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Biomedical subjects

R Welsh

Publications and source records attributed to R Welsh.

At least 19 recordsLinked to original sources

Diminished lifespan and acute stress-induced death in DNA-PKcs-deficient mice with limiting telomeres.

An adequate and appropriate response to physiological and pathophysiological stresses is critical for long-term homeostasis and viability of the aging organism. Previous work has pointed to the immune system, telomeres and DNA repair pathways as important and distinct determinants of a normal healthy lifespan. In this study, we explored the genetic interactions of telomeres and DNA-PKcs, a protein involved in non-homologous end-joining (NHEJ) and immune responses, in the context of a key aspect of aging and lifespan--the capacity to mount an acute and appropriate immune-mediated stress response. We observed that the combination of DNA-PKcs deficiency and telomere dysfunction resulted in a shortened lifespan that was reduced further following viral infection or experimental activation of the innate immune response. Analysis of the innate immune response in the DNA-PKcs-deficient mice with short dysfunctional telomeres revealed high basal serum levels of tumor necrosis factor alpha (TNFalpha) and hyper-active cytokine responses upon challenge with polyinosinic-polycytidylic acid (poly-IC). We further show that serum cytokine levels become elevated in telomere dysfunctional mice as a function of age. These results raise speculation that these genetic factors may contribute to misdirected immune responses of the aged under conditions of acute and chronic stress.

Animals↗

Diffusion tensor imaging of the brain: review of clinical applications.

We review the theoretical background to diffusion tensor imaging (DTI) and some of its commoner clinical applications, such as cerebral ischemia, brain maturation and traumatic brain injury. We also review its potential use in diseases such as epilepsy, multiple sclerosis, and Alzheimer's disease. The value of DTI in the investigation of brain tumors and metabolic disorders is assessed.

Brain↗

Impaired left ventricular systolic function after a half-ironman race.

OBJECTIVE: To assess the effects of prolonged strenuous exercise in the form of a half-ironman (HI) race (2 km swim, 90 km bike ride and a 21 km run) on left ventricular systolic function. METHODS AND RESULTS: The study participants consisted of nine male triathletes (mean age +/- SD 32+/-5 years) who competed in the Great White North HI race. Two-dimensional transthoracic echocardiograms were obtained two to three days before the HI (prerace), immediately after completion of the HI (postrace) and 24 h after cessation of exercise. Compared with before the race, performing an HI was associated with a decline in systolic blood pressure (prerace 127.2+/-15.0 mmHg compared with after the race 116.1+/-10.2 mmHg, P<0.05), the systolic blood pressure to end-systolic cavity area ratio (a surrogate for left ventricular contractility - prerace 14.3+/-3.0 mmHg/cm(2) compared with postrace 11.0+/-2.2 mmHg/cm(2), P<0.05) and the fractional area change (prerace 54.1+/-3.8% compared with postrace 47.4+/-5.5%, P<0.05). There was also a concomitant increase in heart rate (prerace 56.3+/-9.4 beats/min compared with postrace 74.1+/-10.7 beats/min, P<0.05), the end-systolic cavity area (prerace 9.2+/-2.2 cm(2) compared with postrace 10.8+/-1.9 cm(2), P<0.05) and the end-systolic cavity area to end-systolic myocardial area ratio (prerace 0.39+/-0.08 compared with postrace 0.51+/-0.1, P<0.05), which returned toward baseline values 24 h after cessation of the HI. CONCLUSIONS: Performing an HI appears to be associated with a transient impairment in left ventricular contractility and a subsequent decline in left ventricular systolic function that tends to return toward normal values within 24 h after cessation of exercise.

Adult↗

Male and female car drivers--differences in collision and injury risks.

Crash data from two UK resources were examined for differences between male and female passenger car drivers in collision circumstances and injury outcomes. The proportion of female car license holders is growing, women are more likely to be the driver in a collision and are more vulnerable to injury particularly neck strain. Women drive smaller, lighter cars compared to men and are more often the driver of the smaller vehicle in a multivehicle collision. Vehicle design, crash testing programmes and regulation, currently based heavily on the average male, should give more balanced consideration to female characteristics in future activities.

Abbreviated Injury Scale↗

Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas.

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.

Adenocarcinoma↗

The future of criminal violence: juveniles tried as adults.

