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Biomedical subjects

M Howard

Publications and source records attributed to M Howard.

At least 19 recordsLinked to original sources
PubMed2006

Patient choice of treatment for postpartum depression: a pilot study.

OBJECTIVE: The lack of systematic efficacy research makes the selection of optimal treatment for postpartum depression (PPD) difficult. Moreover, the treatment decisions for women with PPD who are breastfeeding are heavily influenced by their concerns about infant exposure to antidepressant medication. The objective of this pilot trial was to examine the clinical characteristics of women with PPD associated with treatment selection. METHOD: This open pilot trial offered 23 women with PPD one of 3 treatment options: sertraline, interpersonal psychotherapy (IPT), or their combination administered in an outpatient mental health setting over 12 weeks. Baseline and treatment outcome measures included the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI) and the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Completers across all 3 treatment groups (n = 18) experienced significant clinical improvement with each of the 3 treatment modalities on the HRSD (p < 0.001), BDI (p < 0.001) and EPDS (p < 0.001). There were trends for women with a prior depression to more frequently choose sertraline as a treatment (alone or with IPT, p = 0.07), and for women who were breastfeeding to choose sertraline (alone or with IPT, p = 0.10) less frequently. CONCLUSION: In this small sample of women with PPD, most women chose IPT with or without sertraline. A larger randomized study could further confirm the suggested predictors of treatment selection identified in this study: previous depression and breastfeeding status.

Adult↗
PubMed2006

A psychiatric mother-baby day hospital for pregnant and postpartum women.

Major depression and other psychiatric disorders are common during pregnancy and the postpartum period, yet these disorders remain largely under-diagnosed and under-treated. Developing programs that are uniquely tailored to meet the needs of perinatal psychiatric patients can improve both the quality and acceptability of care. In this report, we describe the development and implementation of a novel mother-baby day hospital service designed to meet the mental health needs of this special population, and present preliminary data regarding treatment acceptability and effectiveness. Our experience using this model of care for the past five years has suggested that specialized units such as this one represent an acceptable, effective, fiscally viable approach to the care of pregnant and postpartum psychiatric patients. Further research is needed to more thoroughly assess the effectiveness of this type of specialized perinatal service.

Adult↗
PubMed2006

Vaginal self sampling versus physician cervical sampling for HPV among younger and older women.

OBJECTIVES: To estimate the agreement between self collected vaginal swabs and physician collected cervical brush samples for detection of oncogenic human papillomavirus infection (HPV) by the hybrid capture 2 (HC-2) test among women younger and older than 50 years, and to assess women's preference for sample collection method based on age. METHODS: Consecutive women aged 15-49 years due for a 1 year visit in a prevalence study of carcinogenic HPV and a new sample of women aged 50 years and older attending their family physicians for cervical screening, in Ontario, Canada, performed vaginal self sampling and underwent physician cervical sampling and cervical cytology. Women completed a self administered questionnaire on demographics and preference for sampling method. RESULTS: Among the 307 women aged 15-49 years, the prevalence of HPV was 20.8% (64/307) and 17.6% (54/307) in the vaginal and cervical specimens, respectively. Among the women aged 50 years and older, prevalence was 9.9% (15/152) and 8.6% (13/152), respectively. Kappa for agreement between sample collection methods was 0.54 for the younger and 0.37 for the older women (both p< 0.001). Nearly half of the women preferred self sampling or had no preference. CONCLUSIONS: There was fair agreement between self collected vaginal and physician collected cervical specimens for detecting carcinogenic HPV in younger and older women. Vaginal sampling for HPV appears to be promising as a primary screening strategy for cervical cancer prevention programmes in low resource settings in developed and developing countries.

Adolescent↗
PubMed2005

Clinical use of a commercial Monte Carlo treatment planning system for electron beams.

In 2002 we fully implemented clinically a commercial Monte Carlo based treatment planning system for electron beams. The software, developed by MDS Nordion (presently Nucletron), is based on Kawrakow's VMC++ algorithm. The Monte Carlo module is integrated with our Theraplan Plustrade mark treatment planning system. An extensive commissioning process preceded clinical implementation of this software. Using a single virtual 'machine' for each electron beam energy, we can now calculate very accurately the dose distributions and the number of MU for any arbitrary field shape and SSD. This new treatment planning capability has significantly impacted our clinical practice. Since we are more confident of the actual dose delivered to a patient, we now calculate accurate three-dimensional (3D) dose distributions for a greater variety of techniques and anatomical sites than we have in the past. We use the Monte Carlo module to calculate dose for head and neck, breast, chest wall and abdominal treatments with electron beams applied either solo or in conjunction with photons. In some cases patient treatment decisions have been changed, as compared to how such patients would have been treated in the past. In this paper, we present the planning procedure and some clinical examples.

