Search PubMed⌕ Search

Biomedical subjects

M Wallace

Publications and source records attributed to M Wallace.

At least 37 records · Page 2Linked to original sources
PubMed2001

Process evaluation of an on-site water testing program in remote Aboriginal communities in Western Australia.

A unique public health intervention introduced on-site water test kits into 19 communities in Western Australia in order to improve the frequency of water testing in remote Aboriginal communities. Resources, training and support were provided by the Health Department of Western Australia to enable the communities to conduct fortnightly water testing over a 12-month period. This study assesses how effective and appropriate the training and support strategies were, and the extent of acceptance of the program by the community 'water samplers'. A written survey of the participants (community water samplers), enabled their knowledge of the principles and the application of the test regime, and their satisfaction with both the training strategies and the resources to be evaluated. A structured phone survey was conducted mid-trial to re-assess participant knowledge, to ascertain the use of training resources and to identify barriers to regular testing. Details of the support that was provided, was documented systematically during the trial by the Health Department. The participants were satisfied with the format and content of the training workshops. Support services documentation disclosed that contact with the participants throughout the trial was limited. The acceptance of the program by the water samplers varied. Those who participated in the trial expressed the need for more feedback and support. A major reason for not participating in the trial was due to the water sampler leaving the community. The specific outcomes of the program and directions for future programs are discussed.

Adult↗
PubMed2001

Real progress--the patient's perspective.

Experience from a UK national telephone helpline SANELINE (run by the mental health charity SANE), showed that availability and access to better medications and services are among the most important issues for patients with mental illness. SANELINE, therefore, conducted a survey of patients' satisfaction with antipsychotic medication between July 1998 and February 1999. A total of 202 completed questionnaires were available for analysis. A majority of patients (56%) were treated with conventional neuroleptics, 20% with new 'atypical' antipsychotics and 11% were on a combination of conventional and novel antipsychotics. Virtually all respondents (99%) reported suffering from at least one side-effect, of which 31% were perceived as 'severe' or 'very severe'. The most common side-effects reported were depression/low mood (90%), sedation (88%), difficulty in thinking/concentrating (78%), insomnia (68%), dry mouth (65%), muscle/joint stiffness (45%), sexual dysfunction (43%) and weight gain (39%). Notably, 73% of those who had experienced weight gain reported it to be 'quite or extremely distressing'. Depression was rated as 'quite or extremely distressing' by 67% of sufferers and insomnia was similarly rated by 66% of patients. Despite the methodological limitations of the survey, the results suggest there is a high level of patient dissatisfaction and distress related to the currently available medications, which may have unfavourable effects on compliance and treatment outcome.

Adult↗
PubMed2001

Prevalence and extent of distress of adverse effects of antipsychotics among callers to a United Kingdom National Mental Health Helpline.

The aims of this cross-sectional survey were to assess psychotic sufferers' perception of the effectiveness of their medication, the distress caused by adverse effects and the impact these might have on overall patient satisfaction with treatment. Three hundred and forty-one people diagnosed with psychosis who called a national mental health helpline (SANELINE) in the UK, between July 1998 and February 1999, were asked to take part in the survey. They were given a choice of either a postal questionnaire or a telephone interview in which the same questionnaire was used. One hundred and nineteen were interviewed on the telephone and 83 (out of 222) returned completed questionnaires. In total, information was available from 202 callers. Almost one-half of the respondents were dissatisfied with their medication, and almost all of them reported experiencing at least one adverse effect. Depression (or low mood), sedation and difficulty thinking and concentrating were the most prevalent adverse effects. Weight gain was the most distressing, particularly to women. Those taking atypical antipsychotics were significantly more likely than those on typical antipsychotics to experience insomnia and dry mouth, but were less likely to perceive depression and difficulty thinking/concentrating as quite or extremely distressing. Low satisfaction, as opposed to high satisfaction, was significantly associated with reporting weight gain, difficulty thinking/concentrating, insomnia and sexual dysfunction. It was also significantly associated with reporting weight gain, difficulty thinking/concentrating, muscle/joint stiffness and depression as quite or extremely distressing. Attention should be given to the management of cognitive impairment and weight gain as adverse effects of antipsychotics. Doctors should be more open to discussing the risks and nature of adverse effects with patients who should also be encouraged to do so.

Adult↗
PubMed2001

Cholecystokinin-Stimulated mebrofenin (99mTc-Choletec) hepatobiliary scintigraphy in asymptomatic postcholecystectomy individuals: assessment of specificity, interobserver reliability, and reproducibility.

