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Biomedical subjects

T J McMahon

Publications and source records attributed to T J McMahon.

At least 19 recordsLinked to original sources
PubMed2002

Tell them you love them because you never know when things could change: voices of adolescents living with HIV-positive mothers.

This study analyzed the qualitative and quantitative responses of 60 minority teens affected by HIV. Relationships between adolescents' reports of: (1) feeling different, (2) having secrets, (3) worrying, and (4) caretaking were revealed. Six themes emerged from the content analysis of qualitative data that reflect how these adolescents have been affected by HIV: (1) core assumptions about life, (2) fearful anticipation of the death, (3) stigma and isolation, (4) current and future losses, (5) family role reassignment, and (6) lack of resources. Group treatment is presented as an effective method of intervention for adolescents living with an HIV-positive mother.

Adolescent↗
PubMed2001

S-nitrosothiol repletion by an inhaled gas regulates pulmonary function.

NO synthases are widely distributed in the lung and are extensively involved in the control of airway and vascular homeostasis. It is recognized, however, that the O(2)-rich environment of the lung may predispose NO toward toxicity. These Janus faces of NO are manifest in recent clinical trials with inhaled NO gas, which has shown therapeutic benefit in some patient populations but increased morbidity in others. In the airways and circulation of humans, most NO bioactivity is packaged in the form of S-nitrosothiols (SNOs), which are relatively resistant to toxic reactions with O(2)/O(2)(-). This finding has led to the proposition that channeling of NO into SNOs may provide a natural defense against lung toxicity. The means to selectively manipulate the SNO pool, however, has not been previously possible. Here we report on a gas, O-nitrosoethanol (ENO), which does not react with O(2) or release NO and which markedly increases the concentration of indigenous species of SNO within airway lining fluid. Inhalation of ENO provided immediate relief from hypoxic pulmonary vasoconstriction without affecting systemic hemodynamics. Further, in a porcine model of lung injury, there was no rebound in cardiopulmonary hemodynamics or fall in oxygenation on stopping the drug (as seen with NO gas), and additionally ENO protected against a decline in cardiac output. Our data suggest that SNOs within the lung serve in matching ventilation to perfusion, and can be manipulated for therapeutic gain. Thus, ENO may be of particular benefit to patients with pulmonary hypertension, hypoxemia, and/or right heart failure, and may offer a new therapeutic approach in disorders such as asthma and cystic fibrosis, where the airways may be depleted of SNOs.

Administration, Inhalation↗
PubMed2000

Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoglobin.

S-Nitrosohemoglobin (SNO-Hb) is a vasodilator whose activity is allosterically modulated by oxygen ("thermodyamic linkage"). Blood vessel contractions are favored in the oxygenated structure, and vasorelaxant activity is "linked" to deoxygenation, as illustrated herein. We further show that transnitrosation reactions between SNO-Hb and ambient thiols transduce the NO-related bioactivity, whereas NO itself is inactive. One remaining problem is that the amounts of SNO-Hb present in vivo are so large as to be incompatible with life were all the S-nitrosothiols transformed into bioactive equivalents during each arterial-venous cycle. Experiments were therefore undertaken to address how SNO-Hb conserves its NO-related activity. Our studies show that 1) increased O(2) affinity of SNO-Hb (which otherwise retains allosteric responsivity) restricts the hypoxia-induced allosteric transition that exchanges NO groups with ambient thiols for vasorelaxation; 2) some NO groups released from Cys(beta93) upon transition to T structure are autocaptured by the hemes, even in the presence of glutathione; and 3) an O(2)-dependent equilibrium between SNO-Hb and iron nitrosylhemoglobin acts to conserve NO. Thus, by sequestering a significant fraction of NO liberated upon transition to T structure, Hb can conserve NO groups that would otherwise be released in an untimely or deleterious manner.

Allosteric Regulation↗
PubMed2000

Women in treatment: within-gender differences in the clinical presentation of opioid-dependent women.

Despite consistent evidence of gender differences in the nature of drug dependence, there has been little consideration of within-gender differences in the clinical presentation of drug-abusing women. In this study, cluster analysis and standardized ratings obtained from 153 women seeking methadone maintenance treatment were used to define four groups of women with different profiles of problem severity. The four clusters were characterized as Unemployed, Medically Ill, Psychiatrically Distressed, and Higher Functioning. When the validity of this four-cluster solution was examined, there were significant differences in the ethnic composition of the four groups, and the four clusters differed in terms of a) psychiatric status, b) medical status, c) vocational-educational history, d) lifetime history of maltreatment, and e) perception of social support available from friends and family. The findings suggest that, although understanding of gender differences cannot be ignored, understanding of ways women differ from one another may be as important in the development of gender-sensitive treatment programs.

