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Biomedical subjects

H Alexander

Publications and source records attributed to H Alexander.

At least 19 recordsLinked to original sources
PubMed2006

Variations with age in the mechanical properties of human skin in vivo.

To quantitatively assess the viscoelastic properties of human skin, an in vivo testing method has been developed and previously reported. In this method, a strain-gauged pretension device is first used to determine the natural skin tension and then to apply a predetermined tension. A suction cup device with a rectangular cross-section and semi-circular ends is then applied to the pretensioned area and the skin deflection versus negative pressure characteristic is recorded. With the basic characteristics of the skin stress field determined by the geometry of the cup as a homogeneous stress state, the stress-strain response curve is computed from the recorded data. Using a constant pressurisation rate testing mode, the back and forearm of 116 healthy male and female subjects ranging in age from two to 67 years were tested. Variations in the shape and average slope (approximate modulus) of the stress-strain curves have been investigated with changes in age and sex. It has been found that the average slope decreases through maturation, reaches a minimum between the ages of 15 and 25, and then appears to increase with advancing age. The data points begin to diverge after approximately 30 years of age. It is hypothesised that this diverging phenomenon may be a result of the cumulative effect of ultraviolet radiation on the collagen and elastin networks. An examination of the shape of the curves appears to indicate that stiffness of collagen in the dermis increases with increasing age. However, it appears that the lower portions of the curves, possibly associated with the elastin and ground substance components, undergo changes not common to every individual. It is also hypothesised that 'scatter' in the data obtained from females and the sudden change noted in the shape of the curves at puberty may be due to hormonal changes.

Adolescent↗
PubMed2004

Prognostic value of Doppler transmitral filling patterns in patients with chronic heart failure.

BACKGROUND: Chronic heart failure is a significant cause of cardiovascular morbidity and mortality. This study tested the hypothesis that restrictive filling pattern may provide useful prognostic data for identifying patients with chronic heart failure at high risk of all-cause cardiac death. METHODS: Ninety patients with chronic heart failure [70 men and 20 women, mean age (58.1 +/- 11.6) years] were investigated and followed for (18.8 +/- 7.9) months. During this period, 14 patients died of progressive pump failure, 12 patients underwent heart transplantation, 5 patients died suddenly, and 2 patients died of acute myocardial infarction. A new criterion, the restrictive filling index (RFI), was designed to subgroup patients into a restrictive and a nonrestrictive group. RESULTS: Patients with restrictive filling pattern had a more severe left ventricular dysfunction and a higher cardiac mortality. Analysis by the Kaplan-Meier method revealed that patients in the RFI > or = 1 and RFI < 1 groups had a cardiac events-free survival rate of 52% versus 94% at 1 year, and 27.5% versus 92% at 2 years, respectively. The multivariate Cox proportional hazard model selected RFI as the most powerful prognostic factor (chi(2) = 8.8017, P = 0.0030) for all-cause cardiac death. CONCLUSION: These results indicate that RFI is a simple, noninvasive, and specific clinical predictor for adult chronic heart failure patients who are at a high risk for all-cause cardiac death.

Chronic Disease↗
PubMed2003

Expression of beta hCG and alpha CG mRNA and hCG hormone in human decidual tissue in patients during tubal pregnancy.

We recently showed that endometrial tissue produces hCG during the secretory phase of the menstrual cycle. Based on these findings, we hypothesized that the decidua should also be able to secrete hCG. We examined the decidualized endometrium of patients with extrauterine pregnancies. Decidual specimens were obtained for mRNA extraction and paraffin embedding from 24 patients that were between weeks 6-11 of tubal pregnancy. Tissues were evaluated and classified into one of three groups based on the endometrial differentiation that took place prior to conception: (A) high secretory transformation, (B) diminished transformation with restricted decidualization and (C) inferior endometrial proliferation. Decidual gland hCG secretion was demonstrated immunohistochemically and by Western blotting. Serum hCG levels were higher (P < 0.0001) in patients from group A than group C. mRNA expression of both the beta subunit (beta-hCG) and alpha subunit (alpha-CG) was determined by RT-PCR. Furthermore, the specificity of beta-hCG amplification was confirmed by restriction enzymes. beta-LH amplification was not found. Moreover, the degree of endometrial transformation and the level of decidualization was found to correlate with hCG hormone staining and beta-hCG mRNA expression. hCG protein in the decidua was present in the glands of the compact layer and in the spongy layer, and was more pronounced in previously transformed high secretory endometrium than in inferior endometrium. In conclusion, this study provides the first evidence that hCG is produced in the decidua of patients during extrauterine pregnancies and might play a possible paracrine role.

