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Biomedical subjects

J M Hardin

Publications and source records attributed to J M Hardin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Early intervention for low birthweight, premature infants: participation and intellectual development.

The Infant Health and Development Program was an eight-site randomized controlled trial of comprehensive early intervention for low birthweight, premature infants during the first 3 years of life in which intellectual development was an outcome of major importance. At 24 and 36 months, but not at 12 months, higher Mental Development Index and IQ were associated with higher levels of participation in the intervention. In a longitudinal analysis of these data, we found that the intellectual development of children in the intervention group was associated with each of the three intervention modalities (the number of home visits received, days attended at child centers, and the number of parent meetings attended) but not with children's background characteristics (i.e., maternal education, birthweight). We suggest that these findings represent a dose-response relation between intervention and outcome.

Brain Damage, Chronic↗
PubMed1994

The utility of fetal biometry as an adjunct to the multiple-marker screening test for Down syndrome.

OBJECTIVE: Our purpose was to investigate fetal biometry as an adjunct to the multiple-marker screen (maternal age, serum alpha-fetoprotein, estriol, and human chorionic gonadotropin) for Down syndrome. STUDY DESIGN: Fifty-two cases of Down syndrome were compared with 7514 normal fetuses. The measured/predicted femur length ratio had the best discriminant value (1.0 +/- 0.11 vs 0.93 +/- 0.13, p < 0.0001). Multivariate gaussian algorithms were developed and each computed a likelihood ratio for Down syndrome. The trivariate algorithm incorporated the three maternal analytes, whereas the quadrivariate version also included the femur length ratio. The study population included 38 cases of Down syndrome and 1098 euploid controls. The midtrimester risk was the product of the age-related risk and the likelihood ratio. RESULTS: The relative difference in the femur length ratio between normal and affected fetuses was small in comparison to that of the maternal serum analytes. At a risk cutoff of > or = 1:190 the detection rates were similar and actually favored the trivariate algorithm but differed only by one case of Down syndrome. CONCLUSION: The addition of the measured/predicted femur length ratio had a negligible effect on the performance of the multiple-marker screening test.

Adult↗
PubMed1994

Studying disruptive vocalization and contextual factors in the nursing home using computer-assisted real-time observation.

Disruptive vocalization (DV) is both a prevalent and disturbing problem in nursing homes. We developed a computer-assisted data collection system for real-time observation and recording of DV and various environmental contextual factors. Both frequency and duration of DV were recorded for 11 residents along with their location in the nursing home, their activity, environmental sound, the social environment, and whether or not the resident was physically restrained. The actual time of all events was also recorded. Measures of cognitive and ADL status were administered. The average occurrence of DV was 22 per hour and the average duration per occurrence was 26 seconds. The results show a significant upward linear trend in the occurrence of DV across the day. This is consistent with the "sundowning" hypothesis. A Cox Proportional Hazards Regression model indicates that another person present in the setting (p = .004) and resident presence at the nursing home hairdresser (p = .07) were associated with shorter duration episodes of DV. Correlational analyses indicate that both higher frequency and longer duration DV are related to greater cognitive impairment, and higher frequency DV is related to greater ADL impairment. We conclude that this computer-assisted real-time observational system is a useful and promising tool for studying disruptive behavior in its environmental context.

Activities of Daily Living↗
PubMed1992

Acute infection of mice with highly virulent group B streptococci as a host resistance model for immunotoxicity assessment.

This report describes a unique model for immunotoxicity evaluation in mice. The model is adapted from previously described mouse models for group B streptococcus (GBS) infections in human neonates. In this disease as well as a number of human diseases caused by highly virulent pathogens, the mechanisms of innate immunity are unable to protect the host, and survival is strictly dependent on acquired immunity. Unlike other host resistance models widely used in immunotoxicity studies, the GBS model utilizes bacteria that are highly virulent for mice (LD50 = 5-17 colony forming units). GBS is not virulent for adult humans and can be safely handled with typical precautions. Acquired immunity in the GBS model is induced during a 2 week period by two injections of heat-killed GBS. The immunizing doses are the minimum which will allow survival of 80-100% of mice in response to challenge with an otherwise lethal dose of live GBS (100 bacteria). Administration of the immunotoxic agents cyclophosphamide, carrageenan, or cobra venom factor during the immunization period and/or shortly before challenge significantly suppressed host resistance. For example, the composite mortality rate for unimmunized mice was 98% and the rate for immunized mice was 8.5%. For all groups treated with cyclophosphamide (one 75 mg/kg dose 48 h before each immunization) the mean mortality was 41 +/- 18%. The consistency of the model was evaluated by repetition of several treatments in independent experiments, and the model's consistency is comparable to that of other host resistance models.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Septicemia due to Yersinia enterocolitica in a hemodialyzed, iron-depleted patient receiving omeprazole and oral iron supplementation.

