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Biomedical subjects

S Kennedy

Publications and source records attributed to S Kennedy.

At least 91 records · Page 5Linked to original sources
PubMed2000

Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis.

In-vitro fertilization (IVF) is an effective infertility treatment for women with endometriosis, but most women need to undergo several cycles of treatment to become pregnant. This case-control study was designed to assess how consistently women with ovarian endometriosis respond to ovarian stimulation in consecutive treatment cycles compared to women with tubal infertility. We compared outcome measures in 40 women with a history of surgically confirmed ovarian endometriosis and 80 women with tubal infertility, all of whom had at least three IVF treatment cycles. The groups were matched for age and early follicular follicle stimulating hormone (FSH) concentration at their first IVF cycle. Outcome measures included number of follicles, number of oocytes, peak oestradiol concentration and number of FSH ampoules required per follicle. Cumulative pregnancy and live birth rates were calculated in both groups. The ovarian endometriosis group had a significantly poorer ovarian response and required significantly more ampoules of FSH per cycle, a difference that became greater with each subsequent cycle. However, cumulative pregnancy (63.3 versus 62.6% by fifth cycle) and live birth (46.8 versus 50.9% by fifth cycle) rates were similar in both groups. In conclusion, despite decreased ovarian response to FSH, ovarian endometriosis does not decrease the chances of successful IVF treatment.

Adult↗
PubMed2000

Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus.

One-day-old gnotobiotic piglets were inoculated intranasally with in vitro passaged porcine circovirus 1 (PCV-1), PCV-2, and porcine parvovirus (PPV) alone or in combination (PCV-1/PCV-2, PCV-1/PPV, and PCV-2/PPV). Piglets were evaluated for 1) the development of porcine postweaning multisystemic wasting syndrome (PMWS), 2) distribution of viral antigens by immunochemistry, and 3) viremia and the presence of viral DNA in nasal and ocular secretions and feces. All single agent-infected piglets and piglets infected with PCV-1/PCV-2 or PCV-1/PPV were clinically asymptomatic. They were transiently viremic and seroconverted to homologous virus(es). At termination of the study on postinfection day (PID) 35, microscopic lesions were restricted to focal inflammatory cell infiltrates in livers and myocardia. One piglet given PCV-1/PPV was PPV viremic for 2 weeks after infection and had lymphangiectasia of the spiral and descending colon associated with granulomatous inflammation. All four PCV-2/PPV-inoculated piglets developed PMWS, characterized by sudden onset of depression and anorexia, icterus, and submucosal edema. One piglet became moribund on PID 27, and the remaining three piglets were euthanatized between PID 27 and PID 30 because of severe disease. Lymph nodes were small and the livers were mottled. Disseminated angiocentric granulomatous inflammation was present in all tissues examined except the brain. Multiple lightly basophilic intracytoplasmic inclusion bodies were identified in macrophages and histiocytes. PCV-2 antigen was widely distributed within macrophages; PPV antigen was sparse. Hepatocellular necrosis and bile retention were prominent. PCV-2 DNA was identified in ocular, fecal, and nasal secretions. Terminal sera contained antibodies to PPV (4/4) and PCV-2 (3/ 4). Production of PMWS in gnotobiotic swine appears to require PCV-2 and additional infectious agents such as PPV for full disease expression in gnotobiotic piglets.

Animals↗
PubMed1999

Extended half-life and elevated steady-state level of a single-chain Fv intrabody are critical for specific intracellular retargeting of its antigen, caspase-7.

8 h) and high steady-state levels of protein accumulation, while the H2 intrabodies had a half-life of 2 h and less protein at steady state. These results suggest that the choice of sFv as an intrabody depends critically on the intracellular sFv protein having an extended half-life and elevated steady-state level. Thus, extended half-life must be considered together with sFv antibody specificity and affinity when choosing an optimal sFv intrabody for functional studies of cellular proteins.

Animals↗
PubMed1999

Radionuclides in seals and porpoises in the coastal waters around the UK.