Chorionic Gonadotropin↗
PubMed2001

Proteomic analysis of a developmentally regulated secretory vesicle.

Secretion of spore coat proteins from the prespore secretory vesicles (PSVs) in Dictyostelium discoideum is a signal mediated event that underlies terminal cell differentiation, and represents an important case of developmentally regulated secretion. In order to study the biochemical mechanisms that govern the regulated fusion of the PSVs with the plasma membrane and the subsequent secretion of their cargo, we purified this organelle from prespore cells. Analysis of protein extracts of highly purified PSVs indicated that, in addition to the cargo of structural spore coat proteins, many more proteins are associated with the PSVs. Their identification is paramount to the understanding of the mechanism of regulated secretion in this system. In this study we have taken the first comprehensive proteomic approach to the analysis of an entire, previously uncharacterized, organelle, with the goal of identifying the major proteins associated with the PSVs. We show that in addition to the structural spore coat proteins, the PSVs contain the enzymes needed for proper spore coat assembly (thioredoxin 2 and 3), regulatory proteins which we predict receive and transduce the developmental signal for secretion (rab7 GTPase, PI-3 kinase, NDP kinase and the calcium binding proteins calfumirin-1 and calreticulin) as well as proteins that interact with the cytoskeleton to mediate movement of the PSVs to the plasma membrane (actin binding proteins coactosin and profilin 1). In addition, the results suggest that proteins can play multiple roles in the cell, and that protein function can be dictated in part by subcellular localization. The identification of the PSV proteins is allowing us to develop testable hypotheses about the roles of these proteins within the functional context of developmentally regulated secretion.

Animals↗
PubMed2001

Transcript mapping and processing of mitochondrial RNA in Dictyostelium discoideum.

The circular mitochondrial genome of Dictyostelium discoideum has a size of 55,564 base pairs. We present here a complete and detailed transcription map of the mitochondrial DNA. Eight major, polycistronic transcripts encoding polypeptides, ribosomal RNAs and interspersed transfer RNAs were identified in Northern hybridization studies. Most of these polycistronic transcripts are subsequently processed into smaller mono-, di- or tricistronic RNAs. In some cases, the maturation involves endonucleolytic cleavage of the transcripts using transfer RNAs as excision signals. Primer extension experiments mapped the 5' ends of the transcripts, which may represent transcription initiation sites. Two of the polycistronic transcripts were found to be overlapping. Based on sequence alignments of the potential transcription start sites, a short oligonucleotide consensus initiation sequence has been identified which does not reveal any significant sequence homologies to known promoter regions from other organisms.

Animals↗
PubMed2001

Intakes of most nutrients remain at acceptable levels during a weight management program using the food exchange system.

OBJECTIVE: The purpose of this study was to determine if the food exchange system allows subjects' nutrient intake to remain at recommended levels during a weight-loss program. DESIGN: Subjects in an intervention were prescribed an energy-restriction diet and exercise program lasting 32 weeks, and nutrient intake was measured prestudy and after 12, 16, and 32 weeks. SUBJECTS/SETTING: Healthy but overweight and obese premenopausal women (n = 219) were recruited at 6 university sites into community-based weight loss programs. One hundred fifteen women completed all aspects of the study. INTERVENTION: Energy intake was set at 0.8 x resting metabolic rate (RMR) for weeks 1 through 12, 1.0 x RMR for weeks 13 through 20, and 1.2 x RMR for weeks 21 through 32. Energy intake was based on food exchange tables, with the number of food exchanges adjusted to encourage a distribution of 55% carbohydrate, 30% fat, and 15% protein. Subjects increased their daily walking distance to 3.2 km above prestudy levels. MAIN OUTCOME MEASURES: Nutrient intake was measured from four 3-day food records. STATISTICAL ANALYSES PERFORMED: Repeated measures analysis of variance, with specific time point changes assessed from paired t tests adjusted for multiple comparisons. RESULTS: Body mass decreased by a mean +/- SD of 6.7 +/- 3.2 kg at week 12 and 7.8 +/- 6.2 kg by week 32. Walking distance increased by an average of 17.2 +/- 10.0 km/week during the first 12 weeks, and 12.4 +/- 12.4 km/week during the last 20 weeks. Despite a 23% to 36% reduction in energy intake during the study, intake of most nutrients was maintained. Intake of vitamin E, calcium, iron, and zinc decreased significantly from prestudy levels during the first 16 weeks of the intervention, but not at week 32. APPLICATIONS/CONCLUSIONS: Intake of most nutrients can remain at recommended levels when overweight and obese women follow the American Diabetes Association/American Dietetic Association food exchange system during a community-based weight-loss program.

