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Biomedical subjects

A Schmidt

Publications and source records attributed to A Schmidt.

At least 37 records · Page 2Linked to original sources

In vitro analysis of birch-pollen-associated food allergy by use of recombinant allergens in the basophil activation test.

BACKGROUND: Basophil activation is associated with the expression of CD63. In birch-pollen-associated food allergy to celery, carrot and apple, Bet v 1, Api g 1, Dau c 1 and Mal d 1 are major allergens. Recombinant allergens have not yet been used in the CD63-based basophil activation test (BAT). OBJECTIVE: To evaluate the feasibility of using recombinant allergens in the BAT in the diagnosis of allergy to apple, carrot and celery and to compare results with routine tests, i.e. skin prick tests (SPTs) and specific IgE. METHODS: Thirty-two patients with an oral allergy syndrome induced by apple, carrot or celery and 22 controls were studied. SPTs were performed with native foods. Specific IgE was determined by the CAP method and basophil activation by flowcytometry upon double staining with anti-IgE/anti-CD63 monoclonal antibodies after incubating with purified recombinant Bet v 1, Bet v 2, Api g 1, Dau c 1 and Mal d 1. RESULTS: By the combined use of the BAT and the CAP method, sensitization to Bet v 1 and Bet v 2 was detected in 100 and 25% of all subjects, respectively. Sensitivity of specific IgE for apple, carrot and celery was 60, 70 and 75% with corresponding specificities of 64, 86 and 82%. Sensitivity of the BAT for Mal d 1, Dau c 1 and Api g 1 was 75, 65 and 75% with corresponding specificities of 68, 100 and 77%. CONCLUSIONS: The BAT using recombinant allergens provides a valuable new in vitro method for the detection of sensitization to foods. Although double-blind placebo-controlled food challenges remain the gold standard to confirm food allergy, the CD63-based BAT with recombinant allergens may supplement routine tests for allergy diagnosis.

Allergens↗

[Evidence-based evaluation of the effect of Type IV Allergies on the reduction of fitness for work. Survey of occupational skin diseases].

Evidence-based guidelines about the distribution of type IV allergens of the European standard series in different professions and its occupational relevance are missing. Based on published data, epidemiological investigations, work related knowledge about industrial processes, and allergen specific properties, recommendations are given about the clinical impact in the working environment for the following allergens: acrylates/methacrylates, epoxy resins, dichromate, cobalt, nickel, formaldehyde, (chlor-)methylisothiazolone, p-phenylendiamine, colophony, thiurame, mercaptobenzothiazole, dithiocarbamate, n-isopropyl-n'-phenyl-p-phenylendiamine, fragrance mix, composite mix, and neomycinsulfate. These recommendations might improve the clearance rate and allergological evaluation of the occupational relevance of different delayed type sensitizations or allergens.

Allergens↗

Cognitive and motor deficits associated with HIV-2(287) infection in infant pigtailed macaques: a nonhuman primate model of pediatric neuro-AIDS.

Lentivirus-infected nonhuman primates exhibit behavioral and neurological pathology similar to human immunodeficiency virus (HIV)-infected humans and offer a means to examine the effects of lentivirus infection while controlling for confounding factors inherent in human populations. The purpose of this study was to examine cognitive and motor development in infant macaques vertically infected with HIV-2287. Subjects were 20 infant pigtail macaques (Macaca nemestrina); 8 controls born to uninfected dams, and 12 infants whose dams had been inoculated and infected with HIV-2287 in the third trimester of pregnancy. Eight of these pregnancies had undergone surgical procedures in the form of maternal amniotic catheters or maternal amniotic and fetal carotid artery and jugular vein catheters. Data indicated that catheterization had little or no impact on behavioral development. Seven infants were vertically infected (as measured by polymerase chain reaction (PCR) at birth) and five were not infected (as measured by PCR and coculture on repeated testing). Infected infants attained cognitive and motor milestones at significantly later ages than controls. Uninfected infants, born to infected dams, attained developmental milestones at later ages than controls on all tasks, but this reached statistical significance only for the Fine Motor Task. Attainment of milestones was not correlated with viral dose, maternal CD4+ levels at parturition or infant viral RNA levels at birth. Attainment of milestones was negatively correlated with infants' proportions of CD4+ lymphocytes at birth and significantly correlated with proportions of CD4+ lymphocytes 2 weeks after birth, indicating poorer performance in those infants with a more rapid CD4+ depletion. These cognitive and motor deficits closely resemble those observed in human infants and children infected with HIV and indicate that HIV-2287-infected infant macaques represent an excellent model of pediatric neuro-acquired immunodeficiency syndrome (neuroAIDS).

