Biomedical subjects

K Wild

Publications and source records attributed to K Wild.

At least 19 recordsLinked to original sources

PubMed1999

Protein binding of piritramide: influence of various protein concentrations and the postoperative acute phase response.

OBJECTIVE: Piritramide is a lipophilic opioid, which is widely used for postoperative analgesia and analgosedation in Europe. In this study we investigated the influence of various protein concentrations (total protein, alpha1-acid glycoprotein, albumin) and the postoperative acute phase response on the protein binding of piritramide. METHODS: The influence of various protein concentrations on the protein binding of piritramide was investigated by either diluting the serum samples of five volunteers with isotonic saline or by adding different amounts of alpha1-acid glycoprotein. Albumin binding was measured in a 5% human albumin solution. The impact of the postoperative acute phase response was investigated by obtaining daily serum samples from 18 surgical patients until the third postoperative day, and measuring piritramide protein binding, alpha1-acid glycoprotein, total protein and albumin. RESULTS: There was a significant relationship between piritramide protein binding and the concentrations of total protein and alpha1-acid glycoprotein. The binding to albumin was 88%. During the postoperative acute phase response, the protein binding of piritramide did not change. Serum concentrations of alpha1-acid glycoprotein increased, whereas total protein and albumin decreased. CONCLUSION: Although there were significant changes in the piritramide-binding proteins, alpha1-acid glycoprotein and albumin, during the postoperative acute phase response, the protein binding of piritramide did not change. Therefore, a change in protein binding, which might be one factor to be considered in determining piritramide dosage in the postoperative period, does not have to be taken into account.

Acute-Phase Reaction↗

PubMed1999

Selective visual attention in patients with frontal lobe lesions or Parkinson's disease.

Visual selective attention and response competition were tested in patients with frontal lobe lesions or with Parkinson's disease, and matched normal controls. The target stimuli were presented with flanking distractors that were either compatible, incompatible, or neutral to the target stimulus. The distance between the target and distractors was systematically varied. A control condition without distractors was also included. Subjects' response times to target stimuli and accuracy were measured. Both patient groups responded significantly slower and less accurately than their respective matched normal controls across all interference conditions and spatial distances. However, they did not show significantly greater interference or facilitation effects. Thus, the data suggest that the cognitive processes underlying selective attention are, in general, spared in patients with frontal lobe lesions or basal ganglia dysfunction.

Adult↗

PubMed1999

Expression of membrane-bound and cytosolic guanylyl cyclases in the rat inner ear.

Membrane-bound guanylyl cyclases (GCs) are peptide hormone receptors whereas the cytosolic isoforms are receptors for nitric oxide. In the inner ear, the membrane-bound GCs may be involved in the regulation of fluid homeostasis and the cytosolic forms possibly play a role in signal processing and regulation of local blood flow. In this comprehensive study, we examined, qualitatively and quantitatively, the transcription pattern of all known GC isoforms in the inner ear from rat by RT-PCR. The tissues used were endolymphatic sac, stria vascularis, organ of Corti, organ of Corti outer hair cells, cochlear nerve, Reissner's membrane, vestibular dark cells, and vestibular sensory cells. We show that multiple particulate (GC-A, GC-B, GC-D, GC-E, GC-F and GC-G) and several subunits of the heterodimeric cytosolic GCs (alpha1, alpha2, beta1 and beta2) are expressed, albeit at highly different levels. GC-C was not found. GC-A and the soluble subunits alpha1 and beta1 were transcribed ubiquitously. GC-B was present in all tissues except stria vascularis, which contained GC-A and traces of GC-E and GC-G. GC-B was by far the predominant membrane-bound isoform in the organ of Corti (86%), Reissner's membrane (75%) and the vestibulum (80%). Surprisingly, GC-E, a retinal isoform, was detected in significant amounts in the cochlear nerve (8%) and in the organ of Corti (4%). Although the cytosolic GC is a heterodimer composed of an alpha and a beta subunit, the mRNA transcription of these subunits was not stoichiometric. Particularly in the vestibulum, the transcription of the beta1 subunits was at least four-fold higher than of the alpha1 subunit. The data are compatible with earlier suggestions that membrane receptor GCs may be involved in the control of inner ear electrolyte and fluid composition whereas NO-stimulated GC isoforms mainly participate in the regulation of blood flow and supporting cell physiology.

