Biomedical subjects

D W Mahoney

Publications and source records attributed to D W Mahoney.

At least 37 records · Page 2Linked to original sources

PubMed1999

Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial.

BACKGROUND/AIM: Ursodeoxycholic acid in doses of 13-15 mg x kg(-1) x day(-1), is a safe and cost-effective treatment for patients with primary biliary cirrhosis. However, very limited information exists regarding the most appropriate dose of ursodeoxycholic acid. The aim of the study was to compare three dosages of ursodeoxycholic acid with respect to changes in liver biochemistries, Mayo risk score, biliary enrichment with ursodeoxycholic acid and side effects over at least a 1-year period. METHODS: A total of 155 patients were randomized to receive low- (5-7 mg x kg(-1) x day(-1)), standard-(13-15 mg x kg(-1) x day(-1)), and high- (23-25 mg x kg(-1) x day(-1)) doses of ursodeoxycholic acid. RESULTS: The improvements in alkaline phosphatase (p = 0.0001), aspartate aminotransferase (p = 0.0001), Mayo risk score (p = 0.002), and ursodeoxycholic acid enrichment (p = 0.0001) were significantly greater in the standard- and high-dose groups compared to the low-dose group, but not between the standard- and high-dose groups. Changes in serum bilirubin were similar between the three groups (p = 0.07). No significant effects on symptoms were noted with any dose. No patients discontinued ursodeoxycholic acid because of side effects or toxicity. CONCLUSIONS: Ursodeoxycholic acid in doses of 5-25 mg x kg(-1) x day(-1) is safe and well tolerated. The dose of 13-15 mg x kg(-1) x day(-1) appears to be the preferred dose for patients with primary biliary cirrhosis.

Alkaline Phosphatase↗

PubMed1999

Nonexercise stress transthoracic echocardiography: transesophageal atrial pacing versus dobutamine stress.

OBJECTIVES: To compare transesophageal atrial pacing stress echocardiography with dobutamine stress echocardiography for feasibility, safety, duration, patient acceptance and concordance in inducing wall motion abnormalities. BACKGROUND: Transesophageal atrial pacing is an effective method of increasing heart rate and has been used in the assessment of coronary artery disease. METHODS: Both tests were performed in sequence on the same patients in random order. Transesophageal atrial pacing stress echocardiography began at a heart rate of 10 beats/min above the baseline value and was increased by 20 beats/min every two min until 85% of the age-predicted maximum heart rate or another end point was reached. Dobutamine echocardiography was performed using three-min stages and a maximum dose of 40 microg/kg per min. Atropine (total dose < or =2 mg) was administered at the start of the 40 microg/kg per min stage if needed to augment heart rate or during pacing if Wenckebach heart block occurred. RESULTS: Transesophageal atrial pacing stress echocardiography was feasible in 100 of 104 patients (96%); the duration (8.6+/-3.6 min) was significantly shorter than that of dobutamine stress echocardiography (15.1+/-3.9 min) (p = 0.0001). With transesophageal atrial pacing stress echocardiography, the recovery period was shorter, symptoms and dysrhythmias were fewer, hypertension and hypotension were less common and target heart rate was more frequently achieved. No complications occurred with either test. Patient acceptance was satisfactory. Agreement between results of both tests was good for segmental wall motion scoring with a 16-segment model, scores 1 to 5 (kappa: rest, 0.79; peak, 0.57) and test interpretation (normal, ischemia, infarction or resting wall motion abnormality with ischemia) (kappa: 0.77). CONCLUSIONS: Transesophageal atrial pacing stress echocardiography is a feasible, well-tolerated alternative to dobutamine stress echocardiography. It can be performed rapidly and shows good agreement with dobutamine stress echocardiography in the induction of myocardial ischemia.

Adult↗

PubMed1999

Effects of alternative reconstitution procedures on the labelling efficiency and in vitro stability of 99Tcm-labelled radiopharmaceuticals.