Algorithms↗
PubMed2005

Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer's disease.

BACKGROUND: Multiple genes have been provisionally associated with Alzheimer's disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. METHODS: The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. RESULTS: The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A- and T- among APOE4+ subjects when compared with APOE4- subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher's exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. CONCLUSION: These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer's disease.

Aged↗
PubMed2002

Assessment of the cervix after acetic acid wash: inter-rater agreement using photographs.

OBJECTIVE: To estimate the inter-rater agreement on the assessment of cervical photographs after acetic acid wash, using visual inspection with acetic acid categories. METHODS: Three raters individually assessed 144 photographs as negative, positive, or suspicious for cancer. The inter-rater agreement was analyzed using the unweighted and weighted kappa coefficient. To explore the reasons for concordancy and discordancy, photographs were compared on histologic evidence of cervical intraepithelial neoplasia and on testing for oncogenic types of human papillomavirus. RESULTS: Overall raw agreement among the three raters was 66.7% (96 of 144) with a kappa of 0.57 (95% confidence interval 0.48, 0.66). Pair-wise agreement using unweighted and weighted kappa was moderate to substantial: 0.54-0.60 and 0.56-0.63, respectively. There was concordance on negative in 25.7% (37 of 144) and on positive or suspicious for cancer in 41.0% (59 of 144). Cervical intraepithelial neoplasia II or III was not present on biopsy if photographs were concordant-negative, and the human papillomavirus test was less likely to be positive (relative risk 0.3; 95% confidence interval 0.2, 0.6) in concordant-negatives compared with concordant-positives, including suspicious for cancer. Cervical intraepithelial neoplasia II or III was more common in photographs that were concordant-positive, including suspicious for cancer, compared with discordants (relative risk 3.4, 95% confidence interval 1.5, 7.6). CONCLUSION: Based on photographs of the cervix taken after acetic acid wash, the level of agreement among raters using visual inspection with acetic acid categories was moderate to substantial, consistent with other commonly used tests.

Acetic Acid↗
PubMed2002

Preload-adjusted maximal power: a novel index of left ventricular contractility in atrial fibrillation.

BACKGROUND: Left ventricular contractility in atrial fibrillation is known to change in a beat to beat fashion, but there is no gold standard for contractility indices in atrial fibrillation, especially those measured non-invasively. OBJECTIVE: To determine whether the non-invasive index of contractility "preload-adjusted PWR(max)" (maximal ventricular power divided by the square of end diastolic volume) can accurately measure left ventricular contractility in a beat to beat fashion in atrial fibrillation. METHODS: Atrial fibrillation was induced experimentally using 60 Hz stimulation of the atrium and maintained in 12 sheep; four received diltiazem, four digoxin, and four no drugs (control). Aortic flow, left ventricular volume, and left ventricular pressure were monitored simultaneously. Preload-adjusted PWR(max), the slope of the end systolic pressure-volume relation (E(max)), and the maximum rate of change of left ventricular pressure (dP/dt(max)) were calculated in a beat to beat fashion. RESULTS: Preload-adjusted PWR(max) correlated linearly with load independent E(max) (p < 0.0001) and curvilinearly with load dependent dP/dt(max) (p < 0.0001), which suggested the load independence of preload-adjusted PWR(max). After five minutes of diltiazem administration, preload-adjusted PWR(max), dP/dt(max), and E(max) fell significantly (p < 0.0001) to 62%, 64%, and 61% of baseline, respectively. Changes were not significant after five minutes of digoxin (103%, 98%, and 102%) or in controls (97%, 96%, and 95%). CONCLUSIONS: Preload-adjusted PWR(max) correlates linearly with E(max) and is a useful measure of contractility even in atrial fibrillation. Non-invasive application of this method, in combination with echocardiography and tonometry, may yield important information for optimising the treatment of patients with atrial fibrillation.

Animals↗
PubMed2001

Dynamic compartmentalization of bacteria: accurate division in E. coli.

Positioning of the midcell division plane within the bacterium E. coli is controlled by the min system of proteins: MinC, MinD, and MinE. These proteins coherently oscillate from end to end of the bacterium. We present a reaction-diffusion model describing the diffusion of min proteins along the bacterium and their transfer between the cytoplasmic membrane and cytoplasm. Our model spontaneously generates protein oscillations in good agreement with experiments. We explore the oscillation stability, frequency, and wavelength as a function of protein concentration and bacterial length.

Adenosine Triphosphatases↗
PubMed2001

Branching and annihilating Lévy flights.

