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Biomedical subjects

T Maher

Publications and source records attributed to T Maher.

At least 19 recordsLinked to original sources
PubMed2001

Further evidence that extracellular serotonin in the rostral ventrolateral medulla modulates 5-HT(1A) receptor-mediated attenuation of exercise pressor reflex.

We determined changes in extracellular levels of glutamate, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) within rostral ventrolateral medulla (RVLM) during 5-HT(1A)-receptor stimulation-mediated inhibition of cardiovascular responses to static muscle contraction using anesthetized rats. In ten rats, muscle contraction significantly increased (P<0.01) mean arterial pressure (MAP) by 29+/-4 mm Hg, heart rate (HR) by 25+/-3 bpm, and glutamate levels by 4.5+/-0.8 ng/5 microl. Microdialysis of a 5-HT(1A) receptor agonist, 8-OH-DPAT (10 mM), into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effect on glutamate levels. A subsequent administration of 10 mM WAY100635, a 5-HT(1A) antagonist, into the RVLM antagonized the attenuating effects of 8-OH-DPAT. In another ten rats, muscle contraction significantly increased (P<0.01) MAP and HR by 20+/-2 mmHg and 25+/-8 bpm, respectively. In addition, levels of 5-HT, NE, and DA in the RVLM significantly increased (P<0.01) by 3.6+/-0.3, 3.2+/-0.3, and 3.3+/-0.4 pg/10 microl, respectively. Administration of 8-OH-DPAT (10 mM) into the RVLM for 30 min attenuated cardiovascular responses to muscle contraction and had no effects on NE and DA levels. However, the drug significantly attenuated 5-HT levels following a muscle contraction. Microdialysis of 10 mM WAY100635 into the RVLM reversed both cardiovascular and 5-HT changes. These results suggest that stimulation of 5-HT(1A)-receptors within the RVLM attenuates cardiovascular responses to static exercise via a reduction of extracellular 5-HT concentration and most likely not through changes in glutamate, NE or DA levels.

Animals↗
PubMed2001

Modulation of pressor response to muscle contraction via monoamines following AMPA-receptor blockade in the ventrolateral medulla.

We hypothesized that cardiovascular responses to static muscle contraction are mediated via changes in extracellular concentrations of monoamines (norepinephrine, dopamine and serotonin) following the administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, an AMPA-receptor antagonist) into the rostral (RVLM) or caudal (CVLM) ventrolateral medulla. For the RVLM experiments (n= 8), a 2-min static muscle contraction increased the mean arterial pressure (MAP) and heart rate (HR) by 23 +/- 2 mmHg and 28 +/- 8 bpm, respectively. During this contraction, the concentrations of norepinephrine, dopamine, and serotonin within the RVLM increased by 278 +/- 52%, 213 +/- 23%, and 232 +/- 24%, respectively. Microdialysis of CNQX (1.0 microM) for 30 min into the RVLM attenuated the increases in MAP and HR ( 11 +/- 2 mmHg and 14 +/- 5 bpm) without a change in developed muscle tension. The levels of norepinephrine, dopamine, and serotonin within the RVLM were also attenuated. In contrast, microdialysis of CNQX into the CVLM (n= 8) potentiated the contraction-evoked responses in MAP ( 21 +/- 2 vs 33 +/- 5 mmHg) and HR ( 25 +/- 5 vs 46 +/- 8 bpm) without any effect on the monoamine levels within the CVLM region. These results suggest that AMPA-receptor blockade within the RVLM and CVLM has opposing effects on cardiovascular responses during static muscle contraction. In addition, such receptor blockade modulates extracellular concentrations of monoamines within the RVLM but not in the CVLM. These results provide evidence that AMPA receptors within the ventrolateral medulla play a role in exercise pressor reflex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

The Heartmate II: design and development of a fully sealed axial flow left ventricular assist system.

