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Biomedical subjects

J Downey

Publications and source records attributed to J Downey.

At least 19 recordsLinked to original sources
PubMed1995

Antibiotic pharmacokinetics in the inflamed prostate.

We hypothesized that altered pharmacokinetics in the inflamed prostate gland might account for the treatment failure of clinically diagnosed chronic bacterial prostatitis. We employed a rat model of chronic bacterial prostatitis to investigate any pharmacokinetic differences that may exist between uninflamed and inflamed prostate glands. Four groups of animals were studied (treated and untreated control and prostatitis groups). Seven days of norfloxacin therapy cured 60% of the animals with well-established bacterial prostatitis compared with a spontaneous cure rate of 10% in the nontreated prostatitis animals. Norfloxacin levels did not change significantly between the infected and noninfected prostate glands. We conclude that failure of antibiotic therapy in chronic bacterial prostatitis is not due to significantly altered norfloxacin pharmacokinetics in the chronically inflamed prostate gland but rather to the difficulty of eradicating protected bacterial microcolonies within an infection-induced altered microenvironment deep within the prostate gland.

Animals↗
PubMed1995

Adenosine-induced vasodilation: receptor characterization in pulmonary circulation.

Adenosine mediates vascular smooth muscle relaxation in the pulmonary circulation. The A2 receptor has been suggested to mediate adenosine-induced vasodilation (AIV). In this study, the effect(s) of selective adenosine agonist and antagonist on the hypoxic pressor response (HPR) was assessed in the isolated blood-perfused rat lung. Adenosine (0.075-7.5 mM) infusion (0.125 ml/min) into the pulmonary artery dose dependently attenuated the HPR. AIV was mimicked by 10 microM 5'-(N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine agonist. Adenosine- and NECA-induced vasodilation were attenuated by 67 microM 8-(p-sulfophenyl)theophylline. In contrast, NECA-induced vasodilation was not attenuated by the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (1 microM). At 10 microM, a minimal vasodilatory effect was seen with the nonselective adenosine agonists CV-1808 and N6-(2-phenylisopropyl)adenosine (R-PIA) compared with NECA. The highly selective A2a agonist 2-[p-(2-carboxyethyl)phenyl amino]-5'-N-ethyl carboxamido adenosine (CGS-21680C, 10 microM) and A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 10 microM) had no vasodilatory effect. Neither the K+ channel blockers tetraethylammonium chloride (10 mM) and glibenclamide (100 microM) nor the NO synthase inhibitor N omega-nitro-L-arginine methyl ester attenuated NECA-induced vasodilation. These findings suggest that AIV is mediated via the A2b receptor and that AIV occurs via an NO-independent mechanism.

Adenosine↗
PubMed1995

Immunotherapy of an experimental adenocarcinoma of the prostate.

We have developed and tested a fractionated, purified and deproteinized emulsion of a mycobacterial cell wall (MCW) and report on a controlled study of this compound in the treatment of the experimental R3327-H adenocarcinoma of the prostate. The intraperitoneal route of administration was found ineffective at the weekly dose of 500 micrograms. The intratumoral administration of 1000 micrograms of MCW exhibited significant antitumor activity. Tumors larger than 2.2 cm.3 in volume showed evidence of temporary regression, but no cures were recorded in these animals. Complete tumor regression was found in 50% of the rats with tumor volumes less than 2.2 cm.3 at the onset of treatment. The animals in this group not responding initially were treated with a second 3-week course of MCW which resulted in complete tumor regression in one-half of the animals, for a total cure rate, in the smaller tumor cohort, of 75%. Mycobacterial cell wall is an effective biological response modifier in the Dunning R3327-H adenocarcinoma of the prostate in Copenhagen rats. Additional studies to elucidate the effect of the compound in relation to dose and tumor volume are underway.

Adenocarcinoma↗
PubMed1995

The psychological effects of multifetal pregnancy reduction.

