Biomedical subjects

J H Fischer

Publications and source records attributed to J H Fischer.

At least 19 recordsLinked to original sources

PubMed2005

Experimental bile duct protection by intraductal cooling during radiofrequency ablation.

BACKGROUND: The use of radiofrequency ablation (RFA) for liver tumours is limited by the proximity of large bile ducts to the targeted lesion. The aim of this randomized study was to evaluate intraductal cooling as a mean of protecting the bile ducts during RFA. METHODS: Twelve pigs underwent RFA adjacent to the right bile duct. After placement of an intraductal cooling catheter and a RFA probe, pigs were randomized to cooling or no cooling. Intraductal temperature was measured in all animals. The bile ducts were assessed by magnetic resonance imaging (MRI) and cholangiography 1 and 28 days after the procedure. RESULTS: Intraductal cooling abolished the increase of intraductal temperature seen in the absence of cooling. Concurrent cholangiography and MRI showed a biliary lesion in one of six pigs subjected to intraductal cooling and in five of six without cooling (P = 0.040). The biliary injuries were barely visible by MRI on day 1 but were clearly visible on day 28. CONCLUSION: Intraductal cooling can prevent biliary injury induced by RFA. The exact parameters for intraductal cooling require further investigation to establish the best compromise between bile duct protection and complete ablation of surrounding tissue.

Animals↗

PubMed2005

Monitoring cytosolic pH of carboxysome-deficient cells of Synechocystis sp. PCC 6803 using fluorescence analysis.

Disruption of the ccmM gene in the cyanobacterium Synechocystis sp. PCC 6803 causes a deficiency of carboxysomes and impairs growth in ambient CO2. The effect of this gene defect on cellular metabolism was investigated using electron microscopy, biochemical and fluorescence analysis. Mutant cells were devoid of the characteristic dense polyhedral bodies called carboxysomes. The photosynthetic oxygen evolution was considerably lower in mutant cells compared to wild type, while Rubisco activity in cell extracts was similar. During photosynthetic CO2-dependent oxygen evolution, Rubisco Vmax dropped from 142 micromol mg-1 chlorophyll h-1 (WT) to 77 micromol mg-1 chlorophyll h-1 in the mutant cells, and the Km for Ci (inorganic carbon) increased from 0.5 mM (WT) to 40 mM. The fluorescent indicator, acridine yellow, was used for non-invasive measurements of cytoplasmic pH changes in whole cells induced by addition of Ci, making use of the decrease in fluorescence yield that accompanies cytoplasmic acidification. The experimental results indicate that control of the cytoplasmic pH is linked to the internal carbon pool (Ci). Both wild-type and ccmM-deficient cells showed a linear response of acridine yellow fluorescence quenching and, thus, of internal acidification, with respect to externally added inorganic carbon. However, the fluorescence analysis of mutant (carboxysome-free) cells indicated slower kinetics of Ci accumulation.

Carbon Dioxide↗

PubMed2004

Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗

PubMed2004

Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy [RETIRED]: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.

Acetates↗

PubMed2004

Rate of perioperative complications in thermal ablation of bone: an animal trial.

INTRODUCTION: While only few data are available yet for radioablation of bone tissue, the occurrence of bone marrow embolisms during cryoablation has been documented. It was the aim of this study to assess perioperative complication rates of thermoablation in animals using state-of-the-art ablation probes. MATERIALS AND METHODS: Eight adult sheep were placed under general anaesthesia, and using a radioprobe, thermoablation was performed on the medial side of the head of the right tibia. In addition, freezing was performed with miniature cryoprobes on both femurs and the head of the left tibia. Haemodynamic monitoring and determination of blood gases and electrolytes were done intraoperatively. The animals were killed 1 week after surgery, and the ablation sites and lung tissue examined macroscopically and microscopically. RESULTS: None of the animals showed pathological changes in any of these parameters. Blood gases remained unremarkable throughout the operation. All eight animals showed an average drop in haemoglobin of 0.97 g/100 ml. Two animals showed fresh embolisms in the pulmonary vessels. CONCLUSION: Experimental thermoablation of bone tissue in large animals failed to show any significant perioperative complications following surgery. The lung embolisms which did occur were not clinically relevant. The use of mini-cryoprobes or radioprobes as alternative or complementary measures for treating pathologically altered bone tissue seems viable and does not involve any undue risks.

