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Biomedical subjects

K Hughes

Publications and source records attributed to K Hughes.

At least 19 recordsLinked to original sources

Ethnicity modifies the association between diabetes mellitus and ischaemic heart disease in Chinese, Malays and Asian Indians living in Singapore.

AIMS/HYPOTHESIS: The aim of the study was to determine whether the risk of ischaemic heart disease (IHD) associated with diabetes mellitus differs between ethnic groups. METHODS: Registry linkage was used to identify IHD events in 5707 Chinese, Malay and Asian Indian participants from three cross-sectional studies conducted in Singapore between the years 1984 and 1995. The study provided a median of 10.2 years of follow-up with 240 IHD events experienced. We assessed the interaction between diabetes mellitus and ethnicity in relation to the risk of IHD events using Cox proportional hazards regression. RESULTS: Diabetes mellitus was more common in Asian Indians. Furthermore, diabetes mellitus was associated with a greater risk of IHD in Asian Indians. The hazard ratio when comparing diabetes mellitus with non-diabetes mellitus was 6.41 (95% CI 5.77-7.12) in Asian Indians and 3.07 (95% CI 1.86-5.06) in Chinese (p = 0.009 for interaction). Differences in the levels of established IHD risk factors among diabetics from the three ethnic groups did not appear to explain the differences in IHD risk. CONCLUSIONS/INTERPRETATION: Asian Indians are more susceptible to the development of diabetes mellitus than Chinese and Malays. When Asian Indians do develop diabetes mellitus, the risk of IHD is higher than for Chinese and Malays. Consequently, the prevention of diabetes mellitus amongst this ethnic group is particularly important for the prevention of IHD in Asia, especially given the size of the population at risk. Elucidation of the reasons for these ethnic differences may help us understand the pathogenesis of IHD in those with diabetes mellitus.

Adult↗

Economic analysis of a community-based falls prevention program.

OBJECTIVES: To undertake a cost-benefit analysis of 'Stay on Your Feet', a community-based falls prevention program targeting older people at all levels of risk in New South Wales, Australia. Hospital separations were monitored in the intervention region, a control region and for the state of New South Wales as a whole. Changing admission patterns over the intervention period were used to assess the impact of the program. METHODS: Cost-benefit analysis compared the costs of the program with two estimates of savings from avoided hospital admissions. The first compared the cost of hospital admissions in the intervention region to a control region of similar demographics, while the second compared hospital utilization in the intervention region with the state of New South Wales as a whole using falls-related hospital diagnosis related group (DRG) codes. RESULTS: The total direct costs of the program were estimated at A dollars 781,829. Both methods identified clear overall net benefits ranging from A dollars 5.4 million for avoided hospitalizations alone to A dollars 16.9 million for all avoided direct and indirect costs. The confidence intervals around these estimates were small. The average overall benefit to cost ratio for the intervention as a whole was 20.6:1. CONCLUSIONS: These findings suggest that well-designed community-based interventions targeting falls prevention among older people are highly cost effective and a wise investment for all levels of government. The models used are conservative and are likely to underestimate the real benefit of the intervention, which may have lasted for some time beyond the life of the program.

Accidental Falls↗

Immigrant women family caregivers in Canada: implications for policies and programmes in health and social sectors.

Migration has become a profound global phenomenon in this century. In Canada, uncoordinated policies, including those related to immigration, resettlement, employment, and government funding for health and social services, present barriers to immigrant women caregivers. The purpose of this paper is to share relevant insights from individual and group interviews with immigrant women family caregivers, service providers and policy influencers, and discuss these in relation to immigration, health and social policy, and programme trends in Canada. The present authors conducted individual interviews with immigrant women family caregivers (n = 29) in phase 1, followed by two group interviews with women family caregivers (n = 7), and two group interviews with service providers and policy-makers (n = 15) in phase 2. Using an inductive approach, the authors employed thematic content data analysis. Immigrant women experienced barriers to health and social services similar to Canadian-born family caregivers, particularly those who have low incomes, jobs with limited flexibility and heavy caregiving demands. These immigrant women family caregivers avoided certain formal services for a variety of reasons, including lack of cultural sensitivity. However, their challenges were compounded by language, immigration and separation from family in the home country. The identified barriers to support reinforce the importance of modifying and expanding policies and programmes affecting immigrant women's ability to care for family members with illnesses or disabilities within the context of Canadian society. Participants recommended changes to policies and programmes to deal with information, transportation, language, attitudinal and network barriers. The various barriers to services and programmes which were experienced by immigrant women caregivers underscore the importance of reviewing policies affecting immigration, caregiving, and access to health and social services. Intersectoral collaboration among agencies is essential to reduce the barriers identified in the present study, and to establish services which are linguistically and culturally appropriate.