Animals↗

PubMed1999

Expression pattern of adenylyl cyclase isoforms in the inner ear of the rat by RT-PCR and immunochemical localization of calcineurin in the organ of Corti.

Most studies concerning adenylyl cyclases in the inner ear were carried out before the advent of molecular biology. In a PCR approach using cDNAs of six inner ear tissues (stria vascularis, endolymphatic sac, organ of Corti, vestibulum, cochlear and vestibular nerve) we found tissue specific expression of adenylyl cyclase isoforms. Adenylyl cyclases types 2 and 4 are predominant in the fluid controlling tissues, i.e. in the stria vascularis and endolymphatic sac. In the organ of Corti and vestibulum the Ca2+-modulated isoforms types 1, 6 and 9 were expressed. The regulation of adenylyl cyclase 9, which is the major isoform expressed in the organ of Corti, proceeds via the Ca2+-activated protein phosphatase 2B (calcineurin, PPP3). PCR with specific primers for calcineurin demonstrated its abundant expression in the organ of Corti. Using a monoclonal antibody we localized calcineurin immunochemically to the cochlear nerve, the nerve fibers and the inner hair cells. In the cochlear and vestibular nerves a characteristic neuronal expression pattern of adenylyl cyclase isoforms was observed, i.e. adenylyl cyclases types 2, 3 and 8. The functional consequences of the adenylyl cyclase expression pattern in the inner ear are discussed in conjunction with its unique sensory performance.

Adenylyl Cyclases↗

PubMed1999

Dry soda lime markedly degrades sevoflurane during simulated inhalation induction.

We have investigated gas composition during simulated inhalation induction with sevoflurane to elucidate possible mechanisms of incidental prolonged induction times and airway irritation. Using a circle system, 8% sevoflurane in oxygen 6 litre min-1 was washed into an absorbing canister filled with fresh soda lime containing 2.9% KOH (Draegersorb, 'D') or no KOH (< 0.01%, Sofnolime, 'S'). The absorbent was dried by oxygen 20,000 litre before every second experiment. Maximum soda lime temperatures attained after 4-6 min were 107 degrees C using dry D and 62 degrees C (61 degrees C) with dry S. Temperature did not increase with fresh soda lime. With dry soda lime, sevoflurane was not detected at the T-piece for 3 min and reached 6-7% within 6-10 min. After 1 min, we detected methanol and compound A (CH2F-O-C(= CF2) (CF3)). Total amounts over 20 min were: methanol 1125 mg (D dry), 334 mg (S dry) and < 5 mg (fresh soda lime); compound A 148 mg (D dry), 13 mg (S dry) and 3-8 mg (fresh); and fluoride 8.5 mg (D dry), 3.3 mg (S dry) and 1 mg (fresh). Formaldehyde was detected only with dry lime (D > 2.5 mg, S > 0.6 mg). In summary, the use of moist soda lime is of crucial importance during inhalation induction. With dry soda lime, the patient may inhale potentially toxic degradation products in significant amounts. Sevoflurane degradation is aggravated by a high KOH content of the lime. The observed airway irritation may be caused by formic acid, which is generated in isomolar concentrations with methanol (Cannizzaro reaction). The amount of compound A found with dry KOH-containing lime is unlikely to be noxious.

Anesthesia, Closed-Circuit↗

PubMed1998

The effect of anti-diuretic hormone on the endolymphatic sac of the inner ear.

The anti-diuretic hormone vasopressin (AVP) regulates water excretion from the kidney by increasing the water permeability of the collecting duct. AVP binds to V2-receptors and induces the translocation of aquaporin-2 water channels (AQP-2) into the apical plasma membrane of principal cells. By this mechanism AVP controls water reabsorption in the kidney. The effects of AVP on the endolymphatic sac (ES) of the inner ear, which is thought to mediate reabsorption of endolymph, were investigated. Both the V2-receptor and the AQP-2 water channel were found to be expressed in the ES epithelium. In the ES AVP binds to receptors most probably of the V2-subtype. Application of AVP to organotypically cultured ES inhibits membrane turnover in ribosomal-rich cells of the ES epithelia, which is thought to mediate translocation of AQP-2 into the surface membrane. This suggests that AVP has contrasting effects in the inner ear and kidney, which may be physiologically useful for maintaining endolymphatic pressure during severe hypovolemia. Animal experiments show that AVP causes endolymphatic hydrops after systemic application to guinea-pigs, which suggests a causal role for the increased AVP levels found in humans suffering from Ménière's disease.