We consider a system of particles undergoing the branching and annihilating reactions A-->(m+1)A and A+A-->Ø, with m even. The particles move via long-range Lévy flights, where the probability of moving a distance r decays as r(-d-sigma). We analyze this system of branching and annihilating Lévy flights using field theoretic renormalization group techniques close to the upper critical dimension d(c)=sigma with sigma<2. These results are then compared with Monte Carlo simulations in d=1. For sigma close to unity in d=1, the critical point for the transition from an absorbing to an active phase occurs at zero branching. However, for sigma bigger than about 3/2 in d=1, the critical branching rate moves away from zero with increasing sigma, and the transition lies in a different universality class, inaccessible to controlled perturbative expansions. We measure the exponents in both universality classes and examine their behavior as a function of sigma.

Journal Article↗
PubMed2001

Multiple endocytic signals in the C-terminal tail of the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent protein kinase (PKA)-activated chloride channel that is localized to the plasma membrane and endosomal compartment. Endosomal targeting of CFTR is attributed to the Tyr(1424)-based internalization signal, identified in the C-terminal tail of the channel. Mutation of the Tyr(1424) residue could partly inhibit the endocytosis of CFTR and its association with the adapter protein AP-2. To reveal additional endosomal targeting signals, site-directed mutagenesis of both a chimaera, composed of a truncated form of interleukin 2 receptor alpha chain (TacT) and the C-terminal tail of CFTR (Ct), and the full-length CFTR was performed. Morphological and functional assays revealed the presence of multiple internalization motifs at the C-terminus, consisting of a phenylalanine-based motif (Phe(1413)) and a bipartite endocytic signal, comprising a tyrosine (Tyr(1424)) and a di-Leu-based (Leu(1430)-Leu) motif. Whereas the replacement of any one of the three internalization motifs with alanine prevented the endocytosis of the TacT-Ct chimaera, mutagenesis of Phe(1413)-Leu impaired the biosynthetic processing of CFTR, indicating that Phe(1413) is indispensable for the native structure of CFTR. In contrast, replacement of Leu(1430)-Leu- and Tyr(1424)-based signals with alanine increased the cell-surface density of both the chimaeras and CFTR in an additive manner. These results suggest that the internalization of CFTR is regulated by multiple endocytic sorting signals.

Amino Acid Motifs↗
PubMed2001

Ordered and self-disordered dynamics of holes and defects in the one-dimensional complex Ginzburg-Landau equation.

We study the dynamics of holes and defects in the 1D complex Ginzburg-Landau equation in ordered and chaotic cases. Ordered hole-defect dynamics occurs when an unstable hole invades a plane wave state and periodically nucleates defects from which new holes are born. The results of a detailed numerical study of these periodic states are incorporated into a simple analytic description of isolated "edge" holes. Extending this description, we obtain a minimal model for general hole-defect dynamics. We show that interactions between the holes and a self-disordered background are essential for the occurrence of spatiotemporal chaos in hole-defect states.

Journal Article↗
PubMed2001

The work-related fatal injury study: numbers, rates and trends of work-related fatal injuries in New Zealand 1985-1994.

AIMS: To determine the number and rates of work-related fatal injuries by employment status, occupation, industry, age and gender in New Zealand 1985-1994. METHODS: Potential cases of work-related injury deaths of persons aged 15-84 years were identified from the national electronic mortality data files. Main exclusions were deaths due to suicide and deaths due to motor vehicle crashes. The circumstances of the deaths of each fatal incident meeting inclusion criteria were then reviewed directly from coronial files to determine work-relatedness. RESULTS: The rate of work-related fatal injury in New Zealand was 5.03/100000 workers per year for the study period. There was a significant decline in crude rate over the study period. However, this was in substantial part accounted for by changes in occupation and industry mix. Older workers, male workers, self-employed workers, and particular occupational groups, all had substantially elevated rates. Agricultural and helicopter pilots, forestry workers and fishery workers had the highest rates. Farmers, forestry workers, and fishery workers also had high numbers of deaths, together accounting for nearly 40% of all deaths. CONCLUSIONS: This study has demonstrated that work-related fatal injury remains a pressing problem for New Zealand. Several areas in urgent need of prevention efforts were highlighted.

Accidents, Occupational↗
PubMed2001

Durability of combined aortic and mitral valve repair.