Asian People↗

Colorectal cancer screening with faecal occult blood testing: community intention, knowledge, beliefs and behaviour.

The objective of this study was to examine the current community intention, knowledge, beliefs and behaviour regarding colorectal cancer (CRC) screening with faecal occult blood testing (FOBT). A cross sectional telephone survey of the general population was conducted in Queensland, Australia. A random sample of 1,136 residents aged 40-80 years were invited to participate in the survey with a response rate of 77.8%. 77.5% (95% confidence interval [95% CI]: 74.0 to 80.7%) of respondents reported that they would participate in CRC screening by FOBT if recommended to do so by doctors or health authorities. Screening intention was significantly associated with interest in further information concerning CRC or CRC screening (odds ratio: 6.7; 95% CI: 3.4 - 13.1), belief that CRC screening is necessary for persons without symptoms (5.0; 95% CI: 1.5 -17.1), and belief that treating bowel cancer in the early stages increases a person's chance of survival (5.1; 95% CI: 2.6 - 9.9). Knowledge of seeking medical advice (2.8; 95% CI: 0.9 - 8.7) and diarrhoea/constipation as a symptom of CRC (1.7; 95% CI: 0.9 - 3.2), self-initiated screening behaviour (1.5; 95% CI: 0.8 -2.9), and medical check a couple of times a year or more (2.4; 95% CI: 0.9 - 6.5) were also marginally significantly associated with screening intention. Community intention to screen for CRC with FOBT may have increased over recent years. Screening intention is associated with community knowledge, attitudes/beliefs and behaviour.

Adult↗

Population-based interventions for the prevention of fall-related injuries in older people.

BACKGROUND: Fall-related injuries are a significant cause of morbidity and mortality in the older population. Summary information about counter-measures that successfully address the risk factors for fall-related injuries in research settings has been widely disseminated. However, less available is evidence-based information about successful roll-out of these counter-measures in public health programmes in the wider community. Population-based interventions in the form of multi-strategy, multi-focused programmes are hypothesised to result in a reduction in population-wide injury rates. This review tests this hypothesis with regards to fall-related injuries among older people. OBJECTIVES: To assess the effectiveness of population-based interventions, defined as coordinated, community-wide, multi-strategy initiatives, for reducing fall-related injuries among older people. SEARCH STRATEGY: The search strategy was based on electronic searches, handsearches of selected journals and snowballing from reference lists of selected publications. SELECTION CRITERIA: Studies were independently screened for inclusion by two reviewers. Included studies were those that reported changes in medically treated fall-related injuries among older people following the implementation of a controlled population-based intervention. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Meta-analysis was not appropriate, due to the heterogeneity of the included studies. MAIN RESULTS: Out of 23 identified studies, five met the criteria for inclusion. There were no randomised controlled trials. Significant decreases or downward trends in fall-related injuries were reported in all five of the included studies with the relative reduction in fall-related injuries ranging from 6 to 33%. AUTHORS' CONCLUSIONS: Despite methodological limitations of the evaluation studies reviewed, the consistency of reported reductions in fall-related injuries across all programmes support the preliminary claim that the population-based approach to the prevention of fall-related injury is effective and can form the basis of public health practice. Randomised, multiple community trials of population-based interventions are indicated to increase the level of evidence in support of the population-based approach. Research is also required to elucidate the barriers and facilitators in population-based interventions that influence the extent to which population programmes are effective.

Accident Prevention↗

Sexual behaviour of young people in international tourist resorts.

