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Biomedical subjects

S Veit

Publications and source records attributed to S Veit.

At least 19 recordsLinked to original sources

[Surgical curriculum. A model from thoracic surgery].

There is a shortage of new surgeons in Germany. The blame for this is laid on poor working and training conditions in German hospitals. Professional associations suggest restructuring teaching plans to improve surgical education. The study conditions, postgraduate education, and surgical training in a thoracic surgical department are presented as a model curriculum. Surgical training can be structured. Curricula can be delineated for colleagues and applicants and comply with quality management standards. Clear and fair courses would improve surgical training and satisfy the expectations of contemporary surgeons.

Curriculum↗

Regulation of anthocyanin biosynthesis in UV-A-irradiated cell cultures of carrot and in organs of intact carrot plants.

Two cell lines of Daucus carota are known to differ with respect to anthocyanin accumulation. cDNA clones encoding enzymes involved in anthocyanidin biosynthesis, namely phenylalanine ammonia-lyase (PAL; EC 4.3.1.5), chalcone synthase (CHS; EC 2.3.1.74), flavanone 3-hydroxylase (F3H; EC 1.14.11.9), dihydroflavonol 4-reductase (DFR; EC 1.1.1.219) and leucoanthocyanidin dioxygenase (LDOX; EC 1.14.11.-), were isolated from libraries derived from cell cultures. Northern blot analysis of anthocyanin-accumulating (DCb) and non-accumulating (DCs) cell cultures of carrot showed that the anthocyanin pathway in these anthocyanin-free DCs cells is blocked. The expression of CHS1, DFR1 and LDOX is not detectable. However, F3H and DFR2 behave differently. In the European wild carrot (Daucus carota ssp. carota) the structural genes coding for the enzymes responsible for anthocyanin biosynthesis are strongly expressed in organs which accumulate anthocyanins. Only the dark-purple coloured petals of the central flowers of the inflorescence and to a certain extent the white flowers and the leaves but not the stems and the roots transcribe these genes. To study the effect of anthocyanins as UV-screens the expression of a protein indispensable for cell proliferation like alpha-tubulin (TUB) was monitored.

Journal Article↗

A novel protein elicitor (PaNie) from Pythium aphanidermatum induces multiple defense responses in carrot, Arabidopsis, and tobacco.

A novel protein elicitor (PaNie(234)) from Pythium aphanidermatum (Edson) Fitzp. was purified, microsequenced, and the corresponding cDNA was cloned. The deduced amino acid sequence contains a putative eukaryotic secretion signal with a proteinase cleavage site. The heterologously expressed elicitor protein without the secretion signal of 21 amino acids (PaNie(213)) triggered programmed cell death and de novo formation of 4-hydroxybenzoic acid in cultured cells of carrot (Daucus carota). Programmed cell death was determined using the tetrazolium assay and DNA laddering. Infiltration of PaNie(213) into the intercellular space of leaves of Arabidopsis (Columbia-0, wild type) resulted in necroses and deposition of callose on the cell walls of spongy parenchyma cells surrounding the necrotic mesophyll cells. Necroses were also formed in tobacco (Nicotiana tabacum cv Wisconsin W38, wild type) and tomato (Lycopersicon esculentum Mill.) but not in maize (Zea mays), oat (Avena sativa), and Tradescantia zebrina (Bosse), indicating that monocotyledonous plants are unable to perceive the signal. The reactions observed after treatment with the purified PaNie(213) were identical to responses measured after treatment with a crude elicitor preparation from the culture medium of P. aphanidermatum, described previously. The availability of the pure protein offers the possibility to isolate the corresponding receptor and its connection to downstream signaling-inducing defense reactions.

Adaptation, Physiological↗

EPR probes with well-defined, long distances between two or three unpaired electrons

The synthesis of rod- and star-shaped compounds carrying two or three spin labels as end groups is described. The unpaired electrons are 2.8-5.1 nm apart from each other. The shape-persistent scaffolds were obtained through Pd-Cu-catalyzed alkynyl-aryl coupling and Pd-Cu-catalyzed alkyne dimerization in the presence of oxygen using p-phenyleneethynylene as the basic shape-persistent building block. The spin label 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (4) was attached through esterification of the terminal phenolic OH groups of the scaffold.

