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S Kennedy

Publications and source records attributed to S Kennedy.

At least 73 records · Page 4Linked to original sources
PubMed2001

A comparison of diabetes patient's self-reported health status with hemoglobin A1c test results in 11 California health plans.

PURPOSE: To examine the relationship between hemoglobin A1c (HbA1c) test rates and values and various self-reported measures of health status within a sample of diabetes patients drawn from 11 California health plans, with a focus on improving diabetes care in this patient population. DESIGN: The analysis relies on data obtained from medical records of a sample population of 4,747 diabetes patients and a patient survey mailed to a large subsample of patients included in the medical-records analysis. METHODS: Descriptive methods were used to compare the medical records and survey-data results. PRINCIPAL FINDINGS: There were substantive differences noted between diabetes patients' self-reported health status, their level of satisfaction with the care they received, and the actual care they received. There was a large discrepancy between diabetes patients' perceptions of the care they received for their diabetes, which was overwhelmingly positive, and the HbA1c test-frequency rates observed across the 11 health plans studied, which were low. CONCLUSIONS: Patients' self-reports of health status, satisfaction with care, and extent of control over diabetes--a chronic condition that may have few perceptible symptoms--are associated with significant methodological limitations. Our examination of the relationship between perceived levels of self-management of diabetes and test status indicated that for patients who had at least one HbA1c test, some education during that process may have resulted in behavioral change. Patients who received no tests, however, may remain unaware of their glycemic control and the long-term consequences associated with even mild hyperglycemia. A clear need thus exists to educate diabetes patients about their health status. Health plan and provider group investments in educational efforts aimed at increasing testing rates are likely to lead to improved glycemic control and a reduction in the incidence of diabetes-related complications and related expenditures.

California↗
PubMed2000

Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing.

C to U editing of apolipoprotein B (apoB) mRNA involves the interaction of a multicomponent editing enzyme complex with a requisite RNA sequence embedded within an AU-rich context. This enzyme complex includes apobec-1, an RNA-specific cytidine deaminase, and apobec-1 complementation factor (ACF), a novel 65-kDa RNA-binding protein, that together represent the minimal core of the editing enzyme complex. The precise composition of the holo-enzyme, however, remains unknown. We have previously isolated an enriched fraction of S100 extracts, prepared from chicken intestinal cells, that displays apoB RNA binding and which, following supplementation with apobec-1, permits efficient C to U editing. Peptide sequencing of this most active fraction reveals the presence of ACF as well as GRY-RBP, an RNA-binding protein with approximately 50% homology to ACF. GRY-RBP was independently isolated from a two-hybrid screen of chicken intestinal cDNA. GRY-RBP binds to ACF, to apobec-1, and also binds apoB RNA. Experiments using recombinant proteins demonstrate that GRY-RBP binds to ACF and inhibits both the binding of ACF to apoB RNA and C to U RNA editing. This competitive inhibition is rescued by addition of ACF, suggesting that GRY-RBP binds to and sequesters ACF. As further evidence of the role of GRY-RBP, rat hepatoma cells treated with an antisense oligonucleotide to GRY-RBP demonstrated an increase in C to U editing of endogenous apoB RNA. ACF and GRY-RBP colocalize in the nucleus of transfected cells and, in cotransfection experiments with apobec-1, each appears to colocalize in a predominantly nuclear distribution. Taken together, the results indicate that GRY-RBP is a member of the ACF gene family that may function to modulate C to U RNA editing through binding either to ACF or to apobec-1 or, alternatively, to the target RNA itself.

APOBEC-1 Deaminase↗
PubMed2000

Inhibition of CCR5-dependent HIV-1 infection by hairpin ribozyme gene therapy against CC-chemokine receptor 5.

CCR-5 is a major cellular coreceptor for R5 strains of HIV-1. Individuals carrying a homozygous 32-base-pair deletion in this gene are apparently healthy and are relatively resistant to HIV-1 infection. Since CCR5 appears to be dispensable for the host, but important for initial HIV-1 infection, CCR5 mRNA is an excellent therapeutic target for inhibiting HIV-1 replication via ribozyme knockout. We report here that hairpin ribozymes are able to reduce cellular CCR5 mRNA and cell surface CCR5 when stably introduced into PM1 cells by transduction with recombinant adenoassociated viral vector. The ribozymes effectively protect the cells from infection by R5 HIV-1 strains or non-syncytium-inducing clinical isolates commensurate with a reduction in CCR5 mRNA. These results suggest a novel gene therapy approach to preventing or slowing the disease progression of HIV-1 infection.

