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Biomedical subjects

D M Morris

Publications and source records attributed to D M Morris.

At least 19 recordsLinked to original sources
PubMed1999

Differential effects of heparin on the early and late phases of hepatic ischemia and reperfusion injury in the pig.

The mechanisms by which heparin protects the liver during induced episodes of liver ischemia-reperfusion are poorly understood. Previous work in a swine model demonstrated that serum levels of glycohydrolases and lipid peroxide peaked within 3 h after 45 minutes of hepatic ischemia followed by reperfusion. Serum levels of lactate dehydrogenase and aspartate aminotransferase peaked 20-24 h later. The aim of this study was to evaluate the effect of heparin on these two-phases of enzyme release, using a pig model of hepatic ischemia-reperfusion injury. Twenty male swine were divided into control (n = 8) and heparin (n = 12) groups. In the heparin group, heparin was administered prior to and concurrent with ischemia-reperfusion. Following 45 min of hepatic ischemia, the levels of beta-galactosidase, beta-glucosidase, acid phosphatase, purine nucleoside phosphorylase, lipid peroxides, lactate dehydrogenase, and aspartate aminotransferase in serum were monitored for up to 166 h and compared to pre-ischemic and control levels. With heparin infusion, the peak levels of beta-galactosidase, beta-glucosidase, and the lipid peroxide were reduced to 50-60% of the control levels. Acid phosphatase and purine nucleoside phosphorylase activities in serum were reduced to 25% and 60%, respectively. The peak concentrations of lactate dehydrogenase and aspartate aminotransferase were reduced to about 25% of the control level. In addition, the serum enzymes of control pigs did not return to pre-ischemic levels until 2 weeks after hepatic ischemia, while they normalized in less than 1 week in the heparin-treated animals. Systemic heparinization had different protective effects on the first and secondary phases of liver injury. These differences may reflect heparin protection of different types of liver cells. The protection of the parenchymal cells may be the combined result of reduced sinusoidal cell injury and the anticoagulant properties of heparin.

Acid Phosphatase↗
PubMed1999

Lamivudine/zidovudine as a combined formulation tablet: bioequivalence compared with lamivudine and zidovudine administered concurrently and the effect of food on absorption.

A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined lamivudine 150 mg/zidovudine 300 mg tablet relative to the separate brand-name components administered concurrently and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 5- to 7-day washout period: one lamivudine/zidovudine combination tablet after an overnight fast, one lamivudine 150 mg tablet and one zidovudine 300 mg tablet simultaneously after an overnight fast, or one lamivudine/zidovudine combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for the determination of lamivudine and zidovudine plasma concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals for the ratio of least squares (LS) means for the lamivudine and zidovudine area under the plasma concentration-time curve (AUC infinity) and maximum observed plasma concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined lamivudine/zidovudine tablet was bioequivalent in the extent (AUC infinity) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. Geometric LS mean ratios and 90% confidence intervals for AUC infinity and Cmax were 0.97 (0.92, 1.03) and 0.94 (0.84, 1.06), respectively, for lamivudine and 0.99 (0.91, 1.07) and 0.97 (0.82, 1.15), respectively, for zidovudine. The extent of absorption of lamivudine and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of lamivudine and zidovudine. These changes were not considered clinically important. All formulations were well tolerated under fasted and fed conditions.

Absorption↗
PubMed1998

Repair of fascial defects in dogs using carbon fibers.

Hernia repair may involve the use of an implant to augment or replace autologous tissue, but the best material for use in this application has not been established. We developed a dog model to evaluate the mechanical strength of fascial defects repaired using carbon fibers, compared with the strength of similar defects repaired using polypropylene mesh (Marlex). Unrepaired defects were included as an additional control. Bilateral defects (1 cm square) were made in the fascia of the back, and the ultimate mechanical strength and stiffness at the repair sites were measured 3-12 months after operation. Defects repaired with carbon fibers were significantly stronger 12 months after operation compared with defects repaired with polypropylene mesh and compared with unrepaired defects. It is concluded that carbon fibers are biocompatible and significantly increase mechanical strength at the repair site. A randomized clinical trial involving patients undergoing hernia repair seems justified to determine whether carbon fibers are superior to standard therapy.

