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Biomedical subjects

J McQuillan

Publications and source records attributed to J McQuillan.

11 recordsLinked to original sources

Psychological distress by type of fertility barrier.

BACKGROUND: We examined fertility-specific distress (FSD) and general distress by type of fertility barrier (FB). METHODS: In a random sample telephone survey, 580 US women reported their fertility intentions and histories. Six groups of women were identified: (i) no FBs, (ii) infertile with intent, (iii) infertile without intent, (iv) other fertility problems, (v) miscarriages and (vi) situational barriers. Multiple regression analyses were used to compare groups with FBs. RESULTS: Sixty-one percent reported FBs and 28% reported an inability to conceive for at least 12 months. The infertile with intent group had the highest FSD, which was largely explained by (a) self-identification as infertile and (b) seeking medical help for fertility. The no FB group had a mean Center for Epidemiological Studies Depression scale score above the commonly used cut-off of 16, although 23% of the women with FBs did score above 16. CONCLUSIONS: FBs are common. Self-identification as infertile is the largest source of FSD. More women with FBs had elevated general distress than women without FBs; mean general distress was below 16 for all FB groups. It may be that, for some women (even those with children), FBs can have lasting emotional consequences, but many women do heal from the emotional distress that may accompany fertility difficulties.

Abortion, Spontaneous↗

Conventional and experimental treatment of cerebral malaria.

The most severe complication of Plasmodium falciparum infection is cerebral malaria (CM). Cerebral malaria implies the presence of neurological features, especially impaired consciousness. The treatment of CM is limited to: (i) a few conventional anti-malarial drugs (quinine or artemisinins), (ii) adjunctive treatments (initial stabilisation, blood exchange transfusion, osmotic diuretics and correction of hypoglycaemia, acidosis and hypovolaemia) and (iii) immunomodulation. There are clear procedures concerning treatment of CM, which include the use of the anti-plasmodial drugs. Adjunctive treatments are permissible but there is no single official guideline and immune intervention is a possibility currently being examined in rodent models only. The suggested immunomodulation approach is based on the strong likelihood that CM is the result of an immunopathological process. P. falciparum initiates the multifactorial chain of events leading to lethal CM and, after a certain stage, it is impossible to stop the progression even by using anti-malarial drugs. We present evidence that CM is a result of a dysregulated immune response. Therefore, it might be prevented by early modulation of discrete factors that participate in this process. In experimental systems, some immunomodulators delay or prevent CM without affecting the parasitaemia. Therefore, in the future the ultimate treatment of CM may be a combination of an anti-malarial and an immunomodulator. However, the overall effect of an immunomodulator would need to be carefully examined in view of concomitant infections, especially in malaria endemic areas.

Animals↗

History of affective disorder and the temporal trajectory of fatigue in rheumatoid arthritis.

This study examines whether the general level and rate of change of fatigue over time is different for those rheumatoid arthritis (RA) patients with and those without a history of affective disorder (AD). Four hundred fifteen RA patients from a national panel had yearly telephone interviews to obtain fatigue and distress reports, and a one-time semistructured assessment of the history of depression and generalized anxiety disorder Growth-curve analysis was used to capture variations in initial fatigue levels and changes in fatigue over 7 years for those with and without a history. RA patients with a history of major AD reported levels of fatigue that were 10% higher than those without a history in the 1st year of the study. Their fatigue reports remained elevated over 7 years. Further analysis showed that the effects of a history of AD on fatigue are fully mediated through current distress, although those with a history had a significantly smaller distress-fatigue slope. Thus, a history of AD leaves RA patients at risk for a 7-year trajectory of fatigue that is consistently higher than that of patients without a history. The elevation in fatigue reports is, at least in part, a function of enduring levels of distress.

Anxiety Disorders↗

Depression and the long-term risk of pain, fatigue, and disability in patients with rheumatoid arthritis.

OBJECTIVE: To determine whether a previous episode of major depression leaves a "scar" that places previously depressed patients with rheumatoid arthritis (RA) at risk for experiencing high levels of pain, fatigue, and disability. METHODS: A cohort of 203 patients with RA was randomly selected from a national panel and interviewed by phone about pain, fatigue, depressive symptoms, disability, and history of major depression. RESULTS: Excluding patients who met the criteria for current major depression, patients with both a history of depression and many depressive symptoms at the time of the interview (dysphoria) reported more pain than those without current dysphoria, irrespective of whether they had a history of depression. Dysphoria alone was not reliably related to pain reports. CONCLUSION: An episode of major depression, even if it occurs prior to the onset of RA, leaves patients at risk for higher levels of pain when depressive symptoms persist, even years after the depressive episode.

Arthritis, Rheumatoid↗

Gender, paid work, and symptoms of emotional distress in rheumatoid arthritis patients.

OBJECTIVE: To evaluate the relative contribution of gender-related work conditions, gender-related socialization practices, and disease characteristics to the explanation of emotional distress in men and women with rheumatoid arthritis (RA). METHODS: Three hundred sixty-nine RA patients who were employed outside the home were recruited from a national randomized sample of rheumatology practices. Data on paid work and disease characteristics were obtained by telephone interview. Emotional distress was measured by the Center for Epidemiological Studies Depression (CES-D) scale. Hierarchical ordinary least-squares regression was used to assess the relationship of sex, class, work characteristics, and disease characteristics to both the CES-D summary scale and the CES-D factor structure. RESULTS: Differences in emotional distress were explained best by functional ability and pain and secondarily by the characteristics of paid work, with no independent effect for sex. Distress increased with decreasing functional ability, increasing pain, and exposure to such work characteristics as low autonomy, low income, and high demands. No sex differences in any of the CES-D subscales remained after controlling for disease and work variables. CONCLUSION: Among employed RA patients with high levels of functional disability and exposure to stressful work characteristics, men and women are at equal risk of experiencing emotional distress.

