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Biomedical subjects

S Schwarz

Publications and source records attributed to S Schwarz.

At least 55 records · Page 3Linked to original sources
PubMed2003

Neuroendocrine changes in patients with acute space occupying ischaemic stroke.

OBJECTIVE: To evaluate neuroendocrine changes in critical care patients with acute space occupying hemispheric stroke. METHODS: 22 patients with acute space occupying hemispheric stroke were studied (mean age 57.7 years; five women, 17 men). Plasma levels of prolactin, thyrotropin (TSH), total thyroxine (T4), free thyroxine (FT4), and total triiodothyronine (T3) were measured on admission and thereafter on days 3, 5, 7, and 9. Cortisol and ACTH levels were analysed at 8.00, 16.00, and 24.00 hours each day. A TRH stimulation test with measurements of TSH and prolactin was done on day 3. RESULTS: Nine patients underwent decompressive craniectomy and nine were treated with moderate hypothermia. All patients received vasopressor drugs because of arterial hypotension. Plasma ACTH and cortisol values were abnormally low despite systemic hypotension and acute systemic illness, and remained low throughout the observation period. The diurnal rhythm of cortisol was not preserved. Prolactin levels increased during the observation period, and were well above normal on day 9. Thyroid function was slightly suppressed until day 7. TRH stimulation of plasma TSH and prolactin was low. CONCLUSIONS: Patients with an acute space occupying cerebral infarct show profound neuroendocrine changes. The central regulation of adrenal and thyroid function and prolactin release is impaired, which may compromise the clinical course of affected patients and have implications for therapeutic management.

Adrenocorticotropic Hormone↗
PubMed2003

Tumor- and pregnancy-derived isoforms of human chorionic gonadotropin: biological and diagnostic relevance.

OBJECTIVES: Human chorionic gonadotropin (hCG) and hCG variants are of high clinical importance for the diagnosis of pregnancy, monitoring of abnormal and ectopic pregnancies, testing for Down's syndrome or monitoring therapy of hCG-secreting malignancies. In serum and urine, hCG appears in microheterogeneous isoforms with respect to protein backbone structure and the extent of glycosylation. The present study reports on the identification, immunological characterization, biological activity of glycosylation isoforms of pregnancy (preg) and tumor-derived (tu) hCG, and the impact of glycosylation on diagnostic immunoassays. METHODS: Twenty-two urinary preg- and tu-hCG isoforms were separated by preparative isoelectrofocusing (hCG-pI variants) and characterized by Western blot. Number, topography and accessibility pattern of epitopes on their surface was evaluated by two-site radioimmunoassays using 14 different monoclonal antibodies (mabs). Binding of hCG isoforms to four different LH/CG receptors was investigated in radioreceptor assays, and their biological activity determined by measuring cAMP elevation. RESULTS: All 22 hCG glycosylation variants appeared immunologically intact: each isoform, even when highly acidic, expressed all 14 surface epitopes which were arranged in a topographical manner indistinguishable from crude hCG. hCG isoforms were able to bind to four different receptor variants, with slightly varying affinities, but orientations indistinguishable from each other as shown by identical epitope accessibility patterns. Each of the hCG-pI variants was able to activate the LH/CG-Rs, but with varying reactivities. CONCLUSIONS: We conclude that in contrast to deglycosylated hCG, all hCG glycosylation isoforms investigated act as receptor agonists. Moreover, there is no overspecificity of mabs to certain hCG isoforms due to carbohydrate variability that exclude others from diagnostic measurement.

Adult↗
PubMed2003

Synthesis and nicotinic binding studies on enantiopure pinnamine variants with an 8-azabicyclo[3.2.1]octane moiety.

Bioisosteric replacement of the 9-azabicyclo[4.2.1]nonane pharmacophoric element of the novel alkaloidal marine toxine pinnamine (5) by the 8-azabicyclo[3.2.1]octane moiety resulted in conformationally restricted analogues 6a and 6c of (-)-ferruginine (4). Key step in the diastereoselective synthesis of these pyranotropanes was the condensation of enantiopure ecgonine methyl ester (9) from the "chiral pool" with the lithium anion of N-tert-butylbutyraldimin and subsequent cyclisation with TFA. The potential nAChR ligands were tested for their in vitro affinity for the (alpha4)2(beta2)3 and the alpha7* nAChR subtypes. Despite obvious structural similarities with the potent alkaloids pinnamine (5) and (-)-ferruginine (4) the pyranotropanes 6a and 6c exhibited distinctly lower nAChR affinities.