Animals↗

PubMed2003

[In vivo study of degradation of poly-(D,L-) lactide and poly-(L-lactide-co-glycolide) osteosynthesis material].

AIMS: Comparison of the degradation of poly(D,L)lactide (Resorb X) or poly(lactide-co-glycolide) (LactoSorb) in vivo. MATERIAL AND METHODS: LactoSorb and Resorb X osteosynthesis plates were fixed at the lateral aspect of the femora of 26 Chinchilla rabbits using the respective osteosynthesis screws. After intraperitoneal injection of fluorochromes the screw plate bone blocks were resected after 1, 6, 12, 14, 16, 21, 26 months and radiologic, histologic as well as fluorescence microscopic examinations were carried out. RESULTS: Newly formed bone was detectable above and beneath the polymers 1 month after the implantation. The implants were totally covered by newly formed bone after 6 months. While the LactoSorb screws were found to be as birefringent as after 1 month, in the Resorb X screws a continuous resorption by phagocytizing marrow cells starting from the periphery was detectable. Resorb X was totally resorbed in histologic slides 12 months after implantation, while total resorption of LactoSorb lasted 14 months; both polymers were replaced by marrow cells. Bone remodeling was not finished 26 months after implantation in both polymers. CONCLUSION: Resorption of Resorb X was finished earlier than the resorption of LactoSorb. Both materials were found by fluorescence microscope to be completely resorbed after 12 or 14 months, but bone remodeling of the screw holes was not yet finished 26 months after implantation.

Absorbable Implants↗

PubMed2003

Cryosurgery in long bones with new miniature cryoprobe: an experimental in vivo study of the cryosurgical temperature field in sheep.

AIM: The aim of this in vivo study was to determine whether new miniature cryoprobes provide adequate tissue cooling in long bones by measuring the field of temperature under various conditions. METHODS: Freezings were performed in femoral and tibial bones of 10 sheep under general anaesthesia. Applying one cryoprobe, temperatures of -75 degrees C resp. -51 degrees C could be reached within 0.75 cm resp. 1.00 cm of the probe. RESULTS: Histological examinations revealed compact bone and marrow necroses along the isotherm in all 10 sheep. Using two cryoprobes simultaneously, a mean temperature decrease to -71 degrees C between the two cryoprobes was achieved thanks to the synergistic freezing effect. Looking at consecutive freezes, it was apparent that with similar cryoprobe end temperatures, the temperature dropped faster if the number of freezing cycles was increased. CONCLUSION: In conclusion, it was seen that despite its small diameter, the new miniature cryoprobe delivers adequate in vivo tissue cooling in long tubular bones. Employing the synergistic freezing effect by using two or more cryoprobes simultaneously, efficient in vivo freezing of larger bone segments is also possible. Thus, cryosurgery with the new miniature probes can provide a valuable complement to conventional resection of long tubular bones, and offers a viable alternative to surgical treatment of neoplastic diseases of the skeletal system.

Animals↗

PubMed2003

The effect of an admixture of sodium hydrogen phosphate or heparin-coating to poly(D,L)lactide--results of an animal study.

The study was aimed at investigating the effect of an admixture of sodium hydrogen phosphate (NaP) on the pH value around degrading poly(D,L)lactide (PDLLA) and the possible improvement of PDLLA biocompatibility by coating its surface with heparin. PDLLA +/- NaP was injection-molded to form rods (20 x 3 x 2 (mm)) and cubes (3 x 2 x 2 (mm)). Half of the pure PDLLA samples were surface-coated using heparin. One rod and cube each of PDLLA, PDLLA + NaP and PDLLA/Hep were implanted into the dorsal muscles of 42 rats. From the 2nd to 52nd week after operation, pH measurements were performed in the environment around the implants. The samples were then harvested for histological and mechanical analyses. No significant decrease in pH-values was observed in the tissue around the implants. Pure PDLLA and PDLLA/Hep samples were macroscopically resorbed after 52 weeks, while the degradation of PDLLA + NaP was still in progress. Approximately 80% of the initial bending strength of PDLLA or PDLLA/Hep rods was present after six weeks, while the bending strength of PDLLA + Nap was reduced to 50% after 4 weeks. Heparin-coating of PDLLA did not improve its biocompatibility but did increase its resorption. While no significant effect of NaP on pH value was found, its admixture did reduce the mechanical characteristics of the implants.

