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Biomedical subjects

J H Fischer

Publications and source records attributed to J H Fischer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Coronary oxygen persufflation for long-term myocardial protection.

In human heart transplantation limited myocardial ischemia duration remains one of the most restricting factors. A new approach towards prolongation of this duration is the combination of cardioplegic arrest and continuous Coronary Oxygen Persufflation (COP) with gaseous oxygen. This technique, which is based on former experiments, was applied in pig hearts which we transplanted orthotopically after a hypothermic preservation time of 14 hours. For cardioplegic arrest we used either Euro-Flush glutathion solution (EFG; n=5), University of Wisconsin solution (UW; n=5), modified Bretschneider HTK cardioplegic solution (mHTK; n=6). In preliminary experiments all three solutions had shown equal cardioprotective qualities. Hearts of the mHTK group were submitted to continuous COP during storage (mHTK+COP). After 14 hours of preservation and orthotopic transplantation the mHTK+COP hearts showed significantly improved cardiac functional recovery compared to hearts preserved by simple cold storage techniques. Hemodynamics measured after 3 hours reperfusion were significantly better in the mHTK+COP group compared to EFG and UW: dp/dtmax in % of baseline+/-standard deviation (SD): 85+/-22, 65+/-26, 36+/-15, CO in % of baseline: 68+/-13, 35+/-8, 39+/-8. Postoperative preload recruitable stroke work in the mHTK+COP hearts was: 51.4+/-23.1 mmHg compared to preoperative: 57.3+/-17.2. ATP of left-ventricular myocardium in the mHTK+COP group: 14.7+2.1 micromol/g dry weight was significantly higher compared to EFG: 10.3+/-4.5 and UW: 5.9+/-3.2. CK-MB in percent of CK in all groups showed no increase during postoperative reperfusion. This study suggests that COP may present an effective complement to cold storage techniques currently used in heart transplantation. Prior to clinical application further investigations regarding long-term survival and endothelial function are required.

Animals↗
PubMed1997

Stability of fosphenytoin sodium with intravenous solutions in glass bottles, polyvinyl chloride bags, and polypropylene syringes.

OBJECTIVE: To determine the stability of fosphenytoin sodium admixtures with NaCl 0.9% injection and dextrose 5% (D5W) injection when stored in glass or polyvinyl chloride (PVC) containers, to evaluate the compatibility of fosphenytoin with 11 other intravenous solutions, and to determine the stability of fosphenytoin repackaged in polypropylene syringes. METHODS: Dilutions of fosphenytoin sodium 1, 8, and 20 mg phenytoin sodium equivalents (PE)/mL were prepared in NaCl 0.9%, D5W, and 11 other intravenous fluids. Aliquots of each solution in NaCL 0.9% or D5W were transferred to three glass bottles for storage at 25 degrees C and 21 PVC bags for storage at 25, 4, or -20 degrees C. Aliquots of each admixture with the other intravenous fluids were transferred to three PVC bags and stored at 25 degrees C for 7 days. In addition, 63 syringes were filled with fosphenytoin sodium 50 mg PE/mL (undiluted) and stored at 25, 4, or -20 degrees C. Samples of each solution from the three containers were analyzed for visual compatibility, pH, and fosphenytoin concentration initially and at 0.5, 1, 2, 3, 7, 14, and 30 days during storage at 25 and 4 degrees C and at 1, 7, 14, and 30 days during storage at -20 degrees C. Following removal of containers from the freezer, additional samples were obtained after 7 days at 4 or 25 degrees C, and 7 days at 25 degrees C, and then 7 days at -20 degrees C. RESULTS: No visible precipitation or change in color or clarity was observed in any of the fosphenytoin solutions during the study. The concentration of fosphenytoin at each sampling time remained within 97-104% of initial concentration, regardless of container, concentration, intravenous admixture, or storage temperature. CONCLUSIONS: Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room temperature, under refrigeration, or frozen. After removal from the freezer, fosphenytoin can be thawed, kept at 4 or 25 degrees C for 7 days, and then returned to the freezer for another 7 days. Admixtures of fosphenytoin sodium in various other intravenous fluids are stable for at least 7 days at room temperature.

Chromatography, High Pressure Liquid↗
PubMed1996

Minimal amounts of hyaluronidase in HTK or UW solution substantially improve the recovery of preserved hearts.