Adult↗
PubMed2001

Measuring stroke patients' health status in the early post-stroke phase using the SF36.

This paper aims to explore the self-perceived health status of stroke patients, the factors that contribute to the perception and the relevance of the findings to researchers and practitioners. Outcomes were measured at one, three and six months post-stroke for 153 stroke patients and pre-morbid characteristics were gathered from GPs. Health status was measured using the Short Form 36 (SF36). Stroke patients' health status was significantly worse than a general population for four health dimensions (physical functioning, role physical, vitality and social functioning). Regression analyses with the SF36 profile scores as dependent variables revealed one model where associations between independent and dependent variables were relatively strong (physical functioning), the remaining seven models yielded weak associations. Self-perceived health status was not strongly related to impairment, disability or cognitive function. There are implications for researchers and practitioners across a range of professions. Researchers should aim to identify factors that explain stroke patients' perception of their own health and the impact of their perception on rehabilitation. Practitioners should consider the possible effects of low vitality on treatment concordance.

Activities of Daily Living↗
PubMed2001

American cutaneous leishmaniasis in Guyana, South America.

The 185 patients who presented at the dermatology clinic of Georgetown Public Hospital, Guyana, between 1992 and 1998, with skin ulcers indicative of American cutaneous leishmaniasis (ACL) were retrospectively reviewed. The laboratory-confirmed cases of ACL were identified and the corresponding data were analysed for risk factors such as age, gender, areas of residence and of possible exposure to the causative agent (Leishmania braziliensis guyanensis), ethnic origin, longevity of the ulcers, and treatment regimes prior to the definitive diagnosis. Eighty-one (43%) of the 185 subjects were confirmed to be infected with Le. b. guyanensis. Although 53 (66%) of the cases lived in or close to the capital city, Georgetown, most of the cases had travelled to (and probably been infected in) region X in the interior of Guyana (32%) or regions VII (23%), VIII (23%), IX (11%), VI (5%), I (3%) or III (3%), usually because they were involved in the mining (41%) or lumber (21%) industries, the army or hunting. Almost all (95%) of the cases were male and most (58%) were aged 20-39 years. In general, the cases had had their skin lesions for many days before presenting for treatment: 46% for 1-5 weeks and 3% for > 6 months. Prior to presentation at the clinic, many of the cases had attempted to cure themselves, using local herbal remedies (37%), antibiotics and antifungal remedies (39%), other creams (5%), household chemicals (9%) or miscellaneous remedies such as lead salts (especially lead sulphate) and battery acid, all without success. Recommendations are made for an epidemiological study of active ACL among forest workers, eco-tourists and residents of high-risk areas. Diagnostic centres need to be sited in the regions most at-risk, particularly in or near environments in which the main vectors - sandflies such as Lutzomyia umbratilis, Lu. anduzei and Lu. whitmani - are known to be prevalent.

Adolescent↗
PubMed2001

Assessment of body composition change in a community-based weight management program.

OBJECTIVE: The purpose of this study was to validate the use of the leg-to-leg bioelectrical impedance analysis (BIA) system in assessing change in body composition over 32 weeks in overweight and obese women participating in a community weight management program. DESIGN: Intervention, with subjects prescribed an energy-restriction diet and exercise program for 32 weeks and body composition measured pre-study and after 12 and 32 weeks. SUBJECTS AND SETTING: Overweight and obese premenopausal women (n=201) with no overt disease were recruited at six sites into community-based weight loss programs. One hundred and twenty-four women completed all aspects of the study. INTERVENTION: Energy intake was set at 0.8 x resting metabolic rate (RMR) for weeks 1 through 12, 1.0 x RMR for weeks 13 through 20 and 1.2 x RMR for weeks 21 through 32. Energy intake was based on a food exchange table, with the number of food exchanges adjusted to encourage a percent distribution of 55% carbohydrate, 30% fat and 15% protein. Subjects increased their daily walking distance by 3.2 km above pre-study levels. MEASURES OF OUTCOME: Underwater weighing, seven skinfolds, and leg-to-leg BIA tests were used to assess body composition. RESULTS: A 3 x 3 repeated measures ANOVA revealed no significant difference in detecting change in FFM at 12 and 32 weeks among underwater weighing, BIA and skinfold, (F(4,492)=1.73, p=0.141) (decrease in FFM of 1.0+/-3.3 kg, 1.7+/-2.2 kg, and 1.4+/-3.3 kg respectively, 32 weeks). CONCLUSIONS: The leg-to-leg BIA system provides a valid measure of body composition change in overweight premenopausal women during a 32-week community-based weight loss program.