Animals↗
PubMed2002

Estradiol, testosterone, dehydroepiandrosterone and androstenedione: novel derivatives and enantiomers. Interactions with rat liver microsomal cytochrome P450 and antioxidant/radical scavenger activities in vitro.

Interactions of 27 steroids, among them 17 derivatives such as ethers, sulfates and amidosulfonates derived from 17 beta- and 17 alpha-estradiol, from testosterone and alpha- and beta-dihydrotesosterone and from dehydroepiandrosterone with rat liver microsomal cytochromes P450 (P450) were investigated in vitro by assessing binding to P450 and effects on P450 mediated monooxygenase functions as measured by different model reactions: ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD) and ethylmorphine N-demethylation (EMND). With the exception of 17 alpha-estradiol-3-dimethylamidosulfonate, estrone, its -3-methylether and -3-amidosulfonate and testosterone, all other steroids displayed type I or reverse type I binding to P450. All steroids inhibited EROD activity in micromolar concentrations. An additional strong inhibition of ECOD and EMND activities was only demonstrated for the androgens and progestins. Estriol, estrone and mestranol displayed less inhibitory actions on the model reactions than estradiol. No major differences in comparison to the parent compounds were noted with the other derivatives. The only exceptions were 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol, which displayed stronger effects than estradiol, and dehydroepiandrosterone-3-sulfate, which was less effective than dehydroepiandrosterone. Possible antioxidant properties of the steroids were examined by the stimulated lipid peroxidation (LPO), H2O2 production, and lucigenin (LC) and luminol (LM) amplified chemiluminescence (CL) using rat liver microsomes. Additionally, the influence on rat whole blood chemiluminescence (WB-CL) was assessed. All the estrogens, but not their methylethers and amidosulfonates inhibited LPO in micromolar concentrations. The effects on the other oxidase model reactions or on WB-CL were less distinct. Only ethinylestradiol and 17 beta-(8,9-dehydro-14 alpha,15 alpha-methylene)estradiol displayed a strong inhibitory action on all model reactions. With the exception of dehydroepiandrosterone-3-sulfate, which in general had only weak effects, the androgen and progestin derivatives, in contrast, strongly decreased H2O2 formation and LM- and LC-CL, but were mostly ineffective on LPO and WB-CL.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2002

[Current concepts of intensive care of space-occupying middle cerebral artery infarct].

The aim of this paper is to review new developments in the intensive care of patients with space-occupying middle cerebral artery infarctions. Elevated blood pressure should not be treated; however, there is no scientific basis to induce arterial hypertension in these patients. It is not recommended generally to nurse the patients in a position with the head elevated. If therapy is targeted for an optimum cerebral perfusion pressure, the patients should be nursed in a flat position. Decompressive surgery is associated with a marked reduction in an otherwise high mortality. The functional outcome after surgery is similar to the outcome of the survivors after conventional treatment alone. Treatment options for an acutely raised intracranial pressure are mannitol or hypertonic saline solutions, although the long-term effects have not been ascertained yet. There is not enough evidence supporting a prophylactic standard therapy with hypertonic solutions. Patients who require artificial ventilation can be safely ventilated using PEEP or an inverse inspiration/expiration ratio, if the blood pressure is monitored and a possible drop of the arterial blood pressure is treated. Corticoids and hemodilution are obsolete therapies in these patients.

Blood Pressure↗
PubMed2002

[Alcohol and stroke. Is moderate alcohol consumption protective?].

It is now increasingly recognized that mild to moderate consumption of alcohol is associated with reduced mortality and coronary heart disease. Alcohol consumption and mortality follows a J-shaped association, with increasing mortality in heavy drinkers. There is some evidence from epidemiological studies that mild to moderate alcohol consumption may also reduce the risk of ischemic stroke and overall stroke in persons over 40 years of age. However, these studies have been criticized for not adequately considering possible confounding factors. Moreover, alcohol consumption is associated with an increased risk of intracerebral and sub-arachnoid hemorrhage, and binge drinking is a strong risk factor for both ischemic and hemorrhagic stroke. Alcohol consumption probably has no beneficial effects in young subjects. On the basis of the current evidence, it is not justified to advise an otherwise healthy, mild to moderate consumer of alcoholic beverages to quit drinking. However, it seems premature to advise alcohol consumption generally for prevention of stroke.

Adult↗
PubMed2002

A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E epsilon4 allele.