BACKGROUND: This study was undertaken to determine the durability of combined aortic and mitral valve repair. METHODS: From 1979 through 1999, 158 patients underwent simultaneous aortic and mitral valve repair. Multivariable, multi-phase hazard function analysis was used to determine risk factors for the outcomes of death and reoperation. RESULTS: Hospital mortality was 3%. Survival after operation was 97%, 93%, 82%, and 62% after 30 days and 1, 5, and 10 years, respectively. Risk factors for late death included aortic stenosis (p = 0.0001), older age (p = 0.002), and abnormal left ventricular function (p = 0.007). Thirty-six patients required reoperation for valvular dysfunction, and freedom from reoperation was 94%, 82%, and 65% after 1, 5, and 10 years, respectively. Risk factors for reoperation included severe aortic regurgitation (p = 0.004), aortic cusp shaving (p = 0.05), mitral valve chordal transfer (p = 0.004), and bovine pericardial annuloplasty (p = 0.002). Five-year freedoms from endocarditis, thromboembolism, and hemorrhage were 97%, 98%, and 99%, respectively, with freedom from any of these valve-related morbidities of 99%, 95%, and 94% after 1, 5, and 10 years, respectively. CONCLUSIONS: Double valve repair is associated with acceptable late survival and excellent freedom from valve-related morbidity, but limited durability. Therefore, double valve repair should be reserved for patients who cannot be anticoagulated, and should be used with caution in patients with aortic stenosis, rheumatic valve disease, or anterior mitral leaflet pathology.

Adolescent↗
PubMed2001

Is thrombophilia a factor in the development of hemiplegic cerebral palsy?

A population-based study of children with hemiplegic cerebral palsy (CP) was performed to investigate whether thrombophilic tendencies are implicated in the aetiology of the condition. Thirty-eight children (23 males, 15 females; mean age 8.7 years, SD 4.1 years) with hemiplegic CP were ascertained. Twenty-seven children(18 males, nine females; mean age 8.4 years, SD 4.3) gave consent for inclusion. The non-study group comprised five males and six females; mean age 9.4 years, SD 4.1. In six children, seven thrombophilic 'abnormalities' were identified. Five of these abnormalities were of an equivocal nature and probably did not represent true clinical thrombophilia; reasons for this interpretation are discussed. Contrary to other published non-population-based studies, we have not shown an association between thrombophilia and hemiplegic CP. More studies, including maternal studies, are required to explore this complex subject further.

Atrophy↗
PubMed2001

Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo.

Cyclic ADP-ribose is believed to be an important calcium-mobilizing second messenger in invertebrate, mammalian and plant cells. CD38, the best-characterized mammalian ADP-ribosyl cyclase, is postulated to be an important source of cyclic ADP-ribose in vivo. Using CD38-deficient mice, we demonstrate that the loss of CD38 renders mice susceptible to bacterial infections due to an inability of CD38-deficient neutrophils to directionally migrate to the site of infection. Furthermore, we show that cyclic ADP-ribose can directly induce intracellular Ca++ release in neutrophils and is required for sustained extracellular Ca++ influx in neutrophils that have been stimulated by the bacterial chemoattractant, formyl-methionyl-leucyl-phenylalanine (fMLP). Finally, we demonstrate that neutrophil chemotaxis to fMLP is dependent on Ca++ mobilization mediated by cyclic ADP-ribose. Thus, CD38 controls neutrophil chemotaxis to bacterial chemoattractants through its production of cyclic ADP-ribose, and acts as a critical regulator of inflammation and innate immune responses.

ADP-ribosyl Cyclase↗
PubMed2001

A study of the social and physical environment in catering kitchens and the role of the chef in promoting positive health and safety behaviour.

This is the account of a mixed method study of chefs and their kitchens in order to identify the nature of their workplace and how this affects their ability to manage health and safety in the kitchen. It included extended periods of observation, monitoring of physical parameters, analysis of records of reported accidents, and a series of reflexive interviews. The findings were integrated and then fed back in a smaller number of second interviews in order to test whether the findings fitted in with the chefs' understanding of their world. Major factors identified included survival in a market environment, the status of the chef (and the kitchen) within organisations, marked autocracy of chefs, and an increasing tempo building up to service time with commensurate heat, noise, and activity. In particular during the crescendo, a threshold shift in risk tolerance was identified. The factors, their interplay, and their implications for health and safety in the catering kitchen are discussed.

Accidents, Occupational↗
PubMed2001

Postpartum depression in women receiving public assistance: pilot study of an interpersonal-therapy-oriented group intervention.

OBJECTIVE: This study investigated whether a preventive intervention based on the principles of interpersonal psychotherapy administered to pregnant women would reduce the risk of postpartum major depression. METHOD: Thirty-seven pregnant women receiving public assistance who had at least one risk factor for postpartum depression were randomly assigned to a four-session group intervention or to a treatment-as-usual condition. Thirty-five of the women completed the study. Structured diagnostic interviews were administered to assess for postpartum major depression. RESULTS: Within 3 months after they gave birth, six (33%) of the 18 women in the treatment-as-usual condition had developed postpartum major depression, compared with none of the 17 women in the intervention condition. CONCLUSIONS: A four-session interpersonal-therapy-oriented group intervention was successful in preventing the occurrence of major depression during a postpartum period of 3 months in a group of financially disadvantaged women.

Adolescent↗