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Biomedical subjects

D Richardson

Publications and source records attributed to D Richardson.

At least 55 records · Page 3Linked to original sources

Risk of cardiovascular disease measured by carotid intima-media thickness at age 49-51: lifecourse study.

OBJECTIVE: To quantify the direct and indirect effects of fetal life, childhood, and adult life on risk of cardiovascular disease at age 49-51 years. DESIGN: Follow up study of the "Newcastle thousand families" birth cohort established in 1947. PARTICIPANTS: 154 men and 193 women who completed a health and lifestyle questionnaire and attended for clinical examination between October 1996 and December 1998. MAIN OUTCOME MEASURES: Correlations between mean intima-media thickness of the carotid artery (carotid intima-media thickness) and family history, birth weight, and socioeconomic position around birth; socioeconomic position, growth, illness, and adverse life events in childhood; and adult socioeconomic position, lifestyle, and biological risk markers. Proportions of variance in carotid intima-media thickness that were accounted for by each stage of the lifecourse. RESULTS: Socioeconomic position at birth and birth weight were negatively associated with carotid intima-media thickness, although only social class at birth in women was a statistically significant covariate independent of adult lifestyle. These early life variables accounted directly for 2.2% of total variance in men and 2.0% in women. More variation in carotid intima-media thickness was explained by adult socioeconomic position and lifestyle, which accounted directly and indirectly for 3.4% of variance in men (95% confidence interval 0.5% to 6.2%) and 7.6% in women (2.1% to 13.0%). Biological risk markers measured in adulthood independently accounted for a further 9.5% of variance in men (2.4% to 14.2%) and 4.9% in women (1.6% to 7.4%). CONCLUSIONS: Adult lifestyle and biological risk markers were the most important determinants of the cardiovascular health of the study members of the Newcastle thousand families cohort at age 49-51 years. The limited overall effect of early life factors may reflect the postwar birth year of this cohort.

Cardiovascular Diseases↗

Biological function made crystal clear - annotation of hypothetical proteins via structural genomics.

Many of the gene products of completely sequenced organisms are 'hypothetical' - they cannot be related to any previously characterized proteins - and so are of completely unknown function. Structural studies provide one means of obtaining functional information in these cases. A 'structural genomics' project has been initiated aimed at determining the structures of 50 hypothetical proteins from Haemophilus influenzae to gain an understanding of their function. Each stage of the project - target selection, protein production, crystallization, structure determination, and structure analysis - makes use of recent advances to streamline procedures. Early results from this and similar projects are encouraging in that some level of functional understanding can be deduced from experimentally solved structures.

Bacterial Proteins↗

A case control study of multiple myeloma at four nuclear facilities.

PURPOSE: Reported elevations of multiple myeloma among nuclear workers exposed to external penetrating ionizing radiation, based on small numbers of cases, prompted this multi-facility study of workers at US Department of Energy facilities. METHODS: Ninety-eight multiple myeloma deaths and 391 age-matched controls were selected from the combined roster of 115,143 workers hired before 1979 at Hanford, Los Alamos National Laboratory, Oak Ridge National Laboratory, and the Savannah River site. These workers were followed for vital status through 1990 (1986 for Hanford). Demographic, work history, and occupational exposure data were derived from personnel, occupational medicine, industrial hygiene, and health physics records. Exposure-disease associations were evaluated using conditional logistic regression. RESULTS: Cases were disproportionately African American, male, and hired prior to 1948. Lifetime cumulative whole body ionizing radiation dose was not associated with multiple myeloma, however, there was a significant effect of age at exposure, with positive associations between multiple myeloma and doses received at older ages. Dose response associations increased in magnitude with exposure age (from 40 to 50) and lag assumption (from 5 to 15 years), while a likelihood ratio goodness of fit test reached the highest value for cumulative doses received at ages above 45 with a 5-year lag (X2=5.43,1 df; relative risk = 6.9% per 10 mSv). Dose response associations persisted with adjustment for potential confounders. CONCLUSIONS: Multiple myeloma was associated with low level whole body penetrating ionizing radiation doses at older ages. The exposure age effect is at odds with interpretations of A-bomb survivor studies but in agreement with several studies of cancer among nuclear workers.