Adding normal saline (NS) separately before 99Tcm-sodium pertechnetate to MDP cold kits has been shown to reduce substantially the radiation dose to the hand. A similar dose reduction will probably prove to be valid with the preparation of most other 99Tcm-labelled radiopharmaceuticals. However, it is unknown how this altered reconstitution procedure may affect the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals. We have evaluated the effects on the labelling efficiency and in vitro stability of 99Tcm-labelled MDP, mertiatide and sestamibi reconstituted with three different methods: adding normal saline before 99Tcm activity (NS/Tc); adding 99Tcm activity before normal saline (Tc/NS); and the standard reconstitution method of adding both 99Tcm activity and normal saline together. The labelling efficiency and in vitro stability were evaluated by measuring the radiochemical purity of each radiopharmaceutical tested at 0, 1, 3, 6, 12 (except 99Tcm-MDP) and 24 h after reconstitution. For 99Tc-mertiatide, there was a very slight difference in the labelling efficiency, mostly due to the Tc/NS method being approximately 0.29% lower across time post-reconstitution than the standard method. For 99Tcm-labelled MDP and sestamibi, there were no differences between the three methods in terms of labelling efficiency and in vitro stability. In conclusion, both alternative methods (i.e. NS/Tc and Tc/NS) appear not to have any detrimental effect on the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals that we tested. However, of the two alternative kit reconstitution methods, we recommend the NS/Tc method, since it may reduce the hand radiation dose.

Drug Stability↗

PubMed1999

Clinical experience with radiolabelled monoclonal antibodies in the detection of colorectal and ovarian carcinoma recurrence and review of the literature.

A retrospective study was carried out to determine the diagnostic value of OncoScint CR/OV immunoscintigraphy in assessing patients with suspected recurrence of carcinoma of the colon and ovary. The scintigraphic results of 31 patients were compared with surgical and histopathological findings, conventional radiological examinations and clinical disease outcome over an average 3-year follow-up. Detected lesions were divided by location into hepatic or extrahepatic and the latter group was classified as local recurrence at the resection site, pelvic or abdominal regional lymph node involvement and distant metastatic disease. The combined sensitivity and accuracy of immunoscintigraphy in the detection of extra-hepatic disease was significantly higher than that of cross-sectional radiological imaging (87% and 83% vs 44% and 53% respectively) with equal specificity of 74%. Scintigraphy identified 14 (36%) of 39 extra-hepatic malignant lesions not diagnosed by conventional radiological techniques and influenced therapeutic planning in 8 (26%) of 31 patients studied. In the liver, conventional imaging had a significantly higher detection rate than immunoscintigraphy (sensitivity 93% vs 28%). In conclusion, these results show that OncoScint scintigraphy is a sensitive method for the detection of local recurrence and extra-hepatic metastases in colorectal and ovarian carcinoma and has an important role in the therapeutic decision-making process.

Adult↗

PubMed1999

Comparison of three cold kit reconstitution techniques for the reduction of hand radiation dose.