It has been suggested that marine predators be assessed for biologically relevant contamination levels because of their trophic position. Accordingly, in studying radioactive contamination in the marine environment around the UK, tissues from seals and porpoises have been chosen. Liver and muscle tissue from dead seals and porpoises found stranded around the UK coast have been analysed for the following radionuclides: 134Cs, 137Cs, 238Pu, 239Pu + 240Pu. Multifactor analysis of variance indicated that, for radiocaesium, there was no significant difference for harbour seals, grey seals or porpoises in terms of species or gender; however, the tissue activity concentration increased with body weight and decreased with distance from Sellafield, the major nuclear reprocessing plant in the UK. The levels of radiocaesium in muscle were higher than those in liver, while there appeared to be a concentration factor of approximately 3-4 for muscle radiocaesium when compared to radiocaesium levels reported for fish, the main food source of the marine mammals under study. Approximate radiation dose calculations indicated that the average dose from radiocaesium was less than 10% of the dose from the naturally occurring radioisotope of potassium, 40K. The highest tissue activity concentration for plutonium of 0.037 Bq/kg (239Pu + 240Pu) was detected in a grey seal stranded at Rathlin Island in Northern Ireland. Calculation of approximate radiation doses from plutonium contamination showed that, as with radiocaesium, the average dose was small compared with that from 40K. In summary, the radiocaesium contamination in seals and porpoises decreased with distance from Sellafield indicating that the BNF plc processing plant was the major source of the contamination. The marine mammals concentrated radiocaesium from their environment by a factor of 300 relative to the concentration in seawater indicating the value of using marine mammal tissue to measure radiocaesium contamination in the marine environment. The maximum radiation dose to the marine mammals from radiocaesium was higher than doses previously assessed for critical groups of humans living near Sellafield, while the maximum dose from plutonium was comparable to the doses for humans.

Animals↗
PubMed1999

Effect of sulfation substrates/inhibitors on N-(3,5-dichlorophenyl)succinimide nephrotoxocity in Fischer 344 rats.

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) is an acute nephrotoxicant in rats. Our previous studies suggested that sulfate conjugation of NDPS metabolites might be a bioactivation step mediating NDPS nephrotoxicity. In this study, effects of substrates and/or inhibitors of sulfation on NDPS nephrotoxicity were examined to explore further the role of sulfation in NDPS nephrotoxicity. Male Fischer rats (4-8/group) were administered one of the following intraperitoneal (ip) pretreatment (dose, pretreatment time) prior to NDPS (0.6 mmol/kg) or NDPS vehicle (sesame oil, 2.5 ml/kg): (1) no pretreatment, (2) dehydroepiandrosterone (DHEA) (0.5 mmol/kg, 1 h), or (3) 2,6-dichloro-4-nitrophenol (DCNP) (0.04 mmol/kg, 1 h). Following NDPS or NDPS vehicle administration, renal function was monitored at 24 and 48 h. Pretreatment with DHEA, a typical substrate for and an inhibitor of hydroxysteroid (alcohol) sulfotransferase, resulted in marked protection against NDPS nephrotoxicity. A selective inhibitor of phenol sulfotransferase, DCNP, afforded little attenuation in NDPS nephrotoxicity. These results suggest that alcohol sulfate conjugates of NDPS metabolites, rather than phenolic sulfate conjugates, may be a penultimate or ultimate nephrotoxicant species mediating NDPS nephrotoxicity. The marked, but not complete, protection by DHEA also suggests that there are other metabolites or mechanisms responsible for NDPS nephrotoxicity.

Adjuvants, Immunologic↗
PubMed1999

Intramuscular injection of an adenoviral vector expressing hepatocyte growth factor facilitates hepatic transduction with a retroviral vector in mice.

Retroviral vectors can result in therapeutic and stable levels of expression of proteins from the liver. However, most retroviral vectors transduce only dividing cells, and hepatocytes are normally quiescent. The goal of this study was to determine if an adenoviral vector could transiently express hepatocyte growth factor (HGF) in order to induce hepatocyte replication and facilitate retroviral vector transduction of the liver. Intramuscular injection of an adenoviral vector that expressed human HGF from the cytomegalovirus promoter (Ad.CMV.HGF) resulted in moderate levels of HGF in blood and liver, and replication of 3 to 12% of hepatocytes. No cytopathic effect was observed in the liver, and a control adenoviral vector induced no or lower levels of replication. When a retroviral vector expressing beta-galactosidase cDNA was injected into a peripheral vein during the peak period of hepatocyte replication induced by intramuscularly administered Ad.CMV.HGF, 8% of hepatocytes were transduced. We conclude that intramuscular injection of Ad.CMV.HGF is a safe and effective way to induce transient systemic expression of HGF and hepatocyte replication, and to facilitate transduction of hepatocytes with a retroviral vector.

