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Biomedical subjects

D Freeman

Publications and source records attributed to D Freeman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Infection in major sickle hemoglobinopathies: should management strategies change?

Four children with major sickle hemoglobinopathies developed severe pneumococcal infection. Three had sickle cell hemoglobin C (Hb SC) disease and one had sickle cell anemia (Hb SS). In three instances, there was a fatal outcome. The authors' experience with these cases leads them to question whether any patient with a major sickle hemoglobinopathy should be excluded from receiving prophylactic penicillin or if outpatient management with long-acting cephalosporin treatment in the sickle cell patient with suspected sepsis is appropriate therapy.

Adolescent↗
PubMed1993

Effects of a HIV risk reduction education program among injection drug users in Puerto Rico.

This report examines the extent to which an educational component enhanced the efficacy of a community outreach program in reducing HIV transmission behaviors among injecting drug users (IDUs). The experimental enhancement comprised three group educational sessions where detailed information on HIV risk and protective behaviors was conveyed, protective behaviors were shown and practiced, and a problem solving perspective guided discussion of serostatus results. Substantial risk reduction in behaviors were prospectively measured. However, IDUs assigned on a random basis to the enhanced intervention showed no significant differences in levels of risk reduction when compared to those assigned to the standard-only intervention. The chronic and intensive use of injected drugs among the IDUs studied and their high level of HIV infection suggest the need of interventions geared to maximize the utilization of health care services and enhance the supportive functions of familial and social networks of IDUs.

Adult↗
PubMed1992

Simultaneous solid-phase extraction and chromatographic analysis of morphine and hydromorphone in plasma by high-performance liquid chromatography with electrochemical detection.

High-performance liquid chromatography has become an important analytical tool for the quantitation of opioid drugs. Using solid-phase extraction and coulometric electrochemical detection, we have developed a chromatographic method for the simultaneous measurement of morphine and hydromorphone which is both sensitive and specific. Using 1 ml of plasma, intra-assay and inter-assay data show that the detection limit for accurate quantitation of these compounds is about 1.2 ng/ml (coefficient of variation 11.6%) for morphine and 2.5 ng/ml (coefficient of variation 10.5%) for hydromorphone. The method is simple and readily adaptable to most pharmacokinetic studies and toxic screens involving these drugs.

Chromatography, High Pressure Liquid↗
PubMed1992

Differences in metabolism of time-release and unmodified nicotinic acid: explanation of the differences in hypolipidemic action?

The possibility that differences in metabolism might underly the differences in efficacy and toxicity between time-release and unmodified formulations of nicotinic acid was investigated by measuring 24-hour urinary excretion of metabolites in 10 subjects who received both forms. Nicotinic acid has two metabolic fates: formation of nicotinamide adenine dinucleotide (NAD) and formation of nicotinuric acid, the glycine conjugate of nicotinic acid. Catabolism of NAD releases nicotinamide, which is subsequently methylated and/or oxidized to form a number of metabolites, with 2-pyridone predominating. Excretion of nicotinuric acid was more than four times greater when subjects took unmodified nicotinic acid than when they took time-release nicotinic acid (78.2 and 18.8 mg, respectively). In contrast, excretion of 2-pyridone with unmodified nicotinic acid was only 30% more than with time-release nicotinic acid (171.0 and 129.9 mg, respectively). These results demonstrate a marked difference in the metabolism of unmodified and time-release nicotinic acid. It is proposed that nicotinyl coenzyme A (CoA), the metabolic intermediate in the formation of nicotinuric acid, mediates some of the hypolipidemic actions of nicotinic acid, as the acyl-CoA esters of xenobiotics, including clofibrate, have been shown to interfere with lipid metabolism.

Adult↗
PubMed1991

Depressive symptoms among Puerto Ricans: island poor compared with residents of the New York City area.

This paper compares the distribution and sociodemographic patterns of depressive symptoms among two groups of Puerto Ricans. The data employed for the analysis are from a probability sample of two communities of adults. Puerto Ricans living in poor residential areas on the Island (n = 1,658) and those living in the New York City area (n = 1,267). The first group was interviewed during 1989, and the second during 1984. Symptoms of depression were measured with the Center for Epidemiologic Studies Depression Scale. Results show that Puerto Ricans residing in the New York City area and the Island poor have similar levels of high depressive symptomatology, 28.1% and 28.6%, respectively. Results of the logistic regression analysis indicated that female sex, low educational level, low household income, and unemployment are predictors of high depressive symptoms for both samples. These results are similar to findings for other ethnic groups. For Puerto Ricans living in New York, the effect of interviewing in Spanish on high depressive symptoms diminishes after sex, education, and income variables are controlled.

