8.9 to 6.2 6.1 to 4.0 and 15.0 to 10.2, respectively, P < 0.001). Fifty per cent or more of the sample reported a significant improvement in the eight most commonly assessed symptoms. The therapist was initially cautious about using questionnaires, but she gained confidence in using HADS as an assessment tool. The areas covered by her own evaluation tools were broadly comparable to established instruments such as the EORTC QLQ-C30. We conclude that aromatherapy massage has a role in reducing psychological distress, and improving symptom control in cancer patients. Further service evaluation is needed to promote appropriate referral and effective planning of treatment, and to justify cost. Given the multifaceted nature of complementary therapies, the need to develop new research methodologies is acknowledged.

Adult↗
PubMed1998

Comparison of the flutter device to standard chest physiotherapy in hospitalized patients with cystic fibrosis: a pilot study.

STUDY OBJECTIVE: A preliminary study comparing the efficacy and safety of the flutter device (Flutter) to standard, manual chest physiotherapy (CPT) in hospitalized cystic fibrosis (CF) patients undergoing an acute pulmonary exacerbation. DESIGN: Open label, comparative trial with alternate assignment. SETTING: Community and childrens' hospital acute-care wards. PARTICIPANTS: Twenty-two CF patients (ages 8 to 44 years) undergoing a total of 33 hospitalizations for acute pulmonary exacerbation. INTERVENTIONS: Complete pulmonary function tests (PFTs) were done at baseline (admission), weekly, and upon discharge from the hospital. Clinical score (CS) was determined at the time of hospital admission and at discharge. Participants were assigned to receive supervised Flutter therapy or standard, manual CPT four times per day during the hospitalization. Patients were monitored for complications, including hemoptysis, hypoxemia, and pneumothorax. RESULTS: The groups (CPT and Flutter) did not differ at baseline in demographics or Shwachman score, nor was length of hospitalization different. Significant improvements were noted from admission to discharge in CS and PFT results within each group. Mean percent change in CS and PFT results between CPT and Flutter groups showed no significant difference from hospital admission to discharge. Subsequent power analysis using the observed difference in percent change from admission to discharge for FEV1 indicated that to attain 80% power at alpha = 0.05, a sample of 219 subjects in each group would be necessary. SUMMARY: Comparative trials of airway clearance techniques with sufficient sample size are lacking. Although the Flutter appears to be a useful device for independent, cost-effective, and safe administration of CPT in this pilot study, a much larger clinical trial would be necessary to make definitive conclusions.

Acute Disease↗