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Biomedical subjects

K L Woods

Publications and source records attributed to K L Woods.

At least 19 recordsLinked to original sources
PubMed2000

Pathogenicity of avian malaria in experimentally-infected Hawaii Amakihi.

The introduction of avian malaria (Plasmodium relictum) and mosquitoes (Culex quinquefasciatus) to the Hawaiian Islands (USA) is believed to have played a major role in the decline and extinction of native Hawaiian honeycreepers (Drepanidinae). This introduced disease is thought to be one of the primary factors limiting recovery of honeycreepers at elevations below 1,200 m where native forest habitats are still relatively intact. One of the few remaining species of honeycreepers with a wide elevational distribution is the Hawaii Amakihi (Hernignathus virens). We measured morbidity and mortality in experimentally-infected Hawaii Amakihi that were captured in a high elevation, xeric habitat that is above the current range of the mosquito vector. Mortality among amakihi exposed to a single infective mosquito bite was 65% (13/20). All infected birds had significant declines in food consumption and a corresponding loss in body weight over the 60 day course of the experiment. Gross and microscopic lesions in birds that succumbed to malaria included enlargement and discoloration of the spleen and liver and parasitemias as high as 50% of circulating erythrocytes. Mortality in experimentally-infected amakihi was similar to that observed in Apapane (Himnatione sanguinea) and lower than that observed in Iiwi (Vestiaria coccinea) infected under similar conditions with the same parasite isolate. We conclude that the current elevational and geographic distribution of Hawaiian honeycreepers is determined by relative susceptibility to avian malaria.

Altitude↗
PubMed2000

T-ceIl recognition of discrete regions of the thrombolytic drug streptokinase.

Streptokinase (SK) is a bacterial protein used clinically as a thrombolytic agent in humans. Administration of SK causes a rapid increase in the frequency of anti-SK T cells and the titre of specific anti-SK antibodies that, on subsequent administration of SK, may neutralize the activity of the drug or elicit allergic-type reactions. By locating and modifying the immunogenic T-cell epitopes within the SK protein, it is possible that an agent with reduced immunogenicity but equal efficacy may be produced. We have investigated the T-cell epitopes within SK using nine non-overlapping, recombinant peptide fragments of SK. We investigated the proliferative T-cell response of peripheral blood mononuclear cells obtained from patients before and 6 days after administration of SK for myocardial infarction. We also examined the response of cultured anti-SK T-cell lines derived from patients 6 days after treatment with SK. Before administration of SK, peripheral blood mononuclear cells from six of nine patients showed a proliferative response to SK. The response was significantly higher 6 days after administration of SK (P = 0.0004). Cultured T-cell lines showed similar proliferative responses to clinical-grade SK and recombinant SK. Marked differences in T-cell responses were apparent in response to each recombinant SK fragment (P = 0.04). The mean proliferative response exceeded background to only two peptides, peptide 2 (P = 0.04) and peptide 3 (P = 0.009). Peptide 3, representing amino acids 100-150 of mature SK, was recognized preferentially in the majority of assays. Marked variation in the T-cell response to SK following treatment with this agent was observed between subjects. Despite these differences, peptides 2 and 3 induced T-cell proliferation at a level significantly above background in the majority of subjects. These epitopes may represent a region of enhanced immunogenicity within SK.

Analysis of Variance↗
PubMed1999

Influence of endoscopic biopsy forceps characteristics on tissue specimens: results of a prospective randomized study.

BACKGROUND: A large variety of endoscopic biopsy forceps are commercially available. However, little is known regarding the influence of forceps characteristics such as disposability, size, shape, and presence of a needle on the adequacy of the specimens for histologic diagnosis. Our aim was to analyze in a prospective, randomized, pathologist-blinded study the performance of different biopsy forceps. METHODS: Twelve biopsy forceps were tested, 6 each at upper endoscopy and colonoscopy. Two biopsy specimens were obtained with each forceps, for a total of 12 specimens per patient. The tissue samples were examined for the following parameters: weight (mg), size (mm3), depth, crush artifact, sheering effect, and adequacy of the specimens for histologic information (0 = inadequate, 1 = suboptimal, and 2 = adequate). RESULTS: Fifty-five patients undergoing routine upper or lower gastrointestinal endoscopy were included in the study, and a total of 624 tissue samples were available for analysis. Overall, disposable forceps provided specimens of greater size and depth. At upper endoscopy, alligator-shaped forceps improved the depth of the sample as did the absence of a needle within the cup. These factors, however, had no impact on the specimens obtained at colonoscopy. When the adequacy of the specimens was assessed for histologic diagnosis, no significant difference was noted between any of the individual forceps, although collectively oval-shaped forceps were superior to alligator-shaped forceps at colonoscopy. CONCLUSIONS: The biopsy forceps currently available in the market are equally efficient in providing histologic diagnosis. The primary consideration when selecting an endoscopic biopsy forceps, therefore, should be the cost and ease of use and not any perceived advantage in performance.