Adult↗
PubMed1991

A method for the quantitation of hypericin, an antiviral agent, in biological fluids by high-performance liquid chromatography.

Hypericin, a polycyclic aromatic dianthroquinone, is a natural plant product with antiviral properties. We report here the development of a methodology for the extraction and quantitation of hypericin from plasma and biological fluids and the adaptation of a sensitive and selective method for detection of the compound by high-performance liquid chromatography. The methodology offers a rapid and specific means of monitoring drug blood levels in clinical and pharmacokinetic studies. The chromatographic procedure utilizes the substantial retentive properties of hypericin on reverse-phase media and detection by the strong visible absorbance maximum at 590 nm. Verification by the fluorescence spectral properties of hypericin in organic media can also be utilized. The assay is linear over a 3 log concentration range and hypericin is consistently recovered from murine, simian, and human plasma. The methodology was applied to assess the pharmacokinetic properties of hypericin in mice receiving a single bolus injection of 350 micrograms. A distribution half-life of 2.0 h and an elimination half-life of 38.5 h were calculated. We also discuss the limitations of direct analysis of hypericin by absorbance or fluorescence measurements.

Animals↗
PubMed1991

Proton editing and imaging of lactate.

Highly specific NMR assays for the detection, quantitation and imaging of lactate in vivo are described. Applications in animals include tumor monitoring, the determination of hypoxic cell distribution and the demonstration of the efficacy of tumor-sensitizers. The methods (GE-DQCOSY and GE-HMQC) may be particularly useful in heteronuclear NMR in vivo.

Animals↗
PubMed1991

Oxygen free radical injury of IEC-18 small intestinal epithelial cell monolayers.

Oxygen radicals can cause endothelial and epithelial permeability changes and mucosal injury of the small intestine. There is no clear consensus concerning the relative injurious potential of individual oxygen radicals. In this study, the small intestinal cell line IEC-18 was used as an in vitro model to study the relative injurious effects of reactive oxygen metabolites. By introducing different combinations of oxygen metabolite-producing enzymes, xanthine oxidase, superoxide dismutase, and catalase, and an iron chelator, deferoxamine, to the fully confluent monolayers and to proliferating IEC-18 cells, the differential injurious effects of the oxygen metabolites O2-, H2O2, and OH. could be evaluated. The extent of cellular injury was assessed using [3H]thymidine uptake, 51Cr release, and morphological evaluations. Our results suggest that OH. produced as a by-product of O2- and H2O2 via the Haber-Weiss reaction was the most injurious oxygen species involved in cellular injury of IEC-18 monolayers induced by xanthine oxidase. O2- produced by xanthine oxidase appeared to be only minimally injurious, and H2O2 produced by xanthine oxidase and as a result of conversion of O2- by superoxide dismutase was moderately injurious. Superoxide dismutase and deferoxamine at appropriate concentrations were protective against xanthine/xanthine oxidase-induced monolayer injury. H2O2 added directly or produced indirectly by glucose oxidase was very injurious to the intestinal monolayers, and this injury was mitigated by catalase.

Animals↗
PubMed1991

The acute and chronic effects of G-lasing on femoral vein grafts in dogs.

Each year, 5% of all coronary artery bypass operations are repeat procedures, and 15%-30% of coronary artery vein grafts occlude within the first eighteen months postoperatively. To evaluate the macroscopic and histologic effects of G-lasing on vein grafts and their patency, femoral veins were used to bypass bilaterally induced stenoses of femoral arteries in 10 dogs. The left vein grafts were G-lased with a 1.5 mm, hot-tipped argon laser at 5 watts for ninety seconds, while the right grafts were used as the controls. Acutely, each vein graft demonstrated no evidence of charring or perforation. The percentage of endothelium present in the G-lased vein grafts was consistently less than 5%, whereas the control vein grafts had an average of 70%. After ten weeks, the animals were sacrificed, and the vein grafts were evaluated for histologic changes and patency. There were no significant microscopic differences between the G-lased and control vein grafts. A statistically significant difference in graft patency was not achieved between G-Lased and control vein grafts at 10 weeks, but only a small number of grafts were studied. Further studies will be needed to evaluate the effects of G-lasing on the long-term patency of vein grafts.

Angioplasty, Laser↗
PubMed1991

Isoflurane alters the kinetics of oral cyclosporine.