Animals↗
PubMed1998

Localized well-differentiated thyroid carcinoma: survival analysis of prognostic factors and (131)I therapy.

BACKGROUND: Recommendations regarding therapeutic use of (131)I for patients with well-differentiated thyroid cancer remain controversial. Between 1969 and 1993, 1171 patients with papillary (including mixed) or follicular thyroid cancer were reported to the New Mexico Tumor Registry. Of these, 1075 cases (77.6% female, median age 41 years) were available for analysis of survival plots and previously recognized risk factors. Extent of operation was documented for 344 patients. METHODS: One hundred twenty-seven (37%) patients underwent postoperative (131)I ablation. Median follow-up was 99 months. A proportional hazards model was constructed using age, gender, stage, histology, and use of radioiodine. The same variables plus extent of operation were examined in the smaller group. RESULTS: Kaplan-Meier survival estimates at 12 years were 96.2% for patients younger than 45 years and 68.6% for those older than 45 years. Age, gender, and histology, but not stage, were important survival variables (P <.05). Adjusting for other risk factors, there was no apparent survival benefit associated with radioiodine following clinically appropriate thyroidectomy. Findings from the small group mirrored those of the large group. CONCLUSIONS: (131)I may not be as efficacious as previously believed for patients with well-differentiated thyroid cancer confined to the neck.

Adenocarcinoma, Follicular↗
PubMed1998

Evaluation of a commercial accelerometer (Tritrac-R3 D) to measure energy expenditure during ambulation.

This study evaluated the ability of a commercially available accelerometer (Tritrac-R3 D) to measure energy expenditure in 16 subjects at rest (pre- and post-exercise) and during three different intensities of steady-state exercise (40-70% of peak oxygen consumption [VO2peak]) while ambulating on a treadmill (no grade). Oxygen consumption and the respiratory exchange ratio from indirect calorimetry and the vector magnitude of triaxial accelerations were used to estimate energy expenditure using the manufacturers' equations. There was a significant relationship between indirect calorimetry-derived energy expenditure and the energy expenditure derived from the accelerometer (r=0.96). Using analysis of variance, there was no difference in the energy expenditure derived by the two methods at rest before exercise and during the three different intensities of ambulatory exercise. There was a significant difference between energy expenditure derived via indirect calorimetry and with the accelerometer during rest after exercise, probably due to the failure of the accelerometer to accurately estimate the energy expenditure associated with the progressive decline in post-exercise oxygen consumption. Thus, this commercially available accelerometer appears to provide statistically acceptable estimates of energy expenditure at rest and during zero-grade treadmill ambulation up to about 70% VO2peak. This may indicate its acceptable utility for large-scale population studies of physical activity involving this mode of movement. The failure of the accelerometer to accurately estimate energy expenditure during recovery from exercise may contribute to an underestimation of energy expenditure in some physically active individuals.

Adult↗
PubMed1997

Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973-1991.

BACKGROUND: A number of prognostic factors for thyroid carcinoma have been identified, including sociodemographic characteristics, such as age and gender, and tumor characteristics, such as histology and stage. The relative importance of these factors as independent predictors of survival for patients with papillary, follicular, anaplastic, and medullary thyroid carcinoma has been extensively studied but remains uncertain. METHODS: The authors used data collected by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute between 1973 and 1991 to investigate prognostic factors for each of the major histologic types of thyroid carcinoma in a population-based patient series and to assess the effect of these factors as predictors of survival. RESULTS: Both tumor and sociodemographic characteristics were independently associated with survival. Patients with papillary carcinoma had the highest 10-year relative survival (0.98), followed by those with follicular carcinoma (0.92) and medullary carcinoma (0.80). Anaplastic tumors had the lowest 10-year relative survival (0.13). Stage at diagnosis and differentiation status were strong independent prognostic factors for each histologic type. Advanced stage at diagnosis was a stronger prognostic factor for medullary carcinoma than for other histologic types. Increasing age was associated with lower relative survival for each histologic type. Gender, marital status, and ethnicity were significant, but weaker, predictors of survival. CONCLUSIONS: Survival varied markedly among patients with different histologic types of thyroid carcinoma. Stage at diagnosis and tumor differentiation were important prognostic factors for each histologic type. Age at diagnosis was a stronger predictor of survival for patients with follicular and medullary carcinoma than for patients with papillary carcinoma.

