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Biomedical subjects

J Phelan

Publications and source records attributed to J Phelan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Biological effects and fate of a soluble, dimeric, 80-kDa tumor necrosis factor receptor in renal transplant recipients who receive OKT3 therapy.

A preliminary clinical study of renal allograft recipients revealed that a dimeric form of the human 80 kDa soluble receptor (sTNFR:Fc) for tumor necrosis factor (TNF) is well tolerated and attenuates the OKT3-induced acute clinical syndrome. The current study determined the in vivo biological effects and fate of sTNFR:Fc in these patients. Serial assessment of both antigenic and biological activities of circulating TNF and sTNFR:Fc have led to the following observations. (1) Although control patients typically responded to the first OKT3 injection with a rapid increase of biologically active TNFalpha, patients on sTNFR:Fc therapy had markedly higher serum TNFalpha antigenic levels, but no detectable bioactivity. Thus, sTNFR:Fc functioned as a potent antagonist, despite its cytokine-carrier effect. (2) Peak sTNFR:Fc levels averaging 800 and 2500 ng/ml were routinely achieved in vivo, using the low-dose (0.05 mg/kg) and high-dose (0.15 mg/kg) protocols. (3) The half-life of circulating sTNFR:Fc was estimated to be approximately 4.4 days, and levels of p80 receptors in treated patients remained significantly above those in control patients for at least 20 days. (4) In vitro blocking studies demonstrated that circulating sTNFR:Fc remained biologically active for 2 weeks. These results demonstrate that under current protocols, significant serum levels of sTNFR:Fc, capable of effectively neutralizing TNF activity over prolonged periods, can be achieved. The persistent OKT3 side effects observed, despite sTNFR:Fc therapy, are therefore likely to be caused by factors other than TNF.

Dimerization↗
PubMed1997

Serodiagnosis of toxoplasmosis in a common wombat.

An 8-yr-old captive, female common wombat (Vombatus ursinus) from Victoria, Australia was euthanased after an illness of 36 days manifested by lethargy, inappetance and terminal coma with respiratory failure. Toxoplasmosis was diagnosed during life by the Toxoplasma direct agglutination test (DAT) which showed a positive initial titre of 1:1,024 at 22 days after onset of illness and a four fold rise in titre to 1:4,098 2 wk later, just prior to death. The Toxoplasma modified agglutination test (MAT) remained negative over this time period. The serological diagnosis was confirmed by histological diagnosis of granulomatous encephalitis, focal myocarditis, interstitial pneumonia and severe adrenal cortical necrosis and the presence of tachyzoites of Toxoplasma gondii in large numbers within the focal necrotic lesions in the brain, myocardium and adrenal cortices. The serological response in the wombat differed from that of the typical eutherian which exhibits a reaction in both the DAT and MAT within 2 wk of infection with T. gondii. An incidental finding was calcification in the media of the ascending aorta and proximal parts of the major arteries.

Adrenal Glands↗
PubMed1997

Major aphthous-like ulcers in two patients infected with human immunodeficiency virus.

Two patients infected with human immunodeficiency virus (HIV) presented with persistent, large, and painful oral ulcers. Results of cultures and examination of a biopsy specimen were negative for infection and malignancy. Major aphthous-like ulcers should be considered in the differential diagnosis of oral ulcers in the HIV-infected patient.

Administration, Oral↗
PubMed1996

Evaluation of recombinant human soluble dimeric tumor necrosis factor receptor for prevention of OKT3-associated acute clinical syndrome.