OBJECTIVES: Cholecystokinin-stimulated hepatobiliary scintigraphy (CCK-HBS) is a noninvasive method reported to be highly accurate in the diagnosis of sphincter of Oddi dysfunction. Our primary aim was to assess the specificity of CCK-HBS by evaluating its ability to exclude disease in 20 asymptomatic postcholecystectomy individuals. Secondary aims were to assess the interobserver reliability in scoring the CCK-HBS examinations between three blinded observers and to assess reproducibility of CCK-HBS repeated in the same individuals. METHODS: Twenty asymptomatic postcholecystectomy individuals with normal liver serum chemistries underwent CCK-HBS on two separate occasions. Three nuclear medicine specialists read each CCK-HBS study in a blinded fashion. RESULTS: There was good agreement between the three observers reading the same scans for both the first scan (kappa = 0.554) and the second scan (kappa = 0.507). There was poor agreement between the first and second scans on the same patient, read by the same nuclear medicine specialist (kappa = 0.062-0.385). The overall specificity of the CCK-HBS score was 77.5%; however, the specificity was only 60% when a true negative was defined as two negative CCK-HBS examinations. CONCLUSIONS: Quantitative CCK-HBS is of poor specificity in asymptomatic postcholecystectomy individuals. Hence, it is of questionable value in excluding sphincter of Oddi dysfunction in patients suspected to suffer from this disorder.

Adult↗
PubMed2001

CaMKIV/Gr is dispensable for spermatogenesis and CREM-regulated transcription in male germ cells.

The calcium/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is expressed in male germ cells and spermatids and has been implicated in controlling the differentiation of germ cells into mature spermatozoa. The function of CaMKIV/Gr in spermatogenesis was investigated using CaMKIV/Gr-deficient mice generated by targeted gene disruption. CaMKIV/Gr-deficient males exhibited normal spermatogenesis, and their fertility was similar to that of wild-type littermates. Notwithstanding the function of CaMKIV/Gr as an activator of cAMP response element (CRE)-dependent transcription, mRNA levels of several testis-specific CRE modulator (CREM)-regulated genes were unaltered. These results indicate that CaMKIV/Gr is not essential for spermatogenesis or for CRE-regulated gene transcription in the testis.

Alternative Splicing↗
PubMed2001

Sexuality.

Explore the source record for details and available documents.

Aged↗
PubMed2000

Whole body positron emission tomography imaging of activated lymphoid tissues during acute simian-human immunodeficiency virus 89.6PD infection in rhesus macaques.

Mechanisms of acute retroviral pathogenesis have been examined during primary infection of rhesus macaques with simian-human immunodeficiency virus 89.6PD (SHIV(89.6PD)). During acute infection, between initial exposure and establishment of antigen-specific immune responses that stabilize the virus burden, rapid immune system changes influence the viral set-point and dictate subsequent steps in disease progression. In a previous study, we described specific patterns of lymphocyte activation during acute SHIV(89.6PD) infection. We now extend these studies to describe lymphoid tissue activation, using whole body positron emission tomography (PET) and the radioactive tracer 2-[(18)F]fluorodeoxyglucose (FDG). Within a few days after primary infection by intravenous, intrarectal, or intravaginal routes, PET-FDG imaging revealed a distinct pattern of lymphoid tissue activation centered on axillary, cervical, and mediastinum lymph nodes. Increased tissue FDG uptake preceded fulminant virus replication at these sites, suggesting that a diffusible factor of host or viral origin was responsible for lymphoid tissue changes. These data show that activation of lymphoid tissues in the upper body is an early response to virus infection and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies.

Acute Disease↗
PubMed2000

Synergistic activation of p53-dependent transcription by two cooperating damage recognition pathways.

High level activation of p53-dependent transcription occurs following cellular exposure to genotoxic damaging agents such as UV-C, while ionizing radiation damage does not induce a similarly potent induction of p53-dependent gene expression. Reasoning that one of the major differences between UV-C and ionizing radiation damage is that the latter does not inhibit general transcription, we attempted to reconstitute p53-dependent gene expression in ionizing irradiated cells by co-treatment with selected transcription inhibitors that alone do not activate p53. p53-dependent transcription can be dramatically enhanced by the treatment of ionizing irradiated cells with low doses of DRB, which on its own does not induce p53 activity. The mechanism of ionizing radiation-dependent activation of p53-dependent transcription using DRB is more likely due to inhibition of gene transcription rather than prolonged DNA damage, as the non-genotoxic and general transcription inhibitor Roscovitine also synergistically activates p53 function in ionizing irradiated cells. These results identify two distinct signal transduction pathways that cooperate to fully activate p53-dependent gene expression: one responding to lesions induced by ionizing radiation and the second being a kinase pathway that regulates general RNA Polymerase II activity.