Because of its implication in neuroprotection, formation of long lasting memories and a disturbed function in Alzheimer's disease (AD), brain-derived neurotrophic factor (BDNF) may represent an appropriate candidate gene conferring risk to AD. Recently, a single nucleotide polymorphism (C-270T) within the BDNF gene has been associated with late onset AD in a Japanese population giving an odds ratio (OR) of 3.8. Because of the importance of this finding we analysed the BDNF polymorphism in a German sample consisting of 210 patients with AD and 188 cognitively healthy controls. The T-allele frequency was higher in patients with AD (11.9%) compared to controls (6.9%) (P = 0.035; OR = 2.26; 95% CI: 1.04-4.48). The risk conferred by the T-allele was stronger in patients who lack the ApoE epsilon4 allele giving an OR of 2.61 (1.21-5.64) P = 0.015, particularly in patients with early onset of the disease; OR 3.13 (1.32-7.43); P= 0.01. Due to the small number of patients showing both, lack of the ApoE epsilon4 allele and the BDNF T allele (n = 18), the result needs to be confirmed in a larger sample. The results suggest that the BDNF C-270T polymorphism is a relevant risk factor for AD particularly in patients lacking the ApoE epsilon4 allele in this German sample.

Age of Onset↗
PubMed2002

Noninvasive monitoring of hypertensive breakthrough of cerebral autoregulation in a patient with acute ischemic stroke.

BACKGROUND AND PURPOSE: We describe the first documentation of hypertensive breakthrough of cerebral autoregulation in a patient with acute stroke with transcranial Doppler sonography. CASE DESCRIPTION: A 55-year-old patient with acute left hemispheric stroke was treated with moderate hypothermia. He died of transtentorial herniation 4 days after admission. Static cerebral autoregulation (sCA) of the unaffected hemisphere was evaluated 6 times during this period and always found to be intact. A bolus application of epinephrine resulted in a hypertensive episode (mean arterial pressure (MAP) 135 mm Hg); hypertensive breakthrough of cerebral autoregulation was evident when MAP exceeded approximately 110 mm Hg. Interestingly, no such breakthrough was evident during testing of sCA, even when MAP reached 120 mm Hg. CONCLUSIONS: Our observation suggests that (1) the pace of the MAP increase is crucial for the occurrence of a hypertensive breakthrough of the cerebral autoregulation and (2) the disturbance of cerebral autoregulation is potentially longer as previously assumed.

Blood Pressure Monitoring, Ambulatory↗
PubMed2002

Hemicraniectomy and moderate hypothermia in patients with severe ischemic stroke.

BACKGROUND AND PURPOSE: We compared the clinical course of 36 consecutive patients with severe acute ischemic stroke (more than two thirds of the middle cerebral artery territory) treated with hemicraniectomy (CE; n=17) or moderate hypothermia (MH; n=19) in terms of intracranial pressure control, mortality, and specific treatment parameters. METHODS: Over a period of 18 months, patients with severe ischemic stroke were treated with CE when the nondominant hemisphere was affected and with MH when the dominant hemisphere was affected. MH (33 degrees C) was induced with either cold blankets and fans (n=11) or endovascular cooling (n=8). Intracranial pressure was monitored invasively in all cases. RESULTS: Age, sex, cranial CT findings, level of consciousness, and time to treatment were similar between the 2 groups; significant differences were noted in National Institute of Health Stroke Scale (NIHSS) score (20 [range, 18 to 22] and 17 [range, 16 to 18] for MH and CE, respectively) but were not present when NIHSS score was corrected for aphasia (17 [range, 15 to 19] and 17 [range, 16 to 18] for MH and CE, respectively). Mortality was 12% for CE and 47% for MH; 1 patient treated with MH died as a result of treatment complications (sepsis) and 3 of intracranial pressure crises that occurred during rewarming. Duration of mechanical ventilation and of neurological intensive care unit stay did not significantly differ, but duration of catecholamine application and maximal catecholamine dosage were significantly higher in the MH group. CONCLUSIONS: In patients with severe ischemic stroke, CE results in lower mortality and lower complication rates compared with MH. Both treatment modalities, however, are associated with intensive medical treatment and a prolonged stay in the neurological intensive care unit.

Adult↗
PubMed2002

Cerebral autoregulation under moderate hypothermia in patients with acute stroke.