Journal Article↗

Dead-time free measurement of dipole-dipole interactions between electron spins.

A four-pulse version of the pulse double electron-electron resonance (DEER) experiment is presented, which is designed for the determination of interradical distances on a nanoscopic length-scale. With the new pulse sequence electron-electron couplings can be studied without dead-time artifacts, so that even broad distributions of electron-electron distances can be characterized. A version of the experiment that uses a pulse train in the detection period exhibits improved signal-to-noise ratio. Tests on two nitroxide biradicals with known length indicate that the accessible range of distances extends from about 1.5 to 8 nm. The four-pulse DEER spectra of an ionic spin probe in an ionomer exhibit features due to probe molecules situated both on the same and on different ion clusters. The former feature provides information on the cluster size and is inaccessible with previous methods.

Electron Spin Resonance Spectroscopy↗

Nitroglycerin application during cesarean delivery: plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.

OBJECTIVE: We sought to investigate maternal and fetal nitroglycerin metabolization and to assess the clinical condition of neonates after intravenous nitroglycerin application during cesarean delivery. STUDY DESIGN: At the time of the uterine puncture incision, either 0. 25 mg or 0.5 mg nitroglycerin or a physiologic sodium chloride solution was administered as an intravenous bolus. Plasma concentrations of nitroglycerin and its metabolites were measured in maternal venous blood and in umbilical blood samples taken immediately after cord clamping. Arterial blood pressure, pulse rates, and Apgar scores were recorded for the neonates 1, 5, and 10 minutes after birth. RESULTS: Sixty-two patients were included in the pharmacokinetic study. Median maternal plasma levels 1 and 5 minutes after injection of 0.5 mg nitroglycerin were 80 and 3.2 ng/mL, respectively; median maternal plasma levels 1 and 5 minutes after injection of 0.25 mg nitroglycerin were 38 and 1.2 ng/mL, respectively. In the umbilical vein 1 minute after application of 0. 5 mg or 0.25 mg nitroglycerin, the plasma levels were 0.41 and 0.09 ng/mL, respectively, and in the umbilical artery they were 0.03 and 0.008 ng/mL, respectively. Circulatory parameters and Apgar scores in the neonates did not differ significantly from those found in the placebo group. CONCLUSION: The level of nitroglycerin in umbilical plasma was two to three orders of magnitude lower than that found in maternal plasma and clearly in a subtherapeutic range. There was no indication that prenatal application of nitroglycerin to facilitate obstetric management is hazardous for neonates.

Adolescent↗

Ultra-ultra rapid cycling bipolar disorder is associated with the low activity catecholamine-O-methyltransferase allele.

Bipolar spectrum disorders are recurrent illnesses characterized by episodes of depression, hypomania, mania or the appearance of mixed states. Great variability is evident in the frequency of episode recurrence and duration. In addition to regular circannual episodes, a spectrum of cycle frequencies has been observed, from the classical rapid cycling (RC) pattern of four or more episodes per year, to those with distinct shifts of mood and activity occurring within a 24-48 h period, described as ultra-ultra rapid cycling (UURC) or ultradian cycling. RC has a female preponderance, and occurs with greater frequency premenstrually, at the puerperium and at menopause. Tricyclic antidepressants and MAOIs, both of which increase functional monoamines norepinephrine, dopamine and serotonin, are known to precipitate mania or rapid-cycling in an estimated 20-30% of affectively ill patients. We have recently reported a strong association between velo-cardio-facial syndrome (VCFS) patients diagnosed with rapid-cycling bipolar disorder, and an allele encoding the low enzyme activity catechol-O-methyltransferase variant (COMT L). Between 85-90% of VCFS patients are hemizygous for COMT. Homozygosity for the low activity allele (COMT LL) is associated with a 3-4 fold reduction of COMT enzyme activity compared with homozygotes for the high activity variant (COMT HH). There is nearly an equal distribution of L and H alleles in Caucasians. Individuals with COMT LL would be expected to have higher levels of transynaptic catecholamines due to a reduced COMT degradation of norepinephrine and dopamine. We therefore hypothesized that the frequency of COMT L would be greater in RC BPD ascertained from the general population. Significantly, we found that the frequency of COMT L was higher in the UURC variant of BPD than among all other groups studied (P = 0.002). These findings indicate that COMT L could represent a modifying gene that predisposes to ultra-ultra or ultradian cycling in patients with bipolar disorder.