Amino Acid Sequence↗
PubMed2000

Analysis of a gene encoding Rpn10 of the fission yeast proteasome reveals that the polyubiquitin-binding site of this subunit is essential when Rpn12/Mts3 activity is compromised.

Substrates are targeted for proteolysis by the ubiquitin pathway by the addition of a polyubiquitin chain before being degraded by the 26 S proteasome. Previously, a subunit of the proteasome, S5a, was identified that was able to bind to polyubiquitin in vitro and thus proposed to act as a substrate recognition component. Deletion of the corresponding Saccharomyces cerevisiae gene, MCB1/RPN10, rendered cells viable indicating that other proteasomal polyubiquitin receptors must exist. In this study, we describe pus1(+), the fission yeast homologue of RPN10. This gene is also not required for cell viability; however, the Deltapus1 mutant is synthetically lethal with mutations in other proteasomal component-encoding genes, namely mts3, pad1, and mts4 (RPN12, RPN11, and RPN1). Overexpression of pus1(+) is able to rescue mts3-1 at 32 degrees C but overexpression of a cDNA encoding a version of Pus1 that does not bind to polyubiquitin cannot and leads to greatly reduced viability when used to rescue the mts3-1Deltapus1 double mutant. The Mts3 protein was unable to bind to polyubiquitin in vitro, but the Pus1 and Mts3 proteins were found to bind to one another in vitro, which taken together with the genetic data suggests that they are also closely associated in vivo.

Amino Acid Sequence↗
PubMed2000

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial.

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.

Aged↗
PubMed2000

Vaccination with tat toxoid attenuates disease in simian/HIV-challenged macaques.

The Tat protein is essential for HIV type 1 (HIV-1) replication and may be an important virulence factor in vivo. We studied the role of Tat in viral pathogenesis by immunizing rhesus macaques with chemically inactivated Tat toxoid and challenging these animals by intrarectal inoculation with the simian/human immunodeficiency virus 89.6PD. Immune animals had significantly attenuated disease with lowered viral RNA, interferon-alpha, and chemokine receptor expression (CXCR4 and CCR5) on CD4(+) T cells; these features of infection have been linked to in vitro effects of Tat and respond similarly to extracellular Tat protein produced during infection. Immunization with Tat toxoid inhibits key steps in viral pathogenesis and should be included in therapeutic or preventive HIV-1 vaccines.

Animals↗
PubMed2000

Corneal insult affects the production and distribution of FGF-2 within the lacrimal gland.

The purpose of this study was to determine the distribution of FGF-2 within rabbit lacrimal glands and to determine whether corneal insult affects that distribution. The scarified corneas of experimental animals were inoculated either with adenovirus type 5 or buffer. Control animals were either untreated, or animals whose corneas were scarified. Twenty-one days later all animals were killed and the lacrimal glands were studied by immunocytochemistry and Western blotting to detect FGF-2. In untreated control animals, FGF-2 was immunolocalized predominantly within a population of elongated cells in the basal epithelium of ducts, and to a lesser degree in the basal epithelium of the acini. The elongated immunopositive cells appear to be myoepithelial cells known to be present at these sites. Interstitial cells around ducts and acini, and the basement membranes of the ducts and acini, were also immunopositive for FGF-2. Twenty-one days after adenovirus inoculation and scarification of the cornea, immunopositivity for FGF-2 was dramatically decreased in basement membranes, but increased within myoepithelial cells of the duct epithelium. These myoepithelial cells were frequently enlarged, bulging toward the duct lumen. In animals whose corneas were inoculated with buffer and scarified, or animals whose corneas were simply scarified, the changes in the lacrimal gland were similar, but somewhat less pronounced, to those of adenovirus-inoculated animals. Western blots confirmed the presence of FGF-2 immunoreactivity in all groups. The major band in untreated controls was at 24 kD, whereas all animals with corneal scarification had major bands at 38 kD. Densitometry of Western blots demonstrated that the amount of 24 kD FGF-2 present within the lacrimal gland after corneal scarification was at least 50% less than in untreated controls, whereas 38 kD FGF-2 was at least ten-fold greater. Our findings indicate that corneal scarification results in an altered distribution of FGF-2 within the lacrimal gland, which involves a decrease in low molecular weight FGF-2 and a dramatic increase in a higher molecular weight isoform of FGF-2. FGF-2 may be released from myoepithelial cells apically (exocrine) into the tear fluid and basally (autocrine/paracrine) into the connective tissue, as well as from extracellular complexes within basal laminae.

