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Biomedical subjects

S Ulrich

Publications and source records attributed to S Ulrich.

At least 19 recordsLinked to original sources
PubMed2002

[22-year-old patient with left groin pain].

A 22 year old man from Ethiopia suffered from progressive left inguinal pain and weight loss for ten months. The pain aggravated with leg movement, in particular with flexion of the left hip. ESR and CRP were slightly elevated, and a PPD was strongly positive. Abdominal ultrasound was normal but CT-scan revealed a left sided psoas abscess. Pott's disease was suspected and tuberculostatic therapy with INH, PZA, ETH, RIF was initiated immediately. A MRI of the spine excluded spondylodiscitis. Primary Tb psoas abscess was diagnosed. Treatment response after 5 weeks was clinically insufficient and CT-scan showed enlargement of the abscess. Treatment adherence was verified by drug prescriptions and INH urinary stix testing. M. tuberculosis, suspected microscopically in the puncture fluid, grew in culture and was fully drug sensitive. After 12 weeks, surgical abscess debridement had to be performed due to disease progression. The patient's health state improved considerably the first two postoperative months, inflammatory markers normalized, although a small residual abscess was still visible on CT. Subsequently, three months after surgery, pain reemerged, CT showed abscess progression. The patient had to be reoperated. Tb psoas abscess was a frequently described complication of Tb spondylodiscitis (Pott's disease) the first half of the last century and became rare thereafter in the Western hemisphere. However, the last two decades, due to migration policies and a worldwide increase of Tb epidemic because of socioeconomic destabilization and spread of the HIV-pandemic, Tb reemerged in Western countries. Therefore, physicians should be aware of atypical manifestations of tuberculosis. Primary Tb psoas abscess is extremely rare. Only four cases are described in the literature. In analogy to Pott's disease, therapy consists of tuberculostatic treatment, supported by surgical debridement.

Adult↗
PubMed2002

Effect of aspirin treatment in patients with peripheral arterial disease monitored with the platelet function analyzer PFA-100.

We have used the platelet analyzer PFA-100TM to assess the effect of aspirin (ASA) in patients with documented peripheral arterial disease (PAD). Thirty-one previously untreated patients were recruited. Laboratory investigations, including the collagen and adenosine diphosphate closure time (CADP-CT) and the collagen and epinephrine closure time (CEPI-CT) were performed before and 7 days after treatment with 100 mg ASA per day. Five patients were excluded from the final analysis: one patient did not appear for second examination, in one patient type I von Willebrand disease was diagnosed, and three patients with prolonged CEPI-CT admitted the intake of non-steroidal anti-inflammatory drugs. Prior to ASA treatment, CADP-CT was 90 +/- 15 s (range, 67-124 s) and CEPI-CT was 116 +/- 27 s (range, 78-164 s). There was a significant negative correlation between CADP-CT and von Willebrand factor antigen (r = -0.57, P = 0.001). After treatment with 100 mg ASA per day, CADP-CT was not significantly different (96 +/- 22 s; range, 65-158 s). CEPI-CT, however, was prolonged in all patients, compared with pre-ASA values (226 +/- 82 s; range, 89 to > 300 s). In 12 of 26 patients, CEPI-CT was > 300 s and in another four of 26 patients CEPI-CT was prolonged to more than the upper normal range ('responders'). In the remaining 10 patients, CEPI-CT values did not exceed the upper limit of the normal range ('non-responders'). Five non-responders were re-investigated after intake of 300 mg ASA per day for 3 weeks; in none of these was a CEPI-CT > 165 s recorded. We conclude that 40% of PAD patients have an inadequate response to ASA, as determined by the PFA-100TM CEPI-CT. Whether these patients have a reduced benefit from this treatment remains to be investigated.

Adenosine Triphosphate↗
PubMed2001

A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus.

BACKGROUND: It is uncertain whether the administration of benzodiazepines by paramedics is an effective and safe treatment for out-of-hospital status epilepticus. METHODS: We conducted a randomized, double-blind trial to evaluate intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus. Adults with prolonged (lasting five minutes or more) or repetitive generalized convulsive seizures received intravenous diazepam (5 mg), lorazepam (2 mg), or placebo. An identical second injection was given if needed. RESULTS: Of the 205 patients enrolled, 66 received lorazepam, 68 received diazepam, and 71 received placebo. Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001). After adjustment for covariates, the odds ratio for termination of status epilepticus by the time of arrival in the lorazepam group as compared with the placebo group was 4.8 (95 percent confidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95 percent confidence interval, 0.8 to 4.4) in the lorazepam group as compared with the diazepam group and 2.3 (95 percent confidence interval, 1.0 to 5.9) in the diazepam group as compared with the placebo group. The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08). CONCLUSIONS: Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam.