Rat hearts were preserved by simple storage for 18 h at 0-1 degree C and reperfused parabiotically with whole blood from a host rat. The preservation solutions used for flush perfusion and storage were the commercial solutions EuroCollins, HTK, or UW with or without adding 40 mg/l hyaluronidase or EuroFlush-Glutathione (EFG) solution, especially designed for prolonged heart storage. All solutions were filtered (0.45 micron) before use. The functional recovery was measured using a latex balloon in the left ventricle for LVP, dp/dt, and isotonic stroke volume. The metabolic recovery as well as the edema formation was determined from freeze-clamped myocardium at the end of reperfusion. In hearts preserved with hyaluronidase-containing solutions, the edema formation during reperfusion was reduced combined with an improvement in the coronary flow. Functional and metabolic recovery were improved in these hearts with significant increase in the stroke volume and ECP in all groups versus hearts preserved in the hyaluronidase-free basic solutions. The effectiveness of HTK preservation was significantly improved by hyaluronidase in all parameters measured in our study. The best functional and metabolic recovery was found in hearts preserved by HTK + H- or EFG-solution. Thus, preservation solutions containing hyaluronidase, especially HTK + H and EFG, seem best suited for the prolonged storage preservation of the heart.

Adenosine↗
PubMed1995

Effectivity of freshly prepared or refreshed solutions for heart preservation versus commercial EuroCollins, Bretschneider's HTK or University of Wisconsin solution.

Rat hearts were preserved for 18 hr under totally ischemic storage conditions at 0-1 degree C with the commercially supplied EuroCollins, Bretschneider's HTK, and University of Wisconsin (UW) preservation solutions compared with our new preservation solution, Euro-Flush-glutathione solution, and a "refreshed" UW solution (UWG) with 3 mmol/L reduced glutathione added before use. Recovery of the organs was measured during 30 min of parabiotic reperfusion with whole blood of a host rat of the same inbred LEW strain, following an initial warm reflush for 5 min. Functional measurements were performed using a latex balloon in the left ventricle. The metabolic recovery was determined from the myocardium freeze-clamped at the end of reperfusion. The left ventricular pressure (LVP) amplitude during pacing to a heart rate of 300/min, as well as +dp/dtmax, -dp/dtmax, isotonic stroke volume, coronary flow, ATP, and ECP values, recovered significantly better after storage in Euro-Flush-glutathione solution (LVP: 63% of controls on average) compared with when the commercially available solutions were used (EuroCollins: 20%, HTK: 42% of controls in LVP). Hearts preserved in UW solution ViaSpan did not recover during the reperfusion period, when unfiltered solution was used. Filtered ViaSpan resulted in LVP recoveries of 38% of controls, while addition of reduced glutathione immediately before use (UWG) improved the effectivity of this solution significantly (LVP 63% of controls). Similar improvements were found for all other functional and metabolic parameters. Thus, the effectivity of UW solution ViaSpan depends upon extraction of the typical particles by a filtering procedure. Effectivity can be improved by a refreshment procedure with reduced glutathione immediately before use.

Adenosine↗
PubMed1994

Pharmacokinetics of intravaginal metronidazole gel.

The pharmacokinetics of a single 500 mg oral dose of metronidazole and 5 g of 0.75% metronidazole intravaginal gel (37.5 mg metronidazole) were compared in 12 adult volunteers in a randomized crossover manner. Serial serum samples were collected over a 48-hour period and analyzed for metronidazole and hydroxymetronidazole. Metronidazole serum concentrations after intravaginal administration were only 2% of concentrations seen with the standard 500-mg oral dose. The dose-adjusted maximum serum concentration (898 +/- 121 ng/mL vs. 237 +/- 69 ng/mL) and area under the serum concentration-time curve (9362 +/- 2873 ng * hr/mL vs. 4977 +/- 2671 ng * hr/mL) were significantly greater for the oral versus intravaginal dose of metronidazole. The time to reach maximum concentration (1.4 +/- 0.6 hr vs. 8.4 +/- 2.2 hr) was significantly shorter for the oral compared with the intravaginal dose. The mean bioavailability for the intravaginal gel was 56%. Our results show that the 0.75% gel formulation may offer the advantage of fewer systemic adverse effects compared with other formulations for the treatment of bacterial vaginosis.

Absorption↗
PubMed1994

Bioavailability of total and unbound disopyramide: implications for clinical use of the immediate and controlled-release dosage forms.

This study further characterized the impact of concentration-dependent protein binding on the bioavailability and clinical use of the immediate-release (IR) and controlled-release (CR) dosage forms of disopyramide after single doses and during steady-state conditions in ten healthy volunteers. Consistent with the clinical use of these products, steady state has incorporated an IR to CR conversion step. Side effects and electrocardiographic actions were quantitated using a visual analog scale and serial Holter monitor recordings, respectively. Significant decreases resulted in area under the curve for total disopyramide between single dose and steady state: IR, 47.8 +/- 13.6 versus 33.0 +/- 6.4 mg/Lxh (P < .05); and CR, 46.9 +/- 9.5 versus 31.7 +/- 5.9 mg/Lxh (P < .05). In contrast, there were no differences in area under the curve for unbound disopyramide between phases or products. During conversion, the mean IR peak significantly decreased (P < .05) to the nadir before the first CR dose for total (37%) and unbound (60%) concentrations. There were no major differences in change in QT interval or side effects detected between products or phases. These findings indicate that, because of concentration-dependent protein binding, unbound, not total, concentrations should be used to estimate the bioavailability of disopyramide. Also, although the previously recommended conversion method (first CR dose 6 hours after the last IR dose) should provide an adequate transition in most, an alternative method (combined first CR with last IR dose) is indicated in select patients.