Juveniles tried as adults (JTA) represent a select and small subsample of juvenile offenders. This study seeks to provide a profile of habitually violent JTAs transferred to the adult penal system and to compare them with their adult counterparts. Twenty-nine incarcerated violent male juveniles tried as adults were compared with a sample of 27 incarcerated violent male offenders across demographic, neuropsychological, criminal history, psychopathy, and substance abuse variables. The JTAs were characterized by a high rate of gang membership (96%), substance abuse (alcohol, marijuana, and phenylcyclidene), and use of guns. In the juvenile sample, 65 percent used guns in violence not leading to arrest, and 93 percent used guns in a violent crime leading to arrest. Juvenile offenders were similar to their adult counterparts in patterns of criminality, although adult offenders had higher psychopathy scores. Both groups revealed generally intact neuropsychological functioning with the exception of a higher rate of perseverative responses in the adult sample. The results are discussed in terms of the implication of the degree of violence in a young offender population.

Adolescent↗

Incidence and significance of lobar atelectasis in thoracic surgical patients.

Lobar atelectasis, defined by complete lobar collapse and mediastinal shift on chest roentgenogram, represents one extreme form of postoperative atelectasis. We have evaluated the incidence and clinical significance of lobar atelectasis in a thoracic surgical patient group. A retrospective review was done of patients who underwent pulmonary resection over a 2-year period to determine patient characteristics, contributing comorbidities, and associated perioperative care factors. Lung resections were performed for both benign and malignant disease through open or video-assisted techniques. One hundred eighty patients had pulmonary resection, 101 males and 79 females, and they were divided into three groups: I, no complications (112 patients, 62%); II, complications unrelated to lobar atelectasis (60 patients, 33%); and III, complications of lobar atelectasis (8 patients, 5%). There was one death in the series, in the lobar atelectasis group (III). Mean age for the entire group was 64.5 +/- 12.5 years; however, patients in Groups II (67.3 years) and III (69.6 years) were significantly older than in Group I (P < 0.02). Mean hospital length of stay in Group I was 6 +/- 3 days, whereas that in Group II was 13 +/- 12 days (P < 0.001), and in Group III it was 27 +/- 31 days (P < 0.001). In addition, patients who developed lobar atelectasis were more likely to be male (88% vs 48%, P = 0.034), had a longer ICU length of stay (P < 0.001), were more likely to have two or more comorbidities (P < 0.05), and had a lower forced expiratory volume in 1 second (2.34 +/- 0.90 vs 1.96 +/- 0.63). All patients in the lobar atelectasis group were operated on for malignancy, but this was not significantly different from the other groups. None of the 16 patients who had thoracoscopy developed lobar atelectasis, but this also was not a significant finding. We conclude that severe postoperative atelectasis occurs as lobar atelectasis in approximately 5 per cent of patients who undergo pulmonary resection and significantly adds to the intensive care unit and hospital length of stay. The etiology of lobar atelectasis appears to be multifactorial and warrants further study to define mechanisms of occurrence and their prevention.

Aged↗

The relation of story structure properties to recall of television stories in young children with attention-deficit hyperactivity disorder and nonreferred peers.

In this study, the authors examined memory for televised stories to gain insight into similarities and differences in story comprehension between young children with attention-deficit hyperactivity disorder (ADHD) and their typical peers. In particular, the authors investigated the extent to which 4- to 6-year-old children's free recall of story events is predicted by several structural properties of story events (number of causal connections, whether an event is on or off the story's causal chain, story-grammar category, and position in the story's hierarchical structure), whether differences exist between children with ADHD and nonreferred comparison children in their sensitivity to structural features of stories, and whether age differences in sensitivity to structural features are similar for both groups. For both groups, recall of story events was predicted by all four structural properties, but the effects of the two causal properties was stronger for comparison children than for children with ADHD. Further examination revealed that this difference was observed only when a competing activity was available during television viewing. These findings indicate that both groups of preschool children are able to benefit from causal structure when recalling television stories, but that children with ADHD lose this benefit when attention is divided. Consistent with previous findings for nonreferred children (P. W. van den Broek, E. P. Lorch, & R. Thurlow, 1996), in both diagnostic groups the effects of causal properties increased across age, and older children were more likely to include causally important protagonists' goals in their recalls than younger children.

Attention Deficit Disorder with Hyperactivity↗

Prognostic factors in T1 NO MO adenocarcinomas and bronchioloalveolar carcinomas of the lung.

