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Biomedical subjects

J Drewe

Publications and source records attributed to J Drewe.

At least 73 records · Page 4Linked to original sources
PubMed1998

Hemodynamic effects of the somatostatin analog lanreotide in humans: placebo-controlled, cross-over dose-ranging Echo-Doppler study.

Because of their vasoactive effects, somatostatin and its analogs are increasingly used in the management of complications of chronic liver diseases such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow, subsequently increasing portal pressure. The aim of this study was to explore effects of the somatostatin analog, lanreotide, on food-stimulated hemodynamic parameters in healthy human subjects. A dose-response curve was constructed in eight healthy male subjects in a placebo-controlled cross-over study. On 4 different days, either 0 (placebo), 50, 100, or 200 microg/h of lanreotide was infused intravenously in random order, starting at 45 minutes for 7 hours. On each day, a liquid test meal (Ensure plus, 1.5 kcal/mL) was perfused intraduodenally at a rate of 3 mL/min over 7 hours after a 45-minute basal period. Diastolic arterial pressure (dBP), heart rate (HR), superior mesenteric arterial (SMA) average flow velocity (SMA-V), SMA pulsatility index (SMA-PI), portal venous volume flow (PV-F), and renal artery (RA) resistance index (RA-RI) were measured on regular intervals (flows using Echo-Doppler technology). Lanreotide at all doses abolished food-stimulated splanchnic hyperemia both in the SMA and PV over 7 hours. The fall in dBP and increase in HR after food perfusion were blunted under lanreotide. Food as well as lanreotide did not modify RA-RI. In summary: 1) lanreotide inhibits food-induced splanchnic hyperemia in normal subjects; 2) in parallel, systemic hemodynamic alterations to food stimulation are abolished with lanreotide; and 3) renal vascular resistance is unchanged. Because of its persistent splanchnic vasoconstrictive effect, lanreotide should be tested in patients with portal hypertension.

Adult↗
PubMed1998

Propofol reduces succinylcholine induced increase of masseter muscle tone.

PURPOSE: Succinylcholine is known to increase the tone of the masseter muscles. As excessive jaw tension may complicate rapid sequence induction, we investigated three induction techniques, all including the use of succinylcholine, with respect to masseter muscle tone, neuromuscular blockade, intubation conditions, and time course of intubation. METHODS: Sixty adult patients were allocated to one of three induction groups: Group THIO received 5 mg.kg-1 thiopentone, Group THIO/ATR received 5 mg.kg-1 thiopentone plus 0.05 mg.kg-1 atracurium for precurarization, and Group PROP received 2.5 mg.kg-1 propofol. All patients received 3 micrograms.kg-1 fentanyl and 1.5 mg.kg-1 succinylcholine. Time for induction of anaesthesia was recorded, and, after inserting a Grass Force Transducer between upper and lower incisors, jaw tone and the time course of jaw tension was recorded before and after the administration of succinylcholine. RESULTS: No differences in the onset of sleep were observed among the three groups (Group THIO 33 +/- 2 sec: THIO/ATR 30 +/- 2 sec: PROP 35 +/- 2 sec, mean +/- SE). Masseter preloads following induction of anaesthesia were similar in all three groups (THIO 16.4 +/- 2.1 N: THIO/ATR 15.1 +/- 2.0 N: PROP 12.7 +/- 1.6 N). However, after administration of succinylcholine, the increase in masseter tone was less in Groups PROP (5.0 +/- 1.1 N) and THIO/ATR (6.4 +/- 2.1 N) than in Group THIO (12.4 +/- 3.0 N; P < 0.05). CONCLUSION: Jaw tension after administration of succinylcholine is influenced by the choice of induction agent. The increase of masseter muscle tone is lower following propofol or thiopentone/atracurium induction than with thiopentone alone.

Adolescent↗
PubMed1998

Effects of losartan titrated to losartan/hydrochlorothiazide and amlodipine on blood pressure and peripheral capillary microcirculation in patients with mild-to-moderate hypertension.