Septicemia occurred in a long-term hemodialysis patient on oral iron supplementation who had been treated for esophageal ulcer by omeprazole, an ulcer-healing drug. Yersinia enterocolitica serotype 0:3 was recovered from blood cultures. A raised intraintestinal pH and an increased intraluminal iron load may have been contributing factors for the enhanced proliferation and generalized infection of Y enterocolitica.

Aged↗
PubMed1992

Most peripheral, node-negative, non-small-cell lung cancers have low proliferative rates and no intratumoral and peritumoral blood and lymphatic vessel invasion. Rationale for treatment with wedge resection alone.

We investigated the tumor aggressiveness (intratumoral and peritumoral lymphatic and blood vessel invasion by tumor emboli) and proliferative activity (mitotic count) of 45 patients with peripheral, superficially seated, node-negative (T1-2 N0 M0), non-small-cell lung cancer treated with wedge resection alone between January 1982 and June 1988. Most patients were male (n = 39) with T1 (n = 25), small (mean diameter, 2.6 +/- 0.8 cm), squamous (n = 24), right-sided (n = 29) tumors located in either upper lobe (n = 35). The surgical specimens were studied by immunohistochemical staining with a monoclonal antibody targeting the factor VIII-related antigen. None of the tumors had lymphatic peritumoral or intratumoral invasion. Seven neoplasms (15%) harbored blood vessel invasion by tumor cells; all but one of these invasions were within the substance of the tumor. The median mitotic count was 8 mitoses per 10 high-power fields (range, 1 to 42 mitoses), significantly (p = 0.003) higher in patients with blood vessel invasion than in those without. With a 24-month minimum follow-up, projected 3- and 5-year survivals are 79% and 68%, respectively. Eleven patients had relapses and died of their tumors because of either local (n = 5) or extrathoracic (n = 6) recurrence; three patients died without tumors of comorbidity. Among the six tumors recurring in extrathoracic sites, five (83%) harbored intratumoral (n = 4) or peritumoral (n = 1) blood vessel invasion. Both recurrence of disease and death from non-small-cell lung cancer were significantly (p = 0.0009) higher for tumors with blood vessel invasion. By univariate analysis, significant predictors of survival were tumor stage (T1 vs T2, p = 0.008), size (< or = 2.6 cm vs > 2.6 cm, p = 0.039), mitotic count (< or = 8 vs > 8 mitoses, p = 0.0007), and blood vessel invasion (absence vs presence, p = 0.0001). By multivariate analysis, however, only blood vessel invasion retained its level of prognostic significance (p = 0.006). Data demonstrate that peripheral, node-negative non-small-cell lung cancers have a low metastatic potential. Whenever anatomically feasible, wedge resection seems to be an appropriate method of primary treatment.

Blood Vessels↗
PubMed1991

Medication adherence patterns in chronic obstructive pulmonary disease.

While medical treatment of COPD has advanced, the failure to adhere to regimens for medication poses a significant barrier to effective management. Furthermore, no data are available regarding adherence for patients within the United States. Data from this investigation indicate that 78 outpatients from a medical center in the southeastern region of the United States were prescribed an average of 6.26 medications with both various dosing schedules and different modes of administration. Adherence was poor, with 42 patients (54 percent) underutilizing medications, 39 patients (50 percent) overutilizing medications during periods of respiratory distress, and 24 patients (31 percent) employing ineffective inhaler dosing techniques. Prescription patterns and adherence were not associated with demographic variables; however, adherence was related to classes of medication and situational variables.

Administration, Inhalation↗
PubMed1990

Methotrexate therapy in rheumatoid arthritis patients diminishes lectin-induced mononuclear cell proliferation.