BACKGROUND/OBJECTIVES: Increasingly, young people travel abroad to experience nightlife in international resorts. Although media coverage of such resorts suggests high levels of sexual activity, little empirical data are currently available. We have measured: 3 year trends in sexual behaviour of young people visiting Ibiza, levels of sexual risk taking, and their relation to substance use. Additionally, in 2002 we identified levels of homosexual sex and sexual interactions between UK residents and individuals from other countries. METHODS: Data were collected from visitors to Ibiza between 2000 and 2002 just before they left the island. Information on sexual health was surveyed using a short anonymous questionnaire. RESULTS: Over half of individuals (56.0%) visiting Ibiza had sex with at least one person, with 26.2% of males and 14.5% of females having sex with more than one individual. However, of those arriving without sexual partners (75.5%) just under half (47.5%) have sex in Ibiza and most of these (62.4%) always used condoms. Having any sex abroad was associated with using illicit drugs and having more sexual partners in the 6 months before visiting Ibiza. However, having unprotected sex or sex with more than one person was associated with smoking as well as having higher numbers of sexual partners before their visit. Overall, 8.6% of individuals had sex with a non-UK resident in Ibiza although such individuals were no more likely to have sex without condoms. CONCLUSIONS: Substantial numbers of individuals visiting international nightlife resorts have unprotected sex with people they meet while abroad. This poses an increasing threat to the sexual health of UK residents but as yet little attention has been paid to developing interventions that might reduce sexual risk taking among young people holidaying abroad.

Adolescent↗

Ethnic differences among Chinese, Malay and Indian patients with type 2 diabetes mellitus in Singapore.

INTRODUCTION: Ethnic differences exist in patients with diabetes mellitus. Not much is known about such differences in Asian populations. The aim of the study was to determine ethnic differences among Chinese, Malay and Indian patients with type 2 diabetes mellitus in Singapore. METHODS: The study design was cross-sectional, involving 967 patients who were attending follow-up care for type 2 diabetes mellitus at a primary care clinic. Data collection was by patient interview, examination, and from case records. Blood and urine samples were collected for analysis of indicators of diabetic control and albuminuria. RESULTS: Malays had the highest mean body mass index (BMI) after controlling for age, gender, duration of diabetes and exercise status. Adjusted mean BMI for Malays was 27.4kg per square metres, Indians 25.7kg per square metres, Chinese 24.9kg per square metres, with the p value being less than 0.01. HbA1c levels were highest among Indians after controlling for age, duration of diabetes, body mass index and treatment. Adjusted mean HbA1c for Indians was 8.3 percent, Malays 8.0 percent, and Chinese 7.7 percent, with the p value being less than 0.01. Compared with Chinese, Indians were more likely to have a positive family history of diabetes (prevalence rate ratio (PRR) of 1.3, 95 percent confidence interval (CI) of 1.0 to 1.7), but were less likely to have associated hypertension (PRR of 0.7, 95 percent CI of 0.5 to 1.0) and microalbuminuria and macroalbuminuria (PRR of 0.6, 95 percent CI of 0.4 to 1.0). CONCLUSION: Ethnic differences exist with regard to BMI, diabetic control as reflected by HbA1c levels, family history of diabetes, presence of associated hypertension, and severity of albuminuria. Indians, while having poorer control of diabetes, are less prone to hypertension and renal complications than Chinese.

Aged↗

Comparison of the incidence rates of thromboembolic events reported for patients prescribed rofecoxib and meloxicam in general practice in England using prescription-event monitoring (PEM) data.

BACKGROUND: Rofecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit (DSRU) monitored the post-marketing safety of these drugs in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). OBJECTIVES: To compare the incidence rates of selected thromboembolic (TE)(cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed rofecoxib and meloxicam in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and rofecoxib (July to November 1999). Simple questionnaires requesting details of events recorded during/after treatment, indication and potential risk factors (including age, sex and NSAIDs prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event within each TE group were calculated; crude and age- and sex-adjusted rate ratios (RR) obtained using regression modelling. RESULTS: During the 9 months after starting treatment, 21 (0.14%) and 19 (0.10%) patients were reported to have cardiovascular TE events, and 74 (0.48%) and 52 (0.27%) cerebrovascular TE events, and 6 (0.05%) and 20 (0.10%) were reported to have peripheral venous thrombotic events for rofecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from the start of treatment for both the cerebrovascular TE event group (log rank test P = 0.0063) and the peripheral venous thrombotic event group (log rank test P = 0.0264). Indication and use of a NSAID within 3 months prior to starting treatment had no statistically significant effect on the relative risk estimates of the event groups and was excluded from subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, for rofecoxib the adjusted cerebrovascular TE event group rate was higher than for meloxicam [RR 1.68 (95% CI 1.15, 2.46)]; lower than meloxicam for the peripheral venous thrombotic event group [RR 0.29 (95% CI 0.11, 0.78)], and not different for the cardiovascular TE event group [RR 1.38 (95% CI 0.71, 2.67)]. CONCLUSIONS: This study reports a relative increase in the rate of cerebrovascular TE events and a relative reduction in peripheral venous thrombotic events in users of rofecoxib compared with meloxicam. There was no difference in the rate of cardiovascular thromboembolic events. The incidence of these three groups of events reported in each of these two drug cohorts was low (less than 0.5%), therefore the relevance of our findings needs to be taken into consideration with other clinical and pharmacoepidemiological studies.

