Characterization of hepatitis C infection in tuberculosis patients in an urban city in the USA.

The impact of hepatitis C virus infection (HCI), the most common bloodborne virus infection in the USA, on outcome of active tuberculosis (TB) treatment is largely unknown. We aimed to describe characteristics of TB patients with hepatitis C virus infection (TB-HCI) in King County, Washington, including TB treatment duration and outcome. We reviewed 1510 records of patients treated for active TB at the Public Health - Seattle & King County Tuberculosis Control Program between 2000 and 2010, and identified 53 with HCI. Advanced age, being born in the USA, HIV infection, homelessness and injection drug use were independently associated with HCI in TB cases. Independent factors associated with increased treatment duration included HIV infection, excess alcohol use, extrapulmonary TB, and any drug-resistant TB disease. Our findings suggest that TB-HCI patients can be successfully treated for active TB without extending treatment duration.

Longitudinal determinants of consistent condom use by partner type among young injection drug users: the role of personal and partner characteristics.

We investigated the longitudinal influence of individual-, relationship- and social-level factors on condom use by partner type among young injections drug users (IDUs) enrolled in the Collaborative Injection Drug Users Study-III/Drug Users Intervention Trial (CIDUS-III/DUIT) from 2002 to 2004. Based on longitudinal analysis using generalized estimating equations (GEE), consistent condom use with main partners was more commonly reported among males and those with greater self-efficacy for condom use; main partner's desire for pregnancy and needle sharing were negatively associated with consistent condom use. Among those with casual partners, having fewer sex partners was associated with consistent condom use. Positive attitudes toward condom use and partner norms supporting condom use were associated with greater consistent condom use with both partner types. These findings suggest that intervention strategies targeting individual- and partner-level factors may provide avenues for intervening upon sexual risks among young IDUs.

Effects of sodium salts on pressor reactivity in salt-sensitive men.

Blood pressure in patients with essential hypertension is raised by sodium chloride but not by nonchloride sodium salts. Although a high sodium chloride diet is known to augment the pressor response to norepinephrine and angiotensin II, the effect of nonchloride sodium salts on pressor responsiveness has not been studied so far. To examine whether sodium chloride and nonchloride sodium salts evoke different pressor responses to these agonists, we performed graded norepinephrine and angiotensin II infusions in salt-sensitive (n = 7) and salt-resistant (n = 8) normotensive subjects. The subjects were given a low salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo was added for 1 week each. We found that, although sodium chloride raised mean arterial blood pressure in the salt-sensitive subjects (p less than 0.005), sodium citrate did not. However, under both sodium salts pressor response to norepinephrine and angiotensin II was significantly greater than under placebo (p less than 0.02). Furthermore, with both sodium salts, pressor response in the salt-sensitive subjects was greater than in the salt-resistant subjects (p less than 0.01). This study thus demonstrates that, although blood pressure in salt-sensitive individuals is raised by sodium chloride only, both sodium chloride and sodium citrate evoke similar increases in pressor response to norepinephrine and angiotensin II. Since pressor response increased with both sodium salts but resting blood pressure increased only with sodium chloride, enhanced pressor responsiveness alone cannot account for the sodium chloride-induced rise in resting blood pressure.

Antihypertensive and metabolic effects of diltiazem and nifedipine.

The antihypertensive effect of diltiazem (180-270 mg/day) and nifedipine (40-60 mg/day) in slow-release forms was assessed over 8 weeks in a double-blind parallel study in 40 subjects with essential hypertension at rest and during exercise. Blood pressure was comparably reduced in both groups at rest as well as during exercise. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) after 8 weeks of therapy were 53% at rest and 75% during exercise in the diltiazem group and 78% and 50%, respectively, in the nifedipine group. Diltiazem decreased heart rate by 8% (p less than 0.01), while nifedipine did not affect it. As a consequence, myocardial oxygen consumption, as judged by the pressure-rate product, was reduced by diltiazem. Resting plasma norepinephrine levels were increased significantly after 8 weeks of diltiazem therapy. Plasma epinephrine, renin, aldosterone, glucose, insulin, and lactate and routine laboratory parameters were unchanged at the end of the study. No significant changes in total cholesterol and triglyceride levels were observed after 8 weeks. Whereas therapy with diltiazem resulted in an 8% fall in low density lipoprotein cholesterol after 8 weeks (p less than 0.05), nifedipine induced a drop in very low density lipoprotein cholesterol (p less than 0.05) after 8 weeks of therapy. We conclude that both diltiazem and nifedipine are effective antihypertensive agents lacking undesirable metabolic side effect. Diltiazem, however, had the advantage of lowering heart rate and myocardial oxygen consumption.