Tumor necrosis factor alpha (TNFa) has been shown to be the primary cytokine responsible for the OKT3-induced acute clinical syndrome (OKT3-ACS). Recombinant human soluble tumor necrosis factor receptor (TNFR:Fc) is a dimer of the p80 TNF receptor, which binds both TNFa and lymphotoxin (LT). Renal allograft recipients undergoing OKT3 therapy for steroid-resistant rejection were randomized to receive OKT3 alone or in combination with TNFR:Fc to determine its safety and efficacy in decreasing the severity of OKT3-ACS and in restoring renal function. Six of 12 patients were given TNFR:Fc prior to each of the first two injections of OKT3. All patients were monitored for manifestations of OKT3-ACS and changes in renal function. In addition, serial serum samples were assayed for TNFa and TNFR:Fc levels (ELISA) and TNFa bioactivity (L929). No adverse side effects were identified in patients receiving TNFR:Fc. Patients treated with TNFR:Fc had significantly fewer symptoms by day 2 of OKT3, and had a lower overall incidence of chills and arthralgias. Renal dysfunction reversed within 24 hr in the TNFR:Fc-treated group in contrast to the 48-72-hr delay in the control group. Antigenic TNFa levels increased in the control group from < 10 pg/ml pre OKT3 to a mean peak level of 30 +/- 13 pg/ml on day 1 and decreased to pretreatment levels by day 2. TNFR:Fc-treated patients had a mean peak TNFa level of 235 +/- 135 pg/ml, suggesting a carrier effect of TNFR:Fc. In contrast, bioactivity was barely detectable (mean 20 +/- 14 pg/ml) in the day 1 samples from TNFR:Fc-treated patients, whereas significant bioactivity (peak mean 60 +/- 35 pg/ml) was detected in sera from control patients. TNF receptor levels reached 600 ng/ml in treated patients and remained elevated for up to 18 days confirming the long half-life of TNFR:Fc. This phase 1 trial demonstrates that TNFR:Fc is well tolerated and may limit the severity of OKT3-ACS. The most significant observation was a more rapid improvement in renal function in the TNFR:Fc-treated patients. The absence of TNFa bioactivity indicates that TNFR:Fc functions as a TNF antagonist. Further evaluation of higher doses of TNFR:Fc in OKT3-treated patients is currently in progress.

Acute Disease↗
PubMed1996

Effect of cooling and cryopreservation on sperm motility and morphology of several species of marsupial.

The effects of long-term cooling and freezing on sperm motility are described for six marsupial species: the fat-tailed dunnart, koala, brushtail possum, long-footed potoroo, northern brown bandicoot and ring-tailed possum. The effects of up to eight days of cooling at 4 degrees C on the motility of dunnart spermatozoa and the effect of cryopreservation on spermatozoa of the other species were determined. The cryoprotectant used was a Tris-citrate-fructose-egg yolk-glycerol diluent. The percentage and rating of sperm motility, and sperm structure, as determined by light microscopy, were investigated. Sperm motility in the fat-tailed dunnart was retained for up to six days when cooled to 4 degrees C, suggesting that sperm from this species have some degree of tolerance to cold shock. After this time, however, the percentage of motile spermatozoa and their motility rating declined. In all species except the fat-tailed dunnart, reinitiation of motility following cryopreservation occurred across a range of glycerol concentrations (4-17%). Cryoprotectant containing 6% and/or 8% glycerol resulted in little change of motility rating or of the percentage of live sperm after thawing, although there was some decline in the percentage of motile sperm. The unusual structural and motility characteristics of dunnart spermatozoa may account for the lack of success of sperm cryopreservation in this species.

Animals↗
PubMed1995

Cross-sectional study of bone density in asthmatic children.

The emphasis in treatment of asthma in children has shifted from bronchodilators to inhaled anti-inflammatory medications, including inhaled corticosteroids (ICS). Children with chronic asthma and moderate to severe symptoms have been targeted as particularly deserving of maintenance therapy with ICS. We have previously reported a cross-sectional study of bone density in children treated with ICS. There was no significant difference between the total bone density of asthmatic patients and controls. We sought to extend the information available on bone density in asthmatic children by evaluating 15 asthmatic subjects taking daily ICS (beclomethasone dipropionate) and comparing them with age- and sex-matched controls. We compared total and regional bone density, bone age, and calcium intakes in these subjects. Asthmatic subjects were on ICS for 4-60 months, with doses ranging from 200 to 450 micrograms/day. There was no significant difference between asthmatics and matched controls for height, weight, % RDA Ca2+, or bone age. The asthmatic subjects had bone density (total and regional measurements) equivalent to their controls. These results provide additional support for the safety of low-dose ICS on bone density in asthmatic children.

Absorptiometry, Photon↗
PubMed1995

Public knowledge, attitudes, and beliefs about homeless people: evidence for compassion fatigue.

Media reports suggest that the public is becoming impatient with the homeless--that so-called "compassion fatigue" has gripped the nation. This characterization of public sentiment could have important policy consequences-- restrictive measures can be justified by growing public impatience, and progressive housing policies seem feasible within a hostile climate of opinion. But evidence to support the compassion fatigue notion is anecdotal. We examine the issue by tracking the results of public opinion polls and by reporting detailed evidence from a nationwide random-digit dial telephone survey (N = 1,507) concerning knowledge attitudes and beliefs about homeless people. To be sure, the public sees homelessness as an undesirable social problem and wants something done about it. However, although the homeless are clearly stigmatized, there is little evidence to suggest that the public has lost compassion and is unwilling to support policies to help homeless people.