Adult↗
PubMed1999

Humoral and cellular immune responses up to 7.5 years after administration of streptokinase for acute myocardial infarction.

AIMS: Administration of streptokinase results in an immunological response which may lead to increased risk of anaphylactic reaction or reduced thrombolytic efficacy on repeat administration. For these reasons current recommendations suggest that streptokinase should not be given up to 1 year after first administration. We sought to define the profile of both the circulating antibody and T-cell response to streptokinase in patients who had received streptokinase up to 7.5 years previously following acute myocardial infarction. METHODS: Neutralizing anti-streptokinase antibody and total anti-streptokinase IgG were measured in 219 patients who had suffered acute myocardial infarction between 12 and 90 months previously and had received streptokinase. T-cell response to streptokinase was assessed by in-vitro proliferation of peripheral blood mononuclear cells (n=234). Data on all parameters were available in 184 patients. Controls (n=22) had suffered acute myocardial infarction between 73 and 84 months previously but had not received thrombolytic therapy. RESULTS: Compared to controls, anti-streptokinase antibodies were elevated at all time periods from 12 to 90 months after streptokinase treatment. Total anti-streptokinase titres showed the expected correlation with neutralizing anti-streptokinase antibodies (P<0.0001). Peripheral blood mononuclear cells showed a vigorous in-vitro proliferative response to streptokinase 6 days after treatment (P=0.05 vs pre-treatment), but this was not detectable at 6 weeks or subsequently. CONCLUSION: There is as yet no evidence of a time limit beyond which administration of streptokinase on a second occasion can be regarded as safe and likely to be effective. Measurement of neutralizing anti-streptokinase or total anti-streptokinase IgG titre appear to provide equivalent information regarding the antibody status of a population. Further studies are required regarding the apparent lack of peripheral blood mononuclear cells responsiveness in patients previously exposed to streptokinase.

Adult↗
PubMed1999

Mechanism and clinical significance of precordial ST depression in inferior myocardial infarction: evaluation by contrast-enhanced dynamic myocardial perfusion magnetic resonance imaging.

We elucidated the mechanism and clinical significance of precordial ST depression in patients with an inferior myocardial infarction using first-pass, contrast-enhanced, myocardial perfusion magnetic resonance imaging (MRI). Forty-seven patients with acute inferior myocardial infarction underwent first-pass contrast-enhanced MR studies within 2-6 days postinfarction. Patients were followed-up for a minimum of 1 year after infarct (range, 12-32 months). Total perfusion deficit scores derived qualitatively from MRIs were compared in patients with (group 1, n = 30) and without (group 2, n = 17) ST depression precordially. Perfusion remote from the infarct zone was also compared. The combined end points of adverse clinical events and/or the need for further intervention were assessed for each group. Total perfusion deficit scores were significantly higher in group 1 than group 2 (medians 9.7 versus 4.5, p < 0.005). Posterolateral basal extension of hypoperfusion was greater in group 1 versus group 2 (1.23 versus 0.42, p < 0.02), with no evidence of remote anterior perfusion abnormalities. There were more patients with an adverse clinical end point in group 1 versus group 2 (18 versus 1, p < 0.01). Furthermore, in patients with ST depression (group 1), there was a significant increase in number of adverse clinical end points in patients with a global deficit score > 15 versus 0-5 (7/7 versus 1/7, p < 0.01). MRI shows that precordial ST depression in inferior myocardial infarction is a marker for a larger global perfusion abnormality with posterolateral basal extension and an increase in adverse clinical end points. Furthermore, the magnitude of the perfusion deficit correlates with an increase in the number of adverse clinical end points, highlighting the potential of MRI perfusion studies as a research and clinical tool in myocardial infarction.

Contrast Media↗
PubMed1999

Long-term endoscopic management of variceal bleeding.