Adenoviridae↗
PubMed1999

Isolation and characterisation of circoviruses from pigs with wasting syndromes in Spain, Denmark and Northern Ireland.

A porcine circovirus (PCV) was isolated from tissues of pigs with wasting syndromes from Spain, Denmark and N. Ireland. The antigenic profiles of these viruses were determined by indirect immunofluorescence assays using polyclonal antisera and monoclonal antibodies (mAbs) prepared against previously isolated PCVs. A rapid and convenient PCR-based test was developed and used for the genotyping of these PCV isolates. These PCV isolates were found to be antigenically and genomically similar to previously reported isolates of PCV from pigs with wasting disease (PCV2), but distinct from the isolate of PCV from continuous PK/15 cell cultures (PCV1).

Animals↗
PubMed1999

Tenascin is differentially expressed in endometrium and endometriosis.

Endometriosis is characterized by the presence of functional endometrial tissue outside the uterine cavity, most commonly on the ovary and peritoneum. The aetiology of endometriosis is not understood, although the adhesion of endometrial cells to the extracellular matrix (ECM) would be expected to play a central role in its pathogenesis. The expression of ECM molecules in endometrium and in endometriosis has been investigated using immunohistochemistry and western blotting techniques. The ECM components collagen IV, laminin, vitronectin, and fibronectin had a similar pattern of expression throughout the menstrual cycle in endometrium and endometriosis. Expression of tenascin was elevated in the stroma of the functionalis region of the endometrium during the proliferative stage of the menstrual cycle and in endometriosis. Tenascin expression in endometriosis was not modulated according to the stage of the menstrual cycle. It is concluded that expression of tenascin is strictly regulated in endometrium and may be important in endometrial regeneration and in the pathogenesis of endometriosis.

Adult↗
PubMed1999

Sequencing of cognitive-behavioral treatments for bulimia nervosa.

OBJECTIVE: This study investigated the efficacy of a stepped-care trial of brief group psychoeducation (PE) followed by individual cognitive-behavioral therapy (CBT) in the treatment of bulimia nervosa. METHOD: Fifty-six subjects first completed PE and were then randomly assigned to either a 16-week trial of CBT (PE + CBT) or to no further treatment follow-up (PE-alone). RESULTS: Compared to PE-alone, PE + CBT produced significantly greater reductions in the specific eating symptoms of binging and purging and significantly higher remission rates that were maintained over a 16-week follow-up. However, there were no differential treatment effects on measures of nonspecific psychopathology. Among PE + CBT subjects, remission in specific eating symptoms was associated with greatest improvements in non-specific psychopathology. The outcome of nonremitted PE + CBT subjects and PE-alone subjects was no different at posttreatment or follow-up. DISCUSSION: These results provide limited support for offering individual CBT to subjects once they have completed an initial trial of group PE.

Adolescent↗
PubMed1999

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity.

The liver regenerates by replication of differentiated hepatocytes after damage or removal of part of the liver. Although several growth factors and signaling pathways are activated during regeneration, it is unclear as to which of these are essential for hepatocyte replication. We show here that low- (1 mg/kg) and high- (10 mg/kg) dose hepatocyte growth factor (HGF) induced replication of 2.1% and 11.1% of hepatocytes in rats, respectively. Lipopolysaccharide (LPS), an inducer of the acute phase response, augmented hepatocyte replication in response to low- and high-dose HGF by 4- and 2-fold, respectively. HGF alone induced moderate levels of c-Jun-N-terminal kinase (JNK) and p44/p42 mitogen-activated protein kinase (MAPK), resulting in moderate levels of AP-1-DNA binding activity. The combination of LPS + HGF increased JNK and AP-1-DNA binding activity more than levels seen with LPS or HGF alone. The activation of Stat3 that was observed after administration of LPS + HGF, but not HGF alone, could contribute to increased transcription of AP-1 components. Because phosphorylation of the c-Jun component of AP-1 by JNK increases its ability to activate transcription, the AP-1 in hepatocytes from animals treated with LPS + HGF may be more active than in rats treated with LPS or HGF alone. LPS may contribute to hepatocyte replication by potentiating the effect of HGF on the activation of both AP-1-DNA binding and transcriptional activity.