There are few prognostic factors for patients with T1 N0 M0 pulmonary conventional and bronchioloalveolar adenocarcinomas (BACs), despite a 25% to 35% failure rate. To identify prognostic factors related to disease-free survival, we retrospectively studied the histologic features of 218 cases of T1 NO MO adenocarcinomas. The mean overall follow-up was 5.9 years, and the 5-year disease-free survival was 72%; 148 patients (67.9%) were disease-free, and in 57 (26.1%), nonpulmonary metastases developed. Features significantly associated with decreased 5-year disease-free survival were larger tumor size, increasing central fibrosis, most common and highest nuclear grade, lymphatic vascular space invasion, and more than 50% tumor necrosis. Patients with lymphatic vascular space invasion had a 35% 5-year metastases-free survival. A tumor size of 2 to 3 cm, lymphatic vascular space invasion, highest nuclear grade 3, and increased central fibrosis were associated with metastases. Lymphatic vascular space invasion had the strongest odds ratio of 5.4. These histologic features can stratify patients with T1 N0 M0 neoplasms who have an increased risk of metastases. Future studies are needed to address the usefulness of adjuvant therapy for patients with neoplasms that display these negative factors.

Adenocarcinoma↗

Comprehension of televised stories by preschool children with ADHD.

Investigated visual attention to and story comprehension of televised stories in 4- to 6-year-old children with attention deficit hyperactivity disorder (ADHD) and comparison children. Half of the children in each group watched the program with toys in the room, and the other half watched without toys. Visual attention to the television was recorded, and story comprehension was assessed by performance on cued recall questions. All children attended significantly less when toys were present, but the difference when toys were present was greater for children with ADHD. The groups did not differ on recall of factual information when toys were absent. When toys were present, the comparison children showed no decrement in performance on factual questions, whereas the performance of children with ADHD was significantly worse. On questions testing causal connections, the children with ADHD performed more poorly than comparison children regardless of whether toys were present. Implications of these results for understanding and treating the academic and social difficulties of children with ADHD are discussed.

Attention↗

Comparison of stretching with ice, stretching with heat, or stretching alone on hamstring flexibility.

OBJECTIVE: To investigate the efficacy of stretching with ice for increasing hamstring flexibility. DESIGN AND SETTING: Supine hamstring flexibility was measured before and after subjects accomplished a 20-minute hamstring stretching routine. Two groups of eight subjects accomplished the routine using one of two modalities. A control group (n = 8) accomplished the routine without a modality. The measurements were compared. SUBJECTS: Twenty-four male collegiate baseball players. MEASUREMENTS: Heat or ice applied to the hamstring. RESULTS: We found differences in the responses among subject groups. Supine hamstring flexibility after stretching with ice was greater than both stretching with heat and stretching alone. Scores after stretching with heat and stretching alone were not different. CONCLUSIONS: The results of our investigation suggest that the application of ice may provide enhanced short-term improvements in hamstring flexibility over heat or stretching alone. Further research is necessary to investigate the possible mechanisms for these improvements and to determine whether similar results can be obtained with other muscle groups.

Journal Article↗

Athletic performance in relation to training load.

Athletic performance generally is thought to improve with increases in training load. However, few data exist showing the quantitative relationship between training load and performance. We followed 56 athletes (16 runners; 40 cyclists/speed skaters) during 12 weeks of training. We recorded index performances (3.2 km time trial or 5 or 10 km bicycle ergometry) after 6 weeks of baseline training and 6 weeks of a self-selected training increases. Training load was quantitated as the product of intensity (global rating of perceived exertion (RPE)) and the duration (time) of each training session. Load was expressed as the weekly average over the 6 weeks preceding each index performance. We also recorded the duration of high intensity training (RPE>5, hard) (inten). From 6 to 12 weeks, performance improved 12.95 +/- 3.83 to 12.66 +/- 3.00 min (p < .01). Training time (345 +/- 282 to 355 +/- 273 min/wk) and inten (61 +/- 88 to 71 +/- 91 min/wk) did not change significantly, although RPE (3.8 +/- 0.7 to 4.0 +/- 0.8) and load (1242 +/- 957 to 1386 +/- 978) increased significantly. No strong correlations existed between changes in performance and changes in any training measure (TIME, r = -0.031, RPE, r = -0.039, LOAD, r = 0.29, INTEN, r = 0.025.) Data suggest that improved performance in events of 7-20 minutes duration in response to intensified training is primarily dependent upon increases in total load and overall RPE during training and; that a 10-fold increase in training load may be associated with an approximately 10% improvement in performance. These data suggest the possibility of understanding the training responses of athletes on a quantitative basis.