Animals↗

PubMed1998

Metabolic engineering as therapy for inborn errors of metabolism--development of mice with phenylalanine hydroxylase expression in muscle.

Treatment of many inherited liver enzyme deficiencies requires the removal of toxic intermediate metabolites from the blood of affected individuals. We propose that circulating toxins can be adequately cleared and disease phenotype influenced by enzyme expressed in tissues other than the liver. Phenylalanine hydroxylase (PAH) activity was constitutively expressed in skeletal and cardiac muscle of transgenic mice which carried the PAH cDNA under the transcriptional control of the mouse muscle creatine kinase promoter. Muscle PAH-expressing mice were bred to liver PAH-deficient, hyperphenylalaninemic mice to yield progeny that lack PAH activity in liver but express PAH in muscle. These mice exhibited hyperphenylalaninemia at baseline, but serum phenylalanine levels decreased significantly when the mice were supplemented with tetrahydrobiopterin (BH4), a required cofactor for PAH. This is the first demonstration that a liver-specific enzyme, when expressed in a heterologous tissue and supplied with necessary cofactors, can effectively clear toxic metabolites from the circulation of individuals with inherited enzyme deficiency. This result suggests that gene therapy targeted to heterologous tissues, such as muscle, will be effective in the treatment of selected inborn errors of metabolism.

Animals↗

PubMed1997

Structure, catalysis and supramolecular assembly of adenylate kinase from maize.

The crystal structure of adenylate kinase from maize ligated with an inhibitor has been determined by molecular replacement and refined to 3.5-A resolution. The enzyme keeps the ATP/ADP/AMP equilibrium in the cell. In the C4 plant maize, it has the special task to recycle the AMP produced in large amounts in primary CO2 assimilation. The established structure explains the side reaction with CMP. Moreover, it shows infinite rods that can be readily discerned in the crystal packing. In comparison with homologues, two structural differences that are crucial for this supramolecular assembly are evident. We propose that the rods represent a natural inactive storage form that assembles at night when maize stops CO2 assimilation and thus most of the AMP production in its C4 cycle. The enzyme is particularly abundant in mesophyll chloroplasts, where such an assembly would release appreciable amounts of water that can be used in other processes during the night.

Adenylate Kinase↗

PubMed1997

Percutaneous ultrasound-guided abomasocentesis in cows.

The goal of this study was to determine the optimal location for ultrasound-guided centesis of the bovine abomasum and to assess the safety of the procedure. In the first part of this study, the technique was applied to 50 clinically healthy cows which were slaughtered within two hours of the procedure. The abomasum and peritoneum were then examined for lesions. In all but one cow, the location for abomasocentesis was 10 to 27 cm caudal to the xiphoid and on the ventral midline or up to 10 cm to the right of it. No peritoneal lesions were observed in any of the cows. In all cases, the site of centesis was visible as a localised haemorrhage on the serosal surface of the abomasum. In 41 of the cows, a haematoma was visible on the mucosal surface of the abomasum. In the second part of the study, 10 cows were monitored clinically for 10 days after abomasocentesis, to assess the safety of the procedure. The appetite, general behaviour, attitude and rectal temperature of the cows remained normal. The haematocrit, total and differential leucocyte counts, and the concentrations of total solids and fibrinogen were determined daily and remained within their normal ranges. At slaughter minimal changes, such as localised reddening and adhesions between the site of the puncture in the abomasum and the abdominal wall, were visible in three of the cows.

Abomasum↗

PubMed1997

Mice with genetic gamma-glutamyl transpeptidase deficiency exhibit glutathionuria, severe growth failure, reduced life spans, and infertility.