OBJECTIVE: To measure the effects of losartan and amlodipine on peripheral capillary microcirculation in hypertension. SETTING: Medical out-patient clinic, Basel, in a university teaching hospital. METHODS: After a 4-week placebo run-in period 20 patients aged 50 +/- 8 (range 36-65) years with mild-to-moderate hypertension were randomly allocated to receive active treatment with losartan 50 mg titrated to losartan 50 mg/hydrochlorothiazide (HCT) 12.5 mg, or amlodipine 5 mg titrated to 10 mg for a 12 week period. Titration was performed if diastolic blood pressure (BP) was > or=90 mm Hg after 6 weeks of treatment. BP measurements as well as video capillary microscopy of the finger nailfold at the end of the placebo period and after 12 weeks of active treatment were compared. Capillary blood cell velocity was measured at rest and immediately, 1 min and 2 min after local finger cooling. RESULTS: After 3 months of treatment with amlodipine (n = 10) and losartan titrated to losartan-HCT (n = 10) sitting BP decreased significantly from 160 +/- 7/103 +/- 4 mm Hg and 147 +/- 7/98 +/- 6 mm Hg to 131 +/- 10/86 +/- 7 mm Hg and 134 +/- 17/89 +/- 9 mm Hg, respectively (P < 0.01). After local finger cooling the area under the curve (AUC) of capillary blood cell velocities was 1.13 +/- 0.58 mm (median +/- s.d.) at baseline and increased to 1.94 +/- 1.15 (P < 0.05) in losartan/losartan-HCT treated patients. In amlodipine treated patients the increase in AUC of capillary blood cell velocity did not reach the level of statistical significance (1.59 +/- 1.36 to 2.14 +/- 1.05 mm). CONCLUSION: This small trial shows that the area under the curve of capillary blood cell velocity increases in hypertensive patients treated with both losartan/losartan-HCT and amlodipine compared with baseline values.

Adult↗
PubMed1998

General anaesthesia for surgery can influence circulating melatonin during daylight hours.

BACKGROUND: Both melatonin and anaesthetics have been shown to affect sleep and behaviour. The effect of general anaesthesia on circulatory melatonin has not been reported, but anaesthetic-related alterations in hormone profiles are known. We hypothesize that differences in recovery from anaesthesia may be associated with differences in circulatory melatonin levels because of melatonin's sedative effect in humans. METHODS: The influences of general anaesthesia and surgery on circulating melatonin, prolactin, and cortisol concentration were investigated in 32 female patients scheduled for elective gynaecological surgery to study differences in hormone profiles and responses during anaesthesia and the recovery period. Patients were randomly assigned to one of two groups. General anaesthesia was induced with either thiopentone/fentanyl (Group 1: n = 16) or propofol/fentanyl (Group 2: n = 16). Maintenance of anaesthesia was achieved with either isoflurane (0.8-1.0 vol%)/fentanyl (Group 1) or propofol (6 mg.kg-1.h-1)/fentanyl (Group 2) with a N2O/O2 flow ratio of 2:1 in both groups. During anaesthesia, patients' eyes were carefully taped shut to prevent light effects. Blood samples were taken before and after premedication, immediately before induction of anaesthesia, every 15 min during anaesthesia, and hourly in the recovery room for 8 h. The control group consisted of 6 healthy women who were not subjected to surgery, but who were in a similar environment, including light conditions, as the study groups. RESULTS: Isoflurane and propofol anaesthesia as well as darkness elicited elevated plasma melatonin levels that persisted in the recovery period in patients anaesthetized with isoflurane, but gradually decreased during the recovery of patients anaesthetized with propofol. Circulating prolactin and cortisol values were also elevated during anaesthesia and had similar decreases during the recovery period. CONCLUSION: Higher plasma levels of melatonin during the recovery period following isoflurane anaesthesia may, in part, explain increased sedation in these patients compared with patients who received propofol anaesthesia. However, the relationship between recovery from anaesthesia and plasma melatonin levels may not be simple and straightforward.

Adult↗
PubMed1998

Transport of the beta-lactam antibiotic benzylpenicillin and the dipeptide glycylsarcosine by brain capillary endothelial cells in vitro.