Age Factors↗

Investigation of the effect of marathon running on leucocyte counts of subjects of different ethnic origins: relevance to the aetiology of ethnic neutropenia.

Healthy subjects of African ancestry, including Afro-Caribbeans, have been observed to have lower total white cell counts and neutrophil counts than healthy Caucasian subjects. The cause of this ethnic neutropenia is unclear. We have previously found no evidence that increased margination of neutrophils is responsible. In this study, we have investigated mobilization of neutrophils from the bone marrow granulocyte reserve by endurance exercise. We investigated subjects of different ethnic origins before and after they had competed in a marathon race. Before the race, the neutrophil counts of Africans/Afro-Caribbeans were significantly lower than those of Caucasians (means 2.49 and 3.21 x 109/l respectively; P = 0.043). After the race, the difference was greater, as was the degree of significance (means 10.21 and 12.33 respectively; P = 0.017). The percentage increment was almost identical whereas the absolute increment was considerably less, although of marginal statistical significance (increment 7.72 and 9. 12 x 109/l respectively; P = 0.10). Similar changes were observed in the monocyte count. Before the race, the difference in the means was of marginal statistical significance (0.35 and 0.41 x 109/l respectively; P = 0.105), whereas after the race the difference was greater and was highly significant (means 0.75 and 1.05 x 109/l respectively; P = 0.001). These observations support the results of our earlier study, both of which suggested that ethnic neutropenia is likely to result from a diminished bone marrow reserve rather than being consequent on altered distribution of neutrophils within the blood stream.

Adult↗

Impact of a deep saturation dive on semen quality.

The demonstration dive 'Aurora' has provided an opportunity to study the impact of extreme hyperbaric conditions on male fertility. This operation involved a 33-day diving programme during which divers were exposed to a maximum pressure of 4.6 Mega Pascals (Mpa) for 7 days. At days - 4, + 27, + 34, + 82 and + 263 relative to the initiation of the dive, semen samples were analysed to determine the quality of spermatogenesis and the functional competence of the spermatozoa. A dramatic fall in semen quality was observed in association with the dive and by day + 82 the potential fertility of the men was seriously compromised as evidenced by oligoasthenoteratozoospermic semen profiles and the poor fertilizing potential of the spermatozoa. These studies indicate, for the first time, that the severe hyperbaric conditions associated with deep saturation dives have a profound effect on male reproductive function.

Diving↗

Value of flow cytometry with fine needle aspiration biopsy in patients with head and neck lymphoma.

Lymphomas frequently present in the head and neck clinically as painless adenopathy or as a swelling of an extranodal site, such as salivary gland or Waldeyer's ring. Most non-Hodgkin's lymphomas are B-cell neoplasms with distinctive clonal proteins that can be readily detected using flow cytometric analysis. In our experience, flow cytometric analysis has been a useful, convenient adjunct in the diagnosis of head and neck non-Hodgkin's lymphomas by fine needle aspiration biopsy.

Adult↗

Intervention thresholds and ceilings can determine the haemoglobin outcome distribution in a haemodialysis population.