CCR5 Receptor Antagonists↗
PubMed2000

A rapid, quantitative method for measuring leukocyte adhesion to normal and balloon-injured arteries in vitro.

Many of the currently available techniques for quantifying leukocyte adhesion require monolayers of cells and are therefore unsuitable for use in ex vivo arterial tissue. Here we describe a rapid method to measure adhesion of leukocytes to intact artery strips and to determine the effect of artery injury on adhesiveness of leukocytes with and without activation. Leukocytes were isolated from rabbit blood, labelled with 51Cr, and added to the luminal face of the left and right subclavian arteries derived from the same animal. In some experiments the endothelium was removed before addition of leukocytes and in another series of experiments the artery was injured by inflating a balloon catheter within the lumen in vitro before leukocyte addition. After washing, the adhesion of labelled leukocytes was quantified by gamma counting. To determine localization of the leukocytes, some arteries were fixed in situ and examined microscopically, with confirmation of leukocyte identification by enzyme cytochemistry. The adhesion of leukocytes increased progressively during 60 min and was inhibited by reducing the temperature to 4 degrees C. Adhesion was increased by the nitric oxide synthase inhibitor L-NAME. Stretching the artery wall in vitro using a balloon catheter increased leukocyte adhesion within 1 h after injury. In contrast, this did not occur following simple arterial denudation. Histological examination of stained en face preparations and transverse sections of the subclavian arteries revealed loosely adherent granulocytic leukocytes on the endothelial surface. This technique is straightforward and allows accurate and rapid measurement of autologous leukocyte adhesion to normal and pathologically altered arteries ex vivo.

Angioplasty, Balloon↗
PubMed2000

Pulmonary pathology of harbour porpoises (Phocoena phocoena) stranded in England and Wales between 1990 and 1996.

The pathological changes observed in the lungs of 197 freshly dead to moderately decomposed harbour porpoises (Phocoenaphocoena) stranded in England and Wales between October 1990 and December 1996 were reviewed. In 135 (69 per cent of the cases) macroscopic nematode infections of the bronchial tract with Pseudalius inflexus and Torynurus convolutus, either singly or in combination, were recorded, and 106 (54 per cent) also had P inflexus within the pulmonary blood vessels. All the macroscopically parasitised porpoises were adults or juveniles although two neonates had histological evidence of nematode infection. There were 62 cases of mild to severe, subacute to chronic bronchitis and bronchiolitis, 113 cases of mild to severe chronic granulomatous interstitial pneumonia, and 34 cases of mild to severe vasculitis or thrombovasculitis of pulmonary blood vessels attributable to these nematode infections. In 35 cases necropurulent or purulent (broncho)pneumonias were attributed either to secondary bacterial infections of the lungs or to septicaemias associated in seven cases with Streptococcus canis, in two cases with group B Salmonella species, in one case with Escherichia coli and in one case with Streptococcus lactis. The pulmonary lesions in 67 animals known or diagnosed to have been entrapped in fishing gear were non-specific and included persistent foam in the airways in 45 cases, diffuse congestion in 53, oedema in 50, and multifocal intra-alveolar haemorrhage in 33 cases. Seven cases of acute fibrinous or chronic fibrous pleuritis, seven cases of chronic necropurulent pneumonia associated with mycotic infections, four porpoises with traumatic lesions of the thorax and other parts of the body consistent with fatal attack from bottlenose dolphins (Tursiops truncatus), and one case of diffuse bronchointerstitial pneumonia associated with generalised morbillivirus infection were also recorded.

Animals↗
PubMed2000

Modern combined oral contraceptives for pain associated with endometriosis.