Methotrexate (MTX) is an anti-folate drug used in cancer chemotherapy because of its anti-proliferative effects. However, it is unclear whether the anti-proliferative effects of MTX contribute to the efficacy of low-dose MTX in the treatment of rheumatoid arthritis (RA). To date, either no change or a paradoxical increase in lectin-induced proliferation has been observed in cultures of peripheral blood mononuclear cells (PBMC) from MTX-treated RA patients (RA + MTX). In these earlier studies, high folate-containing media and tritiated thymidine (3H-TdR) were used. Our studies were designed to test the hypothesis that the use of a culture medium with a low folate content along with tritiated deoxyuridine (3H-UdR) permits detection of diminished phytohemagglutinin (PHA)-induced proliferative responses of PBMC from RA + MTX. The data demonstrate decreased PHA-induced cellular proliferation of cultured PBMC from RA + MTX compared with controls. When comparing the PBMC proliferative responses in high vs low folate medium, a significantly greater increase (P less than 0.05) in proliferation occurs in the cells from RA + MTX cultured in the high folate medium. This suggests that an in vivo folate-deficient state of the cells from RA + MTX may be corrected in vitro when a high folate medium is used in culture. We conclude that the use of 3H-UdR and a medium containing folate within the normal range of plasma folate levels eliminates artifacts associated with the use of high folate medium and 3H-TdR, which obscures the anti-proliferative effect of MTX in RA patients.

Arthritis, Rheumatoid↗
PubMed1990

Effect of miso (Japanese soybean paste) and NaCl on DMBA-induced rat mammary tumors.

An AIN-76A diet supplemented with miso (Japanese soybean paste) reduced the incidence (p = 0.05, Fishers exact test) and delayed the appearance (p = 0.04, log rank test) of dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas in female Sprague-Dawley rats. A NaCl-supplemented AIN-76A diet (containing the same amount of NaCl as in the miso-supplemented diet) also delayed the appearance of tumors (p = 0.02, log rank test) compared with the AIN-76A control diet. The miso- and NaCl-supplemented diet treatment groups showed a trend toward a lower number of cancers per animal, a trend toward a higher number of benign tumors per animal, and a trend toward a lower growth rate of cancers compared with controls. However, no statistical differences in the total number of tumors per animal or growth rate of the cancers were observed in the miso, NaCl, and control groups. Both miso and NaCl supplementation resulted in increased water intake and urine output but no change in the growth of the animals. These data suggest that miso consumption may be a factor producing a lower breast cancer incidence in Japanese women.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Limited sampling models for HA-1A IgM monoclonal antibody.

In this study, limited sampling models for HA-1A human IgM monoclonal antibody were developed to predict the area under the concentration time curve from timed serum concentrations. Patients were administered 15 minute infusions of 25 mg (11 patients), 100 mg (15 patients), and 250 mg (2 patients). A detailed pharmacokinetic analysis (eight time points) was performed to obtain the area under the curve for each of the 28 patients using a one-compartment model with the values normalized to a dose of 100 mg. Various models were then developed to estimate the area under the curve from one and two timed concentrations using regression analysis methodology. Of these models, four were determined to be of interest with coefficients of determinations ranging from 0.92 to 0.97. They performed quite well in predicting the area under the curve values with relative root mean squared predictive error of 7.1 to 10.8% and relative mean predictive error of -4.5 to + 6.9%. These models should be extremely useful in larger scale, Phase II/III studies of HA-1A in correlating the estimated area under the curve with various demographic data, toxicity, and efficacy.

Antibodies, Monoclonal↗
PubMed1990

Initial evaluation of a human immunoglobulin M monoclonal antibody (HA-1A) in humans.

A human monoclonal antibody (HA-1A) directed against bacterial endotoxin was administered to 15 patients with incurable malignant disease. No adverse effects were noted following single intravenous infusions of 0.05 to 100 mg. Pharmacokinetics were evaluated in nine patients receiving 10 mg (n = 3), 25 mg (n = 3), and 100 mg (n = 3). Seven of these patients had initial peak serum concentrations greater than 80% of predicted values with plasma disappearance curves fitting a one-compartment system and a plasma half-life of 31.5 h (range of 20.3-44.6 h). The peak serum concentrations and area under the curve values were proportional to the dose of HA-1A administered. One patient had a hypercatabolic state with low levels of serum albumin and IgM. He achieved 65% of the predicted value for peak serum concentration of HA-1A with a plasma half-life of 12.3 h. A second patient had detectable serum HA-1A for only 15 min following infusion without an adequate technical or biologic explanation. We were unable to demonstrate antibody to HA-1A in sera from these nine patients either prior to therapy or during 28 days postinfusion using a "double-antigen" radiometric assay. This study suggests that HA-1A human monoclonal antibody administration is well tolerated by patients. Phase I trials will need to be carried out to characterize further the pharmacokinetics and toxicity of HA-1A in patients with gram-negative sepsis.