Adult↗

Molecular analysis of velo-cardio-facial syndrome patients with psychiatric disorders.

Velo-cardio-facial syndrome (VCFS) is characterized by conotruncal cardiac defects, cleft palate, learning disabilities, and characteristic facial appearance and is associated with hemizygous deletions within 22q11. A newly recognized clinical feature is the presence of psychiatric illness in children and adults with VCFS. To ascertain the relationship between psychiatric illness, VCFS, and chromosome 22 deletions, we evaluated 26 VCFS patients by clinical and molecular biological methods. The VCFS children and adolescents were found to share a set of psychiatric disorders, including bipolar spectrum disorders and attention-deficit disorder with hyperactivity. The adult patients, >18 years of age, were affected with bipolar spectrum disorders. Four of six adult patients had psychotic symptoms manifested as paranoid and grandiose delusions. Loss-of-heterozygosity analysis of all 26 patients revealed that all but 3 had a large 3-Mb common deletion. One patient had a nested distal deletion and two did not have a detectable deletion. Somatic cell hybrids were developed from the two patients who did not have a detectable deletion within 22q11 and were analyzed with a large number of sequence tagged sites. A deletion was not detected among the two patients at a resolution of 21 kb. There was no correlation between the phenotype and the presence of the deletion within 22q11. The remarkably high prevalence of bipolar spectrum disorders, in association with the congenital anomalies of VCFS and its occurrence among nondeleted VCFS patients, suggest a common genetic etiology.

Abnormalities, Multiple↗

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome.

Velo-cardio-facial-syndrome (VCFS) is a common congenital disorder associated with typical facial appearance, cleft palate, cardiac defects, and learning disabilities. The majority of patients have an interstitial deletion on chromosome 22q11. In addition to physical abnormalities, a variety of psychiatric illnesses have been reported in patients with VCFS, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. The psychiatric manifestations of VCFS could be due to haploin-sufficiency of a gene(s) within 22q11. One candidate that has been mapped to this region is catechol-O-methyltransferase (COMT). We recently identified a polymorphism in the COMT gene that leads to a valine-->methionine substitution at amino acid 158 of the membrane-bound form of the enzyme. Homozygosity for COMT158met leads to a 3-4-fold reduction in enzymatic activity, compared with homozygotes for COMT158val. We now report that in a population of patients with VCFS, there is an apparent association between the low-activity allele, COMT158met, and the development of bipolar spectrum disorder, and in particular, a rapid-cycling form.

Abnormalities, Multiple↗

Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder?