In the performance of conventional nuclear pharmacy work, personnel usually receive the highest hand radiation dose during reconstitution of 99Tcm-labelled radiopharmaceuticals. This study was conducted to compare the hand radiation doses incurred during the preparation of 99Tcm-labelled radiopharmaceuticals using three different reconstitution procedures: (1) the standard reconstitution method (i.e. withdrawing 99Tcm activity and normal saline [NS] into the same syringe before adding to the cold kit) (standard); (2) an alternative reconstitution procedure using two syringes to add normal saline separately before 99Tcm activity to the cold kit (NS/Tc); and (3) a standard reconstitution procedure using a robotic system (Amercare Syringe Fill Station, model NuMed SFS 3a, Amercare Ltd, Oxon, UK) (robot). Radiation doses were monitored by thermoluminescent dosimeters (Landauer Inc., Glenwood, IL, USA) on the base of the fourth finger (i.e. ring finger) of the non-dominant hand and on the mid-portion of the second finger (i.e. index finger) of the dominant hand. Three sets of ring badges were measured for each procedure, with 10 stimulated or real reconstitutions per set. Two different radiopharmaceutical kits were evaluated: 99Tcm-MDP, as it is the most frequently used radiopharmaceutical in the majority of nuclear medicine departments (all three reconstitution methods; i.e. standard, NS/Tc and robot), and 99Tcm-sestamibi, as it is not only reconstituted with the highest amount of radioactivity but is also the most frequently dispensed radiopharmaceutical in our laboratory (standard and robot). All kits were prepared from an elution vial containing a standardized amount of 99Tcm activity (i.e. 104.4 +/- 3.6 GBq). To each of the cold MDP and sestamibi kits, 20.7 +/- 1.2 GBq and 44.2 +/- 0.7 GBq of 99Tcm activity were added, respectively. Average accumulated radiation doses for 10 reconstitutions to the fingers (non-dominant/dominant) for the preparations of 99Tcm-MDP were as follows: 14.2 +/- 0.9 mSv/2.8 +/- 0.8 mSv (standard), 10.0 +/- 0.6 mSv/2.7 +/- 0.2 mSv (NS/Tc), and 0.6 +/- 0.1 mSv/1.3 +/- 0.1 mSv (robot). For 99Tcm-sestamibi, the average accumulated radiation doses for 10 reconstitutions to the fingers (non-dominant/dominant) were 6.7 +/- 0.7 mSv/4.6 +/- 0.5 mSv (standard) and 1.1 +/- 0.1 mSv/3.1 +/- 0.4 mSv (robot). When compared to the standard reconstitution method, our results show that the NS/Tc method slightly reduced radiation dose to the non-dominant hand, without any significant reduction for the dominant hand. However, the robot has proved to be the most effective method to considerably reduce radiation dose to both hands. A robotic system should be a useful ALARA (as low as reasonably achievable) tool to prepare other high-activity 99Tcm-labelled radiopharmaceuticals, as well as therapeutic and PET radiopharmaceuticals.

Evaluation Studies as Topic↗

PubMed1998

Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension.

Primary pulmonary hypertension is characterized by elevated pulmonary arterial pressure and vascular resistance, frequently producing right heart failure and death. Therefore, the Doppler right ventricular (RV) index, which is a measure of global RV function, could be a useful predictor of outcome in primary pulmonary hypertension. The Doppler RV index, defined as the sum of isovolumic contraction time and isovolumic relaxation time divided by ejection time, was retrospectively measured in 53 patients (38 women, aged 45 +/- 14 years) with primary pulmonary hypertension. Ejection time was measured from the pulmonary outflow velocity signal. The sum of isovolumic contraction time and isovolumic relaxation time was obtained by subtracting ejection time from the duration of tricuspid regurgitation. The Doppler RV index tended to be elevated (median 0.83) compared with normal ranges. Normal Doppler RV index was 0.28 +/- 0.04. After a mean follow-up duration of 2.9 years, 4 patients underwent lung transplantation and 30 patients died; the cause was cardiac in 28, noncardiac in 1, and uncertain in 1. Univariately, the Doppler RV index (chi-square 20.7, p <0.0001), severity of tricuspid regurgitation (chi-square 8.2, p = 0.004), treatment with calcium blockers (chi-square 6.6, p = 0.01), heart rate (chi-square 5.1, p = 0.02), and symptom status (chi-square 4.9, p = 0.03) were associated with adverse outcome (cardiac deaths and lung transplantation). However, only the Doppler RV index and treatment with calcium blockers were independent predictors within the multivariate model. Our results indicate that the Doppler RV index is a useful predictor of adverse outcome in patients with primary pulmonary hypertension.

Adult↗

PubMed1998

Primary sclerosing cholangitis and colorectal carcinoma in patients with chronic ulcerative colitis: a case-control study.

BACKGROUND: Controversy persists regarding primary sclerosing cholangitis (PSC) as a risk factor for colorectal carcinoma in patients with chronic ulcerative colitis. Small sample size and differing endpoints have contributed to variation among reported studies. This large case-control study was conducted to examine the possible association between PSC and colon carcinoma in patients with ulcerative colitis. METHODS: From Mayo Clinic records spanning 1976-1994, 171 cases with both ulcerative colitis and colorectal carcinoma and 171 contemporaneous controls with ulcerative colitis but no colorectal neoplasia matched with regard to age, gender, extent, and duration of colitis were identified. The diagnosis of PSC required cholangiographic confirmation. Analysis employed a multivariate logistic regression model. RESULTS: The prevalence of PSC was similar in cases (18%) and controls (15%) (P = 0.54). The adjusted odds ratio for colorectal carcinoma with PSC was 1.23 (95% confidence interval, 0.62-2.42). CONCLUSIONS: Based on this large case-control study, there was no association between PSC and colorectal carcinoma in patients with ulcerative colitis.