Peripherally administered beta-lactam antibiotics, which are structural analogs of tripeptides, may cause neurotoxic reactions or induce seizures. Previous in vivo studies provided evidence for brain uptake of these antibiotics. In the present work, we studied the extent and mechanism of the uptake of benzylpenicillin and glycylsarcosine by brain microvessel endothelial cells in vitro, using freshly isolated and cultured porcine brain capillary endothelial cells. Characterization of the cell culture model demonstrated the functional expression of the system transporting the neutral amino acids leucine and phenylalanine. The initial rate of uptake of benzylpenicillin was >3-fold greater than the rate of uptake of the extracellular marker sucrose (ratio, 3.29 +/- 0.37), whereas uptake of glycylsarcosine did not differ from that of sucrose. The differences in cellular uptake correlated with the octanol/buffer partition coefficients for glycylsarcosine and benzylpenicillin (1.16 x 10(-3) for glycylsarcosine and 6.83 x 10(-2) for benzylpenicillin). The concentration-dependent uptake of benzylpenicillin (1-2000 microM) was not saturable and was not sensitive to shifts in pH or temperature. The permeability-surface area product for the uptake of benzylpenicillin at pH 7.4 was determined from these experiments and was found to be 8.1 x 10(-5) ml/sec/g of brain. This value was very close to the value determined in in vivo studies. Uptake of benzylpenicillin and glycylsarcosine was not reduced in the presence of 1 mM ceftibuten or 100 microM probenecid. The findings with cultured cell monolayers were confirmed using freshly isolated endothelial cells. These in vitro data are compatible with benzylpenicillin, but not glycylsarcosine, being able to penetrate endothelial cells. Uptake of benzylpenicillin by brain capillary endothelial cells occurs by a slow nonsaturable process, with no evidence for carrier-mediated transport.

Animals↗
PubMed1997

High-performance liquid chromatographic method for an automated determination of local anaesthetics in human plasma.

A method is described that allows the rapid and precise determination of the local anaesthetics bupivacaine and etidocaine from biological fluids. This method uses a fully automated system with solid-phase extraction in combination with a column-switching technique. Both sample extraction on a LiChrocart pre-column and elution onto the analytical LiChrospher column, were performed automatically and concomitantly using conventional HPLC equipment in conjunction with an OSP-2 on-line sample preparator from Merck combined with UV detection. Recoveries were found to be 96.7 and 96.4% for 2 micrograms/ml bupivacaine and etidocaine, respectively. Lower limits of quantification were found to be 0.05 microgram/ml plasma for both of the compounds.

Anesthetics, Local↗
PubMed1997

Diagnostic and therapeutic thoracic surgery in leukemia and severe aplastic anemia.

BACKGROUND: Pulmonary complications often occur in patients with leukemia and severe aplastic anemia. Particularly in patients having undergone bone marrow transplantation, respiratory diseases account for a significant number of deaths. In a retrospective study, we evaluated 41 patients with leukemia and severe aplastic anemia who were operated on consecutively from 1980 to 1995. METHODS: Fourteen open lung biopsies, four video-assisted lung biopsies, and 24 lung resections were performed in 24 male and 17 female patients. Mean age was 32.2 years. RESULTS: Eleven (27%) early deaths occurred (30-day mortality): ten in patients after lung biopsy (56%) and one after lung resection (4%) (p < 0.001). Perioperative morbidity relating to pulmonary disease or operation included 10 (24.4%) cases of prolonged (> 24 hours) postoperative mechanical ventilation and two (4.8%) cases of bleeding or hematoma. In one (2.4%) patient a slowly developing, contained bronchial stump insufficiency appeared after lobectomy, which was successfully operated on 3 weeks later. CONCLUSION: We conclude that resection of localized pulmonary lesions, be it for diagnostic or therapeutic (or combined) purposes, can be carried out with low morbidity and mortality in patients with leukemia and severe aplastic anemia. However, early mortality is high after open or thoracoscopic lung biopsies in patients with acute-onset diffuse pulmonary disease, and little therapeutic benefit is realized in these cases.

Adolescent↗
PubMed1997

Enterohepatic circulation of scymnol sulfate in an elasmobranch, the little skate (Raja erinacea).