Adult↗
PubMed1997

Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient.

The binding of oxygen to heme irons in hemoglobin promotes the binding of nitric oxide (NO) to cysteinebeta93, forming S-nitrosohemoglobin. Deoxygenation is accompanied by an allosteric transition in S-nitrosohemoglobin [from the R (oxygenated) to the T (deoxygenated) structure] that releases the NO group. S-nitrosohemoglobin contracts blood vessels and decreases cerebral perfusion in the R structure and relaxes vessels to improve blood flow in the T structure. By thus sensing the physiological oxygen gradient in tissues, hemoglobin exploits conformation-associated changes in the position of cysteinebeta93 SNO to bring local blood flow into line with oxygen requirements.

Animals↗
PubMed1997

Sustained-release methylphenidate for cognitive impairment in HIV-1-infected drug abusers: a pilot study.

Other investigators have reported clinical improvement from psychostimulant drugs in patients with HIV-1-related cognitive impairment. However, no previous research has substantiated this claim by using a controlled study design. We examined the efficacy of sustained-release methylphenidate (MSR) in a sample of substance abusers with HIV-1-related cognitive impairment. Eight HIV-1-infected methadone patients with impaired neuropsychological test performance participated in an inpatient double-blind placebo-controlled crossover trial of MSR 20-40 mg/day. On a composite neuropsychological measure, patients improved significantly from baseline during MSR but not placebo treatment. Nevertheless, MSR performance did not differ significantly from placebo performance. Patients appeared to improve as a function of time, regardless of sequence, with somewhat more improvement during MSR than placebo treatment.

Adult↗
PubMed1996

A pilot study of dextromethorphan in naloxone-precipitated opiate withdrawal.

Dextromethorphan and its metabolite dextrophan antagonize N-methyl-D-aspartate (NMDA)-mediated activity in pre-clinical studies. We examined dextromethorphan's effects on naloxone-precipitated opiate withdrawal in opiate-dependent subjects stabilized on 25 mg of methadone. Subjects received challenges on three different days with 0.4 mg of intramuscular naloxone. Pretreatment 1 h before naloxone was with dextromethorphan in a double-blind, balanced, randomized design with either placebo, dextromethorphan 60 mg, or dextromethorphan 120 mg for six subjects; and placebo, dextromethorphan 120 mg, or dextromethorphan 240 mg for five subjects. There was considerable inter-individual variability in the response to dextromethorphan, but no net attenuation by dextromethorphan on any withdrawal measure assessed. Two of three subjects detoxified from methadone with dextromethorphan 60 mg orally every 4 h demonstrated considerable withdrawal.

Adult↗
PubMed1996

Effects of U-37883A, a vascular selective KATP+ channel antagonist, in the pulmonary and hindlimb circulation.

The effects of the vascular selective nonsulfonylurea guanidine ATP-sensitive K+ (KATP+) channel-blocking agent U-37883A on vasodilator and vasoconstrictor responses were investigated in the pulmonary and hindlimb vascular beds of the cat. Under elevated tone conditions, both U-37883A and the sulfonylurea KATP+ antagonist, glibenclamide, attenuated pulmonary vasodilator responses to the KATP+ channel openers without altering responses to vasodilator agents that are reported to act by KATP(+)-independent mechanisms. However, under low resting-tone conditions, U-37883A enhanced pulmonary vasoconstrictor responses to the thromboxane mimic U-46619 and to prostaglandin (PG) F2 alpha and PGD2, whereas glibenclamide antagonized responses to U-46619 and the vasoconstrictor PG. In the hindlimb vascular bed, U-37883A and glibenclamide had no effects on responses to U-46619 in doses that inhibited vasodilator responses to the KATP+ channel opener levcromakalim. U-37883A and glibenclamide had no significant effect on baseline tone in the pulmonary or hindlimb vascular beds, and neither U-37883A nor glibenclamide altered pulmonary vasodilator responses to PGE1. The results of the present investigation show that U-37883A and glibenclamide, agents that are used in the study of vascular smooth muscle KATP+ channel mechanisms and attenuate vasodilator responses to the KATP+ channel openers, have pronounced effects on thromboxane/PG receptor-mediated vasoconstrictor responses in the pulmonary vascular bed of the cat.