Adolescent↗

PubMed1998

Familial predisposition for colorectal cancer in chronic ulcerative colitis: a case-control study.

BACKGROUND & AIMS: Familial predisposition as a risk for colorectal cancer in ulcerative colitis has not been rigorously explored. The aim of this study was to compare colorectal cancer frequency among kindreds of patients who had ulcerative colitis and colorectal cancer with that of control patients who had ulcerative colitis but no cancer. METHODS: Questionnaires were mailed to subjects to assess cancer occurrence among relatives. Eligible cases included 174 ulcerative colitis patients with colorectal cancer seen at Mayo Clinic in 1976-1994; 174 contemporaneous ulcerative colitis controls without cancer were matched on birth year, sex, and extent and duration of colitis. RESULTS: The responding 147 case and 150 control subjects reported on 1044 and 1090 first-degree relatives, respectively. Colorectal cancer occurred in 14.3% case kindreds and 6.7% control kindreds (P = 0.03). By logistic regression, a family history of sporadic colorectal cancer was an independent risk factor for cancer in ulcerative colitis (odds ratio, 2.33; 95% confidence interval, 1.06-5.14; P = 0.03). CONCLUSIONS: A familial association exists between colorectal cancers occurring with ulcerative colitis and those in the general population. Colorectal cancer in persons with ulcerative colitis represents a risk factor for colorectal cancer in their noncolitic relatives. Likewise, a family history of sporadic colorectal cancer increases the risk of colorectal cancer with ulcerative colitis.

Adult↗

PubMed1998

Outcome after normal exercise echocardiography and predictors of subsequent cardiac events: follow-up of 1,325 patients.

OBJECTIVES: This study sought to examine the outcome of a large group of patients after normal exercise echocardiography and to identify potential predictors of subsequent cardiac events. BACKGROUND: Earlier studies suggested that prognosis after normal exercise echocardiography is favorable, with a low subsequent cardiac event rate. These studies involved a small number of patients and did not have sufficient statistical power to stratify risk. METHODS: The outcomes of 1,325 patients who had normal exercise echocardiograms were examined. End points were overall and cardiac event-free survival. Cardiac events were defined as cardiac death, nonfatal myocardial infarction and coronary revascularization. Patient characteristics were analyzed in relation to time to first cardiac event in a univariate and multivariate manner to determine which, if any, were associated with an increased hazard of subsequent cardiac events. RESULTS: Overall survival of the study group was significantly better than that of an age- and gender-matched group obtained from life tables (p < 0.0001). The cardiac event-free survival rates at 1, 2 and 3 years were 99.2%, 97.8% and 97.4%, respectively. The cardiac event rate per person-year of follow-up was 0.9%. Subgroups with an intermediate or high pretest probability of having coronary artery disease also had low cardiac event rates. Multivariate predictors of subsequent cardiac events were angina during treadmill exercise testing (risk ratio [RR] 4.1, 95% confidence interval [CI] 1.5 to 11.0), low work load (defined as < 7 metabolic equivalents [METs] for men and < 5 METs for women; RR 3.2, 95% CI 1.4 to 7.6), echocardiographic left ventricular hypertrophy (RR 2.6, 95% CI 1.1 to 6.3) and advancing age (RR 1.04/year, 95% CI 1.0 to 1.1). CONCLUSIONS: The outcome after normal exercise echocardiography is excellent. Subgroups with an intermediate or high pretest probability of having coronary artery disease also have a favorable prognosis after a normal exercise echocardiogram. Characteristics predictive of subsequent cardiac events (i.e., patient age, work load, angina during exercise testing and echocardiographic left ventricular hypertrophy) should be considered in the clinical interpretation of a normal exercise echocardiogram.