Adult↗

Comparison of the incidence rates of selected gastrointestinal events reported for patients prescribed celecoxib and meloxicam in general practice in England using prescription-event monitoring (PEM) data.

BACKGROUND: Celecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors, and were developed to minimize the risk of gastrointestinal (GI) toxicity commonly associated with non-steroidal anti-inflammatory drugs (NSAIDs). The Drug Safety Research Unit (DSRU) monitored the safety of these drugs immediately after launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between celecoxib and meloxicam during use in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and celecoxib (May to December 2000). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RR) obtained using regression modelling. RESULTS: For celecoxib and meloxicam, respectively, 1054 (6.0%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events whereas 42 (0.2%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A higher proportion of the celecoxib cohort had an indication for osteoarthritis (28.1 vs 23.2%), were female (68.3 vs 67.1%), were aged 60 yr or more (59.5 vs 55.0%), were prescribed NSAIDs within 3 months of starting treatment (49.4 vs 47.9%), and had a past medical history of upper GI conditions (54.7 vs 29.2%) than those prescribed meloxicam. This suggests differential channelling of groups at higher risk of such events on to celecoxib compared with meloxicam. There was no difference between the two drugs in the time to occurrence of either group of event. The RR over the 270-day study period for celecoxib compared with meloxicam were 0.77 (95% CI 0.69, 0.85) and 0.56 (95% CI 0.32, 0.96) for symptomatic (acid/peptic) upper GI events and complicated upper GI conditions (perforations/bleeding), respectively, adjusted for age, age2, sex, indication, medical history of upper GI problems and whether NSAIDs were prescribed within 3 months prior to starting treatment. CONCLUSIONS: This study reports a relative reduction (23%) in the incidence of symptomatic (acid/peptic) GI events, and a relative reduction (44%) in the incidence rate of complicated upper GI conditions (perforations/bleeding) for celecoxib compared with meloxicam.

Adult↗

Efficacy of the topical nasal steroid budesonide on improving sleep and daytime somnolence in patients with perennial allergic rhinitis.

BACKGROUND: Improving quality of life is considered to be a major endpoint and motivation for clinical intervention in patients with perennial allergic rhinitis (PAR). In addition to classical symptoms of congestion, pruritus, and rhinorrhea, patients will often complain of not being able to sleep well at night and of feeling fatigued during the day. Like sleep apnea, PAR has also been shown to cause sleep disturbance and consequently worsen daytime fatigue and somnolence. HYPOTHESIS: It is proposed that by decreasing nasal obstruction due to allergic rhinitis by treating with the topical steroid budesonide, symptoms of daytime fatigue and somnolence can be improved. METHODS: Twenty-two subjects were enrolled in a double-blind, placebo-controlled, crossover study using Baalam's design. Patients were treated with either budesonide 128 g/day or placebo. Subjective data include the Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, Rhino-conjunctivitis Quality of Life Questionnaire, and a daily diary recording nasal symptoms, sleep problems, and daytime fatigue. RESULTS: The results illustrated that the topical nasal corticosteroid significantly improved daytime fatigue (P = 0.03), somnolence (P = 0.02), and quality of sleep (P = 0.05) compared to placebo in patients suffering from PAR. SUMMARY: Budesonide is able to improve congestion, sleep, and daytime somnolence.

Administration, Topical↗

Comparison of the incidence rates of selected gastrointestinal events reported for patients prescribed rofecoxib and meloxicam in general practice in England using prescription-event monitoring data.