OBJECTIVE: The purpose of this study was to conduct a systematic assessment of psychiatric illness in patients diagnosed with velo-cardio-facial syndrome, a genetic syndrome that involves over 40 somatic anomalies, learning disabilities, and behavioral disorders and is associated with a microdeletion on chromosome 22q11. METHOD: Subjects were referred for psychiatric diagnostic evaluation without regard to age or previous psychiatric history. In order to establish DSM-III-R consensus clinical diagnoses for patients who ranged in age from 5 to 34 years, the Diagnostic Interview for Children and Adolescents--Revised or the Structured Clinical Interview for DSM-III-R (SCID) was used. A review of available medical and psychiatric records and a clinical interview performed by two research psychiatrists to validate specific symptoms and syndromes reported in the Diagnostic Interview for Children and Adolescents--Revised and the SCID were used to elucidate the chronological appearance and duration of symptoms. RESULTS: Sixty-four percent (N = 16 of 25) of this unselected series of patients with velo-cardio-facial syndrome met DSM-III-R criteria for a spectrum of bipolar disorders with full syndromal onset in late childhood or early adolescence (mean age at onset = 12 years, SD = 3). In addition, 20% (N = 5) met DSM-III-R criteria for attention deficit hyperactivity disorder (ADHD), while 16% (N = 4) met criteria for attention deficit disorder without hyperactivity. In contrast to previous reports of a high prevalence of schizophrenia, none of the patients was diagnosed with schizophrenia, and only four had psychotic symptoms during a phase of their illness, all in their 20s or 30s. CONCLUSIONS: Given that the prevalence of bipolar disorder in the general population is estimated to be 1.5% and that the average age at onset is 24, these findings support an unusually strong association between velo-cardio-facial syndrome and early-onset bipolar disorder and suggest that a gene deleted at the 22q11 chromosomal locus may be involved in its pathogenesis. If confirmed, these findings may provide a new and fruitful line of investigation into the molecular basis of bipolar spectrum disorders.

Abnormalities, Multiple↗

Effects of inhaled nitric oxide on right ventricular function in severe acute respiratory distress syndrome.

OBJECTIVE: To compare the effects of inhaled nitric oxide (NO) and an infusion of prostacyclin (PGI2) on right ventricular function in patients with severe acute respiratory distress syndrome (ARDS). DESIGN: Randomized prospective short-term study. SETTING: Post-surgical ICU in an university hospital. PATIENTS: 10 patients with severe ARDS referred to our hospital for intensive care. INTERVENTIONS: In random sequence the patients inhaled NO at a concentration of 18 parts per million (ppm) followed by 36 ppm, and received an intravenous infusion of PGI2 (4 ng.kg-1.min-1). MEASUREMENTS AND RESULTS: Inhalation of 18 ppm NO reduced the mean (+/- SE) pulmonary artery pressure (PAP) from 33 +/- 2 to 28 +/- 1 mmHg (p = 0.008), increased right ventricular ejection fraction (RVEF), as assessed by thermodilution technique, from 28 +/- 2 to 32 +/- 2% (p = 0.005), decreased right ventricular end-diastolic volume index from 114 +/- 6 to 103 +/- 8 ml.m-2 (p = 0.005) and right ventricular end-systolic volume index from 82 +/- 4 to 70 +/- 5 ml.m-2 (p = 0.009). Mean arterial pressure (MAP) and cardiac index (CI) did not change significantly. The effects of 36 ppm NO were not different from the effects of 18 ppm NO. Infusion of PGI2 reduced PAP from 34 +/- 2 to 30 +/- 2 mmHg (p = 0.02), increased RVEF from 29 +/- 2 to 32 +/- 2% (p = 0.02). Right ventricular end-diastolic and end-systolic volume indices did not change significantly. MAP decreased from 80 +/- 4 to 70 +/- 5 mmHg (p = 0.03), and CI increased from 4.0 +/- 0.5 to 4.5 +/- 0.5 l.min-1.m-2 (p = 0.02). CONCLUSIONS: Using a new approach to selective pulmonary vasodilation by inhalation of NO, we demonstrate in this group of ARDS patients that an increase in RVEF is not necessarily associated with a rise in CI. The increase in CI during PGI2 infusion is probably related to the systemic effect of this substance.

Administration, Inhalation↗

[The effect of nitroglycerin on ornipressin (POR 8)-induced systemic and cardiovascular circulatory changes. An animal experimental study].