Aged↗

PubMed1998

Short deceleration time of mitral inflow E velocity: prognostic implication with atrial fibrillation versus sinus rhythm.

The present study retrospectively identified 367 patients who had restrictive physiology as defined by deceleration time < or = 130 msec; 293 were in sinus rhythm (SR) (194 men and 99 women; mean age 64 +/- 14 years) and 74 were in atrial fibrillation (AF) (51 men and 23 women; mean age 72 +/- 11 years; p < 0.001). Both groups had similar underlying diagnoses and no significant difference in Doppler indices (E wave, 96 +/- 23 vs 99 +/- 22 cm/sec in SR and AF, respectively; deceleration time, 116 +/- 12 vs 116 +/- 13 msec; and left ventricular outflow tract time velocity integral, 14.8 +/- 4.8 vs 14.5 +/- 4.4 cm). Left ventricular ejection fraction was significantly lower in SR patients (29% +/- 16% vs 39% +/- 20%; p = 0.0003). There were 120 deaths (41%) in the SR group and 35 (47%) in the AF group (median follow-up for both groups, 2.2 years). Restrictive physiology as defined by Doppler echocardiography (deceleration time < or = 130 msec) appears to predict a similar poor prognosis with AF as with SR.

Aged↗

PubMed1998

Radiolabelled mixed leukocytes and pure granulocytes with stabilized 99Tcm-exametazime.

Although the methylene blue stabilizer extends the shelf life of 99Tcm-exametazime to 4-6 h after reconstitution, the dark blue appearance of the mixture of stabilized 99Tcm-exametazime and blood components makes it impossible to separate out the leukocyte button. The aim of this study was to assess the feasibility of using stabilized 99Tcm-exametazime to radiolabel mixed leukocytes separated by Volex sedimentation with hypotonic lysis (VL) and pure granulocytes isolated by a single-density Ficoll-Hypaque gradient with hypotonic lysis (FL). Isolated cells from 40-ml and 80-ml donor blood samples were mixed with 0.5 ml stabilized 99Tcm-exametazime (approximately 925 MBq 99Tcm and 62.5 micrograms exametazime) and incubated at room temperature for 15 min. After incubation, two dilution steps with 3 ml and 9 ml of 12.6% ACD/NS (anticoagulant citrate dextrose, solution A, USP, mixed with 0.9% NaCl, v/v) were conducted to dilute the dark blue mixture and to remove any unbound 99Tcm activity. With the addition of 9 ml of 12.6% ACD/NS solution to the 1-ml bottom portion from the first dilution, the supernatant of the centrifuged preparation was clear enough to be withdrawn. The overall labelling efficiency (LE) of labelled leukocytes and granulocytes was 87.1 +/- 4.9% and 87.7 +/- 6.2%, respectively (n = 12 each). Overall, radiolabelled cells (n = 12) from the 80-ml blood samples (LE = 90.3 +/- 2.8%) had an approximately 6% higher labelling efficiency than from the 40-ml blood samples (LE = 84.5 +/- 6.0%) and also had a slightly better in vitro stability compared to the 40-ml samples. The in vitro stability studies showed that only approximately 2% (n = 48) 99Tcm activity was eluted each hour from the radiolabelled leukocytes or granulocytes for the 40-ml or 80-ml blood samples during the 6-h evaluation period. Cell viability of all labelled leukocyte samples was confirmed by the trypan blue staining technique. In conclusion, mixed leukocytes separated by the VL method and pure granulocytes isolated by the FL method can be effectively labelled with stabilized 99Tcm-exametazime with the use of the 'double dilution' technique.

Cell Survival↗

PubMed1997

Cardiorespiratory response to exercise after modified Fontan operation: determinants of performance.

