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Biomedical subjects

M Behne

Publications and source records attributed to M Behne.

At least 19 recordsLinked to original sources
PubMed2005

Extracellular pH Controls NHE1 expression in epidermis and keratinocytes: implications for barrier repair.

We have previously shown that the Na+/H+ antiporter (NHE1) is an essential endogenous pathway responsible for stratum corneum (SC) acidification. Since the epidermis must re-establish its epidermal barrier after acute barrier perturbations, we asked whether the NHE1 was, in turn, regulated by changes in barrier status. We found that in vivo epidermal NHE1 expression was upregulated within hours of barrier disruption. We next asked whether NHE1 was regulated by barrier status per se, or by the SC alkalinization that accompanies barrier perturbation. NHE1 was upregulated by alkalinizing SC pH, whereas this antiporter was downregulated by acidifying SC pH, independent of changes in barrier status. Moreover, acidifying SC pH overrode the effects of barrier break in regulating NHE1 expression, suggesting that SC alkalinization is the major stimulus for increased NHE1 expression. Finally, we confirmed that the keratinocyte NHE1 antiporter is regulated by extracellular pH independent of barrier status, by demonstrating that NHE1 was upregulated in cultured keratinocytes exposed to pH 8.3 medium and downregulated in cultured keratinocytes exposed to pH 6.3 medium. These data suggest that the keratinocyte NHE1 is regulated by extracellular pH. SC barrier break also upregulates NHE1 expression, but this response seems to be mediated by concomitant changes in SC pH.

Animals↗
PubMed2002

The ENaC channel is required for normal epidermal differentiation.

Ionic fluxes are important for critical aspects of keratinocyte differentiation, including synthesis of differentiation-specific proteins, enzymatic catalysis of protein cross-linking, post-transcriptional processing of profilaggrin, and lipid secretion. The epithelial sodium channel is expressed in epidermis and the expression of its alpha and beta subunits is enhanced as keratinocytes differentiate. In order to ascertain the role of the epithelial sodium channel in epidermal differentiation, we examined skin of mice in which the epithelial sodium channel alpha subunit had been deleted. Newborn -/- mice, in which the alpha subunit had been completely inactivated, demonstrated epithelial hyperplasia, abnormal nuclei, premature secretion of lipids, and abnormal keratohyaline granules. In addition, immunohistochemistry demonstrated that expression of the differentiation markers K1, K6, and involucrin were abnormal. These data suggest that the epithelial sodium channel modulates ionic signaling for specific aspects of epidermal differentiation, such as synthesis or processing of differentiation- specific proteins, and lipid secretion.

Animals↗
PubMed2001

[Postoperative pain therapy in pediatrics. Results of a representative survey in Germany].

The last survey addressing postoperative pain management in Germany was published in 1987, special data concerning postoperative pain management in pediatric patients had not been presented previously. The goal of this survey is to present the standard of postoperative pain management in pediatric patients in Germany. A detailed questionnaire was mailed to all German anaesthesia departments and interdisciplinary intensive care units (n = 1,500) to determine the current management of postoperative pain management in pediatric patients. After eight weeks, 42.6% of the survey had been returned. Rectally administered acetaminophen is the standard drug regimen for postoperative analgesia in children. Compared to previous surveys, the use of opioids has increased in popularity. The routine use of non-steroid antiinflammatory drugs (NSAIDs) and spasmolytics as well as the application of regional anaesthesia techniques is uncommon in pediatric postoperative pain management. Compared to other European countries, patient- or parent-controlled analgesia is more popular in Germany. Despite modern concepts of organization and a great variety of drugs available today, 71.1% of the responding anesthesiologists in this survey still believe that pediatric postoperative pain management needs to be improved.

Analgesics↗
PubMed2001

Vitamin C stimulates sphingolipid production and markers of barrier formation in submerged human keratinocyte cultures.