Adamantane↗
PubMed1996

Effect of clonidine pretreatment on naloxone-precipitated opiate withdrawal.

The purpose of this pilot study was to validate a methodology for testing the opioid withdrawal-attenuating effects of new medications using clonidine as a positive control. Seven heroin-dependent subjects stabilized on levorphanol received naloxone challenge tests on 4 consecutive days in a 2 x 2 design with placebo or clonidine (0.4-0.5 mg) pretreatment, followed by 0.2 or 0.4 mg of i.v. naloxone. The change in the area-under-the-curve from the preclonidine base line for various measures of withdrawal was analyzed in a two-factor (naloxone dose and clonidine condition) analysis of variance. Clonidine significantly (P < .05) attenuated systolic and diastolic blood pressure, pulse, lacrimation, nasal congestion and plasma cortisol, but not subject-rated withdrawal severity. There was a robust dose-dependent adrenocorticotropic hormone response to naloxone that was not changed by clonidine pretreatment. The consistency between these results and prior studies of clonidine's antiwithdrawal efficacy suggests the validity of the methodology for testing medications to treat opiate withdrawal. Studies with larger samples are needed to refine this methodology.

Adrenocorticotropic Hormone↗
PubMed1995

Role of K+ATP channels and EDRF in reactive hyperemia in the hindquarters vascular bed of cats.

The mechanism underlying reactive hyperemia was investigated in the feline hindquarters vascular bed under natural- and constant-flow conditions. A 30-s occlusion of the distal aorta produced a marked hyperemic increase in distal aortic blood flow that was attenuated by the ATP-sensitive K+ (K+ATP) channel blocking agent, glibenclamide. When blood flow to the hindquarters vascular bed was held constant with a pump, interruption of blood flow for 5- to 90-s periods produced reactive vasodilator responses that increased in magnitude and duration as the period of ischemia increased. The magnitude and duration of the reactive vasodilator responses were reduced by K+ATP channel antagonists and an inhibitor of nitric oxide synthase, whereas indomethacin had no significant effect. In the pulmonary vascular bed, under constant-flow, elevated tone conditions, a 30-s period of ischemia produced a small reactive vasodilator response and a larger secondary vasoconstrictor response. The present data suggest that reactive hyperemia in the hindquarters vascular bed is mediated by the opening of K+ATP channels and nitric oxide release and that the reactive hyperemic response is not pronounced in the pulmonary circulation.

Adamantane↗
PubMed1995

Reliability of sequential naloxone challenge tests.

To determine the reliability of serial naloxone challenges, five heroin addicts stabilized on methadone were given 0.2 mg naloxone intravenously on three consecutive days. Two-factor ANOVA revealed that the between-subjects effect accounted for at least 63% of the variance in each of the dependent measures, and the effect of challenge number for at most 22%. Withdrawal tended to be slightly more severe for the first challenge. Intraclass correlation coefficients were calculated for the area-under-the-curve of the change from baseline: subject-rated (.74) and observer-rated (.71) withdrawal, pulse (.88), systolic blood pressure (.58), diastolic blood pressure (.85), and skin temperature (.63).

Adrenocorticotropic Hormone↗
PubMed1994

Preoperative diagnostic evaluation of children with Cushing's syndrome.

Recent advances in biochemical and imaging studies have improved the diagnostic accuracy of Cushing's syndrome. To better define roles for these studies in children, the authors reviewed their experience with this rare group of patients. Fifteen children, aged 11 weeks to 17 years, were treated for noniatrogenic Cushing's syndrome over a 33-year period. All children presented with signs of hypercortisolism. Nineteen different diagnostic tests were used, reflecting changes in how these patients are evaluated. Pathological diagnoses were adrenal cortical carcinoma (3), primary adrenocortical nodular dysplasia (PAND) (2), and pituitary adenoma (10). Children with adrenal cortical carcinoma presented with an adrenal mass and at a younger age (mean, 22.3 months). Key diagnostic features of patients with PAND were a low plasma adrenocorticotrophin hormone (ACTH) and no suppression with high-dose dexamethasone. Children with a pituitary cause of Cushing's syndrome presented at an older age (mean, 15.7 years) and were diagnosed using a combination of high-dose dexamethasone testing, simultaneous inferior petrosal sinus sampling, and/or ovine corticotrophin-releasing hormone stimulation test. A strategy for the diagnosis of Cushing's syndrome in children is presented.