OBJECTIVE: To study the psychological effects of multifetal pregnancy reduction. DESIGN AND SETTING: Hour-long semistructured telephone interviews with both multifetal pregnancy reduction patients and control subjects. PATIENTS: Forty-two multifetal pregnancy reduction patients were contacted within 1 year of undergoing the procedure. Forty-four control subjects had become pregnant after infertility evaluation or treatment but conceived only a single fetus or twins and thus did not consider fetal termination. MAIN OUTCOME MEASURES: Standardized measures of depressive disorder and current psychiatric symptoms, as well as questions about emotional reactions to multifetal pregnancy reduction. RESULTS: Reduction patients who were pregnant or postpartum at the time of the interview (n = 34) were no more likely than pregnant or postpartum controls (n = 34) to report episodes of depression or high psychiatric symptom levels. The same proportion (14.7%) of both reduction patients and controls with a successful pregnancy outcome met criteria for an episode of major depressive disorder occurring during the 9 months before the interview. In contrast, the 8 reduction patients who spontaneously aborted the entire pregnancy and the 10 controls who spontaneously aborted reported significantly higher rates of the full depressive syndrome. CONCLUSIONS: Multifetal pregnancy reduction is experienced as stressful and distressing. However, when pregnancy outcome is successful, the medical intervention does not put women at significant risk for affective illness or elevated levels of psychiatric symptoms.

Abortion, Spontaneous↗
PubMed1992

Movement of pseudomonas aeruginosa along catheter surfaces. A mechanism in pathogenesis of catheter-associated infection.

The etiologic mechanism involved in the establishment of catheter-associated bacteriuria is suggested in this in vitro study of the movement of Pseudomonas aeruginosa along a catheter surface against a flowing artificial urine milieu in the presence and absence of antibiotics. Following a lag phase, during which a bacterial biofilm becomes firmly established at a site of contamination, the bacteria ascend the surface of the Foley catheters in a rapidly expanding coherent biofilm. The speed of the bacterial ascent is increased as a result of turbulence-associated planktonic saltatory bacterial movement within the urine column. Bacteriocidal concentrations of antibiotics in the urine can slow down the bacterial ascent, but they do not preclude it.

Catheterization↗
PubMed1992

The psychiatric status of women presenting for infertility evaluation.

Psychiatric symptomatology, incidence of clinical depression, measures of self-esteem, and sexual functioning were not found to be significantly different between a group of 118 women undergoing infertility evaluation and treatment and a demographically similar group of 83 routine-care women patients with no known fertility problems. However, a significant number of the infertility patients reported changes in mood and in sense of self-worth since becoming concerned about conception.

Adult↗
PubMed1992

Cyclooxygenase products are not involved in the protection against myocardial infarction afforded by preconditioning in rabbit. Cyclooxygenase pathway's involvement in preconditioning.

The mechanism whereby preconditioning with a transient period of ischemia renders the heart resistant to infarction from a subsequent ischemic insult is unknown. The purpose of this study was to determine whether cyclooxygenase pathways are involved in preconditioning's protection. Two inhibitors of that pathway, meclofenamate (MEC) and aspirin (ASP), were test in an in situ and a blood perfused isolated heart model, respectively. Preconditioning was achieved with 5 minute ischemia and 10 minutes reperfusion. All in situ hearts underwent 30 minute ischemia followed by 180 minute reperfusion, while the isolated hearts experienced 45 minute ischemia plus 120 minute reperfusion. Infarct size was measured with TTC stain. In the in situ model, 39.9% +/- 4.2% of the ischemic zone was infarcted in control hearts but only 8.8% +/- 2.2% in preconditioning hearts. Pretreatment with MEC (5 mg/Kg) caused no alteration of infarct size in either non preconditioned (34.3% +/- 8.3%) or preconditioned hearts (6.7% +/- 3.3%). In isolated hearts, 45 minute ischemia caused 31.0% +/- 5.9% of the ischemic zone to be infarcted in control hearts and only 5.4% +/- 2.2% in preconditioned hearts. Pretreatment with ASP (1 mg/Kg) failed to affect infarct size in either non preconditioned (35.7% +/- 3.7%) or preconditioned hearts (10.2% +/- 1.9%). The data indicate that cyclooxygenase pathways are not involved in the preconditioning's protection.