Our group is developing the control and power transmission components required to implement a permanent and fully sealed left ventricular assist system (LVAS). Starting with the percutaneously powered HeartMate II blood pump, our development efforts are focused in the following areas: a complete redesign of the transcutaneous energy transmission system (TETS) to include a rectification network and autonomous voltage regulation within the secondary coil, a hermetically sealed electronics package containing a miniaturized implementation of the existing redundant drive and control electronics with several power-input options, an implanted rechargeable lithium ion battery pack capable of providing up to 1 h of untethered operation, implantable electrical connectors that allow components to be connected after placement in the body or to be replaced if needed, and a radio telemetry subsystem to transmit diagnostic information and to permit remote adjustment of selected parameters.

Electric Power Supplies↗
PubMed2001

Highly polymorphic short tandem repeat analyses clarify complex molecular test results.

Judicious application of highly polymorphic short tandem repeat (STR) analyses and modification of assay conditions readily distinguished nonparentage from true parentage, with occasional failure to transmit one parentally derived allele. These categories were resolved with a reliability of >99.9%, the standard applied to most DNA evidence presented in a U.S. court of law. While completing a single prenatal diagnosis submitted at 19 weeks gestation, the authors found that one polymorphic grandpaternal allele did not amplify, a duplicate control propositus' DNA sample had been switched by an outside laboratory, and recombination occurred in maternal meiosis within the mutant gene region. In two parentage cases with one available parent, a Y-linked STR or an autosomal STR was modified when transmitted to the offspring. In contrast, some apparently inconsistent results between parental DNA and offspring were resolved by purifying or diluting the original extracted DNA samples. Thus, the source of each complex molecular test result was characterized unambiguously by testing a sufficient number of highly polymorphic STR loci and by purifying or diluting troublesome DNA samples to diminish polymerase chain reaction amplification artifact.

Adult↗
PubMed2000

Substituting lifestyle management for pharmacological control of blood pressure: a pilot study in Australian general practice.

The HEART project was conducted in general practice to determine whether lifestyle strategies, aimed at increasing physical activity and dietary modification, can be substituted for drug therapy in patients who have been well controlled on antihypertensive medication. In addition to blood pressure (BP) and risk factor outcomes, lifestyle behaviours, quality of life of patients, and the acceptability of the approach to both general practitioners (GPs) and patients involved in the trial were assessed. Patients (n = 45) with a history of hypertension and who had been well controlled for at least the past 6 months (BP < 160/ 95 mmHg) were randomised to a continued medication (C) group (n = 24) or a withdrawal (W) group (n = 21). Subjects had received antihypertensive therapy for an average of 7.8 years (range 1-28 years). Drug therapy in the W group was recommenced if BP exceeded 160/95 mmHg on two consecutive visits. Both groups were counselled regarding lifestyle behaviour change by their GP throughout the study and were provided with specifically developed self-help materials. Subjects were reviewed at least monthly over a 9-month period. Following randomisation, there were no significant differences between the two groups for BP, heart rate, age, duration of therapy, total cholesterol or body mass index. All but three subjects (one from the W and two from the C group) completed 9 months of monitoring following randomisation and there were no cardiovascular events; 71% of subjects remained off drug therapy and were well controlled at the 9-month follow-up (15/21) with mean BP of 141/85 mmHg (W) and 139/ 86 mmHg (C). Systolic BP tended to increase during the study period in both W and C groups, however, no significant differences were observed in mean systolic or diastolic BP either between the two groups or within each group in comparison to baseline values. Resting heart rate, body mass index and cholesterol levels remained unchanged in both W and C groups after 9 months follow-up. There were no changes attributable to the lifestyle intervention in the subjects continuing drug therapy in BP or lifestyle variables over the study period. However, the group stopping therapy had a 6% reduction in body mass index after 9 months. These data suggest that a proportion of motivated patients willing to trial a lifestyle approach can cease drug therapy and be adequately maintained by the prescription of lifestyle advice via their GP for at least a 9-month period. Cessation of drug therapy may be an important motivating factor to achieve weight loss in this group.

Adolescent↗
PubMed1999

Preventive health behaviour among general practitioners in Victoria.