OBJECTIVES: This study sought to measure the cardiorespiratory responses to exercise and to identify the perioperative determinants of exercise performance in children, adolescents and young adults who underwent the modified Fontan operation. BACKGROUND: Several studies of the cardiorespiratory responses to exercise after the Fontan operation have demonstrated subnormal maximal oxygen uptake and exercise heart rate, but the perioperative variables that ultimately affect exercise responses have not been assessed systematically. METHODS: The study included 59 of the 548 patients who underwent a modified Fontan operation between January 1, 1984 and December 31, 1993 at the Mayo Clinic. Spirometry was performed at rest in all patients before exercise testing. The patients then exercised using a previously calibrated cycle ergometer and a 3-min incremental cycle exercise protocol. Multiple linear regression analysis was used to determine a subset of variables associated with oxygen uptake at peak exercise (VO2max), blood oxygen saturation (O2sat) and heart rate at peak exercise (HRmax). RESULTS: VO2max ranged from 29% to 95% of normal value; O2sat at peak exercise ranged from 77% to 96%; and HRmax ranged from 39.7% to 97.4% of normal value. Multivariate analysis showed that log VO2max/kg2/3 was associated with age at exercise, male gender, body surface area, preoperative confluent pulmonary arteries and rest VO2max/kg2/3. Preoperative left pulmonary artery stenosis, the presence of a classic Glenn anastomosis at exercise and rest O2sat were associated with O2sat at peak exercise. Age, body surface area at exercise, heart rate at rest and diastolic blood pressure were associated with HRmax at exercise. CONCLUSIONS: Subnormal VO2max and HRmax values were demonstrated at peak exercise. Several perioperative variables were associated with VO2max and O2sat at peak exercise. The presence of a classic Glenn anastomosis was associated with decreased O2sat at peak exercise, suggesting intrapulmonary shunting with the classic Glenn anastomosis.

Adolescent↗

PubMed1997

Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and intravenous administration.

Ulcerative colitis is predominantly a disease of nonsmokers, and transdermal nicotine is therapeutic but often results in adverse reactions. Colonic administration of nicotine tartrate as a liquid enema could decrease systemic nicotine absorption and adverse reactions. The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes. Thirty healthy volunteers received 45 micrograms nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid enema, and oral solution. All participants also received 15 micrograms nicotine base/kg (as nicotine tartrate) intravenously during a separate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (+/-SD) bioavailabilities of nicotine after administration in the liquid enema formulations (hydrophilic acidic 17 +/- 18%, hydrophilic basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%) were similar to the bioavailability of nicotine after administration by oral solution (20 +/- 25%). The bioavailabilities of nicotine for all five nonintravenous formulations were significantly less than for intravenous nicotine (100%). Serum concentrations of nicotine did not predict adverse reactions. Nicotine tartrate administered as either a liquid enema or as an oral solution had low bioavailability and was well tolerated. The therapeutic potential of nicotine tartrate liquid enemas, which can potentially limit toxicity by local (colonic) delivery of high doses of nicotine should be investigated in patients with left-sided ulcerative colitis.

Administration, Oral↗

PubMed1997

Rapid preparation method for technetium-99m bicisate.

The method currently recommended for the preparation of technetium-99m bicisate (99mTc-bicisate) requires a lengthy 30-min incubation at room temperature. The purpose of this study was to evaluate an alternative method to shorten the preparation time. 99mTc-bicisate was prepared with 3.7 GBq (100 mCi) 99mTc according to the manufacturer's instructions, except for the final incubation step, which was replaced with the microwave heating procedure. A standard thin-layer chromatography (TLC) method (i.e., Baker-Flex silica gel IB-F TLC plate with ethyl acetate as mobile phase) was used for the determination of the radiochemical purity (RCP) of 99mTc-bicisate. Our evaluation with different microwave heating processes (300 W with different heating times) demonstrated that as the microwave heating temperature was increased (i.e., 44 masculine-71 masculine C), an increased percentage of samples reached 95% within 5 min post preparation (n=58). The highest RCP value (i.e., 97.4%+/-0.5%, n=10) could be obtained immediately after an 8-s microwave heating time at 300 W (microwave temperature at 69 masculine C), and an average RCP value of 96.4%+/-1.3% (n=90) was maintained throughout the 24-h evaluation period. However, the trend seemed to reverse at higher microwave temperatures (i.e., 76 masculine-90 masculine C), which reconfirmed our initial findings that overheating had no benefit for the preparation of 99mTc-bicisate. To ensure that temperature was the only determining factor, a hot water incubator set at 69 masculine C was used (n=6). Similar RCP results were achieved. In conclusion, the use of a microwave oven at a low heat cycle provides a rapid and efficient way to prepare 99mTc-bicisate.