Adenocarcinoma, Follicular↗
PubMed1997

The effects of bicycle crank arm length on oxygen consumption.

The purpose of this investigation was to determine the effects of various crank arm lengths on oxygen consumption for trained cyclists. Secondary purposes were, if optimal crank arm lengths existed, to determine if these lengths could be predicted based on an individual's leg length. Six trained cyclists completed four experimental protocols riding at a workload of approximately 68% of VO2 max using crank arm lengths of 165, 170, and 175 mm. During each protocol, the cadence, oxygen consumption, and distance traveled were determined, and values were combined to give a VO2.m-1.min-1 value. The values then were placed in either a high, medium, or low efficiency category. Significant differences were found among the three protocols. No significant correlations were found between each subject's most efficient crank arm length and leg length. The results of the study suggest that each subject has a most efficient crank arm length, but it does not appear that optimal crank arm length can be predicted by leg length.

Adult↗
PubMed1997

Kidney and breast cysts: a comparative study of fluids.

The contributions of amino acids to the overall osmotic activity of cyst fluids were sought in this comparative study of fluids from the cysts of autosomal dominant polycystic disease (ADPKD) and gross cystic disease of the breast (GCDB). Fluids (n = 18) from 18 women with GCDB and from 8 patients with ADPKD (n = 25), grouped on the basis of sodium concentrations, were analyzed for potassium, chloride, protein, and osmolality by routine methods and for amino acids by reversed-phase high-pressure liquid chromatography. Similarities between kidney and breast cyst fluids included relative isosmolality, a wide range of sodium concentrations, an inverse relationship between sodium and potassium concentrations, higher concentrations of amino acids in low-sodium fluids, and significant correlations between sequential concentrations of amino acids in cyst fluids versus blood and some of its components. Therefore, cyst fluids in ADPKD and GCDB share compositional characteristics, and amino acids, possibly of blood protein origin, accumulate in small but osmotically significant amounts in some, particularly low-sodium, cysts of kidney and breast.

Amino Acids↗
PubMed1997

Benefit plans in a changing practice environment.

Managed care is affecting the business of medical practices. Many physicians are joining with larger organizations and employee benefits are even more significant in each physician's financial security. Background on benefit issues and common areas of caution when contemplating joining a large entity are addressed.

Humans↗
PubMed1995

Pharmacokinetics, absolute bioavailability, and absorption characteristics of lamivudine.