BACKGROUND: and objectives. Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal (GI) toxicity. Rofecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the safety of these drugs immediately after their launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in the incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between rofecoxib and meloxicam during use in general practice. METHODS: Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (between December 1996 and March 1997) and rofecoxib (between July and November 1999). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event were calculated, and crude and adjusted rate ratios were obtained using regression modelling. RESULTS: For rofecoxib and meloxicam respectively, 1127 (7.4%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events, whereas 57 (0.4%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A past medical history of upper GI problems was an important risk factor only for symptomatic (acid/peptic) upper GI events for both drugs, despite a two-fold difference in the proportion reporting previous GI problems (48.4 and 25.1% for rofecoxib and meloxicam respectively). The adjusted rate ratio of symptomatic (acid/peptic) upper GI events or complicated upper GI conditions (perforations/bleeding) for rofecoxib compared with meloxicam was 0.71 (95% confidence interval 0.65, 0.79) and 0.91 (95% confidence interval 0.59, 1.42) respectively. CONCLUSIONS: This study reports a relative reduction (29%) in the incidence rate of symptomatic (acid/peptic) GI events, and no difference in the incidence rate of complicated upper GI conditions (perforations/bleeding) for rofecoxib compared with meloxicam.

Adult↗

Efficacy of computerized infrared imaging analysis to evaluate mammographically suspicious lesions.

OBJECTIVE: The purpose of this clinical trial was to determine the efficacy of a dynamic computerized infrared imaging system for distinguishing between benign and malignant lesions in patients undergoing biopsy on the basis of mammographic findings. SUBJECTS AND METHODS: A 4-year clinical trial was conducted at five institutions using infrared imaging of patients for whom breast biopsy had been recommended. The data from a blinded subject set were obtained in 769 subjects with 875 biopsied lesions resulting in 187 malignant and 688 benign findings. The infrared technique records a series of sequential images that provides an assessment of the infrared information in a mammographically identified area. The suspicious area is localized on the infrared image by the radiologist using mammograms, and an index of suspicion is determined, yielding a negative or positive result. RESULTS: In the 875 biopsied lesions, the index of suspicion resulted in a 97% sensitivity, a 14% specificity, a 95% negative predictive value, and a 24% positive predictive value. Lesions that were assessed as false-negative by infrared analysis were microcalcifications, so an additional analysis was performed in a subset excluding lesions described only as microcalcification. In this restricted subset of 448 subjects with 479 lesions and 110 malignancies, the index of suspicion resulted in a 99% sensitivity, an 18% specificity, a 99% negative predictive value, and a 27% positive predictive value. Analysis of infrared imaging performance in all 875 biopsied lesions revealed that specificity was statistically improved in dense breast tissue compared with fatty breast tissue. CONCLUSION: Infrared imaging offers a safe noninvasive procedure that would be valuable as an adjunct to mammography in determining whether a lesion is benign or malignant.

Adult↗

Differential expression of TGF-beta isoforms by normal and inflammatory bowel disease intestinal myofibroblasts.

Intestinal strictures are frequent in Crohn's disease but not ulcerative colitis. We investigated the expression of transforming growth factor (TGF)-beta isoforms by isolated and cultured primary human intestinal myofibroblasts and the responsiveness of these cells and intestinal epithelial cells to TGF-beta isoforms. Normal intestinal myofibroblasts released predominantly TGF-beta(3) and ulcerative colitis myofibroblasts expressed both TGF-beta(1) and TGF-beta(3), whereas in myofibroblast cultures from fibrotic Crohn's disease tissue, there was significantly lower expression of TGF-beta(3) but enhanced release of TGF-beta(2). These distinctive patterns of TGF-beta isoform release were sustained through several myofibroblast passages. Proliferation of Crohn's disease myofibroblasts was significantly greater than that of myofibroblasts derived from normal and ulcerative colitis tissue. In contrast to cells from normal and ulcerative colitis tissue, neutralization of the three TGF-beta isoforms did not affect the proliferation of Crohn's disease intestinal myofibroblasts. Studies on the effect of recombinant TGF-beta isoforms on epithelial restitution and proliferation suggest that TGF-beta(2) may be the least effective of the three isoforms in intestinal wound repair. In conclusion, the enhanced release of TGF-beta(2) but reduced expression of TGF-beta(3) by Crohn's disease intestinal myofibroblasts, together with their enhanced proliferative capacity, may lead to the development of intestinal strictures.

