Biomedical subjects

A Manatunga

Publications and source records attributed to A Manatunga.

11 recordsLinked to original sources

PubMed2001

Smooth estimation of the reliability function.

Problems with censored data arise quite frequently in reliability applications. Estimation of the reliability function is usually of concern. Reliability function estimators proposed by Kaplan and Meier (1958), Breslow (1972), are generally used when dealing with censored data. These estimators have the known properties of being asymptotically unbiased, uniformly strongly consistent, and weakly convergent to the same Gaussian process, when properly normalized. We study the properties of the smoothed Kaplan-Meier estimator with a suitable kernel function in this paper. The smooth estimator is compared with the Kaplan-Meier and Breslow estimators for large sample sizes giving an exact expression for an appropriately normalized difference of the mean square error (MSE) of the two estimators. This quantifies the deficiency of the Kaplan-Meier estimator in comparison to the smoothed version. We also obtain a non-asymptotic bound on an expected L1-type error under weak conditions. Some simulations are carried out to examine the performance of the suggested method.

Humans↗

PubMed2001

Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings.

OBJECTIVE: This study investigated whether cancer patients with and without major depression exhibit immune system abnormalities similar to those reported in medically healthy, depressed subjects without cancer. METHOD: The study subjects consisted of patients diagnosed with pancreatic, esophageal, or breast cancer. Other groups consisted of subjects with major depression (without cancer) and healthy comparison subjects. Subjects' diagnoses were made with the Structured Clinical Interview for DSM-III-R. Severity of depression was measured with the Hamilton Depression Rating Scale. Plasma concentrations of interleukin-6 (IL-6) and postdexamethasone cortisol were measured. RESULTS: Cancer patients with depression had markedly higher plasma concentrations of IL-6 than healthy comparison subjects and cancer patients without depression. Although significant correlations were found between Hamilton depression scale scores and plasma concentrations of postdexamethasone cortisol, no significant correlations were found between plasma IL-6 and postdexamethasone cortisol concentrations. CONCLUSIONS: Higher than normal plasma IL-6 concentrations were associated with a diagnosis of major depression in cancer patients. IL-6 may contribute to sickness behavior that has overlapping symptoms with major depression.

Adult↗

PubMed2000

Platelet reactivity in depressed patients treated with paroxetine: preliminary findings.

BACKGROUND: Alterations in platelet reactivity have been previously posited to underlie the increased vulnerability of patients with depression to ischemic heart disease (IHD). The present study sought to determine whether the increased platelet reactivity associated with major depression is reduced after antidepressant treatment. METHODS: Patients diagnosed as having DSM-IV major depression (n = 15) (mean age, 37 +/- 7 years; range, 23-48 years) and 12 normal comparison subjects (mean age, 36 +/- 7; range, 23-48 years) were recruited. None of the controls or depressed group had evidence of IHD; 10 of 15 patients who were depressed had 1 or more traditional IHD risk factors. In vivo platelet activation, secretion, and dose-response aggregation of the controls and patients was measured after overnight bedrest under basal conditions, and after a mild exercise challenge. After 6 weeks of open-label treatment with the selective serotonin reuptake inhibitor paroxetine (20 mg/d), the patients with depression were readmitted and procedures of the first General Clinical Research Center admission repeated. RESULTS: In comparison with the control group, the depressed group exhibited greater procoagulant activity as detected by increased platelet binding of the monoclonal antibodies anti-ligand-induced binding site and GA6, and increased plasma concentrations of platelet factor 4 under basal conditions. After paroxetine treatment, the patients with depression exhibited significant reductions in all 3 parameters. CONCLUSIONS: Normalization of platelet activation is associated with paroxetine treatment of patients with depression. Because this study design did not allow for the determination of whether this effect of paroxetine on platelet function is caused by a direct effect of the drug or placebo or, alternatively, because of recovery from depression, studies containing a placebo and/or psychotherapy treatment arm may resolve this issue.

Adenosine Triphosphate↗

PubMed2000

Risk factors for premature ovarian failure in females with galactosemia.