Human keratinocytes differentiate in vitro in response to a variety of stimuli, but neither the levels nor the spectrum of ceramides approach those seen in vivo. Ceramide production increases when human keratinocytes are grown at an air-liquid interface, and alterations in ceramide content occur when vitamin C is added to air-exposed, organotypic culture systems (Ponec et al. J Invest Dermatol 109:348, 1997). Here, we assessed whether vitamin C stimulates sphingolipid production in human keratinocytes independent of differentiation and air exposure. When submerged, human keratinocytes were grown in 1.2 mM calcium and serum-containing medium with vitamin C (50 microg per ml) for 9 d, total lipid content remained unchanged, but both glucosylceramide and ceramide content increased. Moreover, selected ceramide and glucosylceramide species: i.e., nonhydroxy ceramide 2 and both alpha- and omega-hydroxylated sphingolipids, increased preferentially [ceramide 4 (6-hydroxy-acylceramide), ceramide 5 (alpha-hydroxyceramide), ceramide 6 (4-hydroxy-alpha-hydroxyceramide), and ceramide 7 (6-hydroxy-alpha-hydroxyceramide); and acylglucosylceramide, glucosylceramide-B, and glucosylceramide-D], whereas ceramide 1, ceramide 3, glucosylceramide-C, and sphingomyelin remained unchanged. Synthesis of the corresponding ceramide and glucosylceramide fractions was enhanced by vitamin C, attributable, in part, to increased ceramide synthase activity (over 2-fold, p = 0.01); both serine palmitoyltransferase and glucosylceramide synthase activities remained unaltered. Finally, increased vitamin C-stimulated sphingolipid production correlated with the presence of lamellar bodies with mature internal contents, an increase in covalently bound omega-hydroxyceramide, and the appearance of prominent, corneocyte-bound lipid envelopes, whereas cornified envelope formation was unchanged. Thus, in submerged human keratinocytes, vitamin C induces both increased sphingolipid production and enhancement of permeability barrier structural markers.

Ascorbic Acid↗
PubMed2001

Prophylactically-administered rectal acetaminophen does not reduce postoperative opioid requirements in infants and small children undergoing elective cleft palate repair.

UNLABELLED: Rectal acetaminophen (Ac) is often administered prophylactically at anesthesia induction for postoperative pain management in small children and is thought to have an opioid-sparing effect. We assessed in this double-blinded, prospective, randomized study early opioid requirements after three doses of Ac (10, 20, and 40 mg/kg versus placebo) in 80 children (ASA physical status I, age 11.4 +/- 9.9 mo) undergoing cleft palate repair. Single Ac plasma concentrations were measured. Pain scores assessed in the postanesthesia care unit of > or = 4 of 10 resulted in the IV administration of 25 microg/kg piritramide, a popular European mu receptor agonist (lockout time, 10 min; maximum 0.125 mg/kg). There were no significant differences between groups with regard to the early postoperative pain scores and the overall cumulative IV opioid requirements. Maximal plasma concentrations achieved were only subtherapeutic (Ac 10 mg/kg: 8 microg/mL; Ac 20 mg/kg: 13 microg/mL; Ac 40 mg/kg: 21 microg/mL after 122, 122, and 121 min, respectively). We conclude that rectal Ac up to 40 mg/kg has no opioid-sparing effect, does not result in analgesic Ac plasma concentrations, and lacks proof of its efficacy in infants and small children undergoing cleft palate repair, whereas titrated IV opioid boluses produced rapid and reliable pain relief. IMPLICATIONS: Acetaminophen is widely used prophylactically for postoperative analgesia in children and is thought to have an opioid-sparing effect. We showed that rectal acetaminophen up to 40 mg/kg administered at anesthesia induction lacked proof of efficacy, whereas IV opioid boluses resulted in reliable pain relief in children undergoing cleft palate repair.

Acetaminophen↗
PubMed2000

[The use of lithium hydroxide for carbon dioxide absorption prevents formation of compound A during sevoflurane anesthesia].