Adult↗
PubMed2001

The prehospital treatment of status epilepticus (PHTSE) study: design and methodology.

Status epilepticus is a neurological emergency that is typically first encountered and managed in the prehospital environment. Although aggressive pharmacological treatment of status epilepticus is well established in the emergency department and hospital settings, the relative risks and benefits of active therapy for status epilepticus in the prehospital setting are not known. The Prehospital Treatment of Status Epilepticus (PHTSE) study is a prospective, randomized, double-blind, placebo-controlled study designed to address the following aims: (1) to determine whether administration of benzodiazepines by paramedics is an effective and safe means of treating status epilepticus in the prehospital setting and whether this therapy influences longer-term patient outcome, (2) to determine whether lorazepam is superior to diazepam for the treatment of status epilepticus in the prehospital setting, and (3) to determine whether control of status epilepticus prior to arrival to the emergency department influences patient disposition. The initial phase of the PHTSE study began in January 1994 and was completed in February 1999 after the successful enrollment of 205 patients into the three treatment arms. In this paper, we describe the rationale for the conceptualization of the study and details of the study design and methodology, and emphasize some aspects of study implementation that are unique to research involving the emergency medical system.

Adult↗
PubMed2001

A novel HLA-DRB1 sequence, DRB1*11272.

We describe the complete exon 2 sequence of a novel HLA-DRB1 allele, DRB1*11272. This allele differs from the DRB1*11271 allele by a synonymous mutation in codon 77 where an AAT is replaced with AAC, both encode for the amino acid asparagine. The same motif at codon 77 has also been found in DRB1*1107, DRB1*1333, DRB1*0422 and in most DRB1*03 alleles. A partial exon 2 sequence of this allele has previously been deposited in the EMBL Sequence Database under the accession number AF186407.

Alleles↗
PubMed2001

Serum levels of amitriptyline and therapeutic effect in non-delusional moderately to severely depressed in-patients: a therapeutic window relationship.

In a prospective, open clinical study, the relationship between serum levels of amitriptyline (At) and nortriptyline (Nt) and the therapeutic effect after 6 weeks of treatment was investigated. Serum levels were measured by gas-liquid chromatography and the therapeutic effect was assessed by the Hamilton Depression Rating Scale (HAMD) and the Clinical Global Impression Scale (CGI). A number of 25 non-delusional, moderate to severely depressed inpatients were included. A therapeutic window relationship was detected by means of regression analysis (quadratic model). Low and high serum levels were associated with low therapeutic effect. In an intermediate range, the probability of good therapeutic effect was increased. This relationship reached significance for the serum levels of At (p < 0.05) and a trend for the sum of serum levels of At and Nt (p < 0.1). As expressed by the regression coefficient r2, about 25% to 35% of the variability of therapeutic effect was explained by serum levels. Dichotomized data sets according to limits of final values of HAMD and CGI as well as limits of a therapeutic window of 70 ng/ml and 200 ng/ml (sum of At and Nt) revealed significant differences by means of Fisher's exact test (p < 0.05). Furthermore, increased ratios of serum level of Nt per serum level of At were found to be associated with decreased therapeutic effect. Thus, the present data support the existence of a therapeutic window of serum levels of At in depression. Also taking into account other reports, this therapeutic window can be defined as being between about 70 and 220 ng/ml. The assay of serum levels of At can be used to lower the risk of unsatisfactory therapeutic outcome.

Adult↗
PubMed2000

Solid-phase microextraction in biomedical analysis.