UNLABELLED: The risk for premature ovarian failure (POF) in females with galactosemia can be predicted by analyzing 3 areas of risk pathology: the patient's molecular genotype for galactose-1-phosphate uridyltransferase (GALT), alternate pathways for galactose metabolism, and the patient's environment at diagnosis and during treatment. STUDY DESIGN: Retrospective cross-sectional information was collected on 53 females with classic galactosemia, and their ovarian function was analyzed by determination of serum follicle-stimulating hormone and luteinizing hormone levels and by clinical observation. The associations were analyzed between POF and the mutations in GALT, the highest erythrocyte galactose-1-phosphate (Gal-1-P) level at diagnosis, the age at which dietary treatment was initiated, mean erythrocyte Gal-1-P level during treatment, and whole-body carbon 13-labeled galactose oxidation to (13)CO(2). RESULTS: The most prevalent mutation, Q188R, had a significant effect of genotype category (Q188R/Q188R, Q188R/Other, Other/Other) on POF (P =.04, Fisher exact test and an odds ratio of 8.3). Mean erythrocyte Gal-1-P level during treatment was a significant risk factor for POF (P =.04). Also, all patients studied with less than 5% total body oxidation of galactose to (13)CO(2) had POF, whereas those with more than 5% did not have POF (P =.008, Fisher exact test). CONCLUSION: The development of POF in females with galactosemia is more likely if the patient's genotype is Q188R/Q188R, if the mean erythrocyte Gal-1-P is >3.5 mg/dL during therapy, and if the recovery of (13)CO(2) from whole-body (13)C-galactose oxidation is reduced below 5% of administered (13)C-galactose.

Adolescent↗

PubMed1997

Mechanisms permitting nephrotic patients to achieve nitrogen equilibrium with a protein-restricted diet.

UNLABELLED: Clinical experience suggests nephrotic patients are at risk for malnutrition. To determine if nephrotic patients can adapt successfully to a protein-restricted diet, nephrotic (glomerular filtration rate, 52+/-15 ml/min; urinary protein [Uprot.], 7.2+/-2.2 grams/d) and control subjects completed a crossover comparison of diets providing 0.8 or 1.6 grams protein (plus 1 gram protein/gram Uprot.) and 35 kcal per kg per day. Nitrogen balance (BN) was determined and whole body protein turnover measured during fasting and feeding using intravenous -[1-13C]leucine and intragastric -[5,5, 5- 2H3]leucine. BN was positive in both nephrotic and control subjects consuming either diet and rates of whole-body protein synthesis, protein degradation, and leucine oxidation did not differ between groups. In both nephrotic and control subjects anabolism was due to a suppression of whole-body protein degradation and stimulation of protein synthesis during feeding. The principal compensatory response to dietary protein restriction was a decrease in amino acid oxidation and this response was the same in both groups. With the low protein diet leucine oxidation rates during feeding correlated inversely with Uprot. losses (r = -0.83; P < 0. 05). CONCLUSIONS: (a) a diet providing 0.8 gram protein (plus 1 gram protein/gram Uprot.) and 35 kcal per kg per day maintains BN in nephrotic patients; (b) nephrotic patients activate normal anabolic responses to dietary protein restriction (suppression of amino acid oxidation) and feeding (stimulation of protein synthesis and inhibition of protein degradation); (c) the inverse correlation between leucine oxidation and Uprot. losses suggests that proteinuria is a stimulus to conserve dietary essential amino acids.

Adult↗

PubMed1997

Multicenter trial validation of a camera-based method to measure Tc-99m mercaptoacetyltriglycine, or Tc-99m MAG3, clearance.

PURPOSE: To evaluate an improved camera-based method for calculating the clearance of technetium-99m mercaptoacetyltriglycine (MAG3) in a multicenter trial. MATERIALS AND METHODS: Tc-99m MAG3 scintigraphy was performed in 49 patients at three sites in the United States and Canada. The percentage of the injected dose of Tc-99m MAG3 in the kidney at 1-2, 1.0-2.5, and 2-3 minutes after injection was correlated with the plasma-based Tc-99m MAG3 clearances. The data were combined with the results obtained in 20 additional patients in a previously published pilot study. RESULTS: Regression models correlating the plasma-based Tc-99m MAG3 clearance with the percentage uptake in the kidney for each time interval were developed; there was no statistically significant difference among sites in the regression equations. Correction for body surface area statistically significantly (P < .005) improved the correlation coefficient for each time interval. For the 1.0-2.5-minute interval, the body surface area-corrected correlation coefficient for the four combined sites was .87, and it improved to .93 when one outlier was omitted from the analysis. Similar results were obtained with the other time intervals. Independent processing by two observers showed no clinically important differences in the percentage dose in the kidney or in relative function. CONCLUSION: An improved camera-based method to calculate the clearance of Tc-99m MAG3 was validated in a multicenter trial.