AIDS Dementia Complex↗

Intensive care treatment of severe mixed metabolic acidosis.

We report a case of severe metabolic acidosis associated with acute renal failure and septicaemia following treatment with maximal therapeutic doses of metformin and diclofenac. On the second day of intensive care the patient deteriorated with respiratory insufficiency and abdominal pain during continuous renal replacement therapy. A laparoscopy revealed a perforated cholecystitis with abscess formation. The patient regained renal function and recovered. Intake of diclofenac 5 days before this episode could have been the main cause of renal insufficiency and metabolic acidosis in this patient and could also have delayed surgical treatment by masking early clinical signs of perforated cholecystitis. The renal failure may also have caused metformin and lactate to accumulate, contributing to the mixed pattern of metabolic acidosis. This case report describes a mixed organic and non-organic metabolic acidosis associated with acute renal failure, presumably resulting from a combination of drugs and diseases often found in the elderly - metformin for diabetes mellitus and a non-steroidal anti-inflammatory drug for cholecystolithiasis. Acid-base balance and electrolyte changes were rapidly normalized by continuous renal replacement therapy.

Abdominal Abscess↗

Cerebral physiological responses to bolus injection of racemic, S(+)- or R(-)-ketamine in the pig.

BACKGROUND: Little is known about the influence of ketamine and its enantiomers on cerebral haemodynamics, and there are no direct comparison reports. This study was designed to evaluate cerebrovascular responses to bolus injections of racemic, S(+)- and R(-)-ketamine in an established experimental model. METHODS: Anaesthesia was induced with propofol in 14 pigs and maintained with fentanyl and vecuronium. The intra-arterial xenon clearance technique was used to calculate the cerebral blood flow (CBF). Eight pigs (part I) were given three consecutive 60-s intravenous (i.v.) bolus injections of 10 mg/kg of racemic ketamine (Ketalar, Pfizer), and cerebral and systemic physiological responses were studied for 30 min after each injection. Following the determination of equipotent doses of the racemate and its enantiomers by recumbency tests, bolus injections of racemic ketamine (10 mg/kg), S-ketamine (5 mg/kg) and R-ketamine (20 mg/kg) were given in randomized sequence to another six pigs (part II) and evaluated at 1, 5, 10, 15, 25 and 40 min. RESULTS: No statistically significant acute tolerance in the CBF response to racemic ketamine was found in part I of the study. In part II, the decreases in the mean arterial pressure (MAP) and CBF by S-ketamine were significantly smaller than those by racemic and R-ketamine (both P < 0.001). No study drug had any significant effect on the cerebral arteriovenous oxygen content difference (C(av)O(2)) over time, but S-ketamine was associated with lower C(av)O(2) than racemic ketamine (P = 0.008) and R-ketamine (P = 0.016). CONCLUSIONS: Bolus injection of S-ketamine was associated with less cerebral and systemic haemodynamic depression than racemic or R-ketamine in equipotent doses in this experimental model. These findings indicate possible advantages of S-ketamine over racemic ketamine.

Anesthetics, Dissociative↗

Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian retrovirus-2 negative rhesus macaque (Macaca mulatta).

Multifocal submucosal stromal tumors were diagnosed in a 5.5-year-old rhesus macaque (Macaca mulatta) experimentally infected with simian immunodeficiency virus, strain SIVsmE660, and CD4+ T cell depleted. The animal was negative for simian retroviruses, SRV-1, -2, and -5. Polymerase chain reaction analysis of DNA from tumor and spleen tissue revealed abundant, preferential presence of retroperitoneal fibromatosis herpesvirus, the macaque homologue of the Kaposi sarcoma-associated herpesvirus (human herpesvirus-8), in the tumors. This was corroborated by demonstration of viral latent nuclear antigen-1 in the nuclei of a majority of the spindeloid tumor cells. Low levels of an additional macaque herpesvirus, rhesus rhadinovirus, were also detected in the spleen and tumor tissues. The spindeloid cells labeled positively for vimentin and CD117 but were negative for CD31, CD68, desmin, and smooth muscle cell actin. Collectively, these findings suggest a relation to but not absolute identity with simian mesenchymoproliferative disorders (MPD) or typical gastrointestinal stromal tumors (GISTs).