OBJECTIVE: Local infiltration of ornipressin (OR) is widely used to reduce intraoperative bleeding. However, OR can cause severe side effects including hypertension, deterioration of cardiac performance and coronary vasoconstriction. Suggestions for therapy of haemodynamic side effects of OR include the use of nitroglycerin (TNG). This experimental study was designed to investigate the influence of TNG on changes of systemic haemodynamics and coronary perfusion produced by i.v. administration of OR. METHODS: 16 anesthetized closed-chest mongrel dogs were studied. Anaesthesia was administered using N2O/O2 (FiO2: 0.33) and enflurane (1Vol%ET). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a cathetertip manometer. Cardiac output (CO) was determined using thermodilution, myocardial blood flow (MBF) using a Pitot catheter. Baseline values were taken (control) followed by a bolus injection of 0.03 U/kg OR i.v. The dogs were randomly assigned to two groups. Group I (Gr.I) (n = 9) received OR only and group II (Gr.II) (n = 7) was treated by infusion of 4 mg/kg.min TNG 7 to 30 min after injection of OR. Haemodynamic and cardiovascular changes were measured for 60 min at fixed time intervals. RESULTS: In both groups (Gr.I; Gr.II) OR produced significant changes in systolic (APS) (+29%; +32%) and diastolic (APD) (+47%; +37%) aortic pressure, cardiac index (CI) (-33%; -33%), peripheral vascular resistance (TPR) (+116%); +104%), stroke volume index (SVI) (-23%; -34%), ejection fraction (EF) (-29%; -29% endsystolic volume (ESV) (+39%; +45%) and left ventricular enddiastolic pressure (LVEDP) (+50%; +66%). Myocardial blood flow (MBF) was reduced by 30% and 29% respectively and coronary vascular resistance (CVR) was increased (+97%; +84%). Coronary venous O2 saturation (SO2cor) decreased to 19% and 20% resulting in high AVDO2cor. As compared to Gr.I the administration of TNG resulted in significant decreases of APS, APD, TPR, ESV and LVEDP close to control values. However, administration of TNG did not effect MBF, CVR, SO2cor and AVDO2cor. CONCLUSION: Systemic haemodynamic effects of OR include hypertension due to peripheral vasoconstriction and impaired cardiac performance resulting in reduced cardiac output with low EF, high ESV and LVEDP. Concomitantly, OR produces coronary constriction with a distinct fall in MBF. Thus, myocardial oxygen balance is impaired. With TNG peripheral vascular effects of OR can be abolished but there is no effect of TNG on OR-induced reduction of coronary blood flow. Therefore, use of TNG for treatment of cardiovascular complications following the administration of OR must be considered with extreme caution.

Animals↗

[Ornipressin (POR 8)--effect on coronary blood circulation and the peripheral circulation. An animal experimental study].

Ornipressin (POR 8), referred to below as OR, is a synthetic derivative of natural vasopressin. It was introduced into clinical practice to replace epinephrine as a local vasoconstrictor because OR was presumed to produce fewer undesirable side-effects. However, mayor cardiovascular complications following local infiltration of OR have been reported in recent time. Beside increased blood pressure and changes in heart rate, there is evidence that the systemic effects of OR include a distinct vasopressor activity on coronary arteries. This study was planned to investigate the effects of OR in haemodynamics and the coronary vascular system. METHODS. The effects of OR on systemic haemodynamics and coronary circulation were studied in nine anaesthetized closed-chest mongrel dogs. Anaesthesia was administered using N2O/O2 (FiO2:0.33) and enflurane (1.0 vol% endtidal). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a tip catheter manometer. Cardiac output (CO) was determined using thermodilution and coronary sinus blood flow, using a Pitot catheter. Recording of baseline values was followed by bolus injection of OR (0.03 U/kg) and changes in haemodynamics were measured for 90 min at fixed time intervals. Statistical analysis was performed by analysis of variance for repeated measures. A value of P < or = 0.05 was considered to indicate statistical significance. RESULTS. Significant maximum changes occurred within 3-5 min after administration of OR. Systolic and diastolic arterial pressures increased by 33% and 39%, respectively. With only minor changes in heart rate, cardiac output markedly decreased by 44% and total peripheral resistance increased by 159%. Impaired pump function of the left ventricle became obvious by a decrease in maximum dP/dt, a decrease in ejection fraction by 35%, and a concomitant sharp increase in left ventricular enddiastolic pressure by 68% and in endosystolic volume by 41%. At the same time, OR produced a marked impairment of coronary perfusion. Myocardial blood flow fell by 32%, while coronary vascular resistance rose by 112%. Increased myocardial oxygen demand and reduced oxygen supply resulted in very low values of coronary venous oxygen saturation (< 20%). CONCLUSIONS. Systemic effects of OR are characterized by a sharp rise in arterial blood pressure. Concomitantly a decrease of myocardial contractility leads to a compromised left ventricular function with marked increases in left ventricular enddiastolic pressure. These haemodynamic changes are associated with an imbalance of myocardial oxygen demand and delivery due to the distinct OR-induced coronary constriction. With regard to the deterioration of systemic and cardiac haemodynamics the indications and use of ornipressin in clinical practice need to be reevaluated.