Chromatographic methods are preferred in the analysis of organic molecules with lower molecular mass (<500 g/mol) in body fluids, i.e., the assay of drugs, metabolites, endogenous substances and poisons as well as of environmental exposure by gas chromatography (GC) and liquid chromatography (LC), for example. Sample preparation in biomedical analysis is mainly performed by liquid-liquid extraction and solid-phase extraction. However, new methods are investigated with the aim to increase the sample throughput and to improve the quality of analytical methods. Solid-phase microextraction (SPME) was introduced about a decade ago and it was mainly applied to environmental and food analysis. All steps of sample preparation, i.e., extraction, concentration, derivatization and transfer to the chromatograph, are integrated in one step and in one device. This is accomplished by the intelligent combination of an immobilized extraction solvent (a polymer) with a special geometry (a fiber within a syringe). It was a challenge to test this novel principle in biomedical analysis. Thus, an introduction is provided to the theory of SPME in the present paper. A critical review of the first applications to biomedical analyses is presented in the main paragraph. The optimization of SPME as well as advantages and disadvantages are discussed. It is concluded that, because of some unique characteristics, SPME can be introduced with benefit into several areas of biomedical analysis. In particular, the application of headspace SPME-GC-MS in forensic toxicology and environmental medicine appears to be promising. However, it seems that SPME will not become a universal method. Thus, on-line SPE-LC coupling with column-switching technique may be a good alternative if an analytical problem cannot be sufficiently dealt with by SPME.

Body Fluids↗
PubMed2000

Disposition of haloperidol pyridinium and reduced haloperidol pyridinium in schizophrenic patients: no relationship with clinical variables during short-term treatment.

In an open clinical trial, serum concentrations of haloperidol pyridinium (C(HP+)) and reduced haloperidol pyridinium (C(RHP+)), as well as haloperidol (CH) and reduced haloperidol (C(RH)), were measured in 57 schizophrenic and schizoaffective inpatients during 6 weeks of short-term treatment. Psychopathology was monitored with the Brief Psychiatric Rating Scale (BPRS), and extrapyramidal adverse effects were assessed with the Extrapyramidal Symptom Rating Scale (EPS). Significantly linear relationships were found between haloperidol dose (D) and pyridinium metabolite serum concentrations, as well as between C(H) and the pyridinium metabolite serum concentrations. C(HP+) (range, 0.2-4.9 ng/mL) and C(RHP+) (range, 0.03-6.23 ng/mL) were low compared with C(H) and C(RH), being as mean values approximately 7% and 14% of C(H) and C(RH), respectively. Additionally, the values of C(RHP+) and the slope of the correlation of C(H) with the C(RHP+)/C(HP+) ratio were considerably lower than in a previous report of long-term treatment with haloperidol. This is explained by the shorter time of treatment of the present study. Carbamazepine comedication was found to not influence relative pyridinium metabolite serum concentrations C(HP+)/D and C(RHP+)/D. However, the aromatization ratios of haloperidol (C(HP+)/C(H)) and reduced haloperidol (C(RHP+)/C(RH)) were increased by concomitant carbamazepine. As the main result, no relationships between the pyridinium metabolite serum concentrations and clinical variables (BPRS change, EPS, dose of biperiden) were detected. For instance, the aromatization ratios C(HP+)/C(H) and C(RHP+)/C(RH) did not predict clinical improvement or extrapyramidal adverse effects. Therefore, no confirmation of the "pyridinium hypothesis," which suggests haloperidol pyridinium metabolites to be the origin of adverse effects and decreased therapeutic effect, can be derived from this study. However, the authors emphasize that pyridinium metabolites cannot be excluded as the origin of decreased therapeutic effect in long-term treatment and of adverse effects not investigated in the present study, such as tardive dyskinesia. Finally, it is concluded that the serum concentration of the parent drug remains the main variable of interest in the therapeutic drug monitoring of haloperidol during short-term treatment.

Adult↗
PubMed2000

Solid-phase microextraction for the assay of levomepromazine in human plasma.

Solid-phase microextraction (SPME) was investigated as sample preparation for the assay of the neuroleptic drug levomepromazine in human plasma. A mixture of human plasma, water, chloramitriptyline as internal standard, and aqueous NaOH was extracted with a 100-microm polydimethylsiloxane (PDMS) fiber (Supelco). The desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C [HP 5890; BPX-5 (SGE): 30 m x 0.53 mm ID, 1-microm film capillary; nitrogen-phosphorus selective detection]. As repeatedly found for SPME analysis of drugs in plasma, the recovery was low (i.e., 7% for levomepromazine). However, the analyte and internal standard were well separated and the calibration was linear from 5 to 180 ng/mL. The within-day precision was 2%, 4%, and 19% at concentrations of 160 ng/mL, 80 ng/mL, and 5 ng/mL, respectively. The between-day precision was 3%, 7%, and 19%, respectively. The limit of determination was 5 ng/mL. The comparison with an established liquid-liquid extraction gas-liquid chromatography method revealed good agreement for spiked samples and patient samples. No interfering peaks of drugs coadministered with levomepromazine or of endogenous substances were found. It is concluded that the method can be used in the therapeutic drug monitoring and clinical toxicology of levomepromazine.