UNLABELLED: This study describes the preventive health behaviour of general practitioners in Victoria, with particular emphasis on hepatitis B prevention, and their use of medical services, and seeks to explain these behaviours. METHODS: Cross sectional postal questionnaire survey of a 10% random sample (n = 544) of all GPs in Victoria, Australia. RESULTS: A valid response rate of 58.5% was achieved. Only 4% of the sample smoked, 93% had a blood pressure check in the past 3 years, and 64% had a cholesterol check in the past 3 years. About half followed a 'healthy' diet and 20% took a high level of physical exercise. With regard to hepatitis B prevention, 87% had completed vaccination, and 49% had confirmed immunity. Needlestick injuries had been suffered by 49% in the previous year, and half of the respondents would take no action after such an event. Over two-thirds (69%) reported having no GP. Psychological factors were associated with preventive health behaviour independent of age and gender. Internal locus of control and health value were positively associated with whether the doctor would take any action after needlestick injury, had a blood pressure or cholesterol test in the past 3 years or had their own GP. CONCLUSION: This study shows that GPs in Victoria have a relatively high level of preventive health activity although they have a low level of utilisation of their GP colleagues in service provision. There are measurable differences in psychological variables between doctors that are associated with their level of preventive care. Plans to improve their personal health care should concentrate on psychological well being.

Adult↗
PubMed1997

Survival following traumatic rupture of the heart in a child.

Blunt force trauma to the chest can result in rupture of the heart. We report the youngest survivor of this injury, followed by a literature review, description of the epidemiology, and mechanism and guidelines for diagnosis and aggressive management.

Child↗
PubMed1995

Anticonvulsant effects of intracerebroventricular adenocard in theophylline-induced seizures.

STUDY OBJECTIVE: To evaluate the potential anticonvulsant effects of Adenocard in theophylline-induced seizures, we developed a rodent model of theophylline neurotoxicity with resultant convulsions. We used this model to investigate the actions of intracerebroventricular (ICV) Adenocard on seizure onset. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTIONS: Surgical cannulation of the jugular veins of the rats was followed by stereotaxic placement of a catheter in the right lateral ventricle. The rats then received 15 micrograms (5 microL) ICV Adenocard or an equivalent. Ten seconds later, continuous infusion of IV aminophylline was begun at a rate of 75 mg/minute until the appearance of generalized convulsions with maximal hindlimb extension. RESULTS: Compared with vehicle-injected controls, rats that received ICV Adenocard had a significant delay in mean time to seizure (162.1 seconds versus 107.4 seconds; P < .001). There was a corresponding increase in the weight-adjusted convulsant dose of aminophylline after the ICV administration of Adenocard (311.4 mg/kg versus 470.4 mg/kg; P < .003). CONCLUSION: Our data indicate that ICV Adenocard ameliorates theophylline-induced seizures. Potential anticonvulsant benefits of Adenocard and other adenosinergic compounds for victims of severe theophylline poisoning should be investigated further.

Adenosine↗
PubMed1994

Phase II study of merbarone (NSC 336628) in patients with advanced gastric carcinoma.

Merbarone, 5-(N-phenylcarboxamido)-2-thiobarbituric acid (NSC 336628), is a derivative of barbituric acid and represents a unique class of antineoplastic agents. We treated 16 patients with advanced gastric carcinoma in a phase II study of merbarone. All patients were previously untreated with chemotherapy or biological therapy. The starting dose of merbarone was 1000mg/m2 infused over 24 hr for 5 consecutive days every 21 days. A median of two courses (range, 1-7) was given. None of the patients achieved a complete or partial response; however, 3 patients achieved a transient minor response. Toxicity was mild to moderate in most patients, but 1 patient died of treatment-related neutropenia and sepsis. Our data suggest that merbarone at this dose and schedule is inactive against gastric carcinoma. The evidence of minor response suggests that analog research may be worthwhile to pursue.

Antineoplastic Agents↗
PubMed1993

Interleukin-2 activity in patients with extensive small-cell lung cancer: a phase II trial of Cancer and Leukemia Group B.