Animals↗

PubMed2002

[Detection of air embolism by a re-usable Doppler probe integrated in a central venous line--application in-vivo].

PROBLEM: Air embolism frequently occurs under neurosurgical operations performed in the sitting position. Recently we reported the idea of inserting a re-usable doppler probe into a blind-ending lumen of a central venous catheter (Schregel-Volk-Catheter, SVC). In vitro testing in a circulation model showed a high sensitivity: air bubbles as small as 0.5 microliter were reliably detected at a distance up to 4 cm from the tip of the SVC. METHOD: After approval by the local ethics committee pigs were anaesthetised and a cardiopulmonary bypass was connected. During the bypass period a 12 F SVC (Medex Medical, Germany) with one blind-ending lumen was positioned into the proximal vena cava cranialis or vena cava caudalis. An 8 MHz doppler probe (MTB Basler, Suisse) was introduced into the SVC and connected with the doppler device Multi-Dop T (DWL, Germany). Well defined air bubbles (3-6 microliter) were generated by a bubble generator and injected into the right femoral vein or the left vena jugularis interna. RESULTS: All bubbles were reliably detected by the re-usable doppler probe. Embolic events can be documented, counted and quantified by the Multi-Dop T. CONCLUSION: Using SVC's with a blind-ending lumen could improve and simplify the detection of air embolism. We see several advantages (e.g. sensitivity, costs) compared with established methods (precordial doppler, TEE) for detection of air embolism.

Animals↗

PubMed2001

Degradation of poly(D,L)lactide implants with or without addition of calciumphosphates in vivo.

The study was aimed at examining the in vivo degradation of pure poly(D,L)lactide (PDLLA) or PDLLA with an admixture of calciumphosphates. One rod (20 x 3 x 2 mm) and one cube (3 x 2 x 2 mm) of pure PDLLA, PDLLA with tricalciumphosphate (PDLLA + TCP) or PDLLA with calciumhydrogenphosphate (PDLLA + CHP), respectively, were implanted into the dorsal muscles of 50 male Wistar Albino rats. After definite intervals (from 2nd to 72nd week), pH measurements were performed in the environment of the implants. Afterwards, the cubes with their surrounding tissues were excised for histological examinations, measurements of the outer dimensions and mechanical analyses of the explanted rods were performed. No drop of more than 0.1 pH units was detectable in the tissue surrounding any type of implants. No advantageous effect of the calciumphosphates could be proved. A mild foreign body reaction could be observed around PDLLA implants. After 72 weeks, pure PDLLA had been totally resorbed from the extracellular space, the degradation of calciumphosphate-enriched PDLLA was still in progress. A large amount of inflammations occurred in the tissues surrounding PDLLA with an admixture of slowly degrading TCP or CHP, leading to two abscesses and four fistulas at PDLLA + TCP, and two abscesses and three fistulas at PDLLA + CHP implantation site. Bending strength of pure PDLLA was constant up to the 4th week post-implantation and reduced to 60% of the initial value up to the 12th week. No traces of crystallinity could be observed during the degradation of PDLLA. As a conclusion of the study, complete resorption from the extracellular space and tissue tolerance of pure PDLLA is proved. An admixture of small calciumphosphate particles is not suitable to improve the biocompatibility of PDLLA but leads to a decrease in the mechanical characteristics.

Animals↗

PubMed2001

The effect of an addition of sodium hydrogenphosphate to poly(D,L)lactide--results of in vitro examinations.

Aim of the study was to examine the influence of sodium hydrogenphosphate (NaP) on the pH value and the mechanical characteristics of degrading poly(D,L)lactide (PDLLA). Test rods of PDLLA with or without NaP amounting to 1, 10, 25 or 50 mol per 100 mol lactate, the degradation product of PDLLA, were produced by injection molding. Molecular weight and bending strength of the rods were measured before and after an accelerated in vitro-test (55 degrees C, Ringer's solution (RS)). For a long-time degradation test PDLLA-rods with or without 1 mol% NaP were placed in RS or Soerensen buffer solution (SB, pH 7.4) at 37 +/- 1 degrees C. Measurements of pH and determination of length, volume and weight of the samples were done in 2-4 week intervals up to the 52nd week after incubation. A pH-drop was measured in RS or SB containing pure PDLLA after 28 or 36 weeks respectively. Stabilization of the pH value due to admixed NaP delayed the degradation related pH drop for 8 weeks in RS or SB. A strong increase of length, volume and weight was measured in PDLLA + NaP-rods. In conclusion minimal stabilization of pH but also an increase of outer dimensions of the samples was found due to the admixture of NaP to PDLLA. Thus, an addition of substantially higher amounts than 1 mol% NaP in PDLLA can not be recommended, regardless of the positive effects on pH stabilization.