Risk factors for HIV infection among injection drug users: results of blinded surveys in drug treatment centers, King County, Washington 1988-1991.

Among injection drug users (IDUs) entering drug treatment in King County, Washington between 1988 and 1991, we investigated HIV seroprevalence in relationship to demographic, sexual, and drug-use characteristics. Eighty-two of 3,039 (2.7%) IDUs tested HIV positive. Gay or bisexual men had the highest HIV prevalence (37.1%), followed by lesbian or bisexual women (8.3%), heterosexual men (2.3%), and heterosexual women (1.5%). American Indians were more likely to be infected with HIV than were whites. Those with no permanent address were more likely to be infected than those with an address. Unexpectedly, the prevalence of HIV infection among amphetamine injectors (13.1% of 168) was higher than among those who did not report using amphetamines. After adjustment for sexual orientation, HIV prevalence was four times higher among primary amphetamine injectors and three times higher among secondary amphetamine injectors than among injectors of other drugs. The basis for the strong association observed between HIV infection and a history of injection of amphetamines is not known and should be clarified through further research that obtains more detailed information on IDUs.

Effect of dietary salt restriction on urinary serotonin and 5-hydroxyindoleacetic acid excretion in man.

OBJECTIVE: To determine the effect of dietary salt restriction on urinary excretion of serotonin and its principal metabolite 5-hydroxyindoleacetic acid (5-HIAA) in man. DESIGN: We studied 16 healthy male volunteers (age range 20-28 years) who ate a standard diet containing 20 mmol/day NaCl, to which either 220 mmol/day NaCl or placebo was added as a supplement for 1 week each, according to a randomized, single-blind crossover design. METHODS: Urinary excretion of serotonin, 5-HIAA, noradrenaline and vanillylmandelic acid (VMA) were measured during the low- and high-salt periods using reverse-phase high-performance liquid chromatography. RESULTS: During the low-salt diet, 24-h urinary excretion of serotonin increased by 42%, accompanied by a 52% rise in the excretion of 5-HIAA. Salt restriction also increased noradrenaline excretion by 77% and VMA excretion by 40%. Regression analysis revealed a strong positive relationship between the excretion of serotonin and of noradrenaline (r = 0.84, P < 0.001) and between that of 5-HIAA and of VMA (r = 0.74, P < 0.001). CONCLUSIONS: Salt restriction stimulates the serotonergic system in man. Stimulation of this system, in conjunction with the sympathetic nervous system, may contribute to renal sodium conservation during dietary salt restriction in man.

Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an inhibitor of purine nucleotide de novo synthesis leading to impaired proliferation of activated lymphocytes. Studies in animals show a synergistic effect of MMF and cyclosporine (CsA) in preventing acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. We performed a pilot study evaluating the feasibility of the combined application of MMF and CsA as GVHD prophylaxis after allogeneic blood stem cell transplantation. Toxicity and the bioavailability of MMF in this setting were investigated. METHODS: Fourteen patients who had received grafts from HLA-compatible siblings received 2 g of oral MMF from day 1 to 14 combined with intravenous CsA at 4 mg/kg starting at day-1. Plasma levels of mycophenolic acid (MPA) and its glucoronide were measured by high-performance liquid chromatography. Fifteen patients treated with a combination of CsA and methotrexate at the same institution were referred to as the control group. RESULTS: Trilineage engraftment was achieved in all study and control patients. Acute GVHD > or = grade II was observed in 46.5% and 60% of the study and control patients, respectively. No major differences in the rate of acute toxicities were detectable. The mean trough blood level of MPA in 10 patients was 0.28 microg/ml, and 5.7 microg/ml for MPA glucoronide. Reduced peak levels of MPA indicate a reduced absorption rate of MMF in the early posttransplant phase. CONCLUSIONS: The combined administration of MMF and CsA was shown to be feasible in patients after allogeneic blood stem cell transplantation. Because of the decreased bioavailability of MMF, dose-finding studies for an intravenous formulation are warranted.