Analysis of Variance↗
PubMed1991

Pyrophosphate inhibition of Proteus mirabilis-induced struvite crystallization in vitro.

Struvite (MgNH4PO4.6H2O) crystals, the major mineral component of infectious urinary calculi, were produced in vitro by growth of a clinical isolate of Proteus mirabilis in artificial urine. P. mirabilis growth and urease-induced struvite production were monitored by phase contrast light microscopy and measurements of urease activity, pH, ammonia concentrations, turbidity, and culture viability. In the absence of pyrophosphate, struvite crystals appeared within 3-5 h due to the urease-induced elevation of pH and initially assumed a planar or 'X-shaped' crystal habit (morphology) characteristic of rapid growth. When pyrophosphate was present, initial precipitation and crystal appearance were significantly impaired and precipitates were largely amorphous. When crystals did appear (usually after 7 or 8 h) they were misshapen or octahedral in shape indicative of very slow growth. X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) identified all crystals as struvite. Trace contaminates of carbonate-apatite (Ca10(PO4)6CO3) or newberyite (MgHPO4.H2O) were produced only in the absence of pyrophosphate. P. mirabilis viability and culture pH elevation were unaffected by the addition of pyrophosphate, whereas urease activity and ammonia concentrations were marginally reduced. Struvite could also be produced chemically by titration of the artificial urine with NH4OH. If pyrophosphate was present during titration, the same inhibitory effect on crystal growth occurred, so it is unlikely that urease inhibition is important. Lowering of pyrophosphate concentration from 13-0.45 mumol/l did not reduce its inhibitory activity so it is unlikely to act by chelating free Mg2+. We propose that pyrophosphate inhibits struvite growth principally through direct interference with the chemical mechanisms involved in crystal nucleation and growth, because of its effectiveness at very low concentrations.

Ammonia↗
PubMed1991

Cognitive ability and everyday functioning in women with Turner syndrome.

This paper presents results from an assessment of cognitive ability and everyday functioning in a group of adult women with Turner syndrome (TUS). Twenty-three TUS women were compared with 23 matched controls with constitutional short stature (CSS). A subgroup of 10 TUS women were compared with their nondisabled female siblings. On the Wechsler Adult Intelligence Test-Revised (Wechsler, 1981), no significant group differences were found in Verbal IQ. There were significant group differences for Performance IQ and Full Scale IQ, largely due to specific deficits in the area of spatial and mathematical ability. These difficulties were also evident on the Benton Visual Retention Test-Revised (Benton, 1974). TUS individuals had significantly lower educational attainment than CSS controls but did not differ from their siblings. TUS individuals had significantly lower occupational attainment than the women in both comparison groups.

Achievement↗
PubMed1990

A simple technique for studying struvite crystal growth in vitro.

Struvite urolithiasis forms as a consequence of a urinary tract infection by urease-producing species of bacteria such as Proteus mirabilis. Ammonia, produced by the enzymatic hydrolysis of urea, elevates urine pH causing a supersaturation and precipitation of Mg++ as struvite (NH4MgPO4). Calcium often precipitates as well, forming the mineral carbonate-apatite (Ca10(PO4)6CO3). We have developed a procedure based on direct observation by light microscopy whereby struvite crystal growth can be quickly monitored in response to chemical changes in urine. As struvite crystals assume a characteristic shape or crystal habit based on their growth rate, the effect of urine chemistry and the action of various crystallization or urease inhibitors on struvite formation can be quickly shown. In addition preliminary effects of alkaline pH, or the presence of toxic compounds on bacteria can also be shown through their loss of motility.

Crystallization↗
PubMed1990

Influence of chondroitin sulfate, heparin sulfate, and citrate on Proteus mirabilis-induced struvite crystallization in vitro.