A mouse mutant with glutathionuria was discovered by screening for amino acidurias in the progeny of ethylnitrosourea-mutagenized mice. Total glutathione concentration was increased in both blood and urine but decreased in liver homogenates from affected mice. Glutathionuric mice exhibited lethargy, severe growth failure, shortened life spans and infertility. gamma-Glutamyl transpeptidase activity was deficient in kidney homogenates of glutathionuric mice. The glutathionuric phenotype in these mice is inherited as an autosomal recessive trait. This mouse mutant will be a useful animal model for the study of gamma-glutamyl transpeptidase physiology and glutathione metabolism.

Animals↗

PubMed1997

Ultrasonographic examination of the abomasum of 50 cows.

The purpose of this study was to determine the position, appearance and dimensions of the abomasum of 50 healthy cows by ultrasonography. The ventral abdominal region caudal to the xiphoid process was examined with a 3.5 MHz linear transducer. The abomasum could be visualised from both sides and from the ventral midline of 47 of the cows. The abomasum could be clearly differentiated from adjacent organs because of its contents, which appeared as a heterogeneous, moderately echogenic structure with echogenic stippling. However, the wall of the abomasum appeared, if at all, as a narrow echogenic line. Parts of the abomasal folds were visible occasionally as echogenic structures within the abomasum. Slow movement of the feed in the abomasum was also often visualised. The pylorus was positively identified in only one cow. The cranial margin of the abomasum was situated up to 15 cm caudal to the xiphoid process. The abomasum was between 7.4 and 42.9 cm long, and its maximal extent, measured from the ventral midline to the left, was from 5.0 to 26.0 cm in the cranial region and from 5.0 to 16.0 cm in the caudal region. From the ventral midline to the right, it was from 5.0 to 33.0 cm in the cranial region and from 28.0 to 36.0 cm in the caudal region. The minimal dorsoventral dimension of the abomasum ranged from 0.7 to 7.2 cm, and its maximal dorsoventral dimension ranged from 3.6 to 11.1 cm.

Abomasum↗

PubMed1997

The structures of thymidine kinase from herpes simplex virus type 1 in complex with substrates and a substrate analogue.

Thymidine kinase from Herpes simplex virus type 1 (TK) was crystallized in an N-terminally truncated but fully active form. The structures of TK complexed with ADP at the ATP-site and deoxythymidine-5'-monophosphate (dTMP), deoxythymidine (dT), or idoxuridine-5'-phosphate (5-iodo-dUMP) at the substrate-site were refined to 2.75 A, 2.8 A, and 3.0 A resolution, respectively. TK catalyzes the phosphorylation of dT resulting in an ester, and the phosphorylation of dTMP giving rise to an anhydride. The presented TK structures indicate that there are only small differences between these two modes of action. Glu83 serves as a general base in the ester reaction. Arg163 parks at an internal aspartate during ester formation and binds the alpha-phosphate of dTMP during anhydride formation. The bound deoxythymidine leaves a 35 A3 cavity at position 5 of the base and two sequestered water molecules at position 2. Cavity and water molecules reduce the substrate specificity to such an extent that TK can phosphorylate various substrate analogues useful in pharmaceutical applications. TK is structurally homologous to the well-known nucleoside monophosphate kinases but contains large additional peptide segments.

Adenosine Diphosphate↗

PubMed1997

[Removal of the small intestine in autologous jejunum transplantation for reconstruction of the mouth cavity is a secondary intervention with few complications].

Reconstruction after radical tumor resection in the oropharyngeal region still represents an interdisciplinary challenge. Autotransplantation of the jejunum is a popular procedure, in which the abdominal surgeon's main task is that of harvesting enteral tissue. To evaluate this technique, a careful analysis of accompanying perioperative abdominal complications was performed. Additionally, we reexamined 35 of 66 patients still living after a follow-up period of 21 (range 2-63) months on average. The perioperative mortality of 90 patients treated for oropharyngeal malignancy using the described procedure was 7.8%. None of the perioperative deaths was caused by an abdominal complication associated with enteral resection. One abdominal reoperation was performed because of abdominal wall dehiscence. For reasons not related to enteral resection, four further patients had to be relaparotomized, two of them during their hospital stay and two after leaving hospital. In five cases we observed minor complications which could be treated nonsurgically. In the follow-up reexamination we detected no abdominal late-onset complication except small incisional hernias in six cases. Finally, we concluded that despite an elevated overall operative risk in this population, complications owing to jejunal resection were comparably low. The data regarding the rate of complications classify jejunal resection as a safe procedure for reconstructive purposes in patients suffering from oropharyngeal malignancy.