Lamivudine is a novel cytosine nucleoside analog, reverse transcriptase inhibitor that has shown activity against human immunodeficiency virus (HIV) types 1 and 2 and hepatitis B virus in vitro. This study was conducted to compare the absolute bioavailability, pharmacokinetics, and absorption characteristics of oral solution, 100-mg capsule, and 100-mg tablet formulations of lamivudine with those of intravenous lamivudine. Twelve patients with HIV were enrolled in a single-center, randomized, open-label, four-way cross-over study. Treatment arms consisted of 100 mg intravenous lamivudine (administered over 1 hour), 100 mg oral lamivudine (1 mg/mL), a 100-mg capsule, and a 100-mg tablet, each followed by a 3- to 14-day washout period. Serial blood samples over 24 hours were obtained after each dose administration. Serum concentration data were analyzed to determine pharmacokinetic parameter estimates including area under the curve (AUC), terminal half-life (t1/2), mean residence time (MRT) for each formulation, systemic clearance, oral clearance, and apparent volume of distribution (Vd). Absolute bioavailability and in vivo mean absorption time (MAT) and mean dissolution time (MDT) were calculated for the oral formulations. Deconvolution techniques were used to calculate the input rate for the oral solution, capsule, and tablet. The two one-sided t test was used to determine bioequivalency among oral formulations with respect to logarithmic transformed estimates of AUC and maximum peak concentration (Cmax). Mean (CV) systemic clearance and Vdss after intravenous administration of lamivudine were 22.6 L/h (15%) and 99 L (28%), respectively; mean t1/2 ranged from 8.41 to 9.11 hours for all formulations; and MRT ranged from 4.42 to 5.77 hours for all formulations. Mean absolute bioavailability ranged from 86% to 88% for the oral solution, capsule, and tablet. All oral formulations were considered bioequivalent for AUC and Cmax. The MAT was 1.32 hour for the oral solution, and MDT was 0.03 and -0.11 hours for the capsule and the oral solution, respectively. The oral formulations of lamivudine examined in this study demonstrated acceptable bioavailability for oral administration. The solid oral formulations (capsule and tablet) show rapid dissolution properties with an absorption rate similar to or exceeding those observed with the oral solution. This suggests that dissolution is not an important factor for the rate of absorption of lamivudine. The use of deconvolution techniques using PCDCON provides valuable insight into the absorption characteristics of lamivudine.

Absorption↗
PubMed1995

Determination of the novel sialic acid analog GG167 (GR121167X) in human urine by liquid chromatography: direct injection with column switching.

GG167 is a novel compound which selectively inhibits viral neuraminidase and has demonstrated activity against influenza A and B. A liquid chromatography (LC) method for the determination of GG167 in human urine has been developed and validated. The method allows direct injection of urine (7 microliters) using LC column switching followed by UV detection. Initial chromatography is performed using a Nucleosil-Diol column (7 microns, 250 mm x 4.6 mm), eluted with 20 mM phosphate buffer (pH 2.5):acetonitrile (18:82, v/v) at 2.0 ml min-1. GG167 is "heart-cut" to a Spherisorb-SCX column (5 microns, 100 mm x 4.6 mm) and eluted with 35 mM phosphate buffer (pH 2.5):acetonitrile (50:50, v/v) at 1.5 ml min-1 for final separation. GG167 is detected by UV absorbance at lambda = 238 nm. UV detection and peak shape are enhanced at pH < 2.5. The quantitation range of the assay is 0.3-100 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of GG167 clinical trials.

Administration, Intranasal↗
PubMed1994

High-performance liquid chromatographic assay for 2'-deoxy-3'-thiacytidine in human serum.

A high-performance liquid chromatographic method for the determination of 2'-deoxy-3'-thiacytidine (3TC), a novel dideoxy-nucleoside analogue, in human serum is described. 3TC was extracted from serum samples using Bond Elut Certify solid-phase extraction cartridges prior to reversed-phase chromatography with UV detection. The method has been shown to be valid over the concentration range 10-5000 ng/ml using a 1-ml sample volume, both before and after heat treatment of the samples at 60 degrees C for 3 h. The method has been automated using a Zymark robot and used in the analysis of serum samples from HIV positive patients.

Antiviral Agents↗
PubMed1994

Coexistent thyroid cancer and pregnancy.