The sulfated bile alcohol scymnol sulfate (ScyS), 3 alpha,7 alpha,12 alpha,24 xi, 26,27-hexahydroxy-5 beta-cholestane-26(27)-sulfate, is the major bile salt in bile of an elasmobranch, the little skate. To investigate hepatic transport of bile alcohols in skate liver, [3H]ScyS and a potential precursor, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane (chtriol), were used as model compounds. Their transport into isolated hepatocytes was partially saturable, temperature sensitive, and Na+ independent. The uptake of ScyS was inhibited by cholyltaurine, and uptake of cholyltaurine was inhibited by ScyS in a competitive manner. In contrast, uptake of chtriol was not inhibited by cholyltaurine, suggesting separate transport systems. ScyS and chtriol showed a choleretic effect in isolated perfused livers. When ScyS was added to the perfusate of isolated perfused livers, > 25% was found in bile within 7 h. When chtriol was added to the perfusate, 10% of the dose was secreted into the bile mainly in the form of polar metabolites, whereas only nonmetabolized chtriol remained in the livers. The slow bile flow of 40-50 microliters/h and the high recovery in the liver suggest that metabolism may be the rate-limiting step in the hepatic elimination of chtriol. The major metabolites secreted into bile were identified by mass spectrometry and chromatography as scymnol and ScyS. To study the enterohepatic circulation, [3H]ScyS or [3H]chtriol was administered into the duodenum of free-swimming skates, and bile was collected through exteriorized indwelling cannulas over a 4-day period. More than 90% of the radioactivity was recovered from bile, indicating that there was a highly effective absorption in the intestinal epithelium, as well as specific transport mechanisms for hepatic uptake and biliary secretion of these compounds. This is the first direct demonstration of an enterohepatic circulation for a bile alcohol sulfate in fish liver.

Animals↗
PubMed1997

Transport of clonidine across cultured brain microvessel endothelial cells.

Brain penetration of clonidine, an alpha-2 adrenoceptor agonist, was studied using an in vitro cell culture system consisting of primary cultures of porcine brain capillary endothelial cells. Uptake of clonidine was measured as a function of its concentration in the incubation mixture. Saturation of uptake was apparent and could be described by Michaelis-Menten-type kinetics (K(M) = 1.34 mM; Vmax = 0.099 nmol/min/cm2). Saturation was not observed at a low temperature (4 degrees C). Transendothelial transport experiments revealed that translocation of clonidine cannot be attributed solely to paracellular leakage. Uptake was reduced at low extracellular pH or by using an incubation buffer that contained the K+ ionophore valinomycin. Time-dependent uptake of clonidine and transendothelial transport were slower than expected considering the high octanol-to-buffer partition coefficient of this compound. On the basis of transendothelial transport experiments, we concluded that the carrier system responsible for active transport of clonidine is located at both the apical and the basolateral membrane domain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

p-Glycoprotein-mediated transport of a fluorescent rapamycin derivative in renal proximal tubule.

The transport of a fluorescent rapamycin derivative was measured in killifish (Fundulus heteroclitus) renal proximal tubules by means of confocal microscopy and image analysis. Renal cells and tubular lumens rapidly accumulated the rapamycin analog from the medium and attained steady state within 60 min. At steady state, luminal fluorescence intensity was two to four times higher than cellular fluorescence. Cellular fluorescence intensity was a linear function of medium substrate concentration and was not affected by any treatment used. In contrast, luminal fluorescence exhibited a saturable component as the medium concentration of the rapamycin derivative was increased. Secretion into the lumen was blocked by KCN, rapamycin, cyclosporin A and substrates for p-glycoprotein (verapamil, PSC-833 and FK506), but not by substrates for the renal organic anion or organic cation transport systems, such as p-aminohippurate, leukotriene C4 or tetraethylammonium. Finally, rapamycin blocked p-glycoprotein-mediated secretion of a fluorescent cyclosporin A derivative. The data are consistent with the fluorescent rapamycin analog entering proximal tubule cells by simple diffusion and then being pumped into the tubular lumen by p-glycoprotein. They suggest that the parent compound, rapamycin, would be handled similarly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Experimental data on the interactions of alpha 2-adrenoceptor agonists with anaesthetics, analgesics and local anaesthetics].