Antipsychotic Agents↗
PubMed2000

Unnatural ligands for engineered proteins: new tools for chemical genetics.

Small molecules that modulate the activity of biological signaling molecules can be powerful probes of signal transduction pathways. Highly specific molecules with high affinity are difficult to identify because of the conserved nature of many protein active sites. A newly developed approach to discovery of such small molecules that relies on protein engineering and chemical synthesis has yielded powerful tools for the study of a wide variety of proteins involved in signal transduction (G-proteins, protein kinases, 7-transmembrane receptors, nuclear hormone receptors, and others). Such chemical genetic tools combine the advantages of traditional genetics and the unparalleled temporal control over protein function afforded by small molecule inhibitors/activators that act at diffusion controlled rates with targets.

Alleles↗
PubMed2000

Unique properties of R-type calcium currents in neocortical and neostriatal neurons.

Whole cell recordings from acutely dissociated neocortical pyramidal neurons and striatal medium spiny neurons exhibited a calcium-channel current resistant to known blockers of L-, N-, and P/Q-type Ca(2+) channels. These R-type currents were characterized as high-voltage-activated (HVA) by their rapid deactivation kinetics, half-activation and half-inactivation voltages, and sensitivity to depolarized holding potentials. In both cell types, the R-type current activated at potentials relatively negative to other HVA currents in the same cell type and inactivated rapidly compared with the other HVA currents. The main difference between cell types was that R-type currents in neocortical pyramidal neurons inactivated at more negative potentials than R-type currents in medium spiny neurons. Ni(2+) sensitivity was not diagnostic for R-type currents in either cell type. Single-cell RT-PCR revealed that both cell types expressed the alpha1E mRNA, consistent with this subunit being associated with the R-type current.

Animals↗
PubMed1999

[Tenascin: a simple tool in the diagnosis of collagenous colitis].

BACKGROUND: Collagenous colitis is characterised clinically by chronic, voluminous, watery diarrhoea, and histopathologically by a thickened subepithelial collagen layer and infiltration of the lamina propria with inflammatory cells. In practice, the exact measurement of this subepithelial collagen layer is complicated by its blunt limit, a nonorthogradely affected cell layer and often only focal findings. Immunohistochemically, the subepithelial collagen layer stains positively with the glycoprotein tenascin, a marker for extracellular matrix remodeling. AIM: To assess if immunohistochemical staining with tenascin could be used as a simple and practical tool in the diagnosis of collagenous colitis. METHODS: 86 of the routinely examined colon biopsy specimens with the following initial diagnosis: 33 collagenous colitis, 21 lymphocytic colitis, 15 inflammatory bowel disease (ulcerative colitis or Crohn's disease), 8 unspecific inflammation and 9 without histopathological findings, were incubated with tenascin. They were then evaluated blindly by 5 different investigators (2 senior pathologists, 2 assistant doctors and 1 chief assistant of the laboratory experienced in immunohistochemistry). Each specimen was evaluated semiquantitatively from 0 (for no tenascin-positive subepithelial collagen layer) to 3 (wide, clearly tenascin-positive collagen layer). RESULTS: In specimens with the initial diagnosis "collagenous colitis" the semiquantitatively assessed subepithelial collagen layer was significantly wider than in specimens with other initial diagnosis. Experience and educational level of the investigators did not influence the results. CONCLUSIONS: Immunohistochemical incubation with tenascin is a simple, economical and rapid tool in the diagnosis of collagenous colitis. With the aid of tenascin staining collagenous colitis can be differentiated histopathologically with sufficient accuracy from other colitis.

Biomarkers↗
PubMed1999

Fishing for a drug: solid-phase microextraction for the assay of clozapine in human plasma.