BACKGROUND: Chemotherapy may induce overall (complete plus partial) response rates of more than 50% and complete response rates up to 25% in extensive small-cell lung cancer (stage IIIB or IV), but survival is generally limited to 8-12 months. Interleukin-2 (IL-2) has demonstrated activity against this disease in vitro and has produced regression in melanoma and renal cell carcinoma. PURPOSE: The purpose of this study was to determine in a prospective, nonblinded, phase II trial the activity of IL-2 in patients with extensive small-cell lung cancer who had not achieved complete remission with chemotherapy. METHODS: The 68 patients eligible for the study were initially treated with at least one dose of combination chemotherapy with cisplatin, doxorubicin, cyclophosphamide, and etoposide (PACE). Of the 50 who did not obtain complete remission with PACE, 24 who had measurable or evaluable disease and whose medical condition allowed further therapy were treated with IL-2. Beginning 3 weeks after the last dose of PACE, IL-2 was administered intravenously at 4.5 million Nutley units/m2 per day as a continuous infusion for 96 hours, followed by a 3-day rest. The planned duration of therapy was 8 weeks. RESULTS: Of the 24 patients eligible to receive IL-2, four (17%) with measurable disease or evaluable but not measurable disease obtained a complete response after IL-2 therapy; one (4%) patient had a partial response. The overall response rate was 21%. Complete responses continued for 8, 9, and more than 11 months in three patients; the remaining patient developed acute myelomonocytic leukemia while in complete remission approximately 8 months after the start of IL-2 therapy. Only five of the 24 patients were able to complete the planned 8 weeks of IL-2 therapy. Therapy was discontinued in 11 patients because of life-threatening side effects, in six because of disease progression, and in two who withdrew from the study, probably related to IL-2 toxicity. CONCLUSIONS: These results indicate that IL-2 has some activity in extensive small-cell lung cancer and suggest that IL-2 is not cross-resistant with PACE therapy. IMPLICATIONS: Further studies are needed to define the optimum timing, dose, and schedule of IL-2 and to determine whether the agent has a role in the therapy of small-cell lung cancer.

Adult↗
PubMed1990

Trisomy 12 mosaicism in phenotypically normal fetuses following prenatal detection.

We report three cases of amniocentesis in which mosaicism for trisomy 12 was detected in two or more independent cultures. The parents elected to terminate the pregnancy in all three cases. Follow-up studies in two of the cases confirmed the mosaicism in fetal tissues (in subcutaneous tissue in one case; in fetal lung in the other), but not in blood. No fetal anomalies were evident by ultrasound or at autopsy. These results along with other reported cases demonstrate the difficulty in counselling for mosaic trisomy 12.

Adult↗
PubMed1989

Surgical therapy for left ventricular aneurysms. A ten-year experience.

We reviewed retrospectively the surgical results of left ventricular aneurysm reduction in 197 consecutive patients operated on in 1977-1987. There were 19 hospital deaths (9.6%) and 38 late deaths. The cumulative 5- and 10-year survival probabilities were 79% and 67%. Of the 140 late survivors, 130 underwent follow-up study in 1988 (mean, 5 years postsurgery). We analyzed preoperative, perioperative, and postoperative variables to evaluate the efficacy of surgical therapy. The risk of early mortality was increased by worsening preoperative New York Heart Association class, operation within 30 days of myocardial infarction, combinations of ventricular arrhythmia and congestive heart failure, renal failure, and preoperative cardiogenic shock. There was a trend toward increased early mortality with multivessel coronary artery disease. Late mortality and length of survival were not predicted by any variable examined.

Actuarial Analysis↗
PubMed1984

Amelioration of metabolic acidosis by dietary potassium restriction in hyperkalemic patients with chronic renal insufficiency.