Acute-Phase Proteins↗
PubMed1999

Patients' perspective on their relatives' involvement in treatment during a short-term psychiatric hospitalization.

With the growing interest in the patient's perspective regarding mental health services, several instruments have been developed for this area of research. However, despite the availability of multidimensional questionnaires, the dimensions evaluated have rarely addressed the issue of the involvement of relatives in treatment. The present study aimed at documenting the preferences and level of satisfaction of 92 patients hospitalized in short-term psychiatric units regarding the involvement of their relatives in treatment. Data was collected using an open-ended question and two standardized scales developed for the purposes of this study. The results demonstrated that the majority of patients preferred that their relatives be involved in many aspects of their treatment. In fact, a relatively high rate of dissatisfaction of 35.6% was observed among patients concerning the lack of notification of their relatives about changes in their treatment. In the context of deinstitutionalization, where relatives are invited to play an increasing role in the community reintegration of the patient, these findings highlight the pertinence of addressing the patient's perspective with regard to treatment planning with relatives.

Adult↗
PubMed1999

The effects of single dose nefazodone and paroxetine upon 5-HT2A binding potential in humans using [18F]-setoperone PET.

RATIONALE: Alterations in 5-HT2A receptor binding are implicated in suicidality and depression. 5-HT2A receptors may also be involved in the therapeutic effects of antidepressants. OBJECTIVES: The purpose of this study was to assess the effect of paroxetine and nefazodone on 5-HT2A receptors after a single dose. METHODS: Seven subjects received a single dose of nefazodone 200 mg and five subjects received a single dose of paroxetine 20 mg. Before and after the dose, 5-HT2A binding potentials (Bmax/Kd) were determined in each subject using [18F]-setoperone PET. RESULTS: Nefazodone induced a significant change in 5-HT2A binding potential (-39+/-17%,, P = 0.003) while paroxetine showed no significant alteration of 5-HT2A binding potential (+3+/-13%, P = 0.73). CONCLUSIONS: The change in 5-HT2A binding potential seen with nefazodone represents blockade of 5-HT2A receptors by the drug. We do not find evidence for acute downregulation of 5-HT2A receptors with paroxetine within 9 h.

Adult↗
PubMed1999

A comparison of in situ hybridization and immunohistochemistry for the detection of a new porcine circovirus in formalin-fixed tissues from pigs with post-weaning multisystemic wasting syndrome (PMWS).

Post-weaning multisystemic wasting syndrome (PMWS) is a recently identified condition affecting pigs in North America and Europe. Porcine circovirus antigen and nucleic acid have been demonstrated associated with lesions, and a new porcine circovirus designated PCV2 has been recovered from tissues of these animals. In this study, in situ hybridisation and immunohistochemical protocols were developed, optimized and compared for their relative sensitivity in detecting PCV2 antigens and nucleic acid in tissues from cases of PMWS that had been fixed for up to 6 months in formalin. For both immunohistochemistry and in situ hybridization, an increase in specific signal was observed following increased exposure to both protease XIV and proteinase K. Maximum signal and minimal loss of tissue morphology was seen after 40 min treatment with protease XIV (0.5 mg/ml). After optimisation, a comparison of these techniques on sequential sections demonstrated that both techniques successfully detected antigen or nucleic acid in all of the tissues examined. More positive cells, with increased signal intensity, were detected following immunohistochemistry.

Animals↗
PubMed1999

The genetics of endometriosis.

There is mounting evidence that endometriosis is inherited as a complex trait, like diabetes or asthma. This implies there are environmental factors, such as dioxin, that are interacting with multiple genetic susceptibility loci to produce the phenotype. The Oxford Endometriosis Gene (OXEGENE) study, an international collaborative project, seeks to identify the susceptibility loci using linkage analysis; the aim then is to use positional cloning techniques to identify genes that predispose women to the disease. Analysis of the biochemical function of the gene products will lead to a better understanding of the pathophysiology and aetiology of endometriosis. New therapies may be designed based upon knowledge of the gene function and disease associated genetic markers may be used to identify women at high risk of developing the disease.