BACKGROUND: Endometriosis is a major women's health-care problem. It causes pain and/or infertility, and affects millions of women worldwide. Endometriosis is defined according to histological criteria by the presence of tissue resembling endometrium in sites outside the uterus, most commonly the ovaries and peritoneum. The aim of treatment has been to remove the deposits of ectopic endometrium that are thought to be responsible for the symptoms of endometriosis. This can be achieved surgically by destroying or removing the implants; medical therapies induce atrophy within the hormonally-dependent ectopic endometrium. The duration of hormonal treatment may be limited by unwanted side effects. There is some evidence, however, from epidemiological research that current use of the combined oral contraceptive pill (OCP) is associated with a reduced incidence of endometriosis. The combined pill has the great advantage over other hormonal treatments that it can be taken indefinitely. OBJECTIVES: The aim of this review was to establish the role of modern oral contraceptives in the management of painful symptoms ascribed to endometriosis. SEARCH STRATEGY: The search strategy of the Menstrual Disorders Group was utilised to identify all randomised trials of the use of oral contraceptives in the treatment of symptomatic endometriosis. In addition a search of the Cochrane Controlled Trials Register was undertaken together with approaches to pharmaceutical companies. SELECTION CRITERIA: All truly randomised controlled trials of the use of oral contraceptive pills in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis made visually at a surgical procedure, were included. DATA COLLECTION AND ANALYSIS: Study quality assessment and data extraction was carried out independently by two reviewers. One of the assessors was an expert in the content matter. MAIN RESULTS: Only one study was identified which satisfied the inclusion criteria. The oral contraceptive used in a conventional manner was less effective than a GnRH analogue in the relief of dysmenorrhoea. No significant difference was noted between the effectiveness of the oral contraceptive pill and a GnRH analogue in the relief of dyspareunia or non-menstrual pain. Headaches and weight gain were more commonly associated with oral contraceptive usage than with GnRH analogue usage whereas hot flushes, insomnia and vaginal dryness were less common. REVIEWER'S CONCLUSIONS: There is a paucity of data relating to the use of oral contraceptive preparations in the treatment of symptomtic endometriosis. The data such as it is supports the common practice of the use of the oral contraceptive pill as a first line therapy but further research is required to fully evaluate its role in the management of endometriosis.

Contraceptives, Oral↗
PubMed2000

Experimental infection of colostrum deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiates PCV2 replication.

Experimental infection of colostrum-deprived (CD) pigs with a combined inoculum of porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) potentiated the replication and distribution of PCV2 virus, when compared with pigs inoculated with PCV2 alone. The replication and distribution of PRRSV in dually infected pigs was not enhanced, when compared to pigs inoculated with PRRSV alone. The mechanisms involved in the potentiation of PCV2 replication in PCV2/PRRSV and PCV2/porcine parvovirus (PPV) dually infected pigs may relate to the fact that monocyte/macrophage cell types are common targets of these 3 viruses.

Animals↗
PubMed2000

Neurohormonal responses to D-fenfluramine in healthy elderly subjects. A placebo-controlled study.

Considering age-related changes in serotonin (5HT) function, we examined normative data of prolactin (PRL) and cortisol (CORT) responses to D-fenfluramine (D-FEN) in healthy elderly subjects. Twenty-three healthy male and female volunteers aged 60-86 participated in a single-blind, placebo-controlled, fixed-order, crossover-design challenge test. Two baseline PRL and CORT values and the responses of these hormones to 30 mg of oral D-FEN and placebo over a 4 h period were measured on two separate sessions. PRL and CORT responses were significantly greater following D-FEN than after placebo. Peak PRL responses (maximum change from baseline following D-FEN) were relatively robust compared to peak CORT responses. Peak PRL concentration was positively correlated with plasma D-nor-FEN concentration. Gender and aging had no effect on hormonal responses in the elderly. Although the weight adjusted dose used in this study was higher than the therapeutic dose of D-FEN, PRL responses were modest and only two participants experienced side effects. D-FEN is a safe serotonergic probe and PRL responsivity to D-FEN is a reliable index of central 5HT function in the elderly. An age-related decline in serotonergic function must be considered in determining the dose requirement for maximal hormonal responses to D-FEN challenge tests in the elderly.

Aged↗
PubMed2000

Correlation of leukocyte adhesiveness, adhesion molecule expression and leukocyte-induced contraction following balloon angioplasty.