Actins↗

Description and simulation of an active imaging technique utilizing two speckle fields: root reconstructors.

Quasi-monochromatic light will form laser speckle upon reflection from a rough object. This laser speckle provides information about the shape of the illuminated object. Further information can be obtained if two colors of coherent light are used, provided that the colors are sufficiently close in wavelength that the interference is also measurable. It is shown that no more than two intensities of two speckle patterns and their interference are required to produce an unambiguous band-limited image of an object, to within an overall spatial translation of the image, in the absence of measurement errors and in the case where all roots of both fields and their complex conjugates are distinct. This result is proven with a root-matching technique, which treats the electric fields as polynomials in the pupil plane, the coefficients of which form the desired complex object. Several root-matching algorithms are developed and tested. These algorithms are generally slow and sensitive to noise. So motivated, several other techniques are applied to the problem, including phase retrieval, expectation maximization, and probability maximization in a sequel paper [J. Opt. Soc. Am. A 19, 458 (2002)]. The phase-retrieval and expectation-maximization techniques proved to be most effective for reconstructions of complex objects larger than 10 pixels across.

Journal Article↗

Description and simulation of an active imaging technique utilizing two speckle fields: iterative reconstructors.

Quasi-monochromatic light will form laser speckle upon reflection from a rough object. This laser speckle provides information about the shape of the illuminated object. In a prior paper [J. Opt. Soc. Am. A 19, 444 (2002)], it was shown that two intensities of two speckle patterns and their interference are sufficient to produce an unambiguous (except for object translation) band-limited image of the object, based on a root-matching technique described therein, in the absence of measurement error and in the case of distinct roots of the field polynomials and their complex conjugates. On the other hand, algorithms based on the root-matching technique are found to be slow and sensitive to noise. So motivated, several other techniques are applied to the problem, including phase retrieval, expectation maximization, and statistical maximization. The phase-retrieval and expectation-maximization techniques proved to be most effective for reconstructions of complex objects larger than 10 pixels across, and high-quality images were formed by using three independent sets of two-field data (three frames of two-wavelength data), each comprising two speckle intensity patterns and their interference. Two additional results of note are reported. First, the expectation-maximization algorithm produced relatively good images when three or more frames each of only one speckle intensity pattern (data at just one wavelength) were used and second, the phase-retrieval algorithm when only the object autocorrelation was used also produced relatively good images for the chosen test object.

Journal Article↗

Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.

Administration, Inhalation↗

Calmodulin-dependent kinase II mediates T cell receptor/CD3- and phorbol ester-induced activation of IkappaB kinase.

Numerous fundamental biological processes involve the NFkappaB family of transcription factors. The mechanisms by which this family of proteins is regulated are therefore of widespread importance. In most cells, NFkappaB is bound to inhibitory IkappaB proteins and sequestered in the cytoplasm. NFkappaB-inducing signals result in activation of a large multisubunit kinase complex, IKK, which phosphorylates IkappaB. IkappaB is subsequently degraded, releasing NFkappaB, which translocates to the nucleus. We previously reported that inhibitors of the calcium-binding protein calmodulin (CaM) prevent phorbol ester-induced phosphorylation of IkappaB. Here we show that KN93, an inhibitor of CaM-dependent kinases (CaMKs), also inhibits the phosphorylation of IkappaB. The effect of both CaM and CaMK inhibitors on IkappaB phosphorylation is due to the inhibition of the activity of CaMK II because neither drug has any effect when a derivative of CaMK II that is insensitive to these inhibitors is expressed. When CaMK II is inhibited, phorbol ester is no longer able to activate IKK, placing CaMK II in the signaling pathway that leads to IKK activation. CaM and CaMK inhibitors also block T cell receptor/CD3-induced activation but have no effect on the ability of the cytokine tumor necrosis factor alpha or the phosphatase inhibitor calyculin A to induce degradation of IkappaB. Finally we show that expression of a constitutively active CaMK II results in the activation of NFkappaB. The results identify CaMK II as a mediator of IKK activation specifically in response to T cell receptor/CD3 and phorbol ester stimulation.

CD3 Complex↗