The interactions of alpha(2)-adrenoceptor agonists with anaesthetics, analgesics and local anaesthetics are not only of practical importance in many areas of anaesthesia and pain therapy, but also of significant theoretical interest. Laboratory investigations and animal research allow us to study the pharmacological mechanisms of these drug interactions by using the tools of molecular biology. This may lead to the establishment of a scientific basis allowing the definition of rational drug therapies. In the first part of this overview, recent data on local anaesthetic effects of alpha(2)-adrenoceptor agonists on peripheral nerve conduction and their interaction with local anaesthetics are presented. Some important experimental work focusing on additive and synergistic spinal interactions of alpha(2)-adrenoceptor agonists with opioids and some other agents are then discussed. Finally, there is a brief reference to the central role of the spinal cord in mediating and controlling nociception.

English Abstract↗
PubMed1996

Comparison of cyclosporin A absorption from LCT and MCT solutions following intrajejunal administration in conscious dogs.

Absorption from the intestine of cyclosporin A (CsA), dissolved in either a medium-chain (MCT) or a long-chain triglyceride (LCT) solution, was investigated in a chronic dog model. Following intrajejunal administration of 20 mg of CsA/kg of body weight, absorption, judged by the portalvenous appearance of CsA, was determined by measuring whole blood CsA concentrations in the portalvenous and arterial blood and the portalvenous flow. Appearance of CsA from LCT commenced earlier and attained significantly higher mean peak values (+/- SEM) in the portalvenous blood (2557 +/- 436 ng/mL) than from MCT (274 +/- 80 ng/mL). Portalvenous concentrations of CsA were always higher than arterial concentrations for both LCT and MCT, suggesting that CsA is transported by portalvenous blood following uptake from the gut. Absorption of CsA, measured over 300 min, was 10 times higher with LCT (9.96 +/- 2.00%) than with MCT (0.95 +/- 0.21%). This significant difference is believed to result from the formation of mixed micelles which occurs during digestion of LCT but not MCT.

Animals↗
PubMed1996

A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine.

Recent reports suggest that transient neurologic symptoms are common after spinal anesthesia with 5% lidocaine. To determine whether reducing the anesthetic concentration might decrease the incidence of symptoms, 50 ASA class I or II patients undergoing brief gynecologic procedures under spinal anesthesia were randomly allocated to receive 1 mg/kg of either 5% or 2% lidocaine in 7.5% glucose. Patients were evaluated on the first postoperative day by an anesthesiologist who was unaware of the solution administered or the details of the anesthetic procedure. Symptoms suggestive of transient radicular irritation were observed in 8 patients (32%) receiving 5% lidocaine, and in 10 patients (40%) receiving 2% lidocaine (NS). These results confirm our previous findings that transient neurologic symptoms may occur in up to one third of the patients receiving 5% lidocaine, and indicate that a modest reduction in lidocaine concentration does not reduce risk.

Adult↗
PubMed1996

Intravenous sedation for retrobulbar injection and eye surgery: diazepam and/or propofol?

Principle goals of sedation for eye surgery are to provide patient comfort and to allow the patient to stay calm during both retrobulbar injection and surgery. Insufficient sedation may not prevent the patient from moving during retrobulbar injection, whereas very deep sedation may result in respiratory complications during surgery. The aim of the present study was to evaluate the effectiveness and suitability of a combination of diazepam and propofol for sedation for both application of retrobulbar block and subsequent elective eye surgery. One-hundred and fifty patients were randomly allocated to receive either diazepam, propofol or a combination of both drugs before retrobulbar injection. Tolerance of retrobulbar injection and comfort during the surgical procedure were assessed by comfort scores using a nominal analogue scale between 1 (worst possible condition) and 6 (best conceivable condition). Side effects related to sedation were recorded. The combination of diazepam and propofol resulted in the highest comfort scores for both retrobulbar block (5.3 +/- 0.3) and the surgical procedure (5.4 +/- 0.4). Diazepam alone did not produce adequate sedation for retrobulbar block (3.1 +/- 0.3), whereas comfort scores during surgery were significantly higher (5.3 +/- 0.3) compared to propofol alone (3.6 +/- 0.4). No severe side effects induced by sedation were noted in any of the study groups. The combination of diazepam and propofol proved able to provide a reliable degree of sedation with minimal side effects for both retrobulbar block and surgery. The combination was clearly superior to the sedation induced by propofol or diazepam alone.

Adult↗