1. The aim of this study was to examine the changes in leukocyte adhesion and leukocyte-induced contraction in balloon-injured rabbit subclavian artery and to correlate these changes with vessel morphology and expression of adhesion molecules on the injured arteries. 2. Rabbits were anaesthetized and their left subclavian arteries were injured by balloon inflation and withdrawal followed by sacrifice at 2, 24, 48 h or 8 days after injury. The left and right subclavian arteries were removed and leukocytes were isolated from autologous rabbit blood. Leukocyte-induced contraction was measured in 5-HT precontracted artery rings and leukocyte adhesion was measured using (51)Cr-labelled leukocytes. Immunocytochemistry using paraffin-embedded tissue was employed to detect changes in the expression of adhesion molecules on injured arteries. 3. Autologous leukocytes caused a contraction of rabbit subclavian artery rings, which was prevented by L-NAME (10(-3) M). Balloon-induced injury abolished the contractile response to leukocytes, which correlated with loss of carbachol-induced relaxation 4. Balloon injury markedly enhanced the adhesiveness of the subclavian artery for leukocytes, most notably at 24 and 48 h after injury (1.7 and 1.8 fold respectively). Increased leukocyte adhesion at these two time points correlated with an upregulation of E-selectin, P-selectin and VCAM-1 expression on the remaining endothelium of the injured artery. 5. Vessel morphology revealed that balloon inflation had induced an infiltration of inflammatory cells into the vessel wall, the greatest increase being seen at 24 h after injury. 6. It is concluded that an increase in the expression of E-selectin, P-selectin and VCAM-1 following balloon-induced injury leads to enhanced leukocyte adhesion and migration into the injured vessel.

Angioplasty, Balloon↗
PubMed2000

A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation.

The sequential tissue distribution of virus was investigated using virus isolation and immunofluorescence tests in 1-day-old piglets inoculated with porcine circovirus 2 (PCV2) and/or porcine parvovirus (PPV). Enlarged mesenteric lymph nodes were seen in the pig inoculated with PCV2 alone and killed at 26 days post-inoculation (PI). One of the pigs inoculated with PCV2 and PPV and killed at 21 days PI had an enlarged liver. The pig killed at 26 days PI in this group had enlarged liver, kidneys and heart. Histopathological changes were seen in lymphoid tissues of the pigs inoculated with PCV2 alone and killed at 14 and 26 days PI. Similar, but more severe, lesions were observed in the pigs infected with PCV2 and PPV and killed from 10 days PI onwards. Histological lesions of nephritis, pneumonia and hepatitis were also apparent in these animals. Mild nephritis was also seen in the pigs infected with PPV alone and killed at 14 and 26 days PI. Moderate amounts of PPV antigen were detected in tissues from the pigs inoculated with PPV alone and killed at 14 days PI. Low levels of PCV antigen were detected, mainly in lymphoid tissues, in the pigs inoculated with PCV alone and killed at 14 days PI. Low to moderate amounts of PCV antigen were detected in a wider range of tissues in the pig in this group killed at 26 days PI. In the pigs inoculated with both viruses, PPV antigen was detected in tissues of pigs killed from 3 to 26 days PI with maximal amounts detected between 6 and 14 days PI. PCV2 antigen was detected in low to moderate amounts in the tissues of pigs killed at 14 days PI. Large amounts of PCV2 antigen were detected in most of the tissues from pigs in this group killed between 17 and 26 days PI. Virus isolation results for PCV2 generally correlated well with the results for immunofluorescent staining. PPV was isolated from almost all tissues from pigs inoculated with PCV2 and PPV, a much higher incidence of positive tissues than observed for immunofluorescent staining.

Animals↗
PubMed2000

Causes of chronic pelvic pain.

Chronic pelvic pain (CPP) is a common and debilitating condition, and yet remarkably little is known about what causes the pain. In this chapter we present a model of CPP which emphasizes the multifactorial nature of the problem. A range of physical causes are discussed, including endometriosis, pelvic inflammatory disease (PID), adhesions, irritable bowel syndrome, interstitial cystitis, musculo-skeletal factors and nerve-related pain. The role of the nervous system in the genesis and moderation of pain is explored. The importance of psychological factors is discussed, both as a primary cause of pain and as a factor which affects the pain experience. As with other chronic syndromes, the biopsychosocial model offers a way of integrating physical causes of pain with psychological and social factors.