We have explored the consequences of setting different thresholds and ceilings for erythropoietin dose changes in two randomized controlled studies of renal anaemia management based on an established algorithm. STUDY 1: A large (n=236) unselected haemodialysis cohort was randomized to monthly intervention (increased erythropoietin (Epo)) at haemoglobin (Hb) levels falling below either 10.5 g/dl (group A) or 11.5 g/dl (group B) and followed for 6 months. The mean Hb was 0.6 g/dl higher in the 11.5 g/dl threshold group (11.1 g/dl vs 11.7 g/dl) at 6 months (P=0.001++). The Epo dose did not differ between them (median 133 IU/kg/week, Interquartile range (IQR) 86-217 and 140, IQR 74-227 respectively) (P=NS(**)). STUDY 2: A large (n=211) unselected haemodialysis cohort was randomized to a reduction in Epo dose at Hb levels above either 12.0 g/dl (group C) or 13.0 g/dl (group D). The Hb outcome at 8 months differed between group C (mean 11.5 g/dl, SD 1.4) and group D (12.2, SD 2.1) (P=0.03++). The Epo dose did not significantly differ between groups C and D (median 60 IU/kg/week, IQR 32-142 and 71, IQR 38-117 respectively) (P=NS(**)). Study 1 showed that an intervention threshold of 11.0 g/dl with a mean Hb outcome of 11.6 g/dl and SD 1.6 g/dl would produce the desired UK Renal Association Standards outcome of 85% Hb > or =10.0 g/dl. Study 2 demonstrated that a ceiling of 12.0 g/dl narrowed the range of Hb values (P:<0.001##), achieving a SD of 1.37 g/dl, and reduced the number of patients with a Hb >13.0 g/dl from 25 to 12%. This narrowing of the distribution has cost implications for reaching minimum standards in a haemodialysis population. Formal use of threshold and ceiling values for intervention within an anaemia management system enabled the haemodialysis population outcome mean and SD to be literally prescribed.

Adult↗

Educating future physicians for Ontario: phase II.

In 1990, a collaborative project was launched to determine what the people of Ontario expect of their physicians and how the programs that prepare future physicians should be changed in response. The project, called Educating Future Physicians for Ontario (EFPO), brought together the five Ontario medical schools, the Council of Ontario Faculties of Medicine (COFM); a nonprofit, charitable organization, Associated Medical Services (AMS); and the Ontario Ministry of Health. The first phase ran for five years and was described in the November 1998 issue of Academic Medicine. After an external review, the project was continued for a second phase (EFPO II) for four more years until December 1998; that second phase is the topic of this article. EFPO II (1) focused more on residents' education; (2) emphasized four of the EFPO I-created physician roles in project activities; (3) maintained the province-wide, inter-institutional medical education framework of phase I, but fostered greater involvement of the seven sites (five medical schools and two regional health centers) in project activities; (4) stressed five project components (e.g., needs assessment and community partnerships) and worked for collaboration among components at all sites; (5) enhanced the original EFPO I Fellowship Program by adding residents and community fellows to the existing fellowships and by initiating leadership development activities, all of which bode well for the future leadership of medical education in Ontario. Students and residents played a vital role in EPFO II. Most of EFPO II's objectives were met, but the overall view of external reviewers was that the project was less successful than EFPO I. For example, the impact on clinical education, especially residency education, was less than anticipated. On the other hand, the project helped encourage the wide adoption of the eight physician roles that originated in EFPO I and advanced faculty development and assessment activities based on these roles. A third phase of EFPO concerning continuing medical education was planned, but support was not available. However, one of the funders will continue to support the successful fellowship and leadership program and the provincial education network for the next three years. Overall, the two phases of EFPO substantially modified medical education in Ontario to make it more responsive to evolving social needs.

Education, Medical↗

ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group.

BACKGROUND: Inhibition of the renin-angiotensin system is known to raise serum potassium [K(+)] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K(+)] in people with renal insufficiency. METHODS: The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 +/- 2 years. Mean baseline serum [K(+)] was 4.4 +/- 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 +/- 5 mL/min/1.73 m(2), and blood pressure was 150 +/- 2/88 +/- 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods. RESULTS: For the total group, serum [K(+)] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of < or = 60 mL/min/1.73 m(2) who received lisinopril demonstrated significant increases in serum [K(+)] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K(+)] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K(+)] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of < or = 60 mL/min/1.73 m(2). The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K(+)], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K(+)] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14). CONCLUSIONS: In the presence of renal insufficiency, the ARB valsartan did not raise serum [K(+)] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K(+)] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K(+)] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.

Aldosterone↗

Evaluating the role of botulinum toxin in the management of focal hypertonia in adults.