Chromatography, Thin Layer↗

PubMed1997

Exercise tolerance in patients with Ebstein's anomaly.

OBJECTIVES: The purpose of this study was to identify the determinants of exercise tolerance in patients with Ebstein's anomaly. BACKGROUND: Patients with Ebstein's anomaly of the tricuspid valve may have exercise limitation that improves after surgical repair. METHODS: One hundred seventeen patients performed cycle ergometry for a total of 124 tests (preoperative test in 76 patients, postoperative test in 23, test but no operation in 18, preoperative and postoperative test in 7). Multiple linear regression analysis was used to identify predictors of maximal oxygen uptake, oxygen saturation and heart rate at peak exercise. RESULTS: Age at the time of exercise ranged from 6 to 60 years (median 15). An atrial septal defect was present in 67 patients (88%) preoperatively. Compared with the preoperative group, the postoperative group had significantly higher maximal oxygen uptake (mean [+/- SD] 20.5 +/- 7.4 vs. 25.3 +/- 7.0 ml/kg body weight per min, p = 0.006). Postoperative rest and exercise blood oxygen saturation was higher than that measured preoperatively (p = 0.0001). Six of seven patients tested before and after the operation showed improved exercise tolerance. Preoperatively, major predictors of maximal oxygen uptake were oxygen saturation at rest (p = 0.01) and age (p = 0.0001). Preoperatively, the major predictor of oxygen saturation at peak exercise was rest oxygen saturation (p = 0.0001), and major predictors of peak exercise heart rate were rest heart rate (p = 0.01) and rest oxygen saturation (p = 0.01). In the postoperative group, predictors of maximal oxygen uptake included age at exercise testing, male gender and heart size. CONCLUSIONS: Definitive operation for Ebstein's anomaly results in improved exercise tolerance. Before the operation, rest oxygen saturation is the major predictor of exercise tolerance, oxygen saturation at peak exercise and peak heart rate. Postoperatively, age, gender and heart size influenced maximal oxygen uptake.

Adolescent↗

PubMed1997

A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration.

BACKGROUND: Ulcerative colitis is predominantly a disease of non-smokers, and transdermal nicotine is therapeutic but often results in side-effects. Administration of nicotine tartrate as a liquid enema decreases systemic nicotine absorption and may be effective for treatment of active distal ulcerative colitis. Ileocolonic delivery of nicotine tartrate via a delayed release oral capsule would be the preferred route to deliver nicotine to the colon. AIM: To determine the bioavailability and pharmacokinetic parameters of delayed-release oral nicotine tartrate capsules (Eudragit S100 coated) at doses of 3 mg and 6 mg nicotine. METHODS: Twenty healthy human subjects received delayed-release oral nicotine tartrate at one of two doses (each group n = 10): 3 mg and 6 mg nicotine. All subjects also received intravenous nicotine tartrate (at a dose of 15 micrograms nicotine base/kg) during a separate study period. Serum nicotine concentrations were determined by gas chromatography-mass spectrometry. In addition, concentrations of serum cotinine (major nicotine metabolite) were determined by high-performance liquid chromatography in all samples for two subjects (both given 6 mg nicotine). Adverse reactions were determined by questionnaire. RESULTS: The mean bioavailabilities of nicotine after ileocolonic nicotine tartrate administration via delayed-release oral capsules at doses 3 mg and 6 mg nicotine were 41% and 42%, respectively. The ratios (after adjusting for nicotine dose) of cotinine area under the curve (AUC) for delayed-release oral nicotine to cotinine AUC for intravenous nicotine were 1.5 and 1.6 for the two subjects undergoing cotinine pharmacokinetics, demonstrating significant first-pass metabolism. Serum nicotine concentrations did not predict adverse reactions. CONCLUSIONS: Nicotine tartrate delivered to the ileocolon as a delayed-release oral capsule at doses of 3 mg and 6 mg nicotine considerably reduced systemic nicotine bioavailability. This reduction in bioavailability appears to be a result of first-pass hepatic metabolism rather than poor mucosal absorption of nicotine. The therapeutic potential of an ileocolonic delivery formulation of nicotine tartrate, which can potentially limit toxicity by local delivery of high doses of nicotine, should be investigated in patients with ulcerative colitis.