Chronic Disease↗
PubMed2000

Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus.

Post-weaning multisystemic wasting syndrome (PMWS) has recently emerged as an important disease of pigs in North America, Europe and Asia. Porcine circovirus type 2 (PCV2) and porcine parvovirus (PPV) have been isolated from affected pigs. To investigate the pathogenicity of these isolates, groups of colostrum-deprived conventional pigs were inoculated with PCV2 alone (n=4), PPV alone (n=3) or dually with PCV2 and PPV (n=7) and examined post mortem between 21 and 26 days post-infection (dpi). Two control pigs were inoculated with an uninfected cell culture lysate. All pigs that received both viruses became dull at approximately 10-12 dpi and six of these animals subsequently developed jaundice. Hepatomegaly and enlarged kidneys were prominent post-mortem findings in these animals. Histopathological examination revealed severe macrophage infiltration, syncytia formation and numerous cytoplasmic and nuclear amphophilic inclusion bodies in lymphoid tissues. Granulomatous lesions were apparent in liver, lung, kidney, pancreas, myocardium, intestines, testis, brain and salivary, thyroid and adrenal glands. Abundant PCV2 antigen was detected in affected tissues. Only one of the four pigs inoculated with PCV2 alone developed clinical signs, but they all had histopathological lesions which, although less severe, were similar to those in the dually infected animals. The control pigs and those infected with PPV alone remained clinically normal and did not have gross lesions. The only histopathological lesion seen in these animals was mild interstitial nephritis in the pigs infected with PPV alone. These results indicate that lesions of PMWS can be induced by inoculating pigs with PCV2 alone, thereby fulfilling Koch's postulates. Concurrent infection with PPV increased the severity of the lesions, suggesting that co-factors are important in the pathogenesis of PMWS.

Animals↗
PubMed2000

Toxoplasmosis in beluga whales (Delphinapterus leucas) from the St Lawrence estuary: two case reports and a serological survey.

Toxoplasmosis was diagnosed in two free-ranging beluga whales from the St Lawrence estuary, Quebec, Canada, in 1988 and 1998. Histologically, tachyzoites and bradyzoites were present in the brain, spleen, lymph nodes, adrenals and lungs of both animals, and in the thymus of one. These organisms were readily labelled by an indirect immunohistochemical method for Toxoplasma gondii antigens. In the lymph nodes, spleen and lungs the organisms were associated with histiocytic infiltration. In the brain of one animal they were associated with mild multifocal gliosis and haemorrhages. There was no evidence of concomitant morbillivirus infection. Serum samples were collected from 22 beluga whales stranded between 1995 and 1998 on the shores of the St Lawrence Estuary and examined for antibodies to T. gondii by the modified agglutination test. Antibody titres of s25 were found in six (27%) of the animals. This is the first confirmed report of toxoplasmosis in beluga whales.

Animals↗
PubMed2000

Pre-treatment EEG and it's relationship to depression severity and paroxetine treatment outcome.

An array of variables have been assessed as potential early predictors of antidepressant response in depressed patients. This exploratory study examined the relationship of clinical outcome, following pharmacotherapeutic treatment, with quantitative electroencephalographic (EEG) features assessed prior to treatment onset. In 70 major affective disorder patients, pre-treatment spectrum-analysed topographic EEG indices (absolute power, relative power, mean frequency, inter-hemispheric power asymmetry and coherence for 4 frequency bands) were assessed in relation to baseline HAM-D ratings and HAM-D rating changes following 6 weeks of open-label paroxetine treatment. EEG slow wave (theta) activities were positively correlated with depression ratings prior to treatment. Of the patients (n = 51) completing treatment, 80% evidenced a >50% reduction in HAM-D ratings. Improved rating changes in general were found to be negatively related to slow (delta and theta) wave activity and positively related to fast (beta) activity at frontal recording sites. Findings are discussed in relation to the neurochemistry and neurobiology of depressive disorders.

Adult↗