Adult↗
PubMed1987

Partitioning of natural radionuclides in the waste streams of coal-fired utilities.

Five coal-fired electric utility plants were sampled to determine radionuclide concentrations in all major process streams. The results, together with plant operating data, were used to track the following six naturally occurring radionuclides: 238U, 226Ra, 210Po, 210Pb, 230Th and 232Th. For each plant, radionuclide balances were computed and the amount and extent of volatilization and enrichment of any radionuclides in the stack effluent were determined. In general, most of the radioactivity was found in boiler bottom ash or particulate control equipment hopper ash; atmospheric emissions were quite small in comparison. Radionuclides in the stack effluent were not detected in the gaseous state and some (especially 210Po and 210Pb) were preferentially associated with the smallest fly-ash particles.

Carbon↗
PubMed1984

[Primary hyperparathyroidism. Lack of effect of cimetidine on plasma levels of parathyroid hormone and calcium].

Because of the contradictory results formerly published as regards the effect of cimetidine in primary hyperparathyroidism, we have studied the effect of cimetidine at the daily dose of 1200 mg in 14 cases of primary hyperparathyroidism. The diagnosis was ascertained in all cases by the coexistence of an otherwise unexplained hypercalcemia and of a concomitantly elevated plasma concentration of immunoreactive parathyroid hormone (PiPTH) measured by 2 different antibodies and confirmed in 10 cases by surgical neck exploration. In 5 cases with severe hypercalcemia (greater than 12.0 mg/l) cimetidine was discontinued after 5 days because of its lack of effect on both plasma concentrations of calcium and PiPTH, and the patients were successfully operated. In 8 cases with milder hypercalcemia, cimetidine was given for 1.5-6 months. There was no significant change in both plasma concentrations of calcium (PCa) and PiPTH but a regression analysis showed that PCa was negatively correlated to time with a correlation coefficient which would have become significant if the follow-up had been 9 months. In the last patient severe hypercalcemia was controlled by simultaneous administration of phosphate, indomethacin and cimetidine without concomitant decrease of PiPTH; and 6 weeks after cimetidine discontinuation no significant increase of PCa and PiPTH occurred. These data show that cimetidine has no clinically therapeutic value in primary hyperparathyroidism.

Adolescent↗
PubMed1984

Lung-clearance classification of radionuclides in coal fly ash.

Lung-clearance classifications for 238U, 232Th, 230Th, 228Th, 226Ra, 210Pb and 210Po in respirable coal fly ash were estimated for use with the lung clearance model proposed by the ICRP Task Group on Lung Dynamics. Estimates were based on measurements of the dissolution rates for these radionuclides from sized fly-ash samples into simulated lung fluid at 37 degrees C. The estimates were expressed in the classification terms of the model, i.e. D, W and Y, indicating lung clearance half-times of 0-10 days, 11-100 days, and more than 100 days, respectively. Ash from eastern bituminous coal, western bituminous coal and mid-western bituminous coal was examined. Both Class-D and Class-Y components of 238U were found in all samples, whereas all the other radionuclides dissolved very slowly and were classified 100% Class Y. The fraction of 238U in Class D increased with decreasing particle size and increased linearly from 0.02 to 0.17 as the concentration of U in the volatile-metal portion of the samples increased. This relationship suggests that a major fraction of the U in coal fly ash may be shielded from exposure to simulated lung fluid by more-abundant metals deposited on the outer surface of fly ash during coal combustion.

Carbon↗
PubMed1981

[Control of hypertension and blood lactate during exercise. Comparison of central antihypertensive agents with the cardio-selective beta blockers metoprolol and atenolol].

To assess whether betablockers (BB) would better control blood pressure than central antihypertensive drugs (CAD) clonidine or alpha methyldopa in hypertensive patients during exercise, comparable triangular ergometric bicycle exercises were performed by the same patients while their hypertension had been controlled at rest either with CAD or BB. Blood pressure, heart rate and blood lactate before and during exercise were compared in II patients treated with metoprolol and CAD, and in 12 other patients treated with atenolol and CAD. Systolic and diastolic blood pressure on exercise were significantly lower with BB than with CAD. Heart rate and rate-pressure product were always lower with BB than with CAD. Blood lactate increase was greater with BB than with CAD. The work capacity was greater with atenolol than with CAD, but comparable between metoprolol and CAD.

Adrenergic beta-Antagonists↗