Absorbable Implants↗

PubMed2000

Film-induced sadness as a trigger for disinhibited eating.

OBJECTIVE: We tested whether film-induced sadness enhances food intake in restrained eaters. METHOD: Female participants scoring either high or low on a measure of dietary restraint viewed two film segments in counterbalanced order on successive days: an emotionally neutral travelogue and a sad film depicting the death of the young female protagonist. RESULTS: Contrast analyses revealed that film-induced sadness significantly reduced food intake in low-restraint individuals, but only nonsignificantly increased it in high-restraint individuals. DISCUSSION: When sadness is induced without an apparent ego threat, high-restraint participants may not exhibit as much disinhibited eating as when they are exposed to mood inductions that threaten their self-esteem.

Adult↗

PubMed2000

The permeability of dental procedure and examination gloves by an alcohol based disinfectant.

OBJECTIVES: The usage of gloves in dentistry has increased greatly over the last 10 years and this has highlighted certain problems when gloves are being worn extensively. While skin irritations and allergies caused by latex proteins and accelerators have been the main focus of attention, dental materials such as disinfectants have also become known as a source of skin reactions. This study was performed to evaluate the permeability of various gloves by ethanol. METHODS: The tip of the middle finger of 13 glove brands (natural latex gloves (NLG) powdered or unpowdered, powdered vinyl, nitrile and synthetic elastomer) was exposed to 5 ml of a hand disinfectant (Desderman). After a penetration time ranging from 2 min to 8 h the permeation of Desderman was detected with a gas chromatograph. RESULTS: Only one component of the disinfectant (ethanol) could be detected to have gone through the gloves. After only 2 min the vinyl and one nitrile glove and after 10 min all glove types were permeated. Powder seemed to have no real influence on the penetration of ethanol. Some natural latex gloves showed a low rate of leakage, while vinyl and nitrile gloves were penetrated quickly and to a great extent. The synthetic elastomer (Biogel Neotech) was the only one with a significantly lower penetration even after 2-8 h. SIGNIFICANCE: While there are reports of adverse skin reactions to alcohol the amount of ethanol (up to 40 microliters after 2 h) detected in this study is much too low to cause irritations and certainly not toxicity, but it could possibly initiate allergic reactions.

Analysis of Variance↗

PubMed2000

Coronary oxygen persufflation combined with HTK cardioplegia prolongs the preservation time in heart transplantation.

BACKGROUND: One of the most restricting factors remaining in heart transplantation is the limited myocardial ischemia time. A new approach towards the prolongation of this time is the combination of primary cardioplegic arrest followed by continuous coronary oxygen persufflation (COP) with gaseous oxygen. METHODS: This technique was applied in pig hearts, which we transplanted orthotopically after cardioplegic arrest by original (n = 5) and modified (addition of hyaluronidase: n = 11) Bretschneider HTK solution and 14 h of hypothermic preservation. Depending on the different preservation techniques, we created four groups: (1), original HTK (HTK), n = 5; (2), modified HTK (mHTK), n = 5; (3), modified HTK solution plus COP (mHTK + COP), n = 6; and (4), as a control five hearts were transplanted after cardioplegic arrest by the original HTK solution and a cold ischemia time of 3 h comparable to clinical routine procedure. RESULTS: After 14 h of preservation and orthotopic transplantation, cardiac functional recovery in mHTK + COP hearts was similar to control hearts, and improved compared to hearts of both other groups. Hemodynamics were significantly better in hearts preserved by mHTK + COP and in the control group compared to the HTK-hearts (P < 0.05), not significant compared to mHTK hearts (dp/dt(max) in % of preoperative +/- standard error of mean (SEM): mHTK + COP, 85 +/- 9; control, 85 +/- 10.5; mHTK, 59 +/- 14; HTK, 50 +/- 4). The cardiac output (CO) in % of preoperative was: mHTK + COP, 68 +/- 5.4; control, 64 +/- 4; mHTK, 44 +/- 2.7; HTK, 25 +/- 11. The ATP of left ventricular myocardium in mHTK + COP hearts at 14.7 +/- 1 micromol/g dry weight (DW) and in the control at 14.59 +/- 1.8 was higher compared to that in mHTK at 12.2 +/- 2.8 (P is non-significant (n.s.) versus mHTK + COP and control) and in HTK-hearts at 7.0 +/- 0.5 (P < 0.05 versus mHTK + COP and control). CK-MB in percent of CK showed no increase in either group. CONCLUSIONS: These data show that COP combined with a mHTK solution represents a potential alternative to complement currently used cold storage techniques for prolonged preservation periods.