OBJECTIVES: To investigate the effects of EMG guided botulinum toxin (BTX-A) on impairment and focal disability in adults presenting with focal hypertonia. METHODS: A prospective, randomised, double blind, placebo controlled, parallel group trial was carried out with standardised assessment before and at 3 week intervals until 12 weeks after injection, in patients with focal hypertonia affecting upper or lower limbs. Botulinum toxin or placebo was injected with EMG guidance after multidisciplinary assessment. The modified Ashworth scale of spasticity, percentage passive range of joint motion, subjective rating of problem severity, the Rivermead motor assessment scale, a timed 10 metre walk (lower limb patients), nine hole peg test (upper limb patients), and a modified goal attainment scale were used as outcome measures. The patients were 52 adults; 34 male, 18 female; mean age 40.31, range 16-79 years; mean duration of symptoms 35 months (range 3 months to 22 years). Diagnoses included cerebrovascular accidents (23), head injury (12), incomplete spinal cord injury (six), tumour (five), cerebral palsy (three), and anoxic episodes (three). RESULTS: For each variable an overall score for the treatment period was computed by summing the scores from the 3, 6, 9, and 12 week assessments. These overall scores were significantly better in the treated group for the Ashworth scale, percentage passive range of movement, Rivermead lower limb, and subjective rating of problem severity. The significant treatment effect on the Ashworth scale was seen on analysis of variance (ANOVA) at 3 weeks and the subjective rating of problem severity at 3 and 6 weeks. The goal attainment scale score in both groups was similar at 12 weeks. CONCLUSION: Selective use of botulinum toxin to weaken muscles can lead to a reduction in resistance to passive movement about a distal limb joint. This allows for improvements in passive range of movement and focal disability, particularly in patients presenting with focal spasticity of the lower limb.

Adolescent↗

Effects of an applied supplemental course on student performance in elementary physiology.

The objective of this study was to determine whether students within a large (100-160 students) didactic lecture-based course, "Elementary Physiology" (EP), who were given an active-learning opportunity would perform better on objective examinations over EP material compared with their classroom peers who did not have the same active-learning experience. This was achieved by offering the EP students the option of taking a supplemental one credit hour discussion-based course, "Case Studies in Physiology" (CSP). Approximately 14% of the EP students opted for the CSP course. The format of CSP consisted of a one-hour-per-week discussion of applied problems based on the factual information presented in EP. On a subjective scale of 1 to 4, the CSP students felt that the course helped them to understand the EP material (3.5). This was reflected in the EP examination results for which the CSP students scored significantly higher compared with their non-CSP peers (81.1% vs. 75.7%; P < 0.05). These results indicate that when active-learning methods, such as discussion of applied problems, are used as a supplement to didactic lectures in physiology, performance on objective examinations of lecture material is improved.

Analysis of Variance↗

Particle concentrations in urban microenvironments.

Although ambient particulate matter has been associated with a range of health outcomes, the health risks for individuals depend in part on their daily activities. Information about particle mass concentrations and size distributions in indoor and outdoor microenvironments can help identify high-risk individuals and the significant contributors to personal exposure. To address these issues in an urban setting, we measured particle count concentrations in four size ranges and particulate matter (3/4) 10 microm (PM(10)) concentrations outdoors and in seven indoor microenvironments in Boston, Massachusetts. Particle counts and PM(10) concentrations were continuously measured with two light-scattering devices. Because of the autocorrelation between sequential measurements, we used linear mixed effects models with an AR-1 autoregressive correlation structure to evaluate whether differences between microenvironments were statistically significant. In general, larger particles were elevated in the vicinity of significant human activity, and smaller particles were elevated in the vicinity of combustion sources, with indoor PM(10) concentrations significantly higher than the outdoors on buses and trolleys. Statistical models demonstrated significant variability among some indoor microenvironments, with greater variability for smaller particles. These findings imply that personal exposures can depend on activity patterns and that microenvironmental concentration information can improve the accuracy of personal exposure estimation.

Air Pollutants↗