Adolescent↗
PubMed1994

Pharmacokinetic evaluation of two theophylline dosing methods for infants.

Theophylline is often used in infants, yet few studies have evaluated the serum concentrations achieved with currently recommended dosing guidelines. Two theophylline dosing regimens, a postnatal age (PNA) equation and the Federal Drug Administration (FDA) dosing guidelines, were retrospectively evaluated in a group of infants, postconceptional age (PCA) 31-96 weeks, with known theophylline clearances. Large variations in theophylline concentrations were observed for both dosing regimens. Mean +/- SD projected steady-state theophylline serum concentrations, Css, were 17.7 +/- 7.6 micrograms/ml with the PNA equation (n = 40) and 5.6 +/- 2.9 micrograms/ml with the FDA guidelines (n = 52). Over one-third of Css with the PNA equation were > 20 micrograms/ml. Using the FDA guidelines, 40% of Css were < 5 micrograms/ml. The majority of infants < 40 weeks PCA attained projected Css > 20 micrograms/ml (21.7 +/- 5.1 micrograms/ml) with the PNA equation, but < 5 micrograms/ml (4.3 +/- 1.4 micrograms/ml) with FDA guidelines. An age-related bias was also observed for each dosing method. For the PNA equation, projected Css were significantly higher in infants < 40 weeks versus > or = 40 weeks PCA (21.7 +/- 5.1 versus 15.8 +/- 7.9 micrograms/ml, p < 0.01). For FDA guidelines, projected Css were significantly lower in infants < 40 weeks PCA versus older infants (4.3 +/- 1.4 versus 8.5 +/- 4.3 micrograms/ml, p < 0.001). Clinical application of currently accepted theophylline dosing guidelines for infants results in a high frequency of Css, which are potentially toxic or subtherapeutic.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Gabapentin: a new agent for the management of epilepsy.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of gabapentin, a new antiepileptic drug (AED). Gabapentin's potential role in the treatment of epilepsy also was assessed. DATA SOURCE: A MEDLINE search was performed to identify all published literature (manuscripts and abstracts). Abstracts presented at the American Epilepsy Society, International Epilepsy Congress, and American Academy of Neurology meetings from 1991 to 1993 also were reviewed. A copy of the proceedings from the Food and Drug Administration Peripheral and Central Nervous System Advisory Committee meeting and package insert were obtained from Parke Davis. STUDY SELECTION: All pertinent literature was reviewed. Emphasis was placed on published information, particularly placebo-controlled clinical trials. DATA SYNTHESIS: Gabapentin is effective as adjunctive treatment for patients with partial seizures with or without secondary generalization refractory to the standard AEDs. It has a unique pharmacokinetic profile for an AED, including no binding to plasma proteins, primary elimination by the kidney, and dose-dependent oral absorption at high dosages. No drug interactions occur with the other AEDs. The most frequent adverse reactions noted in patients receiving gabapentin have been mild and transient central nervous system effects. No serious hypersensitivity or systemic reactions have been observed. CONCLUSIONS: Gabapentin appears to be a useful new AED. Further studies evaluating its use as monotherapy, in higher dosages, and in pediatric and elderly patients are required to better delineate its therapeutic role relative to that of other AEDs.

Acetates↗
PubMed1993

Alterations in theophylline metabolism during the first year of life.

Maturational changes in theophylline disposition were evaluated in 52 infants (gestational age, 24 to 40 weeks; postnatal age, 2 to 69 weeks) receiving maintenance theophylline therapy. Theophylline and metabolites were measured in serum and urine at steady state, and the influence of clinical parameters on the maturational changes was analyzed by multiple stepwise linear regression. Theophylline clearance and urine metabolite pattern reached adult values at 55 weeks' postconceptional age. Serum caffeine concentrations greater than 1 microgram/ml occurred in infants up to 50 weeks' postconceptional age. Disappearance of serum caffeine concentrations and maturation of theophylline clearance were primarily related (p < 0.001) to development of the demethylation pathway to 3-methylxanthine. Postconceptional age was the major factor (p < 0.001) explaining the interpatient variability in theophylline clearance (r2 = 0.57), serum caffeine to theophylline ratio (r2 = 0.46), and urinary excretion of theophylline (r2 = 0.51), caffeine (r2 = 0.49), 1,3-methyluric acid (r2 = 0.32), 1-methyluric acid (r2 = 0.53), and 3-methylxanthine (r2 = 0.58). Our findings indicate that postconceptional age rather than postnatal age should be used as a maturational marker during theophylline therapy in infancy.