Struvite crystals were produced by Proteus mirabilis growth in artificial urine, in the presence of a number of naturally occurring crystallization inhibitors. The use of phase contrast light microscopy enabled the effects of added chondroitin sulfate A, chondroitin sulfate C, heparin sulfate, or sodium citrate, on struvite crystal growth rates to be rapidly monitored as changes in crystal habit. Struvite crystals formed as a consequence of the urease activity of P. mirabilis under all chemical conditions. In the absence of inhibitor, early crystal development was marked by large quantities of amorphous precipitate, followed immediately by the appearance of rapidly growing X-shaped or planar crystals. Addition of the glycosaminoglycans, chondroitin sulfate A, chondroitin sulfate C, or heparin sulfate to the artificial urine mixture had no effect on the rate of crystal growth or appearance. When sodium citrate was present in elevated concentrations, crystal appearance was generally slowed, and the crystals assumed an octahedral, slow growing appearance. None of the added compounds had any influence on bacterial viability, pH, or urease activity. It is therefore likely that the inhibitory activity displayed by sodium citrate might be related to its ability to complex magnesium or to interfere with the crystal structure during struvite formation. From these experiments it would appear that citrate may be a factor in the natural resistance of whole urine to struvite crystallization.

Chondroitin Sulfates↗
PubMed1989

Mood disorders, psychiatric symptoms, and distress in women presenting for infertility evaluation.

Women who undergo treatment for infertility frequently report depression, but it is crucial to distinguish between subjective distress, symptoms, and clinical depressive disorders. In the initial assessment of a prospective, longitudinal study, 59 women presenting for infertility treatment were compared with 35 women presenting for routine gynecological care. Infertility patients and controls were not significantly different on self-report measures of partner satisfaction, sexual functioning, or self-esteem. There was also no difference in psychiatric symptomatology, or in the percentage of subjects who were currently experiencing or had ever experienced a major depressive episode. However, the infertility patients perceived themselves to have been already quite affected by their inability to conceive. For instance, 49.2% reported changes in their sexual functioning and 74.6% reported changes in their mood.

Adolescent↗
PubMed1989

Psychopathology and social functioning in women with Turner syndrome.

Turner syndrome (TUS) in women is associated with sex chromosome abnormalities, ovarian dysgenesis with estrogen deficiency, and short stature. The goal of this study was to assess the long-term effects of these sex chromosome and hormonal anomalies on psychopathology and social functioning. We report interview and questionnaire data concerning lifetime history of mental disorders and current psychiatric symptoms. Also reported are data from questionnaires and interviews evaluating social functioning as measured by education, occupation, personal resources, and sexual behavior. Twenty-three TUS women were studied and compared with 23 closely matched women with constitutional short stature (CSS) and with 10 normal sisters of the TUS women. TUS women reported generally less mental disorder and comparable rates of psychiatric symptoms. On the other hand, they had lower overall functioning on a measure of global psychological health and had more impairment in social functioning as measured by achievement of adult milestones. We conclude that TUS women display less mental illness by positive symptom-oriented criteria but also less mental health when day-to-day functioning is considered. Our data suggest that differences in TUS women cannot be explained solely by short stature and may be related to other psychosocial, genetic, endocrine, or CNS effects of the syndrome.

Achievement↗
PubMed1987

Sex hormones in lesbian and heterosexual women.

The authors measured plasma testosterone (T), androstenedione (A), and cortisol (C) levels in seven lesbian and seven heterosexual women matched for age and socioeconomic status. In addition, psychiatric symptoms, physical activity levels, depression, subjective sense of stress, and sexual behavior variables were assessed. There were no significant differences in sex hormone levels between the two groups of women, who were also comparable in psychiatric symptom levels, depression, and self-perceived stress. Lesbian women reported significantly more current physical activity relative to peers. Other than the sexual orientation difference which was a prerequisite for entry into the study, there were virtually no significant differences in sexual behavior although lesbian women tended to have achieved psychosexual milestones at a younger age. We were not able to corroborate the finding of Gartrell, Loriaux, and Chase (1977) that lesbian women have higher T levels, possibly due to the fact that the two groups were closely matched on several behavioral variables potentially affecting testosterone levels.

Adult↗