Animals↗

PubMed2000

Incidence of intravenous site reactions in neurotrauma patients receiving valproate or phenytoin.

OBJECTIVE: To determine the incidence of intravenous site reactions to phenytoin and valproate in a large population of patients with neurotrauma. DESIGN: Retrospective chart review of two double-blind, randomized clinical trials evaluating the use of antiepileptic drugs to prevent posttraumatic seizures in patients with neurotrauma: phenytoin versus placebo (n = 390), and valproate versus phenytoin with placebo (n = 385). Information collected from the charts included the number, type, and location of intravenous lines and intravenous site events. SETTING: Tertiary care trauma and university teaching hospital. MAIN RESULTS: Intravenous site reactions occurred in 18% and 25% of patients receiving valproate or phenytoin, respectively, with the majority of events (70%) occurring in the first intravenous site. Patients received the neurosurgery study drug (NSSD) by either central or peripheral lines; all intravenous site reactions occurred in peripheral administration sites. When patients who received the drug by central line during the course of therapy were excluded, the estimated incidence of site reactions was 21% and 30% for valproate and phenytoin, respectively (p = 0.056). The time to the first event was shorter with phenytoin compared with valproate (2.0 +/- 1.3 vs. 3.0 +/- 1.9 d; p = 0.009). Fewer adverse events were noted with phenytoin in the phenytoin-without-valproate study than in the phenytoin-with-valproate study, with 4.3% and 8.2% of intravenous site events recorded in patients receiving placebo or phenytoin, respectively. There was no significant difference in the number of intravenous lines per patient used during NSSD drug infusion for phenytoin versus placebo or phenytoin versus valproate. CONCLUSIONS: Both intravenous phenytoin and valproate resulted in intravenous site reactions, with the loading doses responsible for the majority of the events.

Adult↗

PubMed1999

Intracoronary shunt insertion prevents myocardial stunning in a juvenile porcine MIDCAB model absent of coronary artery disease.

OBJECTIVE: The relevance of regional LV myocardial ischemia/reperfusion induced by temporary left anterior descending (LAD) coronary artery occlusion during minimally invasive direct coronary artery bypass (MIDCAB) grafting is controversial. The purpose of our study was (1) to determine the impact of conventional LAD occlusion during left internal thoracic artery (LITA)-LAD anastomosis on regional LV myocardial ischemia and function, and (2) to evaluate if intra-LAD shunt insertion during LITA-LAD anastomosis prevents potential regional LV ischemia and dysfunction in a pig model. METHODS: In 20 anesthetized, mechanically ventilated pigs we performed LITA-LAD anastomosis on the beating heart without cardiopulmonary bypass during either 15 min LAD occlusion (occlusion-group; n = 10) or 15 min intra-LAD shunt insertion to maintain blood supply to the myocardium beyond the anastomosis (shunt-group; n = 10). Besides standard hemodynamics we determined the global and regional LV wall motion score index (WMSI) using epimyocardial echocardiography. To quantitate structural myocardial alteration we determined the inducible heat-shock protein-70 (HSP-70) in LV anterior wall myocardial biopsies. Data were recorded at baseline, at 15 min of LAD occlusion or shunt insertion, respectively, and at 30 min of reperfusion. At the end of the experiments we determined myocardial adenine nucleotide (ATP, ADP, AMP) and glycogen content. RESULTS: In both groups WMSI was not significantly different at 15 min LAD occlusion or shunt insertion, respectively, as compared to baseline. However, at 30 min reperfusion both global and regional WMSI demonstrated significant LV dysfunction in the occlusion-group, whereas LV function in the shunt-group remained normal. This was associated with higher myocardial HSP-70 expression in the occlusion-group (P < 0.05). Myocardial adenine nucleotide and glycogen contents were significantly better preserved in the shunt-group. CONCLUSIONS: Our data show that in a porcine MIDCAB model 15 min LAD occlusion and 30 min reperfusion result in significant myocardial stunning. In contrast, maintenance of LAD perfusion using intracoronary shunt insertion minimizes ischemia/reperfusion injury and prevents regional LV dysfunction. Although our experiments were conducted in healthy pig hearts absent from coronary artery disease, similar results may--at least partially--be expected in humans, and thus, intracoronary shunts could be a useful tool for myocardial protection during 'off-pump revascularization'.