Adult↗

PubMed1997

Effects of desflurane and isoflurane on systemic vascular resistance during hypothermic cardiopulmonary bypass.

OBJECTIVE: The objective of this study was to examine the dose-related effects of desflurane and isoflurane on systemic vascular resistance during hypothermic cardiopulmonary bypass. DESIGN: Randomized, prospective trial. SETTING: University hospital. PARTICIPANTS: Sixty consenting patients, 65 years of age or older, scheduled for elective coronary artery surgery. INTERVENTIONS: Patients were randomly allocated to one of five groups to receive 0.5 or 1.0 minimum alveolar concentration (MAC) (exhaust gas concentration) desflurane or 0.5 or 1.0 MAC isoflurane during hypothermic (32 degrees to 33 degrees C) nonpulsatile cardiopulmonary bypass or to a control group that did not receive any anesthetic agent. Systemic vascular resistance index was recorded at baseline, every 2 minutes for the first 10 minutes during initial administration and every 5 minutes for another 15 minutes during maintenance of anesthesia. MEASUREMENTS AND MAIN RESULTS: In patients receiving 0.5 MAC desflurane and isoflurane, there were significant differences in systemic vascular resistance index only at 20 and 25 minutes compared with control values. In the desflurane 1.0 MAC group, significant decreases were observed at 15, 20, and 25 minutes compared with controls. In the 1 MAC isoflurane group, the 10-, 15-, 20-, and 25-minute value differed significantly from the control. There were significant decreases in systemic vascular resistance index in the 1.0 MAC groups at 20 and 25 minutes compared with 0.5 MAC values, as well. CONCLUSIONS: Equi-MAC concentrations of desflurane and isoflurane had similar effects on systemic vascular resistance; 0.5 MAC maintained systemic vascular resistance; 1.0 MAC decreased systemic vascular resistance during hypothermic cardiopulmonary bypass.

Aged↗

PubMed1997

Occupational exposure to desflurane and isoflurane during cardiopulmonary bypass: is the gas outlet of the membrane oxygenator an operating theatre pollution hazard?

We have compared occupational exposure to isoflurane and desflurane during cardiopulmonary bypass, with and without a scavenging system at the membrane oxygenator outlet. Trace concentrations of volatile anaesthetics were measured by a direct reading instrument in 40 elective heart surgery procedures. Measurements were obtained in the breathing zones of the anaesthetist and perfusionist. When a scavenging system was used, median desflurane values were less than 0.3 ppm and isoflurane values less than 0.2 ppm. Without a scavenging system values were, in general, three- (isoflurane) to five- (desflurane) fold higher. We conclude that the use of a scavenging system at the membrane oxygenator outlet can reduce occupational exposure to volatile anaesthetics. We therefore recommend routine use of scavenging devices during cardiopulmonary bypass.

Adult↗

PubMed1996

Dual action of a carbohydrate epitope on afferent and efferent axons in cortical development.

During development of the mammalian cerebral cortex, ingrowing afferents from the thalamus take a path that is different from that of axons leaving the cortical plate. Thalamic axons arrive at the cortex at the time before their target cells of layer 4 are generated in the ventricular zone, but they invade the cortex only shortly before these cells have migrated to their final position in the cortex. Growth-promoting molecules are up-regulated in the developing cortical plate during this period. To identify such molecules, we have generated monoclonal antibodies against membrane preparations from rat postnatal cortex. In Western blots, one antibody (mAb 10) recognized a carbohydrate epitope of a glycoprotein with an apparent molecular weight extending from 180 to 370 kDa. Immunohistochemical staining revealed that the staining pattern of mAb 10 at embryonic stages delineates the pathway of thalamocortical axons, with only very faint labeling of the corticofugal pathway. In vitro assays in combination with time-lapse imaging indicated that mAb 10 has opposite effects on the growth of thalamic and cortical axons. The growth speed and axonal elongation of thalamic fibers on postnatal cortical membranes preincubated with mAb 10 was reduced compared with untreated cortical membranes. In contrast, cortical axons grew faster and stopped their growth less frequently after addition of mAb 10 to a cortical membrane substrate. Taken together, these results suggest that a carbohydrate moiety of a membrane-associated glycoprotein plays a role in the segregation of afferent and efferent cortical axons in the white matter. Moreover, the epitope recognized by mAb 10 might also contribute to regulation of the timing of the thalamocortical innervation at later developmental stages.