Adolescent↗

PubMed1997

Background subtraction in technetium-99m-MAG3 renography.

UNLABELLED: Correction represents a potential source of error in estimating split renal function and camera-based clearances. The purpose of this study was to determine which of five background options and four time intervals was associated with the least error for 99mTc-mercaptoacetyltriglycine (MAG3). METHODS: Fifteen single-kidney patients were imaged supine after 111-370 MBq (3-10 mCi) 99mTc-MAG3 injection. A phantom kidney was drawn on the 2-3-min images, approximately equal in size to the solitary kidney and used for all time intervals. Counts in the phantom and native kidneys were calculated using manual inferior and lateral regions of interest (ROIs), automated elliptical and perirenal background ROIs and no background correction at various time intervals (1-2, 1-2.5, 1.5-2.5 and 2-3 min) postinjection. With optimal background correction, counts and the relative function in the phantom kidney should be zero. The error was measuring by estimating both the relative function and absolute function expressed as the percent injected dose in the phantom kidney. RESULTS: The percent injected dose in the phantom kidney as well as the error in measuring relative function were significantly greater than zero for the inferior background correction and the no background correction options at all time intervals, p < 0.05. The percent dose in the kidney and the error associated with the lateral, elliptical and perirenal ROIs were not significantly different from zero. CONCLUSION: Regardless of time interval, the greatest error was associated with no background correction. The inferior ROI consistently underestimated the background correction and probably should not be used for 99mTc-MAG3. There was no significant difference between errors generated using the lateral and automated ROIs, although automated ROIs are probably more reproducible for sequential studies.

Adult↗

PubMed1995

Measuring technetium-99m-MAG3 clearance with an improved camera-based method.

UNLABELLED: Because commercially available camera-based methods are not optimized, they fail to account for dose infiltration, table attenuation and correspondence between time of injection and starting the camera. We have developed a more optimized technique to calculate camera-based clearances and applied this technique in the design of a camera-based clearance method for 99mTc-MAG3. METHODS: Technetium-99m-MAG3 scintigraphy was performed in 20 patients who had varying degrees of renal function. Data were acquired posteriorly in supine patients at 2 sec/frame for 24 frames, 15 sec/frame for 16 frames and 30 sec/frame for 40 frames. Background correction was performed using an automated elliptical region of interest. Renal depth was estimated using improved regression equations and an empirically determined attenuation coefficient derived from phantom studies. Corrections were made for table attenuation and time discrepancies between dose injection and starting the camera. The percent injected dose in the kidney at 1-2, 1-2.5 and 2-3 min postinjection and the percent injected dose at those time periods corrected for body surface area were correlated with MAG3 clearance based on a single injection, two-compartment model. RESULTS: There was high correlation between the percent injected dose in the kidney at all three time periods and the multisample clearance. Correcting for body surface areas significantly improved the correlation coefficients. Consequently, regression equations were developed to predict multisample clearance based on percent dose and body surface area. CONCLUSION: The optimization features described in this method should improve precision when sequential studies are conducted in the same patient.

Adult↗

PubMed1994

Effectiveness of two feeding methods in improving energy intake and growth of infants with cleft palate: a randomized study.

OBJECTIVE: To compare two feeding methods advocated for infants with cleft palate: (a) a squeezable plastic container with a narrow, long crosscut nipple (squeezable cleft palate nurser); and (b) a standard nipple with a crosscut (crosscut nipple). The effectiveness of a nutrition intervention protocol for these infants was also documented. DESIGN: Thirty-one infants (median age = 15 days) were randomized to one of two feeding methods (18 infants, squeezable cleft lip/palate nurser; 13 infants, crosscut nipple) within sex (21 boys, 10 girls) and palatal defect (22 cleft lip and palate, 9 isolated cleft palate) categories. The intervention included feeding technique instructions, nutrition counseling at each clinic visit, use of the same 20 kcal/oz standard formula for 12 months, and introduction of infant and soft table foods at 6 months. Four-day food records and growth data were obtained. MAIN OUTCOME MEASURES: Mean energy and protein intakes at 3 and 6 months of age and growth measurements during the first 18 months of life were obtained. STATISTICAL ANALYSES: A repeated measures analysis of variance for intakes was performed with time as the repeated measure and feeding method as the covariable. Similar analyses were completed for growth measures with sex and feeding method as covariates. RESULTS: Mean energy intake at 3 and 6 months of age (P = .24) and growth measurements during the first 18 months of life (P values: weight gain [grams per day], .73; weight, .21; length, .07; head circumference, .18; triceps and subscapular skinfolds and mid-arm circumference, .47, .48, and .69, respectively) were not significantly different. Both feeding methods were effective in supporting normal growth. APPLICATIONS: With adequate instruction related to the use of either feeding technique and close nutrition follow-up early in infancy, a dietitian or other health care practitioner may advise the use of either feeding method. These data support the need for feeding and nutrition education and early nutrition intervention.