UNLABELLED: Aim of the study was the clinical investigation of sevoflurane degradation when using water-free lithiumhydroxide versus moist Drägersorb 800 for carbon dioxide absorption. METHODS: Concentrations of Compound A in the inspiratory gas mix and serum fluoride levels were measured in two groups of 8 patients each. RESULTS: When water-free lithiumhydroxide was used for carbon dioxide absorption, concentration of Compound A in the inspiratory gas mix was ca. 1 ppm (near minimal level of detection) as compared to ca. 20 ppm for moist Drägersorb 800. The concentration of fluoride increased during sevoflurane anesthesia (15.0 +/- 4.8 mumol/l with lithiumhydroxide versus 21.9 +/- 4.0 mumol/l with Drägersorb 800 after 60 mins). CONCLUSIONS: When lithiumhydroxide is used, there is only minimal formation of compound A from sevoflurane degradation. Since serum fluoride levels increased in both patient groups, we conclude that this is caused mainly by metabolism of sevoflurane. Capacity of lithiumhydroxide for carbon dioxide absorption is similar to that of Drägersorb 800. Therefore, the use of lithiumhydroxide increases patient safety.

Absorption↗
PubMed2000

Omega-hydroxyceramides are required for corneocyte lipid envelope (CLE) formation and normal epidermal permeability barrier function.

Omega-hydroxyceramides (omega-OHCer) are the predominant lipid species of the corneocyte lipid envelope in the epidermis. Moreover, their omega-esterified-derivatives (acylCer) are major components of the stratum corneum extracellular lamellae, which regulate cutaneous permeability barrier function. Because epidermal omega-OHCer appear to be generated by a cytochrome P450-dependent process, we determined the effects of a mechanism-based inhibitor of omega-hydroxylation, aminobenzotriazole (ABT), on epidermal omega-OH Cer formation and barrier function. We first ascertained that ABT, but not hydroxybenzotriazole (OHBT), a chemical relative with no P450 inhibitory activity, inhibited the incorporation of [14C]-acetate into the omega-OH-containing Cer species in cultured human keratinocytes (68.1% +/- 6.9% inhibition versus vehicle-treated controls; p < 0.001), without altering the synthesis of other Cer and fatty acid species. In addition, ABT significantly inhibited the omega-hydroxylation of very long-chain fatty acids in cultured human keratinocytes. Topical application of ABT, but not OHBT, when applied to the skin of hairless mice following acute barrier disruption by tape-stripping, resulted in a significant delay in barrier recovery (e.g., 38.3% delay at 6 h versus vehicle-treated animals), assessed as increased transepidermal water loss. The ABT-induced barrier abnormality was associated with: (i) a significant decrease in the quantities of omega-OHCer in both the unbound and the covalently bound Cer pools; (ii) marked alterations of lamellar body structure and contents; and (iii) abnormal stratum corneum extracellular lamellar membrane structures, with no signs of cellular toxicity. Furthermore, pyridine-extraction of ABT- versus vehicle-treated skin, which removes all of the extracellular lamellae, leaving the covalently attached lipids, showed numerous foci with absent corneocyte lipid envelope in ABT- versus vehicle-treated stratum corneum. These results provide the first direct evidence for the importance of omega-OHCer for epidermal permeability function, and suggest further that acylCer and/or corneocyte lipid envelope are required elements in permeability barrier homeostasis.

Administration, Topical↗
PubMed2000

Pharmacodynamics and tolerability of acetyl starch as a new plasma volume expander in patients undergoing elective surgery.