OBJECTIVE: A study was performed to determine the appropriate time for the initiation of therapy for thyroid carcinoma first diagnosed during pregnancy. DATA SOURCES: Material on thyroid cancer cases was obtained from the New Mexico Tumor Registry, Albuquerque, a computerized population-based registry for the state of New Mexico, and the Indian reservation facilities in New Mexico and Arizona (a Surveillance, Epidemiology, and End Results Registry funded by the National Cancer Institute, Bethesda, Md) for the period 1970 to 1991. STUDY SELECTION: All cases of thyroid cancer, except medullary and anaplastic, in patients aged 18 to 46 years were evaluated. Subgroups were established for (1) all women who were noted to be pregnant at the time of their initial diagnosis and (2) all women with thyroid cancer in the 18- to 46-year-old age group. DATA EXTRACTION: The information was extracted by a certified tumor registrar for age, sex, thyroid cancer, specific type of thyroid cancer, period, race, year of diagnosis, accession date, last date seen, tumor status, treatment, and patient status. DATA SYNTHESIS: There have been no deaths in the pregnant group with a follow-up ranging from 0.5 to 20 years. There was no statistically significant difference in observed survival rates between the pregnant group and 465 women, aged 18 to 46 years, with comparable thyroid cancers or in the death rates of women aged 18 to 67 years in the general population. CONCLUSIONS: Surgical treatment for patients with well-differentiated thyroid cancer diagnosed during pregnancy can be delayed until after parturition.

Adolescent↗
PubMed1994

Peritoneal cultures and antibiotic therapy in pediatric perforated appendicitis.

We retrospectively reviewed 70 cases of perforated appendicitis in children to examine the relationship between postoperative antibiotic selection and culture results from the peritoneal cavity. Initial antibiotic therapy chosen for the children consisted of a three-drug combination in 54 (77%) patients. Peritoneal cultures were performed in 58 (83%) patients. Escherichia coli and Bacteriodes fragilis were the most common bacterial isolates from the peritoneal culture. Only 7 (10%) patients had their antibiotic regimen changed after the culture results were available, of which 2 changes brought drug therapy into compliance with the cultures and 5 changes were inappropriate with respect to the peritoneal cultures. Of the remaining 51 patients with culture data available, 39 should have had changes to bring the antibiotic therapy into compliance with the observed culture results. These data indicate that surgeons select antibiotic therapy for perforated appendicitis in children based on assumptions of which organisms should be present in the infection and not on culture data. There appears to be no clinical usefulness to the routine culturing of the peritoneal cavity in children with perforated appendicitis.

Anti-Bacterial Agents↗
PubMed1994

Determination of 2'-deoxy-3'-thiacytidine (3TC) in human urine by liquid chromatography: direct injection with column switching.

3TC (GR109714X) is a cytidine dideoxynucleoside analogue which has been shown to have in vitro activity against a variety of strains of HIV-1 and is currently being investigated in clinical trials as a treatment for HIV infection. An HPLC method for the determination of 3TC in human urine has been developed and validated. The method allows direct injection of urine (10 microliters) using HPLC column switching followed by UV detection. On-line extraction is performed using a Spherisorb-SCX (5 microns, 20 x 4.0 mm) eluted with deionized water at 1 ml min-1. 3TC is retained while the bulk of urine constituents are eluted to waste. The SCX column is then backflushed to a BDS-Hypersil-C18 (5 microns, 250 x 4.6 mm) and eluted with 100 mM acetate pH 4.5-methanol (95:5, v/v) for final separation. 3TC is detected by UV absorbance at lambda = 285. The quantitation range of the assay was 0.5-500 micrograms ml-1. The method has demonstrated sufficient ruggedness to be used in support of 3TC clinical trials. Application to other cytidine analogues including DDC has been demonstrated.

Chromatography, High Pressure Liquid↗
PubMed1994

Electrical potential measurements in human breast cancer and benign lesions.

Electrical potentials were measured on the breast and at other sites in 110 women with palpable breast masses. The tumor site was significantly electropositive compared with control sites only when the tumor was a cancer, as determined by a subsequent biopsy; the electrical potentials were not influenced by age or menstrual cycle. The results indicate that, on average, altered electrical potentials detected by a noninvasive measurement on the skin reflect the presence of transformed cells in patients with breast cancer. Previous in vitro studies of breast tissue and breast epithelial cells suggest that the observed effect was due to a change in interstitial K+ concentration that arose from alterations in the activity of K+ channels. Electrical potentials may be suitable for diagnosis of individual patients if refinements are made in the measurement technique.

Adolescent↗