BACKGROUND AND PURPOSE: We undertook this study to examine the integrity of cerebral autoregulation in patients with acute ischemic stroke treated with moderate hypothermia (33 degrees C). METHODS: Fourteen patients, aged 58+/-11 years, with an acute anterior circulation infarction and National Institutes of Health Stroke Scale score >15 were evaluated. Patients received catecholamines (norepinephrine) via continuous intravenous infusion and were mechanically ventilated. Alpha-stat was used for pH maintenance. Arterial pressure (AP) and intracranial pressure (ICP) were invasively monitored. Flow velocity in the middle cerebral artery (MCA) supplying the unaffected hemisphere was continuously monitored. Instantaneous maximum flow velocity (V(max) MCA), ICP, and AP were simultaneously recorded in real time. Mean values of V(max) MCA (V(mean) MCA) and AP (MAP) were calculated over 1 minute. Static cerebral autoregulation (sCA) was calculated as sCA=(%DeltaCVR/%DeltaMAP)x100% (where %DeltaCVR is an estimate of percent change in cerebrovascular resistance). An sCA value of 0% indicates absent autoregulation, and a value of 100% indicates perfect autoregulation. Autoregulation is considered impaired when sCA values are <40%. MAP changes were produced by increasing the rate of the norepinephrine infusion. Six patients were examined under both normothermic and hypothermic conditions, while 8 were examined only under hypothermia. RESULTS: The induced MAP increase was 22+/-7 mm Hg (minimum 13, maximum 40 mm Hg). Mean sCA was 64+/-16% (minimum 40%, maximum 100%). No effect of moderate hypothermia on sCA or V(mean) MCA was evident in any of the 6 serially examined patients. Normocapnia was observed in all cases. CONCLUSIONS: sCA appears intact under moderate hypothermia with the use of alpha-stat for pH maintenance.

Acute Disease↗
PubMed2001

Occurrence and linkage of genes coding for resistance to sulfonamides, streptomycin and chloramphenicol in bacteria of the genera Pasteurella and Mannheimia.

Twenty-three isolates of the two genera Pasteurella (P.) and Mannheimia (M.) were analysed for the presence of genes specifying resistance to sulfonamides, streptomycin, and chloramphenicol. Specific PCR assays for the detection of the genes sulII, strA and catAIII, but also for the confirmation of their physical linkage were developed. A resistance gene cluster consisting of all three genes and characterised by a PCR amplicon of 2.2 kb was detected on four different types of plasmids and also in the chromosomal DNA of seven isolates. Physically linked sulII and strA genes were detected on three different types of plasmids and in the chromosomal DNA of three isolates. Sequence analysis of the different PCR amplicons revealed that these genes were present in either the orientation sulII-strA separated by differently sized spacer sequences, or strA-sulII. A truncated strA gene preceding a sulII gene was also detected in two cases.

Animals↗
PubMed2001

Breakdown of the isobaric multiplet mass equation at A = 33, T = 3/2.

Mass measurements on (33,34,42,43)Ar were performed using the Penning trap mass spectrometer ISOLTRAP and a newly constructed linear Paul trap. This arrangement allowed us, for the first time, to extend Penning trap mass measurements to nuclides with half-lives below one second ( 33Ar: T(1/2) = 174 ms). A mass accuracy of about 10(-7) (deltam approximately 4 keV) was achieved for all investigated nuclides. The isobaric multiplet mass equation was checked for the A = 33, T = 3/2 quartet and found to be inconsistent with the generally accepted quadratic form.

Journal Article↗
PubMed2001

Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients.

OBJECTIVES: To describe the clinical, CSF, and radiologic findings and long-term follow-up in a cohort of patients with acute disseminated encephalomyelitis (ADEM), and to determine possible prognostic factors for progression to MS. METHODS: Forty adults (28 women, mean age 33.5 years) diagnosed with ADEM were analyzed. Clinical symptoms, cranial MRI and CSF findings, and the response to a standardized treatment during the acute phase of the disease were analyzed by chart review. The final diagnosis of ADEM or clinically definite MS was established upon follow-up examination after 8 to 137 months. The patients with ADEM and MS were compared to detect differences between the two groups. RESULTS: Fifteen patients had a preceding infection (n = 14) or immunization (n = 1). The most frequent clinical signs were motor deficit (80%), followed by sensory deficits, brainstem signs, and ataxia. CSF findings were highly variable; normal results were present in 20% of patients. Oligoclonal bands were positive in 65% of patients. Ninety-five percent of all patients improved during the acute phase of the disease. Upon follow-up, 14 patients had developed clinically definite MS. Of the 26 patients with the final diagnosis of ADEM, two patients had died, nine had minor deficits, three had moderate deficits, and 12 patients had no remaining symptoms. Patients with the final diagnosis of ADEM were older, and more often had a preceding infection, clinical signs of brainstem involvement, a higher CSF albumin fraction, and infratentorial lesions. CONCLUSIONS: Many patients initially diagnosed with ADEM develop clinically definite MS upon long-term follow-up. The authors found no useful diagnostic criteria for the differentiation of a first episode of MS from monophasic ADEM. The term ADEM may still be employed as a description of a clinical syndrome, but should not be used as a distinct entity until reliable diagnostic criteria have been developed.