Recurrent hemorrhage from esophageal varices is a major source of morbidity and mortality in patients with portal hypertension. Esophageal sclerotherapy (EST) and more recently esophageal band ligation (EVL) can obliterate varices in 3-6 treatment sessions. Multiple band ligators make the use of overtubes unnecessary and make the procedure faster and more tolerable for the patient. EVL has several advantages, including fewer complications, fewer treatment sessions to obliteration, lower rebleeding rates, and lower mortality as compared to EST; the other advantages of EVL make it the treatment of choice for bleeding varices and long term management. The recommendations and rational for long term EST and EVL are presented and combination therapy and EUS guided EVL are discussed.

Endoscopy, Gastrointestinal↗
PubMed1998

Ontogeny of prolactin-secreting cells during chick embryonic development: effect of vasoactive intestinal peptide.

It was previously reported that prolactin (PRL)-containing cells differentiate by days 15 to 19 of embryonic development and that vasoactive intestinal peptide (VIP) increased plasma PRL concentrations and pituitary PRL protein and mRNA levels in vivo. In the present study, anterior pituitaries derived from day 15, 16, 17, 18, and 19 embryos were subjected to reverse hemolytic plaque assays (RHPA) for chicken PRL to determine the ontogeny of lactotrophs. We found that PRL secreting cells were first consistently detected on day 17 of embryonic development, indicating that lactotroph differentiation during normal development occurs by this age. However, extended treatment in the RHPA with VIP exposed lactotrophs as early as day 15, suggesting that a lactotroph precursor population was present earlier. Next, primary cultures of embryonic anterior pituitary cells from day 12, 13, 14, 15, 16, and 17 embryos were incubated for 0, 2, or 4 days in serum-free medium or medium supplemented with 10 nM VIP. After the culture periods, cells were subjected to RHPAs for chicken PRL. PRL-secreting cells differentiated spontaneously by 2 days in culture for day 15 and 16 cells and by 4 days in culture for all embryonic ages tested, except day 17. Culturing with VIP for 2 days did not increase PRL-secreting cells at any embryonic age tested, whereas VIP treatment for 4 days increased lactotroph numbers at all ages except day 12. Cells from days 15, 16, and 17 were responsive to VIP in the RHPA after 2 days in untreated cultures, but after 4 days only day 17 cells continued to respond to VIP in the RHPA. Treatment with VIP in culture for 4 days maintained VIP responsiveness in the RHPA for cells derived from embryos as early as day 14. We conclude that lactotroph differentiation during normal chicken development occurs by embryonic day 17. Moreover, our results indicate that responsiveness to VIP is an early event in PRL cell development and that lactotroph differentiation may be stimulated in vitro by VIP as early as embryonic day 13.

Animals↗
PubMed1998

Beta-blockers and antithrombotic treatment for secondary prevention after acute myocardial infarction. Towards an understanding of factors influencing clinical practice. The European Secondary Prevention Study Group.

AIMS: Long-term beta-blockade reduced mortality after acute myocardial infarction by about a quarter in a series of published trials. Representative data on beta-blocker use for secondary prevention are scanty but indicate wide variations. We have analysed European practice, and sources of variation, by regional sampling of acute myocardial infarction patients admitted to hospital in 11 countries during the period January 1993-June 1994. METHODS AND RESULTS: Treatment data for 4035 representative patients were collected for the hospital phase and 6 months after discharge. A logistic regression model was developed to describe the predictors of beta-blocker use. In the 11 regional samples, 6-38% (20% overall) of patients had no recorded contraindications but were discharged without a beta-blocker. In the absence of perceived contraindications, there was a strong, independent negative association between age and odds of treatment (P < 0.001), and women were less likely to be treated than men (adjusted odds ratio 0.76, 95% CI 0.58-0.99). Discontinuation of beta-blocker treatment by 6 months was significantly less likely in regions where the proportion given such treatment at discharge was high. In contrast, use of antithrombotic agents in the samples was consistently high. CONCLUSIONS: There is persisting low use of beta-blocker secondary prophylaxis, particularly in the elderly and in women, not attributable to perceived contraindications or intolerance. Considerable regional variations persist despite shared trials evidence. Discharge treatment strongly influences long-term medication.

Adrenergic beta-Antagonists↗
PubMed1998

Use of coronary angiography and revascularization procedures following acute myocardial infarction. A European perspective.