Adipose Tissue↗
PubMed2001

Significance of fever in Jamaican patients with homozygous sickle cell disease.

OBJECTIVE: To investigate the cause and outcome of high fever in Jamaican children with homozygous sickle cell disease. DESIGN: Retrospective review of febrile episodes in a three year period (1 September 1993 to 31 August 1996). SETTING: Sickle cell clinic, an outpatient clinic in Kingston run by the Medical Research Council Laboratories (Jamaica). PATIENTS: Patients with homozygous sickle cell disease under 17 years of age presenting with an axillary temperature >/= 39.0 degrees C (102.4 degrees F). MAIN OUTCOME MEASURES: Diagnosis, death. RESULTS: There were 165 events in 144 patients (66 (45.8%) boys) with a median age of 6.1 years. Bacteraemia was found in 10 (6.1%) events (three Streptococcus pneumoniae, two Haemophilus influenzae type b, two Salmonella sp, one Escherichia coli, one Enterobacter sp, and one Acinetobacter sp), and urinary tract infections in four (2.4%). All cultures of cerebrospinal fluid were sterile. Acute chest syndrome occurred in 36 (21.8%) events. A painful crisis was associated with 45 (27.3%) events and was the only pathology identified in 20 events (12.1%). Hospital admission was necessary in 66 cases including all those with bacteraemia and 31 with acute chest syndrome. There were two deaths: a 5 year old boy with septic shock associated with H influenzae septicaemia, and a 3 year old boy with the acute chest syndrome. CONCLUSIONS: Painful crisis and acute chest syndrome were the most common complications associated with high fever, but other important associated features included bacteraemia and urinary tract infection. Enteric Gram negative organisms accounted for 50% of positive blood cultures.

Adolescent↗
PubMed2001

What is the association between the different components of stroke rehabilitation and health outcomes?

OBJECTIVES: To describe the rehabilitation input stroke patients received from health professionals during the early post stroke period and to explore possible associations between health outcomes and these rehabilitation inputs. DESIGN: Community-based study with prospective identification of stroke patients from a random sample of 24 general practices stratified by geographical area and practice size. SETTING: Ayrshire and Arran Health Board area, West of Scotland. INTERVENTIONS: All physiotherapy, occupational therapy, dietetics, podiatry, speech and language therapy and community nursing inputs given to stroke patients in the course of normal treatment were recorded. OUTCOME MEASURES: Barthel Index and Medical Outcomes Study Short Form-36 (SF-36). Both recorded at one, three and six months post stroke. RESULTS: Of the 152 people providing data, more had received physiotherapy than any other rehabilitation input at all three follow-ups (81%, 47%, 39%), with occupational therapy being the next most common service (65%, 44%, 25%). Amount of rehabilitation input was significantly negatively correlated with health outcomes measured at each discrete time point: those patients with the poorest outcomes received greatest input. However, regression analysis of change in outcome scores showed that increasing amounts of rehabilitation input were significantly associated with a reduction in disability, particularly between one and three months post stroke. CONCLUSIONS: Not only have we shown that those stroke patients with poorest outcomes received most rehabilitation input, but, from analysis of the individual rehabilitation inputs, we have identified some rehabilitation inputs that significantly predict improved outcomes. This suggests that there would be merit in further investigation of these associations.

Activities of Daily Living↗
PubMed2001

Sphingosine-1-phosphate lyase has a central role in the development of Dictyostelium discoideum.

Sphingosine-1-phosphate, a product of sphingomyelin degradation, is an important element of signal transduction pathways that regulate cell proliferation and cell death. We have demonstrated additional roles for sphingosine-1-phosphate in growth and multicellular development. The specific disruption in Dictyostelium discoideum of the sphingosine-1-phosphate lyase gene, which encodes the enzyme that catalyzes sphingosine-1-phosphate degradation, results in a mutant strain with aberrant morphogenesis, as well as an increase in viability during stationary phase. The absence of sphingosine-1-phosphate lyase affects multiple stages throughout development, including the cytoskeletal architecture of aggregating cells, the ability to form migrating slugs, and the control of cell type-specific gene expression and terminal spore differentiation. This pleiotropic effect, which is due to the loss of sphingosine-1-phosphate lyase, establishes sphingolipids as pivotal regulatory molecules in a wide range of processes in multicellular development.