Adenine Nucleotides↗

PubMed1999

Saturable transport of gabapentin at the blood-brain barrier.

Gabapentin readily crosses the blood-brain barrier and concentrates in brain tissue via an active transport process believed to be system-L. Blood-brain barrier system-L has a low K(m), making it particularly susceptible to substrate saturation. The purpose of this study was to determine whether the fraction of gabapentin crossing the blood-brain barrier remains constant over a broad range of doses. Using a rat model, microdialysis techniques were employed to determine if fluctuations in gabapentin concentrations in the brain extracellular fluid (ECF) coincided with proportional changes in plasma concentrations. Area under the concentration-time curve was calculated for plasma (AUCplasma) and brain extracellular fluid (AUCECF). The ratios of AUFECF to AUCplasma (AUCratio) and brain extracellular fluid to midpoint plasma gabapentin concentration for each collection interval (Cratio) were determined to provide indicators of the relative (i.e. fractional) amount of gabapentin crossing the blood-brain barrier. Analysis of the association between AUCECF and AUCplasma using linear regression analysis revealed a small, but significant relationship (r = 0.62; p < 0.01). Although higher AUCECF values were obtained with higher AUCplasma values, changes in AUCECF were less than proportional to observed changes in AUCplasma. Blood-brain barrier saturation of gabapentin transport was evident as the AUCratio decreased with increased AUCplasma. Collectively, these results support a trend towards saturation at higher plasma concentrations of the carrier-mediated transport mechanism of gabapentin through the blood-brain barrier.

Acetates↗

PubMed1998

Excellent recovery after prolonged heart storage by preservation with coronary oxygen persufflation: orthotopic pig heart transplantations after 14-hr storage.

BACKGROUND: Improvement of heart preservation is still the greatest challenge in preservation research. The unchanged severe restriction of acceptable storage periods of heart grafts since the beginning of clinical heart transplantation indicates that technical innovations are necessary if a substantial improvement is to be achieved. METHODS: Here, we present the results of hypothermic preservation using the innovative technique of coronary oxygen persufflation (COP). COP simply adds gaseous oxygen to hypothermic graft storage and requires only a "valve guard" for reversible closure of the aortic valve. Fourteen-hr preservation was followed by orthotopic transplantation and evaluations of functional as well as metabolic recovery. Mature pig hearts, a model with restricted preservation tolerance similar to the human heart, were used to guarantee the clinical relevance of this study. RESULTS: After 14-hr hypothermic storage, COP-preserved hearts were able to recover within 2 hr of cardiopulmonary bypass to a steady cardiovascular function without mechanical or pharmacologic support. The left ventricular pressure amplitude of mHTK-COP-preserved hearts as well as energy charge potential recovered to pregrafting values and the ventricular power output to 66%. Hearts simply stored in University of Wisconsin (UW), modified Bretschneider's histidine-tryptophan-ketoglurate (mHTK), or Euro-Flush with glutathione (EFG) solution had only limited recovery, with significantly lower ventricular power output of 18%, 29% or 30% of pregrafting controls on average. CONCLUSIONS: Fourteen-hr oxygenated pig heart preservation using COP results in optimal recovery. Storage preservation in solutions containing hyaluronidase (mHTK and EFG) results in higher recoveries as compared to UW solution, an effect that may support the excellent recovery after mHTK-COP preservation.

Adenosine↗