Adenoviridae Infections↗
PubMed2000

Distribution of growth factors and immune cells are altered in the lacrimal gland during pregnancy and lactation.

We have undertaken a series of studies to elucidate the roles of growth factors (FGF-2, EGF, TGF-beta1) and prolactin (PRL) in lacrimal gland function during pregnancy and lactation, and to better understand the status of the immune system within the lacrimal gland during those physiological states. In this initial study, lacrimal glands of pregnant (d15, d29), lactating (9d, 22d), and adult female control rabbits, were evaluated by immunohistochemistry, Western blotting and image analysis. In control rabbits EGF, TGF-beta1, and PRL, were immunolocalized primarily in the apical cytoplasm of intralobular ductal epithelial cells, and acini demonstrated a basement membrane-associated immunopositivity for TGF-beta1. FGF-2 immunolocalized in myoepithelial cells in the basal ductal epithelium and complexed to the basement membrane enclosing ducts and acini. Cells immunopositive for immune cell markers (RTLA and CD18) were apparent primarily around interlobular ducts. In d29 pregnant rabbits immunopositivity for EGF and TGF-beta1 was increased within intralobular ducts, both apically and basally, and within some interlobular ductal epithelial cells. Immunopositivity for PRL was strongest in d29 pregnant rabbits within the apical and basal cytoplasm of intralobular ductal epithelial cells. Immunopositivity for FGF-2 in myoepithelial cells was strong in d15 and d29 pregnant rabbits, although basement membrane-associated immunopositivity around acini was often decreased. Immunostaining for EGF and TGF-beta1 in lactating rabbits was similar to that in d29 pregnant rabbits, although basement membrane-associated immunopositivity around acini was more comparable to controls. By 22d lactation immunopositivity for FGF-2 closely resembled that in controls. Image analysis of pregnant and lactating rabbits demonstrated that cells immunopositive for RTLA and CD18 were less abundant around ducts and more abundant between acini, although in 22d lactating rabbits the size of periductal foci was increased to nearly that of controls. Western blots correlated well with the immunohistochemistry. Our findings demonstrate that pregnancy and lactation are accompanied by a shift in the distributions of growth factors and PRL, suggestive of increased release both apically into the lacrimal fluid and basally into the interstitium. Additional shifts in the distributions of cells of the immune system from periductal foci to interacinar sites suggest that there is a recruitment of immune cells away from ducts and toward the connective tissue interstitium surrounding the acini, possibly as part of a heightened state of immune readiness during pregnancy and lactation.

Animals↗
PubMed2000

Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP.

We generated transgenic mice in which red, green, yellow, or cyan fluorescent proteins (together termed XFPs) were selectively expressed in neurons. All four XFPs labeled neurons in their entirety, including axons, nerve terminals, dendrites, and dendritic spines. Remarkably, each of 25 independently generated transgenic lines expressed XFP in a unique pattern, even though all incorporated identical regulatory elements (from the thyl gene). For example, all retinal ganglion cells or many cortical neurons were XFP positive in some lines, whereas only a few ganglion cells or only layer 5 cortical pyramids were labeled in others. In some lines, intense labeling of small neuronal subsets provided a Golgi-like vital stain. In double transgenic mice expressing two different XFPs, it was possible to differentially label 3 neuronal subsets in a single animal.

Animals↗
PubMed2000

Predicting substance abuse among youth with, or at high risk for, HIV.

This article describes data from 4,111 males and 4,085 females participating in 10 HIV/AIDS service demonstration projects. The sample was diverse in age, gender, ethnicity, HIV status, and risk for HIV transmission. Logistic regression was used to determine the attributes that best predict substance abuse. Males who were younger; HIV positive; homeless; involved in the criminal justice system; had a sexually transmitted disease (STD); engaged in survival sex; and participated in risky sex with men, women, and drug injectors were most likely to have a substance abuse history. For females, the same predictors were significant, with the exception of having an STD. Odds ratios as high as 6 to 1 were associated with the predictors. Information about sexual and other risk factors also was highly predictive of substance abuse issues among youth.

Acquired Immunodeficiency Syndrome↗