Actins↗
PubMed2001

What does receiving the care programme approach mean for service users?

OBJECTIVE: To explore what receiving the Care Programme Approach means for service users. DESIGN: A qualitative study based on peer group discussion, the transcript being subjected to issues analysis to generate key themes. SETTING: Ayrshire and Arran, West of Scotland. SUBJECTS: Six people with severe and enduring mental illness who were receiving the Care Programme Approach. The size of the group was restricted to allow service users time to express their views. (A representative response was not being sought.) RESULTS: Four major themes emerged from the service users: the power of user involvement, how receiving CPA can help to avert potential problems, the rights of service users, and the benefits of advocacy. These service users felt that CPA had made a real difference to their lives. CONCLUSION: As user involvement is an integral part of CPA, it is important that we develop strategies that allow their views to shape, in a genuine way, the services being put in place to meet their needs. In Ayrshire they seem to have learned that their participation mattered.

Female↗
PubMed2000

Differential developmental expression and cell type specificity of Dictyostelium catalases and their response to oxidative stress and UV-light.

Cells of Dictyostelium discoideum are highly resistant to DNA damaging agents such as UV-light, gamma-radiation and chemicals. The genes encoding nucleotide excision repair (NER) and base excision repair (BER) enzymes are rapidly upregulated in response to UV-irradiation and DNA-damaging chemicals, suggesting that this is at least partially responsible for the resistance of this organism to these agents. Although Dictyostelium is also unusually resistant to high concentrations of H(2)O(2), little is known about the response of this organism to oxidative stress. To determine if transcriptional upregulation is a common mechanism for responding to DNA-damaging agents, we have studied the Dictyostelium catalase and Cu/Zn superoxide dismutase antioxidant enzymes. We show that there are two catalase genes and that each is differentially regulated both temporally and spatially during multicellular development. The catA gene is expressed throughout growth and development and its corresponding enzyme is maintained at a steady level. In contrast, the catB gene encodes a larger protein and is only expressed during the final stages of morphogenesis. Cell type fractionation showed that the CatB enzyme is exclusively localized to the prespore cells and the CatA enzyme is found exclusively in the prestalk cells. Each enzyme has a different subcellular localization. The unique developmental timing and cell type distribution suggest that the role for catB in cell differentiation is to protect the dormant spores from oxidative damage. We found that exposure to H(2)O(2) does not result in the induction of the catalase, superoxide dismutase, NER or BER mRNAs. A mutant with greatly reduced levels of catA mRNA and enzyme has greatly increased sensitivity to H(2)O(2) but normal sensitivity to UV. These results indicate that the natural resistance to oxidative stress is not due to an ability to rapidly raise the level of antioxidant or DNA repair enzymes and that the response to UV-light is independent from the response to reactive oxygen compounds.

Amino Acid Sequence↗
PubMed2000

Crossing the finish line of development: regulated secretion of Dictyostelium proteins.

The genesis of the spore coat of Dictyostelium represents an exquisite example of developmentally regulated protein secretion. The proteins that are destined to be assembled into the extracellular matrix of the spore coat are stored in unique prespore vesicles that are triggered to secrete their contents at terminal differentiation. The regulation of this process is being revealed by the identification of the individual proteins in these vesicles.

Animals↗
PubMed2000

Mechanical and fracture behavior of a fiber-reinforced bioabsorbable material for orthopaedic applications.

Tensile and fracture tests were conducted on thin panels of a fiber-reinforced bioabsorbable material. The composites were made of polycarbonate matrix and calcium phosphate fibers. Both matrix and fibers were bioabsorbable orthopaedic biomaterials. The fibers were short and randomly distributed. The properties were compared for composites with and without a coating of methane on the fibers. Composites with the methane coating had a higher elastic modulus, a higher proportional limit, but a lower load at failure on pre-cracked panels. Electron microscopy showed that the coating resulted in a better bond between the matrix and the fiber.

Journal Article↗
PubMed2000

Transcript imaging of the development of human T helper cells using oligonucleotide arrays.

Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation. Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.

Apoptosis↗