Anthropometry↗

PubMed1994

Influence of diagnostic radioiodines on the uptake of ablative dose of iodine-131.

The uptakes of thyroablative doses of 131I by postoperative thyroid remnants and/or thyroid carcinoma metastases following diagnostic surveys with 131I or 123I were retrospectively compared by visual inspection. Only those patients with a diagnostic scan demonstrating functioning tissue, remnant, and/or metastasis, following thyroidectomy for differentiated thyroid carcinoma, were evaluated. The 131I survey group (n = 26) had received a diagnostic dose of 3 to 10 mCi of 131I. The 123I group (n = 14) had received the usual diagnostic dose of 300 microCi of 123I. The age, sex, and tumor type in the two groups were not statistically different. The uptake of the ensuing thyroablative dose of 131I appeared, by visual inspection, to be impaired in 20 of 26 patients in the 131I group and in none of the 14 patients in the 123I group (p < 0.00003). In the 131I group there was suggestion of a dose-response, that is, the higher the administered activity of 131I for the diagnostic scan, the more reduced was the subsequent apparent uptake of the thyroablative dose (p = 0.0007). Thyroid remnants or cervical lymph node metastases appeared to be affected more frequently than were the distant (pulmonary or skeletal) metastases (p = 0.004). This study suggests that iodine uptake function may be suppressed by the absorbed radiation from the 3 to 10 mCi "diagnostic" scanning dose of 131I. In this regard, 123I may be a better initial diagnostic agent to be used prior to radioablation therapy.

Adolescent↗

PubMed1987

Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography.

To impact on the development of clinical congestive heart failure as a complication of doxorubicin therapy, left ventricular ejection fraction was monitored with serial resting radionuclide angiocardiography in 1,487 patients with cancer over a seven-year period in both university and community hospital environments. A high-risk subset of 282 patients was selected for retrospective analysis of their clinical outcome. High-risk patients were identified by one or two of the following three criteria: decline of 10 percent or more in absolute left ventricular ejection fraction from a normal baseline to 50 percent or less; high cumulative dose of doxorubicin (more than 450 mg/m2); abnormal baseline left ventricular ejection fraction (less than 50 percent). Clinical congestive heart failure occurred in 46 (16 percent) during the treatment period, and in an additional three patients (1.3 percent) at last follow-up examination 11.8 +/- 14.2 months following discontinuation of doxorubicin. Total cumulative dosages of doxorubicin that precipitated congestive heart failure (75 to 1,095 mg/m2) and those that did not (30 to 880 mg/m2) varied widely. Decline of 10 percent or more in absolute left ventricular ejection fraction to a value of 50 percent or less preceded administration of the final dose of doxorubicin that precipitated clinical congestive heart failure in the majority of patients in whom congestive heart failure developed. Clinical congestive heart failure improved in 87 percent given routine therapy with digitalis, diuretics, and/or vasodilators. Criteria for monitoring left ventricular ejection fraction and discontinuing doxorubicin were formulated. The occurrence of clinical congestive heart failure was compared in those patients whose management was concordant with proposed criteria (Group A) and in those whose management was not (Group B). Group A had a lower incidence of congestive heart failure compared with Group B (2.9 percent versus 20.8 percent, p less than 0.001) and had only mild congestive heart failure that resolved with treatment (n = 2) and no deaths due to congestive heart failure. Multivariate analysis with proportional-hazards regression (Cox's model) demonstrated a fourfold reduction in the incidence of congestive heart failure independent of other clinical predictor variables in those patients whose management was concordant with proposed guideline criteria. The incidence, persistence, late development, predictability, and reversibility of clinical congestive heart failure were comparable in university and community hospital settings.(ABSTRACT TRUNCATED AT 400 WORDS)

Doxorubicin↗