Adult↗

Predictors of work disability in rheumatoid arthritis patients. A five-year followup.

OBJECTIVE: To evaluate regression models that include social, attitudinal, work structure, health status, and family characteristics, with regard to their prediction of work disability in a national sample of patients with rheumatoid arthritis (RA). METHODS: Four hundred ninety-eight employed RA patients were recruited from a national sample of private rheumatology practices. Three hundred ninety-two remained in the study after 5 years. Data were collected from patients by telephone interview, and patients' physicians provided written clinical assessments. Only variables on which information was obtained in year 1 were used to predict work status in year 5, using hierarchical multiple logistic regression analysis. RESULTS: The significant predictors of work disability were age (odds ratio [OR] 1.04), number of deformed joints (OR 1.26), number of joints with flare (OR 1.23), the complexity of working with things at work (OR 0.88), and the desire to remain employed (OR 2.3). The risk of work disability increased with increasing age, more severe disease, greater complexity of involvement with things at work, reduced work hours, and desire to not be working outside the home. CONCLUSION: The risk of becoming work disabled in 5 years was predicted more by clinical status at entry into the study than by work structure. These results, which contradict previous research on work disability in arthritis, prompt a rethinking of future studies of work disability in RA.

Adult↗

Chemistry and positive inotropic effect of pelrinone and related derivatives. A novel class of 2-methylpyrimidones as inotropic agents.

A novel series of pyrimidine derivatives was synthesized and evaluated for positive inotropic activity. Inotropic and chronotropic effects were determined in vitro in cat papillary muscle and right atrium, respectively. Selected compounds were then evaluated in vivo in a dog heart failure model. Changes in ventricular dP/dt, heart rate, and blood pressure were monitored. Several of these agents produced relatively minor changes in heart rate. This class of agents demonstrated a varying degree of vasodilator effects concomitant with increases in ventricular contractility. The most potent analogues, 9, 48, and 49, were evaluated orally in conscious dogs with implanted Konisberg pressure transducers, and their effect on left ventricular dP/dt was compared with that of milrinone. Mechanistically, the agents of this novel class appear not to mediate their effect via beta-receptors or inhibition of Na+/K+-ATPase. A major component of their inotropic effect is mediated by the inhibition of cardiac phosphodiesterase (PDE)-Fr. III. This was clearly demonstrated by 9, 48, and 49. Compound 48 was found to be the most potent inhibitor of PDE-Fr. III from among the compounds tested in this assay.

Animals↗

Ligand-receptor interactions via hydrogen-bond formation. Synthesis and pharmacological evaluation of pyrrolo and pyrido analogues of the cardiotonic agent 7-hydroxycyclindole.

The syntheses of N,N-dimethyl-6,7,8,9-tetrahydro-3H,10H-pyrrolo[3,2-a] carbazol-7-amine (8), N,N-dimethyl-7,8,9,10-tetrahydro-11H-pyrido[3,2-a] carbazol-8-amine (9a), and the N,N,11-trimethyl analogue (9b) are described. The in vitro inotropic activity of these compounds, as well as the known cardiotonics amrinone and 7-hydroxycyclindole (7), was investigated. Compound 8, a pyrrolo analogue of 7, was devoid of inotropic activity, while the pyrido analogues 9 were equiactive to 7 and amrinone. These results suggest that the hydroxyl group of 7 functions as an H-bond acceptor, rather than a donor, and that on interaction of 7, and the pyrido analogues 9, with a common receptor, an orbital occupied by one of the oxygen lone pair electrons of 7 must assume the same orientation as the orbital occupied by the pyridine nitrogen lone pair.

Aminopyridines↗

Chlorpromazine: a potential anticancer agent?

The antipsychotic drug chlorpromazine causes scission of the DNA in PY815 mouse mastocytoma cells or isolated PY815 cell nuclei and the broken DNA reseals when chlorpromazine is removed from nuclei. These properties suggest that chlorpromazine interferes with topoisomerase action as do several other DNA-intercalating anti-cancer drugs. However, protein is not associated with the broken DNA after chlorpromazine treatment suggesting a different mode of action on the topoisomerase. Reasons why chlorpromazine may have potential as anti-cancer agent are considered.

Aminoacridines↗

Dibutyryl cyclic AMP effects on calcium metabolism by mouse mastocytoma cells.

The ability of mouse mastocytoma cells to take up 45Ca2+ was measured in normal growth medium. As previously observed in physiological buffers with succinate and Pi, cells grown for 18h with N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate (DB cyclic AMP) to inhibit growth took up more 45Ca2+ than untreated cells. However 45Ca2+ uptake by cells in growth medium was less sensitive to respiratory inhibitors or uncouplers than 45Ca2+ uptake in physiological buffer. Increased 45Ca2+ uptake by 18h cyclic nucleotide-treated cells was not a result of tighter mitochondrial coupling since mitochondria prepared from cyclic nucleotide-treated cells were less coupled than those from untreated cells. Nevertheless studies with uncouplers suggested that the bulk of the intracellular Ca2+ was associated with mitochondria. DB cyclic AMP-treated cells contained less total Ca2+ than untreated cells indicating that net Ca2+ efflux occurred during the 18h period of drug treatment. These observations suggest that Ca2+ fluxes increase in DB cyclic AMP-treated PY815 cells and that a net efflux of Ca2+ occurs during growth inhibition by the cyclic nucleotide.

Animals↗