Solid-phase microextraction (SPME) was investigated as a sample preparation method for assaying the neuroleptic drug clozapine in human plasma. A mixture of human plasma, water, loxapine (as internal standard) and aqueous NaOH was extracted with a 100-micron polydimethylsiloxane (PDMS) fiber (Supelco). Desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C (HP 5890; 30 m x 0.53 mm I.D., 1 micron film capillary; nitrogen-phosphorous selective detection). Fibers were used repeatedly in up to about 75 analyses. The recovery was found to be 3% for clozapine from plasma after 30 min of extraction. However, in spite of the low recovery, the analyte was well separated and the calibration was linear between 100 and 1000 ng/ml. The within-day and between-day precision was consistently about 8 to 15% at concentrations of 200 ng/ml to 1000 ng/ml. No interfering drug was found. The limit of detection was 30 ng/ml. The sample volume was 250 microliters. The influence of the concentration of proteins, triglycerides and salt, i.e., changes in the matrix on the peak areas and peak-area ratios was studied. The method is not impaired by physiological changes in the composition of the matrix. Good agreement was found with a liquid-liquid extraction-gas-liquid chromatography (LLE-GLC) standard method and an on-line column-switching high-performance liquid chromatography (HPLC) method for patients' samples and spiked samples, respectively. It is concluded that the method can be used in the therapeutic drug monitoring of clozapine because the therapeutic window of clozapine is from 350 to 600 ng/ml.

Chromatography, Gas↗
PubMed1999

[Renal oncocytomatosis].

Multiple and bilateral oncocytomas are rare. There are only ten cases that have been previously described. Three of these displayed multiple and bilateral oncocytomas and microoncocytomas, a so-called oncocytomatosis. This report describes a case of renal oncocytomatosis found at autopsy. In addition, we found an adrenal adenoma, a pheochromocytoma and thoracic cicatrices 4 years after curatively resected large cell carcinoma of the lung. In the distal renal tubules we found oncocytic epithelial cells, with partial transition into microoncocytomas. Immunohistochemically, these and the main oncocytomas were CD 10 negative. These findings support the origin of oncocytoma from oncocytically transformed distal tubular epithelium. CGH analysis of the different tumors revealed no common cytogenetic changes. Coexistence of renal oncocytoma with other tumors is rare. Hitherto, coexistence of a renal oncocytomatosis with multiple tumors has not been described.

Adenoma↗
PubMed1999

Prehension with the ipsilesional hand after unilateral brain damage.

Sensorimotor deficits in the hand ipsilateral to a brain lesion have been reported in different motor tasks. We evaluated performance of the ipsilesional hand in 12 patients with either left (LBD) or right brain damage (RBD) by kinematic analysis in order to precisely characterize possible deficits in the two components of prehension (transport and grasp). Both patient groups exhibited performance deficits in the main kinematic parameters, e.g., reduced velocity of the transport component and prolonged movement time. However, while LBD patients showed a more general slowing, RBD patients prolonged in particular the last phase of the movement toward the object. We suggest that relevant visuospatial representations and the adequate mapping of motor processes may be impaired after RBD. In contrast, LBD caused a more unspecific disturbance pattern, supporting the view that the precise parameterization of motor programs is impaired. Maximum grip aperture was normal in both patient groups. However, since aperture could be biased by slowed movement, the notion that the grasp component was preserved remains speculative. The patient's ability to scale the maximum velocity of the transport component to adapt to changes in movement amplitude and to scale the maximum hand aperture of the grasp component to adapt to object size was preserved in both groups. Thus both hemispheres can have competence for this scaling mechanism.

Adult↗
PubMed1999

Crooked tail (Cd) models human folate-responsive neural tube defects.

Genetic correlation of human neural tube defects (NTDs) with NTD genes identified in mouse may unravel predisposing complex traits for assessment of individual risk and treatment in clinical settings. Folic acid (FA) can reduce the recurrence of NTDs in human populations by as much as 50-70%, though the mechanism of this rescue is unknown. We examined whether Crooked tail ( Cd ), a mouse strain prone to exencephaly, could provide a genetic animal model for folate-responsive NTDs. The Cd locus was localized to a 0.2 cM interval of the Mouse Genome Database genetic map, identifying tightly linked markers for genotyping prior to phenotypic expression. In a controlled diet study, Cd was found to mimic closely the clinical response to FA. FA supplementation reduced the recurrence risk of Cd exencephaly by as much as 55%. This rescue was dose dependent and did not require subjects to be inherently folate deficient. Like the female predominance of NTDs in humans, female Cd embryos were most likely to display exencephaly and were more responsive than males to the FA rescue. Importantly, FA supplementation shifted the severity of Cd phenotypic expression from early embryonic lethality to longer survival, and reduced the incidence of NTDs. The Cd locus is distinct from the known genes associated with neurulation defects, and isolation of this gene will assist identification of biochemical, genetic and gender-dependent factors contributing to folate-responsive NTDs.

Animals↗