Adult↗

Effects of specific versus cross-training on running performance.

The cross-training (XT) hypothesis suggests that despite the principle of specificity of training, athletes may improve performance in one mode of exercise by training using another mode. To test this hypothesis we studied 30 well-trained individuals (10 men, 20 women) in a randomized longitudinal trail. Subjects were evaluated before and after 8 weeks of enhanced training (+10%/week), accomplished by adding either running (R) or swimming (XT) to baseline running, versus continued baseline running (C). Both R (-26.4s) and XT (-13.2s) improved time trial (3.2 km) performance, whereas C did not (-5.4s). There were no significant changes during treadmill running in maximum oxygen uptake (VO2peak; -0.2, -6.0, and +2.7%), steady state submaximal VO2 at 2.68 m.s-1 (-1.2, -3.3 and +0.2 ml.kg-1.min-1), velocity at VO2peak (+0.05, +0.25 and +0.09 m.s-1) or accumulated O2 deficit (+11.2, -6.1 and +9.4%) in the R, XT or C groups, respectively. There was a significant increase in velocity associated with a blood lactate concentration of 4 mmol.l-1 in R but not in XT or C (+0.32, +0.07 and +0.08 m.s-1). There were significant changes in arm crank VO2peak (+5%) and arm crank VO2 at 4 mmol.l-1 (+6.4%) in XT. There was no significant changes in arm crank VO2peak (+1.3 and -7.7%) or arm crank VO2 at 4 mmol.l-1 (+0.8 and +0.4%) in R or C, respectively. The data suggest that muscularly non-similar XT may contribute to improved running performance but not to the same degree as increased specific training.

Adult↗

The pig as a potential organ donor for man. A study of potentially transferable disease from donor pig to recipient man.

Ten pigs, reared in an unmodified laboratory animal house environment, have been investigated to ascertain the incidence of diseases or disorders, including infection, neoplasia, or metabolic abnormalities, that might preclude the transplantation of major organs from the pig to man. Noninvasive studies were performed in the second month of life (study 1) and repeated after an interval that varied between 3 and 5 1/2 months (study 2). Necropsy was then performed as a means of assessing the accuracy of the 2 screening examinations. A total of 150 tests were performed on each pig. At both studies the feces contained cysts and/or trophozoites of several parasites, all of which were considered commensals. No other organisms potentially infective for man were identified either at study or at necropsy. Neither congenital anomalies nor malignant neoplasia was found at necropsy. However, in 2 pigs a vasculitis of uncertain etiology was present in the kidneys on microscopic examination, and in one of these the same condition affected the heart. This pathology was suspected neither from the screening examinations nor from the macroscopic appearance of these organs. Biopsy and microscopic examination would therefore appear to be essential before any organ is transplanted into a human.

Animal Feed↗

A simplified approach to estimating the maximal lactate steady state.

The exercise intensity associated with an elevated but stable blood lactate (HLa) concentration during constant load work (the maximal steady state, MSS) has received attention as a candidate for the "optimal" exercise intensity for endurance training. Identification of MSS ordinarily demands direct measurement of HLa or respiratory metabolism. The purpose of this study was to test the ability of heart rate (HR) to identify MSS during steady state exercise, similar to that used in conventional exercise prescription. Trained runners (n = 9) and cyclists (n = 12) performed incremental and steady state exercise. MSS was defined as the highest intensity in which blood lactate concentration increased < 1.0 mM from minutes 10 to 30. The next higher intensity workbout completed was defined as > MSS. HR models related to the presence or absence of steady state conditions were developed from the upper 95% confidence interval of MSS and the lower 95% confidence interval of > MSS. Cross validation of the model to predict MSS was performed using 21 running and 45 cycling exercise bouts in a separate group. Using the MSS upper 95% confidence interval model 84% and 76% of workbouts were correctly predicted in cyclists and runners, respectively. Using the > MSS lower 95% confidence interval model, 76% and 81% of workbouts were correctly predicted in cyclists and runners, respectively. Prediction errors tended to incorrectly predict non-steady state conditions when steady state had occurred (16/26) (62%). We conclude that use of these simple HR models may predict MSS with sufficient accuracy to be useful when direct HLa measurement is not available.

Adult↗