Sympathetic nervous activity and noradrenaline reactivity during angiotensin converting enzyme inhibition.

The effect of the angiotensin converting enzyme inhibitor ramipril on catecholamine disposition and noradrenaline reactivity was studied in normotensive volunteers. In the first study 5 mg of ramipril or placebo was given 3 times at 12-hour intervals in a randomized, double-blind, cross-over manner (n = 10). In the second study, ramipril 10 mg daily was given for 2 weeks (n = 6). Noradrenaline reactivity increased significantly (p less than 0.05) both in short- and long-term application, while blood pressure decreased (p less than 0.01). Sulfoconjugated plasma noradrenaline decreased significantly (p less than 0.05) possibly indicating a decrease in sympathetic tone. These findings suggest that a decrease in sympathetic tone could contribute to the blood pressure-lowering effect of ramipril, whereas the increase in noradrenaline reactivity is probably a consequence of the primary change in sympathetic activity.

Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects.

The effects of moclobemide and toloxatone, two reversible monoamine oxidase-A inhibitors, on biochemical parameters that reflect monoamine metabolism and on psychomotor performance parameters were investigated in a study in 12 healthy volunteers. Treatments were given double-blind in a randomized, placebo-controlled cross-over design, with 1 week wash-out between the treatments. Drugs were given thrice daily in the following doses: moclobemide 150-150-150 mg and toloxatone 400-200-400 mg. All assessments were performed on day 8 under standardized conditions. There was no difference with regard to adverse events between moclobemide and toloxatone: both drugs induced a slight decrease in both supine and standing heart rate. Judged on the basis of the area under the curve, the two MAO-inhibitors reduced the plasma levels of DHPG and HVA, with more pronounced effects for moclobemide than for toloxatone. After moclobemide MAO-A inhibition was almost constant over 24 h, whereas the effect of toloxatone was short lasting after each dose. The same differences were reflected in plasma 5-HIAA concentrations and urinary excretion of 3-methoxytyramine and normetanephine. Neither of the compounds tested had any influence on the memory, vigilance, mood, or sleeping habits of the subjects.

Endogenous dopa in rat brain. Occurrence, distribution and relationship to changes i catecholamine synthesis.

Dopa was isolated from rat brain by cation exchange chromatography and determined by a radioenzymatic method using catechol-O-methyl-transferase and [3H]-S-adenosyl-methionine as cofactor. The product [3H]-methoxytyrosine was purified by cation and anion exchange chromatography. For identification of presumed endogenous dopa isolated from rat brain and rat blood plasma the [3H]-labelled product was purified further by thin-layer chromatography. In the brain of rats killed by decapitation, dopa in a concentration of 7 ng/g was identified. When unstressed rats were killed by focussed microwave irradiation at 2.450 MHz and 8 kW for 1.3 s dopa levels as high as 20 ng/g were measured. The regional distribution of dopa in brain or rats killed by microwaves was similar to the distribution of catecholamines, dopa levels being highest in c. striatum and lowest in cerebellum. Inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine methylester HCl, 250 mg/kg i.p. 90 min before death did not change the brain dopa levels in rats killed by decapitation or in rats killed by microwaves. Compounds, such as haloperidol, chlorpromazine, apomorphine and pentobarbital which are known to increase or decrease catecholamine synthesis did not change the basal level of dopa. The data indicate that in rat brain, the main portion of dopa is associated with catecholamine-containing nerve terminals and that this portion is present in a pool which is only slowly metabolized. A second very small pool of dopa must exist, which is serving as precursor pool for catecholamines and which is turned over at a higher rate. It can be concluded that the basal dopa level cannot be used as an indicator of catecholamine synthesis.

Conjoint radioenzymatic measurement of catecholamines, their catechol metabolites and DOPA in biological samples.