Adolescent↗
PubMed1995

Lifetime and five-year prevalence of homelessness in the United States: new evidence on an old debate.

A 1990 household-based telephone survey of 1,507 people was followed up by surveying a subsample of those interviewed for the initial report. Results showed very high prevalence figures for homelessness, quite close to those found in the earlier survey. Moreover, using explicit and stringent definitions of literal homelessness and doubling up, most periods of homelessness were found to last for more than one month and, particularly with regard to literal homelessness, to involve serious deprivations and violent victimization.

Adult↗
PubMed1995

Social conditions as fundamental causes of disease.

Over the last several decades, epidemiological studies have been enormously successful in identifying risk factors for major diseases. However, most of this research has focused attention on risk factors that are relatively proximal causes of disease such as diet, cholesterol level, exercise and the like. We question the emphasis on such individually-based risk factors and argue that greater attention must be paid to basic social conditions if health reform is to have its maximum effect in the time ahead. There are two reasons for this claim. First we argue that individually-based risk factors must be contextualized, by examining what puts people at risk of risks, if we are to craft effective interventions and improve the nation's health. Second, we argue that social factors such as socioeconomic status and social support are likely "fundamental causes" of disease that, because they embody access to important resources, affect multiple disease outcomes through multiple mechanisms, and consequently maintain an association with disease even when intervening mechanisms change. Without careful attention to these possibilities, we run the risk of imposing individually-based intervention strategies that are ineffective and of missing opportunities to adopt broad-based societal interventions that could produce substantial health benefits for our citizens.

Disease↗
PubMed1994

Six-month stability of psychiatric diagnoses in first-admission patients with psychosis.

OBJECTIVE: The short-term diagnostic stability of schizophrenic and other psychotic disorders was examined in first-admission patients, with attention to the principal reasons for diagnostic change. METHOD: Hospitalized first-admission patients (N = 278) participating in an epidemiologic study were interviewed at baseline and after 6 months with the Structured Clinical Interview for DSM-III-R. A best estimate diagnosis was made at both time points with the use of all available sources of information. Reasons for changes in diagnosis were determined by two psychiatrists. RESULTS: Affective psychosis and schizophrenic disorders were relatively stable broad diagnostic categories over the 6-month period, with 86.5%-88.9% of the patients remaining in the same category, although findings for specific diagnoses within these categories ranged from 61.5% to 85.7%. The groups with unknown and nonspecific diagnoses showed less stability; the diagnoses of more than one-third of these patients remained unknown or nonspecific at the 6-month evaluation. If the 6-month diagnoses are used as the research standard, somewhat lower percentages of patients received the same diagnoses at baseline. Forty-three percent of the changes in diagnosis were attributed to the clinical course of illness; the rest were attributed to the diagnostic process itself. CONCLUSIONS: A longitudinal diagnostic assessment based on multiple sources of information is crucial for categorizing first-admission psychotic patients, particularly those who do not initially fit into a DSM-III-R category. The short-term stability of a diagnosis is a function of multiple factors, including the changing clinical picture, additional sources of information, and new interpretations of original data.

Adolescent↗
PubMed1994

A 12-month study of the efficacy of a pre-brushing rinse in plaque removal.

A 12-month clinical trial was conducted to compare the effectiveness of a pre-brushing rinse (PBR) in plaque removal with that of water. Four groups participated in the study; group 1 (test group) rinsed with PBR before brushing; group 2 rinsed with plain tap water; group 3 brushed only; and group 4 rinsed with sterile water (same color as the PBR). Pre-brushing and post-brushing plaque scores were recorded at baseline, 3 months, 6 months, 9 months (Ramjford surfaces) and 12 months for groups 1, 2, and 3 and at baseline, 3 months and 6 months for group 4. Pre-brushing minus post-brushing plaque scores (decrements) were significantly higher in the PBR group at baseline, and 6, 9, and 12 months. Using a single criterion (gingival bleeding index) there were no differences between the 4 groups at any of the 5 assessments, hence, the clinical significance of the higher plaque removal scores in the PBR group remains in doubt.

Adolescent↗
PubMed1994

Lifetime and five-year prevalence of homelessness in the United States.