AIMS: There is little evidence to inform routine practice in the use of coronary angiography and revascularization procedures after acute myocardial infarction. Large differences in the uptake of these procedures have been reported but representative data are scarce. Outcome studies have produced opposing conclusions concerning the impact of the high rate of these cardiac procedures. METHODS AND RESULTS: A population-based patient sampling approach was utilized to identify routine practice in representative samples from 11 European countries. Data were collected retrospectively on treatment in the 6 months following acute myocardial infarction (n=2807). There was wide variation in utilization of coronary angiography and revascularization procedures. Even after restricting the analysis to patients <65 years (n=1262), there remained a 6 13 fold variation in the use of these procedures. A decreased likelihood of undergoing these procedures was associated with older age. In addition, there was an independent and negative association between female sex and utilization of coronary angiography and coronary artery bypass grafting (CABG). CONCLUSION: The effect on patient outcome of the observed variation in use of these procedures is not known but has important cost and resource implications for the health services. Outcome research is needed to define patient selection criteria and to measure the cost-utility of different angiography and revascularization rates.

Adult↗
PubMed1998

Utilisation of thrombolytic therapy in older patients with myocardial infarction.

Empirical evidence from many countries, obtained from sampling populations of patients admitted to hospital with acute myocardial infarction, has confirmed that elderly patients are significantly less likely to receive thrombolytic therapy. This difference persists after controlling for confounding factors such as admission delay and contraindications to thrombolysis. However, evidence supporting the efficacy of thrombolysis in reducing mortality after acute myocardial infarction is less clear cut in patients aged 75 years or above than in younger patients. These older patients are substantially under-represented in the clinical trials although they constitute one third of the clinical population. Observational studies indicate that older patients are at slightly higher risk than younger patients of experiencing haemorrhagic stroke after thrombolysis. It is, however, unlikely that efficacy and tolerability considerations alone account for the low use of thrombolytics in the elderly as similar trends are seen for other modalities of treatment of acute myocardial infarction. Since older patients have the highest mortality risk after myocardial infarction, they have the greatest potential gain from thrombolytic treatment, assuming a uniform treatment effect across age. The estimated cost effectiveness (cost per quality-adjusted life-year gained) improves with increasing age. It is concluded that patient age should not influence the treatment decision concerning thrombolysis. To ensure that elderly patients receive maximum benefit from this therapeutic advance requires attention to referral patterns from the community, speed of assessment in hospital and a clear treatment policy without age constraints. The effectiveness of these measures should be routinely audited.

Age Factors↗
PubMed1997

First myocardial infarction in patients of Indian subcontinent and European origin: comparison of risk factors, management, and long term outcome.

OBJECTIVE: To compare long term outcome after first myocardial infarction among British patients originating from the Indian subcontinent and from Europe. DESIGN: Matched pairs study. SETTING: Coronary care unit in central Leicester. SUBJECTS: 238 pairs of patients admitted during 1987-93 matched for age (within 2 years), sex, date of admission (within 3 months), type of infarction (Q/non-Q), and site of infarction. MAIN OUTCOME MEASURES: Incidence of angina, reinfarction, or death during follow up of 1-7 years. RESULTS: Patients of Indian subcontinent origin had a higher prevalence of diabetes (35% v 9% in patients of European origin, P < 0.001), lower prevalence of smoking (39% v 63%, P < 0.001), longer median delay from symptom onset to admission (5 hours v 3 hours, P < 0.01), and lower use of thrombolysis (50% v 66%, P < 0.001). During long term follow up (median 39 months), mortality was higher in patients of Indian subcontinent origin (unadjusted hazard ratio = 2.1, 95% confidence interval 1.3 to 3.4, P = 0.002). After adjustment for smoking, history of diabetes, and thrombolysis the estimated hazard ratio fell slightly to 2.0 (1.1 to 3.6, P = 0.02). Patients of Indian subcontinent origin had almost twice the incidence of angina (54% v 29%; P < 0.001) and almost three times the risk of reinfarction during follow up (34% v 12.5% at 3 years, P < 0.001). The unadjusted hazard ratio for reinfarction in patients of Indian subcontinent origin was 2.8 (1.8 to 4.4, P < 0.001). Adjustment for smoking, history of diabetes, and thrombolysis made little difference to the hazard ratio. Coronary angiography was performed with similar frequency in the two groups; triple vessel disease was the commonest finding in patients of Indian subcontinent origin and single vessel disease the commonest in Europeans (P < 0.001). CONCLUSIONS: Patients of Indian subcontinent origin are at substantially higher risk of mortality and of further coronary events than Europeans after first myocardial infarction. This is probably due to their higher prevalence of diffuse coronary atheroma. Their need for investigation with a view to coronary revascularisation is therefore greater. History of diabetes is an inadequate surrogate for ethnic origin as a prognostic indicator.

Coronary Angiography↗