An assay is described for the simultaneous determination of dopamine, noradrenaline, adrenaline, dopa, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, 3,4-dihydroxymandelic acid and 3,4-dihydroxy-phenylglycol, capable of detecting amounts in the femtomol range. The assay is based on the O-methylation of the catechol moiety utilizing S-[3H-methyl]-adenosyl-L-methionine and a partially purified catechol-O-methyl transferase to form the various O-[3H-methyl]-catechol derivatives. The O-[3H-methyl]-catechol derivatives are purified by thin layer chromatography, solvent partitions and/or ion exchange chromatography. The assay was successfully applied to biological sample. It was possible for the first time, to detect free 3,4-dihydroxyphenylglycol, free 3,4-dihydroxyphenylethanol and 3,4-dihydroxymandelic acid in a small volume (25 microliter) of blood plasma of man, rat, dog and rabbit. The conjoint measurement of catecholamines and their catechol metabolites in minute amounts of biological samples may contribute to a more detailed understanding of catecholamine metabolism in the peripheral and central nervous system.

Inhibition of MAO and COMT by hypericum extracts and hypericin.

The influence of hypericin, hypericum total extract, and hypericum fractions on the activity of MAO and COMT, prepared in vitro from pork liver, were investigated in several concentration steps. An inhibition of MAO could be shown in the following concentrations (extract correlated to a mean molecular value of 500): hypericin to 10(-3) mol/L, hypericum total extract to 10(-4) mol/L, one extract fraction up to 10(-5). A COMT inhibition could not be shown for hypericin, with hypericum extract to 10(-4) mol/L and with two extract fractions also up to 10(-4) mol/L. The MAO inhibiting fraction contained hypericins as well as flavonols, the COMT-inhibition fraction being mainly flavonols and xanthones. The concentrations of inhibition shown might not be sufficient to explain the clinically proven antidepressive effect of hypericum particularly with regard to the inhibition of MAO activity.

Reduced injection frequency and increased entry and retention in drug treatment associated with needle-exchange participation in Seattle drug injectors.

The association between needle exchange, change in drug use frequency and enrollment and retention in methadone drug treatment was studied in a cohort of Seattle injection drug users (IDUs). Participants included IDUs classified according to whether they had used a needle exchange by study enrollment and during the 12-month follow-up period. The relative risk (RR) and the adjusted RR (ARR) were estimated as measures of the association. It was found that IDUs who had formerly been exchange users were more likely than never-exchangers to report a substantial (> or= 75%) reduction in injection (ARR = 2.85, 95% confidence limit [CL] 1.47-5.51), to stop injecting altogether (ARR = 3.5, 95% CL 2.1-5.9), and to remain in drug treatment. New users of the exchange were five times more likely to enter drug treatment than never-exchangers. We conclude that reduced drug use and increased drug treatment enrollment associated with needle exchange participation may have many public health benefits, including prevention of blood-borne viral transmission.

The prevalence of urogynecologic disorders.

Although the field of urogynecology spans a wide range of lower urinary tract disorders, urinary incontinence and urinary infections remain the two most common disorders of the urinary tract encountered by the health care provider practicing obstetrics and gynecology. Both problems have a higher prevalence in the older population, and in addition they both have a predilection for recurrence. Together they account for considerable personal and public expense, as well as untold individual emotional and physical distress. Much remains to be learned before significant measures can be initiated to prevent the problems. Urinary incontinence is particularly challenging because it is a manifestation of so many other disorders or their treatment.

A glance at the urodynamic database.

Three hundred sixty-four patients with urinary incontinence as their presenting complaint were evaluated in the urogynecology laboratory, Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York. Of them, 226 (62%) were found to have genuine stress urinary incontinence (GSI). This subset of demonstrably incontinent patients was characterized as to symptoms of stress and urge incontinence, incidence of nulliparity, occurrence of incontinence during intercourse and influence of weight on bladder pressure. Using clusters of symptoms did not accurately distinguish GSI from the other types of urinary incontinence. Four percent of the GSI patients were nulliparous. All had a reasonable explanation for incontinence other than anatomic relaxation. Twenty-three percent of the 154 sexually active GSI patients acknowledged having incontinence with intercourse. None of the anatomic and urodynamic parameters evaluated distinguished that group from their GSI counterparts who did not lose urine with intercourse. Increasing weight, expressed as the body mass index, correlated with an increase in the vesical pressure in the supine and standing positions.

Hypotensive action of calcium antagonists as related to plasma noradrenaline and reactivity to noradrenaline.