Aging↗
PubMed1993

Valproic acid pharmacokinetics in children. IV. Effects of age and antiepileptic drugs on protein binding and intrinsic clearance.

Pharmacokinetic data from 48 children who were taking valproic acid were analyzed by multiple stepwise linear regression. Children who were receiving enzyme-inducing antiepileptic drugs (n = 27) had greater (p < 0.01) clearances, elimination rates, and dosage requirements and greater (p < 0.05) variability in pharmacokinetic values than patients receiving monotherapy. Age and polytherapy explained most of the interpatient variability in total (r2 = 0.80; p < 0.001) and intrinsic (r2 = 0.77; p < 0.001) clearances and the elimination rate (r2 = 0.61; p < 0.002). Free fraction variability was related to valproate concentration and phenobarbital (r2 = 0.47; p < 0.001). Distribution volume variance was associated with free fraction (r2 = 0.48; p < 0.001). The effect of age and polytherapy on valproate clearance is primarily attributable to changes in metabolism rather than in protein binding. Valproic acid dosage requirements are greater and more variable for children who are receiving other enzyme-inducing antiepileptic drugs.

Adolescent↗
PubMed1993

Effectiveness of a dapsone compliance program in leprosy.

BACKGROUND: Long-term effectiveness of a dapsone compliance program was assessed in patients with leprosy. METHODS: The monitoring program consists of urine dapsone/creatinine ratio determination at each visit with subsequent patient feedback and education. Eighty-eight patients receiving dapsone and seen in a leprosy clinic from 1985-1990 were included. RESULTS: The proportion of patients compliant with dapsone during a given year ranged from 70.0% (1987) to 94.4% (1989). Overall compliance for the 6-year period was 81.6%. This level of compliance was significantly different (P < 0.05) than the baseline compliance in the leprosy clinic of 46.7%. CONCLUSIONS: Compliance monitoring, combined with active patient involvement, was effective in sustaining high compliance over a 6-year period.

Adult↗
PubMed1993

Therapeutic monitoring and pharmacist intervention in a Hansen's disease clinic.

OBJECTIVE: To describe the role of the clinical pharmacist in a Hansen's disease (HD, leprosy) clinic and to describe the development, validation, and operation of a dapsone compliance monitoring program. RATIONALE: HD remains a major, worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD; however, high rates of noncompliance with this agent have been reported by many treatment centers. The assessment of compliance in HD patients is important to help distinguish between treatment failure secondary to noncompliance or to the development of resistance. SETTING: In the US, the Chicago Regional Hansen's Disease Center at the University of Illinois at Chicago is one of ten centers that provide comprehensive care to patients diagnosed with this condition. This article reviews the clinical pharmacy services and dapsone compliance program in the clinic encompassing the years 1983-93. RESULTS: The clinical pharmacist provides a variety of clinical services in the clinic as well as coordinating the clinical research program. A pharmacist-generated dapsone compliance program led to improvement in compliance rates and clinical outcome. This improvement in compliance has been sustained over an extended period of time. CONCLUSIONS: The clinical pharmacy services performed in the HD clinic provide a model for pharmacy involvement in other chronic disease states. The dapsone compliance program has been successful in improving patient care and obtaining reimbursement for clinical pharmacy services.

Academic Medical Centers↗
PubMed1991

Hepatocellular metabolic change after orthotopic liver transplantation in rats.

The hepatocellular metabolic change after liver transplantation following 2 hr cold ischemia was investigated. Of 55 orthotopic liver transplantation in male Wistar rats, 47 animals were sacrificed at 3 hr, and 1, 2, 7 and 30 days to determine hepatic metabolite levels, in the form of adenine nucleotides, lactate and glycogen. Using the other 8 recipients, biochemical examinations were done at 1, 3, 5, 7, 30 and 60 days and metabolic levels estimated at 60 days. The SGOT and SGPT levels decreased gradually after a remarkable increase on the first postoperative day, while the alkaline phosphatase level revealed a peak value at 30 days. All levels recovered to within the normal range in 60 days. The total adenine nucleotide level reached the normal range within 3 hr following the blood reflow and remained at a normal level thereafter. However, all the metabolic levels apart from total adenine nucleotides deteriorated to reach their worst level at 7 days. The results of this investigation indicate that the posttransplanted deterioration of metabolic levels were possibly caused by the imperfect oxygenation due to cellular edema after blood reflow. However, the levels of these metabolites recovered within 60 days after transplantation.

Adenine Nucleotides↗