OBJECTIVE: Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase II clinical trials. We compared the pharmacodynamics and tolerability of ACS with those ofhydroxyethyl starch (HES) in 32 patients (American Society of Anesthesiologists physical status I and II) undergoing elective surgery. SUBJECTS, MATERIAL AND METHODS: In this prospective, randomized, double-blind trial patients received either 15 ml/kg ACS 6% (average molecular weight (Mw) 200,000/molar substitution (MS) 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximum dose of 1000 ml. Hemodynamic parameters, rheologic parameters, volume effect, acid-base status as well as effects on hemostasis were studied. RESULTS: After infusion of ACS and HES there was a similar increase in central venous pressure and mean arterial pressure in both groups. Acid-base status was not significantly altered after the end of the colloid infusions. After ACS infusion, plasma acetate concentration increased from 0.13+/-0.16 mg/dl to 2.87+/-1.13 mg/dl, however, after 24 h there was no significant difference in plasma acetate concentration compared to HES. The volume effect ranged from 104-116%(ACS) and from 88-118% (HES) of the colloid dose administered. These differences were not statistically significant. Partial thromboplastin time (aPTT) was only slightly increased after ACS infusion (from 38.6+/-5.7 sec to 41.4+/-5.1 sec), but was significantly increased after HES infusion (from 38.7+/-5.7 sec to 46.1+/-7.0 sec). CONCLUSION: ACS and HES are equally effective plasma volume expanders; ACS might be a new, alternative colloid solution with fewer coagulation side-effects than HES.

Adolescent↗
PubMed1999

[Ketoacidosis in a 14 month old child caused by fasting].

Preoperative starvation in order to prevent pulmonary aspiration is mandatory in elective pediatric surgery. Hypoglycemia, thirst and unwellness have been reported as undesired side effects. The metabolic response towards decreasing blood-glucose concentrations in fasting children includes gluconeogenesis and production of ketone bodies to meet the energetic demand. Accumulation of beta-hydroxybutyrate und acetoacetate in blood can lead to ketoacidosis. We report a case of a severe intraoperative ketoacidosis in a fourteen months old child complicating 36 hours of starvation.

Acid-Base Equilibrium↗
PubMed1999

Recovery and pharmacokinetic parameters of desflurane, sevoflurane, and isoflurane in patients undergoing urologic procedures.

STUDY OBJECTIVE: To compare the pharmacokinetics and the speed of recovery after inhalation anesthesia with desflurane, sevoflurane, and isoflurane in elective surgery. DESIGN: Prospective, randomized study. SETTING: University medical center. PATIENTS: 30 ASA physical status I and II adults presenting for elective surgery. INTERVENTIONS: Anesthesia was induced with etomidate and maintained with desflurane (n = 10), sevoflurane (n = 10), or isoflurane (n = 10) and nitrous oxide. The inhalation drugs were titrated until an adequate clinical depth of anesthesia was reached. At the end of anesthesia, the patients breathed oxygen via the endotracheal tube and after extubation via a face mask. MEASUREMENTS AND MAIN RESULTS: The groups were similar with respect to age, weight, duration of anesthesia, and mean arterial pressure. Mean end-tidal concentration (FA = FA0) at the end of anesthesia was 6.34 +/- 1.15% after desflurane, 1.85 +/- 0.42% after sevoflurane, and 1.10 +/- 0.24% after isoflurane. FA/FA0 decreased significantly faster with desflurane than with isoflurane, while there was little difference between desflurane and sevoflurane. As for the terminal half-life (t1/2), there were no differences among the groups (8.16 +/- 3.15 min after desflurane, 9.47 +/- 4.46 min after sevoflurane, and 10.0 +/- 5.57 min after isoflurane). The time until a command was followed for the first time was the same in all three groups (13.0 +/- 4.7 min after desflurane, 13.4 +/- 4.4 min after sevoflurane, and 13.6 +/- 3.4 min after isoflurane). There was no significant correlation between duration of anesthesia and the time until recovery. CONCLUSIONS: There are only minor differences with regard to the recovery phase in premedicated patients who receive clinically titrated inhalation anesthesia with desflurane, sevoflurane, or isoflurane.