Aging↗

PubMed1996

Brain activation during script event processing.

Regional cerebral blood flow was measured with positron emission tomography in seven normal volunteers while they performed various script event verification tasks. The left frontal lobe, left anterior cingulate and the anterior part of the left superior temporal gyrus were more activated in the script event membership and action categorization conditions, whereas the right frontal lobe, left superior temporal gyrus and the middle temporal gyrus bilaterally were more activated in the script event temporal order verification condition. These results indicate that the temporal ordering of script events and determining whether an event belongs to a particular script or action category are processed by distinctive distributed neuronal networks.

Adult↗

PubMed1996

[Serum fluoride concentrations and exocrine kidney function with sevoflurane and enflurane. An open, randomized, comparative phase III study of patients with healthy kidneys].

UNLABELLED: Sevoflurane is a "new" volatile inhaled anaesthetic. Owing to its lower blood-gas solubility coefficient, emergence from anaesthesia is faster with sevoflurane than with isoflurane, enflurane, or halothane. Sevoflurane undergoes metabolic biodegradation, releasing inorganic fluoride ions that could produce nephrotoxicity. In this study, we compared serum inorganic fluoride concentrations (IFCs) in patients receiving either sevoflurane or enflurane. Furthermore, indices of renal function were evaluated until the 3rd postoperative day. METHODS: Thirty patients with no history of renal or hepatic disease and with an anticipated duration of anaesthesia of at least 3 h were studied in an open, prospective, randomised clinical trial. Anaesthesia was induced with fentanyl, thiopentone, and vecuronium for facilitating endotracheal intubation. Anaesthesia was maintained with sevoflurane or enflurane, 60% nitrous oxide in oxygen, and additional doses of fentanyl. Blood samples for serum IFCs were obtained preoperatively and 2 and, if possible, 4 and 6 h after starting sevoflurane or enflurane, at the end of anaesthesia, and 1, 2, 4, 8, 12, 24, 48 and 72 h post-anaesthesia. Fluoride analysis was performed using an ion-selective electrode. Indices of renal function (serum sodium, osmolality, creatinine, urea, and uric acid, urine specific gravity, osmolality, and pH) were evaluated preoperatively, at the end of anaesthesia, and 24, 48, and 72 h post-anaesthesia. RESULTS: The duration of anaesthetic exposure was approximately 1.65 MAC-h for both inhaled anaesthetics. Peak serum IFCs were higher with sevoflurane (34.5 mumol/l) than with enflurane (19.4 mumol/l). Fluoride levels decreased more rapidly with sevoflurane: 24 h post-anaesthesia there was no difference between sevoflurane and enflurane (Fig. 1). The area under the curve (AUC) was greater with sevoflurane (688 mumol/l.h) than with enflurane (591 mumol/l.h). For both groups correlation coefficients were higher for MAC-h and AUC than for MAC-h and peak serum IFC (Figs. 2 and 3). Indices of renal function did not change in either group. DISCUSSION: In our study 1.69 MAC-h sevoflurane produced peak serum IFCs of 34.5 mumol/l. This is in accordance with the investigation of Frink et al. [4], who reported approximately 30 mumol/l after 1.4 MAC-h sevoflurane. Peak serum IFCs with sevoflurane were twice those with enflurane. Within the first 24 h post-anaesthesia, fluoride levels decreased more rapidly after sevoflurane. AUC may be more important than peak serum IFC in evaluating patients who are at risk for renal concentrating defects. In our study there was no evidence of renal dysfunction in either group.

Adult↗