Adult↗
PubMed2001

Point mutant mice with hypersensitive alpha 4 nicotinic receptors show dopaminergic deficits and increased anxiety.

Knock-in mice were generated that harbored a leucine-to-serine mutation in the alpha4 nicotinic receptor near the gate in the channel pore. Mice with intact expression of this hypersensitive receptor display dominant neonatal lethality. These mice have a severe deficit of dopaminergic neurons in the substantia nigra, possibly because the hypersensitive receptors are continuously activated by normal extracellular choline concentrations. A strain that retains the neo selection cassette in an intron has reduced expression of the hypersensitive receptor and is viable and fertile. The viable mice display increased anxiety, poor motor learning, excessive ambulation that is eliminated by very low levels of nicotine, and a reduction of nigrostriatal dopaminergic function upon aging. These knock-in mice provide useful insights into the pathophysiology of sustained nicotinic receptor activation and may provide a model for Parkinson's disease.

Animals↗
PubMed2001

Proton MR spectroscopy of the lumbar spine in patients with glycogen storage disease type Ib.

Glycogen storage disease type Ib is an autosomal recessive inherited metabolic disorder resulting from deficiency of the microsomal glucose-6-phosphatase enzyme system. Six patients (three of which were treated with granulocyte colony stimulating factor) suffering from this disease were examined using image guided localized proton magnetic resonance (MR) spectroscopy. The relative signal intensities of water and lipid protons of the lumbar spine were determined. Comparison was made with iliac crest biopsies in the glycogen storage disease type Ib patients and localized proton MR spectroscopic values of the lumbar spine obtained by thirteen healthy volunteers. The data demonstrate for the first time that hypercellularity and myeloid hyperplasia in subjects with glycogen storage disease type Ib due to functionally impaired leucocytes results in a strongly increased water proton signal with a very low or absent lipid signal in localized proton MR spectroscopy. Upon granulocyte colony stimulating factor treatment, the water proton signal in the lumbar spine is not further augmented.

Adolescent↗
PubMed2001

Equi-lasting doses of rocuronium, compared to mivacurium, result in improved neuromuscular blockade in patients undergoing gynecological laparoscopy : [Des doses de durée équivalente de rocuronium, comparé au mivacurium, améliorent la curarisation chez des patientes qui subissent une laparoscopie gynécologique].

PURPOSE: To compare equi-lasting doses of a short-acting (mivacurium) to an intermediate-acting (rocuronium) neuromuscular relaxant, with regard to intubating conditions, efficacy, number of maintenance doses, hemodynamic alterations, adverse events and costs, in patients undergoing laparoscopic gynecological surgery. METHODS: Sixty patients were randomly allocated to receive either 0.2 mg*kg(-1) (3 x ED(95)) mivacurium or 0.5 mg*kg(-1) (1.7 x ED(95)) rocuronium, under propofol/fentanyl anesthesia. T1, first twitch of the train-of-four (TOF) and TOF ratio (T4:T1) were used to evaluate neuromuscular block using the Relaxometer(R) mechanomyograph. The trachea was intubated when T1 was maximally suppressed. Neuromuscular block was maintained at 25% T1 with equi-lasting doses of 0.075 mg*kg(-1) mivacurium or 0.15 mg*kg(-1) rocuronium. RESULTS: Mean (min) +/- SD mivacurium onset time (1.9 +/- 0.4) was longer than that of rocuronium (1.3 +/- 0.3). This did not yield a statistical difference in intubating conditions between the two groups. Interval 25-75% T1 recovery and time to 0.8 TOF recovery were prolonged following rocuronium (11.9 +/- 3.9, 52.6 +/- 15.5 respectively) compared to mivacurium (6.7 +/- 2.3, 39.2 +/- 8.1 respectively). More patients, 22/30, required mivacurium maintenance doses compared to 14/30 patients in the rocuronium group. Arterial blood pressure declined and 13/30 patients manifested erythema following mivacurium administration. The acquisition costs of rocuronium (6.93 Euro/patient) were 23% lower compared to mivacurium (8.96 Euro/patient). CONCLUSION: Equi-lasting doses of rocuronium resulted in favourable intubating conditions more rapidly, improved hemodynamic stability, required less frequent administration of maintenance doses and were not associated with erythema, compared to mivacurium.

Adolescent↗