Adolescent↗
PubMed1999

Carbon dioxide absorption: toxicity from sevoflurane and desflurane.

The degradation of volatile anaesthetics by desiccated carbon dioxide absorbents can result in adverse outcomes. Desiccated carbon dioxide absorbent reacting with desflurane can cause potentially life-threatening intraoperative carbon monoxide exposure; the reaction with sevoflurane can cause the formation of several toxic breakdown products, e.g. compound A. Compound A-related renal toxicity in humans is still a matter of controversy.

Journal Article↗
PubMed1999

Clinical pharmacokinetics of sevoflurane.

Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more rapid uptake and induction than the 'older' inhalational agents, improved control of depth of anaesthesia and faster elimination and recovery. The more rapid pharmacokinetics are a result of the low blood/gas partition coefficient of 0.69. With an oil/gas partition coefficient of 47.2, the minimum alveolar concentration (MAC) of sevoflurane is 2.05%. Two to 5% of the drug taken up is metabolised by the liver. The pharmacokinetics of sevoflurane do not change in children, obese patients or patients with renal insufficiency. The pharmacokinetics and pleasant odour of sevoflurane make mask induction feasible, which is an obvious advantage in paediatric anaesthesia. The hepatic metabolism of sevoflurane results in the formation of inorganic fluoride. Upon contact with alkaline CO2 absorbent, a small amount of sevoflurane is degraded and a metabolite (compound A) is formed and inhaled in trace amounts. Whether inorganic fluoride or compound A are nephrotoxic is presently a matter of controversy.

Age Factors↗
PubMed1999

[Infection or SIRS--the problem of definition].

Despite the knowledge about sepsis for many years, the definition of sepsis is contested more than ever since the early 90th. Therefore, the comparability of many clinical investigations and scientific work in the past is still impaired. To define the entrance criteria for further clinical studies, in 1991 a consensus conference was held in the USA, but its recommendations have not found unequivocal acceptance. Therefore, these recommendations are presented and their meaning will be discussed.

Diagnosis, Differential↗
PubMed1998

[Uptake and distribution of sevoflurane].

Sevoflurane is characterized by a low blood/gas partition coefficient of 0.69, only desflurane and nitrous oxide have lower blood/gas solubilities. Alveolar equilibration is fast, a feature useful for rapid induction of anesthesia. Because of its pleasant smell, mask induction is feasible and routinely used in clinical settings. Formation of inorganic fluoride by metabolism and by compound A by degradation in CO2-absorbent has not yet been shown to be nephrotoxic in humans. Pulmonal elimination of sevoflurane is rapid because of its low blood solubility. Clinical results showed that rapidity of recovery from sevoflurane anesthesia is equal to that of desflurane anesthesia. Physicochemical properties of sevoflurane allow its application in conventional vaporizers.

Anesthetics, Inhalation↗
PubMed1998

Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing.

Epidermal permeability barrier homeostasis requires the postsecretory processing of polar lipid precursors into nonpolar lipid products within the stratum corneum (SC) interstices by a family of lipid hydrolases. A specific requirement for beta-glucocerebrosidase (beta-GlcCer'ase), which exhibits a distinct acidic pH optimum, is particularly well documented. Therefore, we sought to determine whether the recovery of the barrier after acute insults requires acidification of the SC. We examined permeability barrier recovery by assessing changes in transepidermal water loss (TEWL), SC membrane ultrastructure utilizing ruthenium tetroxide (RuO4) postfixation, and beta-GlcCer'ase activity by in situ zymography at an acidic vs neutral pH. Barrier recovery proceeded normally when acetone-treated skin was exposed to solutions buffered to an acidic pH. In contrast, the initiation of barrier recovery was slowed when treated skin was exposed to neutral or alkaline pH, regardless of buffer composition. In addition, enhancement of the alkaline buffer-induced delay in barrier recovery occurred with Ca2+ and K+ inclusion in the buffer. Moreover, the pH-dependent alteration in barrier recovery appeared to occur through a mechanism that was independent of Ca(2+)- or K(+)-controlled lamellar body secretion, since both the formation and secretion of lamellar bodies proceeded comparably at pH 5.5 and pH 7.4. In contrast, exposure to pH 7.4 (but not pH 5.5) resulted in both the persistence of immature, extracellular lamellar membrane structures, and a marked decrease in the in situ activity of beta-GlcCer'ase. These results suggest first that an acidic extracellular pH is necessary for the initiation of barrier recovery, and second that the delay in barrier recovery is a consequence of inhibition of postsecretory lipid processing.