OBJECTIVE: Intense debate exists concerning the number of homeless people in the United States. Previous studies, counting currently homeless people, have provided point-prevalence estimates of homelessness but have been criticized on methodological grounds. This study reports lifetime and 5-year prevalence estimates of homelessness using a different methodological approach. METHODS: Random-digit dialing was used to interview 1507 adults living in households with telephones in the 48 contiguous states in the fall of 1990. Respondents were asked whether they had ever been homeless and if so, where they had slept while homeless. RESULTS: Lifetime and 5-year prevalence of all types of homelessness combined were 14.0% (26 million people) and 4.6% (8.5 million people), respectively. Lifetime "literal homelessness" (sleeping in shelters, abandoned buildings, bus and train stations, etc.) was 7.4% (13.5 million people). Five-year (1985 through 1990) prevalence of self-reported homelessness among those who had ever been literally homeless was 3.1% (5.7 million people). CONCLUSIONS: The magnitude of the problem of homelessness is much greater than most previous attempts to enumerate homeless people have led us to believe. This finding requires reconsideration of inferences about the causes of homelessness that were derived from point-prevalence studies of currently homeless people.

Adolescent↗
PubMed1992

Relative role of B and T lymphocytes in pathogenesis of a murine herpes virus.

Pathogenesis of a murine herpes virus was investigated in inbred strains (BALB/c, CBA, AKR and C57BL/10) of mice. After intranasal inhalation, virus was found to replicate primarily in the lungs, followed by haematogenous spread to the target organs (adrenal glands and ganglia). AKR (H-2k) were found to be most susceptible to virus infection while CBA (H-2k) mice appeared to be relatively resistant. Infection of B-cell depleted BALB/c mice resulted in detection of lower lung virus titres in B-cell depleted animals as compared to normal intact mice. Moreover, 3 of 12 normal mice in untreated group died of virus infection while deaths did not occur in the B-cell depleted group. Results of T-cell subset depletion experiments in BALB/c mice revealed maximum mortality in the group depleted of both Lyt-2+ and L3T4+ subpopulations. Infectious virus titres were also higher in lungs of T-cell depleted animals.

Animals↗
PubMed1991

Work stress, family stress and depression in professional and managerial employees.

Detailed interviews were conducted with 1523 married professional and managerial employees of a major US corporation to test associations of acute and chronic occupational and domestic stress with DSM-III-R major depression and current depressive symptoms. After controlling for demographic and clinical risk factors, both sources of stress were significantly associated with the two measures of depression. On the other hand, neither the demographic and clinical risk factors, nor several psychosocial characteristics (social support, sense of mastery and organizational commitment) moderated the relationship between stress and depression.

Adaptation, Psychological↗
PubMed1990

Epidemiology of depression and alcohol abuse/dependence in a managerial and professional work force.

Detailed clinical interviews focusing on depression and alcohol abuse/dependence were conducted with 1870 managers and professionals drawn from a major US corporation. Among men, the lifetime and 1-year prevalence rates of DSM-III-R major depression were 23% and 9%, respectively. Among women, the rates were 36% and 17%, respectively. Lifetime and 1-year prevalence rates of DSM-III-R alcohol abuse/dependence were 16% and 4% for men, and 9% and 4% for women. Imposing a requirement that alcohol-related symptoms cluster together in time reduced the lifetime and 1-year prevalence rates to 11% and 3% for men and 5% and 2% for women. The odds ratio for the lifetime occurrence of depression and alcohol abuse/dependence with such clustering was 2.28. The three most important risk factors for depression were being female, separated or divorced, and having a family history of depression. For alcohol abuse/dependence, the most important risk factors were being male, unmarried, and having a family history of alcoholism. Manager/professional status, length of employment, hours worked per day, and supervisory responsibility were not statistically associated with either DSM-III-R major depression or alcohol abuse/dependence.

Administrative Personnel↗
PubMed1989

Central hemodynamic assessment of normal term pregnancy.

Ten carefully screened primiparous patients between 36 and 38 weeks' gestation underwent pulmonary artery catheterization, arterial line placement, and central hemodynamic assessment in the left lateral recumbent position. Studies were repeated in the same patients between 11 and 13 weeks post partum. Compared with the nonpregnant state, there was a significant fall in systemic vascular resistance, pulmonary vascular resistance, colloid oncotic pressure, and colloid oncotic pressure-pulmonary capillary wedge pressure gradient by the late phase of the third trimester (p less than 0.05). Pregnancy was associated with a significant rise in cardiac output and pulse in all patients (p less than 0.05). There was no significant change in pulmonary capillary wedge pressure, central venous pressure, left ventricular stroke work index, or mean arterial pressure. Normally the late phase of the third trimester is not associated with hyperdynamic left ventricular function as assessed by the left ventricular stroke work index/pulmonary capillary wedge pressure ratio.

Adult↗