Adenoma↗
PubMed1994

Buprenorphine: duration of blockade of effects of intramuscular hydromorphone.

Six opioid-dependent in-patients were maintained on daily sublingual doses of buprenorphine at 2, 6, and 12 mg/day for five days at each dose in a randomized, balanced sequence. Placebo buprenorphine was substituted for the next three days, and challenge doses of the mu agonist hydromorphone were administered on the three days. Planned comparisons in a 3-factor ANOVA showed dose-dependent hydromorphone effects, significant blockade of 'high' by the 12 mg buprenorphine dose, and no differences on hydromorphone-induced 'high' across 72 h of active buprenorphine. The data suggest that the blockade by buprenorphine of 'high' persists for at least 72 h after the last dose of buprenorphine.

Administration, Sublingual↗
PubMed1994

SPECT regional cerebral blood flow alterations in naltrexone-precipitated withdrawal from buprenorphine.

The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow (rCBF) were studied in 11 opiate-dependent patients. Patients initially received buprenorphine, 2 mg sublingually, every day for 7 days. They were then challenged sequentially with placebo and naltrexone, 25 mg orally, before single photon emission computed tomography with technetium-99m-d,l-hexamethyl-propylene amine oxime as tracer. Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration. Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo. Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios. Severity of withdrawal, however, showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone. These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia.

Adult↗
PubMed1994

Comparison of pressor responses to angiotensin I, II, and III in pulmonary vascular bed of cats.

Pulmonary vascular responses to angiotensin (ANG) peptides were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. Intralobar injections of ANG I, II, and III caused dose-related increases in lobar arterial pressure, whereas ANG (1-7) and ANG (3-8) (ANG IV) had modest pressor activity. ANG I, II, and III had similar activity and were more potent than norepinephrine and ANG (1-7) and ANG IV but less potent than the thromboxane A2 mimic, U-46619, in increasing lobar arterial pressure. The time course of responses to ANG I, II, and III was similar, and after administration of ANG receptor antagonists, DuP 532 and L-158,809, responses to ANG I, II, and III was reduced, whereas responses to norepinephrine, serotonin, and U-46619 were not altered. After administration of the ANG-converting-enzyme inhibitor, captopril, responses to ANG I were reduced. The converting-enzyme inhibitor enhanced pressor responses to ANG II and III but did not alter responses to norepinephrine, U-46619, or serotonin. Moreover, under elevated-tone conditions, pulmonary vasodilator responses to bradykinin were increased following administration of captopril, whereas vasodilator responses to acetylcholine and nitrovasodilators were not altered. These results demonstrate that ANG I, II, and III have similar pulmonary pressor activity and that responses are mediated by ANG II type 1 receptors. Pressor responses to ANG I are reduced, whereas vasodilator responses to bradykinin are enhanced by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗
PubMed1994

Analysis of responses to bradykinin in the pulmonary vascular bed of the cat.

Responses to bradykinin (BK) were investigated in the pulmonary vascular bed of the cat under conditions of controlled pulmonary blood flow and constant left atrial pressure when lobar arterial pressure was elevated to a high steady level. Under elevated-tone conditions, BK caused dose-related decreases in lobar arterial pressure. After administration of Hoe-140, a BK B2-receptor antagonist, vasodilator responses to BK were reduced in a selective manner. Vasodilator responses to BK were unchanged by atropine, glibenclamide, meclofenamate, or bronchial occlusion, suggesting that responses are not dependent on the activation of muscarinic receptors or K+ATP channels, the release of vasodilator prostaglandins, or changes in bronchomotor tone. The nitric oxide (NO) synthase inhibitors N omega-nitro-L-arginine benzyl ester and N omega-nitro-L-arginine reduced vasodilator responses to BK in a selective manner, indicating that responses to BK are mediated in part by the release of NO. Methylene blue, an inhibitor of the activation of soluble guanylate cyclase, increased lobar arterial pressure and decreased responses to BK. The increases in lobar arterial pressure in response to methylene blue were partially reversed by the administration of superoxide dismutase, indicating that generation of O2- may inactivate basally released NO. The duration of the response to BK was enhanced by the guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor Zaprinast, suggesting that responses to BK involve increases in cGMP levels. Responses to BK were enhanced by captopril, indicating that BK is rapidly inactivated by kininase II in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