Administration, Oral↗

PubMed1997

A dose-ranging study of azathioprine pharmacokinetics after single-dose administration of a delayed-release oral formulation.

6-Mercaptopurine and its prodrug azathioprine are an effective treatment for inflammatory bowel disease, but widespread use has been limited by concern about toxicity. Ileocolonic delivery of azathioprine as a 50-mg delayed-release oral capsule has been shown to decrease bioavailability, thus potentially decreasing toxicity. This study aimed to determine the bioavailability and pharmacokinetic parameters of delayed-release oral azathioprine capsules at doses of 200 mg, 400 mg, and 600 mg relative to 100 mg of standard oral azathioprine tablets. Thirty healthy human volunteers each received delayed-release oral azathioprine at one of the three doses (n = 10 for each group). All participants also received a 100-mg tablet of standard oral azathioprine. Plasma concentrations of 6-mercaptopurine were determined by high-pressure liquid chromatography. The relative bioavailabilities of 6-mercaptopurine after ileocolonic azathioprine administration via delayed-release oral capsules at doses of 200 mg, 400 mg, and 600 mg (means of 15%, 15%, and 12%, respectively) were all significantly less than 100% compared with standard oral azathioprine at a 100-mg dose. Ileocolonic delivery of azathioprine by a delayed-release oral capsule formulation at doses up to 600 mg considerably reduces 6-mercaptopurine bioavailability, relative to standard oral azathioprine tablets. The therapeutic potential of this ileocolonic delivery formulation, which can limit toxicity by local delivery of azathioprine, should be investigated in patients with inflammatory bowel disease.

Administration, Oral↗

PubMed1996

Predictors of reversibility of pulmonary hypertension in cardiac transplant recipients in the first postoperative year.

BACKGROUND: Pulmonary hypertension remains a risk factor for early postoperative mortality in heart transplantation and may reduce the long-term benefits of the procedure. This study was undertaken to assess the value of baseline hemodynamic studies with nitroprusside used to predict the degree of postoperative reversibility of pulmonary hypertension in cardiac transplant recipients and to identify clinical risk factors for fixed pulmonary hypertension. METHODS AND RESULTS: Hemodynamic data from 55 consecutive patients who underwent orthotopic cardiac transplantation from June 1988 through September 1993 were analyzed. The effects of nitroprusside and transplantation on pulmonary artery pressure, cardiac output, and pulmonary vascular resistance were compared. Multiple regression analysis was used to identify the predictors of reversibility of pulmonary hypertension. Nitroprusside reduced pulmonary vascular resistance by increasing cardiac output and, to a lesser extent, by reducing the transpulmonary gradient. Pulmonary hypertension was less reversible in patients with ischemic heart disease (versus dilated cardiomyopathy) and in former smokers (versus nonsmokers). Patients with nonischemic heart failure and no smoking history had significantly lower posttransplant pulmonary vascular resistance (1.24 +/- 0.45 Wood units) than ischemic patients (who were all former smokers; 2.20 +/- 1.01 wood units) or nonischemic former smokers (1.72 +/- 0.70 Wood units). The correlation of pulmonary vascular resistance during nitroprusside challenge with posttransplant pulmonary vascular resistance was better than that of baseline pulmonary vascular resistance with posttransplant pulmonary vascular resistance. CONCLUSIONS: Nitroprusside testing improves the prediction of late posttransplant pulmonary vascular resistance; hence, it provides data that may be relevant to both early operative risk and later long-term effectiveness of cardiac transplantation. The finding of increased risk of fixed pulmonary hypertension associated with ischemic heart disease and smoking suggests that underlying atherosclerotic vascular disease may contribute to the irreversibility of pulmonary vascular resistance.

Adult↗