Animals↗
PubMed1998

The pharmacokinetics of acetyl starch as a plasma volume expander in patients undergoing elective surgery.

UNLABELLED: Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume expansion and is now undergoing phase 2 clinical trials. We compared the pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients (ASA physical status I and II) undergoing elective surgery. In this randomized, double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5) i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations were detected using a high-pressure liquid chromatography controlled enzymatic test. Standard pharmacokinetics were calculated, including initial half-life (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma colloid concentration at the end of drug infusion. Whereas HES was eliminated by second-order kinetics, ACS followed first-order characteristics. In the first hours after i.v. administration, t(1/2init) and clearances were similar in both groups. However, the terminal half-life of HES was significantly longer than that of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed significantly lower plasma concentrations than HES, which indicates that the final degradation of ACS by esterases and amylase was significantly more rapid. ACS might be an alternative plasma volume expander, which avoids the accumulation of persisting macromolecules. IMPLICATIONS: We studied the pharmacokinetics of acetyl starch, a newly developed colloid solution for plasma volume substitution, compared with hydroxyethyl starch in 32 surgical patients undergoing elective major general surgical procedures. In contrast to hydroxyethyl starch, this new agent undergoes rapid and nearly complete enzymatic degradation.

Adolescent↗
PubMed1998

Thoracoscopic microsurgical technique for vertebral surgery--anesthetic considerations.

BACKGROUND: The thoracoscopic microsurgical technique (TMT) for vertebral and spinal cord surgery is associated with the benefits of reduced postoperative pain, accelerated return to physical activity and reduced complication rates. However, because of the surgeon's requirement of a non-ventilated lung, it confronts the anesthesiologist with the need for extremely long duration of single-lung ventilation (SLV). METHODS: We describe our experiences with 82 patients, whom we anesthetised from 1993 until 1996 for TMT. Because of the potential risk of depression of hypoxic pulmonary vasoconstriction during SLV by volatile anesthetics, we primarily used a total intravenous technique (55 patients). With more experience, we also used a combination of volatile and intravenous anesthetics (16 patients) and, finally, volatile anesthetics only (11 patients). Data from patients anesthetised for TMT were compared with data from 22 patients operated with open thoracotomy from 1984 until 1992. RESULTS: While the operating time (290.1 +/- 133.2 min for TMT vs. 312.3 +/- 113.6 for thoracotomy) and the anesthesia time (431.2 +/- 140.3 for TMT vs. 416.4 +/- 102.1 for thoracotomy) showed no significant differences, the TMT required an extremely long time of SLV (270.2 +/- 133.2 min) to gain access to the spine using left-sided double-lumen tubes. While the oxygenation index (PaO2/FiO2), as a marker for pulmonary oxygenation capacity, decreased significantly after initiation of SLV for TMT, it was markedly enhanced with increasing duration (270.2 +/- 133.2 min) of SLV. Oxygenation index showed no significant difference when comparing the different anesthetic techniques for TMT. CONCLUSION: We conclude that despite the long duration of SLV, TMT is a reasonable alternative to open thoracotomy for thoracic neurosurgical spine procedures because of the substantial clinical benefits of accelerated return to physical activity, reduced complication rates and reduced intensive care unit and hospital stay.

Activities of Daily Living↗