Animals↗

[Signs of a severe myocardial ischemia following peritonsillar infiltration with ornipressin (POR 8)].

Ornipressin (OR), a synthetic derivative of natural vasopressin, is widely used in combination with local anaesthetics in order to reduce surgical bleeding and systemic absorption of the local anaesthetic. As shown previously in experimental studies, OR causes severe coronary vasoconstriction. The myocardial oxygen balance is compromised by an increase in myocardial oxygen demand due to hypertension and impaired oxygen delivery following coronary vasoconstriction. We describe the case of a 19-year-old male who was admitted to the hospital for elective tonsillectomy. There was no evidence of systemic or cardiovascular disease (ASA I). Following the induction of anaesthesia with thiopentone 4 mg/kg and ventilation with N2O/O2 (FiO2:0.25), vecuronium was administered to facilitate orotracheal intubation. Anaesthesia was maintained with N2O/O2 (FiO2:0.33) and 2 MAC isoflurane. After reaching an anaesthetic steady state with stable haemodynamic conditions, peritonsillar infiltration with a prilocaine solution containing a total of 0.8 IU OR (0.1 IU/ml) produced marked tachycardia and hypertension. Concomitantly, distinct ST-segment-depression was observed in a lead II ECG. Hypertension and tachycardia occurred within 3 min after the local infiltration with prilocaine/OR. Maximum ST-segment depression and haemodynamic changes were recorded 11 min after infiltration, with an increase in heart rate from 58 to 136 min and a rise in blood pressure from 115/50 to 217/130 mmHg. Considering experimental results, the ECG changes in this case show clear evidence that even in healthy humans OR-induced systemic haemodynamic changes may be complicated by severe myocardial ischaemia due to coronary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Silent pilin genes of Neisseria gonorrhoeae MS11 and the occurrence of related hypervariant sequences among other gonococcal isolates.

Pilin variation in Neisseria gonorrhoeae depends on a family of variant genes that undergo homologous, intragenic recombination. This work focuses on the repertoire of silent variant pilin genes in strain MS11, which contribute to the extensive variation of the expressed gene copy. A total of 17 silent copies were identified, which are, to varying degrees, truncated at their 5' coding region and grouped in seven distinct pil loci. Most silent copies belong to loci pilS1, pilS2 and pilS6, which contain six, two and three silent copies, respectively, tandemly arranged. The pilS5 and pilS7 loci each contain only a single copy. In addition, two silent copies are associated with each of the two pilE loci. By comparison with sequences present in the expressed gene of other variants of the same strain, it is suggested that each silent locus is capable of donating variant sequences into the expression locus and, thus, each silent copy can contribute to the variability of pilin expression. Often, concomitant with changes in the expressed copy, the silent copies of the pilE1 locus undergo recombinations as well. Analyses of unrelated clinical isolates of N. gonorrhoeae reveal homologies of hypervariant pilin sequences with those present in strain MS11, suggesting a limited diversity of such sequences within the gonococcal population and the existence of substantial functional constraints on the variability of pilin and pili. The data further indicate that hypervariant pilin sequences are subject to horizontal exchange and interstrain recombination.

Bacterial Outer Membrane Proteins↗