Cyclosporine is an important immunosuppressive agent often given orally preoperatively to patients undergoing organ transplantation. The aim of the present study was to evaluate the effects of anesthesia on the pharmacokinetics of orally administered cyclosporine. Sixty unanesthetized fasting female Lewis rats were given 25 mg/kg cyclosporine by gastric tube and were then randomized to immediately receive an isoflurane anesthetic (n = 30) or to serve as nonanesthetized controls. At 1, 2, 3, 4, and 6 h after the administration of the cyclosporine, six animals from each group (while still anesthetized for those in the anesthesia group) were killed, and arterial blood and the entire bowel from the esophagogastric junction to the ileocecal junction were removed for measurement of cyclosporine concentrations. A subsequent study with six animals in each group was performed to examine more closely the distribution of cyclosporine in the stomach and small intestine 4 h after the oral dose. In these animals the cyclosporine concentration in the stomach and in five 10-cm-long segments of small bowel was assayed. In all studies of gastrointestinal specimens, the cyclosporine extracted is a combination of that contained in the lumen and the wall. At all times except at 6 h, the blood cyclosporine levels were significantly higher in the control group than in the isoflurane group. Conversely, the amount of cyclosporine in the distal small bowel of control rats was increased as compared with the anesthetized animals. In the animals studied at 4 h, the amount of cyclosporine in the stomach of control rats was significantly lower than that in the anesthetized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Modulation of experimental cyclosporine nephrotoxicity by inhibition of thromboxane synthesis.

The clinical usefulness of Cyclosporine is limited by its intrinsic nephrotoxicity. A potential mechanism of CsA-mediated renal injury may involve an alteration in the prostaglandin-thromboxane (PG-TX) cascade. In our studies, pharmacological manipulation of the PG-TX system in normal and nephrotoxic animals was conducted using a specific thromboxane synthetase inhibitor U63,557A, and the cyclooxygenase inhibitor indomethacin. Administration of CsA 50 mg/kg/day for 7 days to Sprague Dawley rats resulted in a 99% increase in urinary thromboxane B2 excretion compared with controls (48.2 +/- 3.1 vs. 24.2 +/- 2.6 ng/24 hr, P less than 0.001), while plasma levels remained unchanged. Glomerular and tubular function was significantly reduced at this time, with a 48% decrease in creatinine clearance (CCr), and a 25% reduction in the fractional excretion of sodium (FeNa) (P less than 0.001). Histological injury included cortical tubular vacuolization and necrosis. Administration of indomethacin 8 mg/kg/day to both normal and CsA-treated rats resulted in a significant reduction in prostanoid excretion. Indomethacin alone had no adverse effect on glomerular function; however, when coadministered with CsA an exaggerated decrease in renal function was observed. CCr in this group fell by a further 27% compared with the CsA-50 group, while FeNa decreased by 76% (P less than 0.001). Histologic injury intensified, with an increase in vacuolization and necrosis. In contrast, coadministration of U63,557A with CsA prevented the rise in urinary TXB2 excretion, improved CCr by 20% (P less than 0.05), and restored FeNa to control levels. The severity of CsA-induced vacuolization was significantly diminished. Selective inhibition of thromboxane production may therefore be valuable in mitigating the clinical nephrotoxicity of CsA.

Animals↗
PubMed1990

Therapeutic monitoring of cyclosporine: impact of a change in standards on 125I-monoclonal RIA performance in comparison with liquid chromatography.

This study examines the measurement of cyclosporine (CsA) by 125I-monoclonal RIA, and describes the impact of the recent change in the standard curve provided. CsA concentrations in serum and whole-blood control samples measured by 125I-RIA were initially 8-18% higher than those by HPLC. During the first two months of 1989, a significant and sustained deviation in the 125I-RIA produced results that exceeded the HPLC results by 21-28% (P less than 0.001). Introduction of the new standard curve in March 1989 returned the concentration of the whole-blood controls to the previous range (11-12% above HPLC, P less than 0.001). Measurement of clinical samples from heart, liver, and bone-marrow graft recipients by 125I-RIA by both old and new kit standards produced a close linear correlation (y = 0.89 x - 19.02; r = 0.99; n = 75, range = 40-850 micrograms/L), with use of the new standards yielding results 82 (SD 8)% of those with the preceding assay. However, even with the new standard curve, CsA concentrations by 125I-RIA in the clinical samples exceeded those by HPLC by a factor of 1.37 (SD 0.18) to 1.52 (SD 0.19). Segregation for transplant type did not affect the RIA/HPLC ratio. The results suggest cross-reactivity of the 125I-RIA with material present in vivo.

Antibodies, Monoclonal↗