From animal experiments it has been suggested that calcium antagonists owe their antihypertensive potency to a diminished sensitivity of the resistance vessels to circulating noradrenaline. We studied the effects of two calcium antagonists, nifedipine and verapamil, on blood pressure, reactivity to exogenous noradrenaline and plasma noradrenaline concentration in 10 patients with essential hypertension. In a cross-over comparison the patients were treated with nifedipine and verapamil for four weeks each. Both calcium antagonists led to a similar drop in arterial pressure. Resting plasma noradrenaline did not change during either treatment whereas a slight increase (P less than 0.05) in stimulated noradrenaline levels was observed during nifedipine treatment. The hypotensive effect of nifedipine was associated with a marked reduction (P less than 0.01) in the pressor effect of noradrenaline whereas no change in pressor response could be found during verapamil treatment. The results obtained suggest that an impairment of the pressor response to noradrenaline is not a general prerequisite for the antihypertensive action of calcium antagonists.

Alpha 2- and beta 2-adrenoceptor downregulation in marathon runners.

The regulation of platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities by alterations in endogenous catecholamines was examined. In order to activate the sympathetic nervous system eight trained male normotensive subjects carried out a marathon run. Adrenoceptor densities and plasma catecholamine concentrations were measured before and immediately after the run. Platelet alpha 2-adrenoceptor density and lymphocyte beta-adrenoceptor density decreased after the run (P less than 0.05), whereas both plasma noradrenaline and adrenaline concentrations increased (P less than 0.01). Mean arterial pressure decreased (P less than 0.05), and the heart rate increased (P less than 0.001). The data suggest that increases in endogenous catecholamine concentrations cause downregulation of both alpha- and beta-adrenoceptor densities on human blood cells.

Combined beta 1-adrenoceptor blockade and/or beta 2- or beta 1/2 adrenoceptor stimulation as treatment of essential hypertension.

Single and combined therapy with terbutaline (10 mg/day) and metoprolol (200 mg/day) and single therapy with orciprenaline (30 mg/day) were assessed over 8 weeks in a total of 45 patients with essential hypertension. Blood pressure at rest was comparably reduced by metoprolol + terbutaline and metoprolol alone, but with terbutaline and orciprenaline only after 4 weeks. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) at rest were 58% (metoprolol + terbutaline), 63% (metoprolol) and significantly lower with terbutaline alone at 42% and orciprenaline alone at 45%. The heart rate was affected only by metoprolol monotherapy, which caused a significant decrease. The beta-adrenoceptor stimulators terbutaline and orciprenaline in the chosen doses slightly decreased blood pressure and did not increase the heart rate. Metoprolol was an effective antihypertensive agent but decreased the heart rate. Under combined therapy with terbutaline, there was no additional blood pressure decrease, but the heart rate remained unaffected.

Regulation of alpha 2-adrenoceptor density in normotensive and hypertensive man.

We examined normotensive and hypertensive subjects in order to determine whether changes in platelet alpha 2-adrenoceptor density following alterations in plasma noradrenaline are related to changes in noradrenaline (NA) reactivity. Noradrenaline reactivity, plasma NA, alpha 2-adrenoceptor density, and adenylate cyclase activity were measured before and after a 24-h infusion of NA at a subpressor dose (0.02 micrograms/kg per min, n = 13), and also after application of drugs known to increase (nifedipine and furosemide) or decrease (clonidine) plasma NA. Measurements were obtained 60 min after nifedipine (20 mg in a single dose, n = 13), after 3 weeks on furosemide (30 mg twice a day, n = 8) and after 1 week on clonidine (150 micrograms three times a day, n = 5). Infusion of NA decreased alpha 2-adrenoceptor density (P less than 0.01) and NA reactivity (P less than 0.05). Nifedipine decreased alpha 2-adrenoceptor density and NA reactivity (P less than 0.01 for both) in patients with essential hypertension. The alterations in alpha 2-adrenoceptor densities were paralleled by a decreased adrenaline-induced inhibition of adenylate cyclase activity (P less than 0.01). Furosemide decreased alpha 2-adrenoceptor density (P less than 0.01), the fraction of high-affinity binding sites (P less than 0.01) and NA reactivity (P less than 0.05) in normotensive subjects. Following clonidine all three parameters, alpha 2-adrenoceptor density, the fraction of high affinity sites and NA reactivity, increased (P less than 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)