Animals↗
PubMed1999

Pathological, immunohistochemical, and in-situ hybridization studies of natural cases of postweaning multisystemic wasting syndrome (PMWS) in pigs.

Fifteen pigs from five farms on which there had been a previous clinical and histopathological diagnosis of postweaning multisystemic wasting syndrome (PMWS) were investigated. At necropsy, enlargement of lymph nodes was the most obvious lesion; other lesions were non-collapsed lungs, ulceration of the gastric pars oesophagica, and cranioventral pulmonary consolidation. Microscopical lesions attributable to PMWS were found in lymphoid organs (including lymph nodes, tonsil, Peyer's patches and spleen), liver, kidney and lungs. Varying degrees of lymphocellular depletion, affecting both lymphoid follicles and parafollicular zones, and progressive multifocal to diffuse infiltration of lymphoid tissue by large histiocytic cells were the characteristic lesions. Syncytial cells were seen frequently, especially in lymphoid organs. A prominent finding was the presence of sharply demarcated, spherical, basophilic, cytoplasmic inclusions in histiocytic cells. The lymphoid lesions were suggestive of immunosuppression. Non-lymphoid lesions included interstitial pneumonia, periportal mononuclear inflammatory infiltration of the liver in varying degrees, and interstitial nephritis. Porcine circovirus (PCV) antigen and nucleic acid were regularly found in lymphoid organs, lung, liver and, to a lesser degree, kidney. Target cells for PCV replication included monocyte/macrophage lineage and antigen-presenting cells. To a lesser extent, epithelial cells such as renal tubular, bronchial and bronchiolar cells, endothelial cells, hepatocytes and lymphocytes were also labelled. One pig did not show PCV nucleic acid; sequence differences among different viral isolates are discussed as the probable cause of this lack of labelling by the in-situ hybridization PCV-specific probe.

Animals↗
PubMed1999

Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus.

Colostrum-deprived pigs were infected intranasally with a recent isolate of porcine circovirus (PCV2) and a porcine parvovirus (PPV), both from Canadian pigs with post-weaning multisystemic wasting syndrome (PMWS). Four pigs were inoculated with PCV2 alone, three with PPV alone, five with a combined PCV2/PPV inoculum, and two with a chloroform-treated combined PCV2/PPV inoculum. Pigs were killed 21-26 days after infection and tissue samples examined for gross and microscopical lesions and for the presence of viral antigens. No clinical signs, lesions or viral antigens were detected in two uninfected control pigs or in pigs inoculated with PPV alone. One pig inoculated with PCV2 alone became dull and thin. Mild to moderate histopathological lesions containing PCV2 antigen were detected in lymphoid tissues from the pigs inoculated with PCV2 alone. Pigs given the PCV2/PPV inoculum and the chloroform-treated PCV2/PPV inoculum became dull and two died. Jaundice and hepatomegaly were seen at post-mortem examination of most of the dually infected pigs. The latter showed large amounts of PCV2 antigen in numerous tissues; PPV antigen, which was less abundant, was detected in a few tissues, especially kidney. The lesions were similar to those seen in recently described field cases of porcine PMWS in North America and Europe.

Animals↗
PubMed1999

Absenteeism among employees treated for depression.

Depression-related costs include a relatively large share of indirect costs. We describe the impact of antidepressant treatment on absenteeism among workers diagnosed and treated for depression. Monthly absenteeism counts from employers were summed in the 6 months before and after the initiation of antidepressant therapy in 630 workers treated for depression with a tricyclic antidepressant or a selective serotonin reuptake inhibitor (fluoxetine, sertraline, paroxetine). Monthly mean absenteeism was compared using pairwise t tests. Absenteeism increased before antidepressant initiation and decreased after the treatment began for all antidepressant cohorts. Absenteeism in the selective serotonin reuptake inhibitor cohorts decreased at similar rates for 4 months but was higher in the paroxetine cohort in months five and six after the treatment initiation. Our data suggest that alternative treatments for depression may have differential impact on indirect costs, but further research is warranted.

Absenteeism↗