Hyperkalemia has been implicated in the pathogenesis of metabolic acidosis in chronic renal insufficiency because acidosis is ameliorated after administration of medications that correct hyperkalemia: mineralocorticoids, diuretics, intestinal K+-binding agents. However, the acidosis-ameliorating effect of these medications may be a consequence not of their ability to correct hyperkalemia, but of their ability to directly stimulate renal or intestinal excretion of acid. To investigate the specific effect of correcting hyperkalemia, balance studies were performed wherein hyperkalemia was corrected solely by restriction of dietary K+ in three patients with moderate chronic renal insufficiency (Ccreat 36, 44, and 58 ml/min/1.73 m2, respectively). Reduction of K+ intake was effected by substitution of Na+ for K+ in the electrolyte supplement to a whole-food diet of low K+ content. This maneuver resulted in correction of hyperkalemia and sustained amelioration of metabolic acidosis in each patient. Net acid excretion increased only transiently, and not enough to fully account for the magnitude of the increment in plasma [HCO3-], suggesting that an extrarenal mechanism of HCO3- input to the systemic circulation was the major factor that ameliorated the systemic acidosis. Evidence of an extrarenal mechanism was obtained only during the phase of decreasing plasma [K+]. Subsequently, during sustained normokalemia, the increased plasma [HCO3-] was maintained as a consequence of a sustained increase in total renal H+ secretion, evidenced by complete reabsorption of the increased filtered load of HCO3- and no reduction in net acid excretion from control values. These results indicate that in some patients with moderate chronic renal insufficiency, metabolic acidosis is ameliorated when hyperkalemia is corrected by restriction of dietary K+ (Na+ substitution) without otherwise changing diet composition and without administration of medication. Amelioration of the acidosis is predominantly effected by extrarenal mechanisms, and is sustained by an increase in the set point at which plasma [HCO3-] is regulated by the kidney.

Acidosis, Renal Tubular↗
PubMed1983

Effect of diet on plasma acid-base composition in normal humans.

Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P less than 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P less than 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steady-state rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.

Acid-Base Equilibrium↗
PubMed1982

Disorders of distal nephron function.

In this review, the distal nephron is considered to be that portion of the renal tubule commencing with the thick ascending limb of the loop of Henle and ending with the papillary collecting duct. The collecting duct, including its subdivisions in the cortex and medulla, originates from a different embryologic anlage than more proximal nephron segments, which may explain its morphologic and functional dissimilarities from the thick ascending limb and the distal convoluted tubule. This review summarizes selected aspects of the physiology of the distal nephron, with particular emphasis on the physiology of distal nephron transport of sodium, potassium, chloride and hydrogen ion. The pathophysiologic features of the following disorders of distal nephron function are reviewed: (1) pseudohypoaldosteronism, a heterogenous group of disorders in which the signs and symptoms are suggestive of aldosterone deficiency, but in which aldosterone levels are supernormal and administration of exogenous mineralocorticoid is not ameliorative; (2) pseudohyperaldosteronism (Liddle syndrome), a familial disorder in which the clinical manifestations closely resemble those resulting from an aldosterone-producing adenoma of the adrenal gland (primary aldosteronism), but in which the measured rate of aldosterone secretion and excretion is greatly subnormal; (3) Bartter syndrome and related syndromes of renal potassium wasting; (4) type 1 renal tubular acidosis (classic, distal); (5) type 4 renal tubular acidosis (hyperkalemic). Reference citations are generally to articles reporting recent advances in these areas and to review articles that contain comprehensive bibliographies.

Acidosis, Renal Tubular↗
PubMedDate not supplied

Prenatal diagnosis for Schmid metaphyseal chondrodysplasia in twins.

We report prenatal diagnostic studies for metaphyseal chondrodysplasia of the Schmid type. Identification of a specific COL10A1 gene mutation in an affected father allowed prenatal diagnosis by chorionic villus sampling in a twin pregnancy. Neither of the nonidentical twins received the abnormal COL10A1 gene from their affected father. This result was confirmed by postnatal DNA analysis. Prenatal diagnosis can be offered to all families with characterized COL10A1 gene mutations.

Chorionic Villi Sampling↗