Animals↗

[Development of cell content and shedding of Prototheca spp. in milk from infected udder quarters of cows].

It was the objective of this study to analyse shedding patterns and somatic cell counts in cows and quarters infected with Prototheca spp. and to evaluate two approaches to identify infected animals by somatic cell count (SCC) or by bacteriological analysis of pooled milk samples. Five lactating dairy cows, chronically infected with Prototheca spp. in at least one quarter were studied over 11 weeks to 13 months. Quarter milk samples and a pooled milk sample from 4 quarters were collected aseptically from all quarters of the cows on a weekly basis. Culture results of quarter milk and pooled samples were compared using cross tabulation. SCC of quarter milk samples and of pooled samples were related to the probability of detection in the infected quarters and cows, respectively. Shedding of Prototheca spp. was continuous in 2 of 8 quarters. In the other quarters negative samples were obtained sporadically or over a longer period (1 quarter). Overall, Prototheca spp. were isolated from 83.6% of quarter milk samples and 77.0% of pooled milk samples of infected quarters and cows. Somatic cell counts were higher in those samples from infected quarters that contained the algae than in negative samples (p < 0.0001). The same applied for composite samples from infected cows. Positive samples had higher SCC than negative samples. However, Prototheca spp. were also isolated from quarter milk and pooled samples with physiological SCC (i.e. < 10(5)/ml). Infected quarters that were dried off did not develop acute mastitis. However, drying off had no effect on the infection, i.e. samples collected at calving or 8 weeks after dry off still contained Prototheca spp. Results indicate that pre-selection of cows to be sampled for Prototheca spp. by SCC and the use of composite samples are probably inadequate in attempts to eradicate the disease. However, due to intermittent shedding of the algae in some cows, single herd sampling using quarter milk samples probably also fails to detect all infected cases. Therefore, continuous monitoring of problem cows with clinical mastitis or increased SCC in herds during eradication programs is recommended.

Animals↗

Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1).

We show that the recently discovered tumor suppressor pdcd4 represses the transcription of the mitosis-promoting factor cyclin-dependent kinase (CDK)1/cdc2 via upregulation of p21(Waf1/Cip1). p21(Waf1/Cip1) inhibits CDK4/6 and CDK2. Decrease of CDK4/6 and CDK2 enhances the binding of pRb to E2F/DP, which in turn together bind to and repress the cdc2 promoter. Upregulation of CDK1/cdc2 accompanied by a malignant change was previously reported in colon cancer. We show that expression of pdcd4 as an indirect suppressor of CDK1/cdc2 is lost in progressed carcinomas of lung, breast, colon, and prostate. Furthermore, it seems that localization and expression of pdcd4 directly correlate with tumor progression. Finally, the CDK1/cdc2 inhibitor roscovitine reduces the proliferation of several tumor cell lines, suggesting that inhibition of CDK1/cdc2 may be a useful strategy against malignant transformation. Therefore, pdcd4 might serve as a novel target for antineoplastic therapies.

Apoptosis↗

Occludin binds to the SH3-hinge-GuK unit of zonula occludens protein 1: potential mechanism of tight junction regulation.

The interaction between tight junction proteins occludin and zona occludens protein 1 (ZO-1) was clarified. The sequence cc1 within the hinge region of ZO-1, connecting its SH3 and GuK domains, was identified as a new association site for the occludin C-terminus, core binding area GLRSSKRNLRKSR (mouse ZO-1(606-618)). Occludin also bound to the sequence H2 within GuK, core area HKLRKNNH (ZO-1(759-766)). In occludin, the binding core was ELSRLDKELDDYREESEEY (mouse occludin(455-473)). Helicity of the sequences was suggested by circular dichroism. Because basic residues in ZO-1, acidic residues in occludin (underlined), coiled-coil helix-forming leucine heptad motifs (bold) in occludin and, probably, in cc1 were essential, we conclude that interactions were both helical and ionic. Moreover, the GuK domain bound other GuK molecules, suggesting oligomerization of ZO-1. Generally, the assumption is supported that the SH3-hinge-GuK region represents a functional and regulatory unit in ZO-1 forming a multiprotein tight junction complex with occludin.

Amino Acid Sequence↗

[Developments in chromate allergy in the German construction industry].

For decades potassium dichromate has been the most important allergen in the construction industry. In Scandinavian countries the prevalence of potassium dichromate sensitization declined following the introduction of low-chromate cement. In contrast, analysis of our register in Northern Bavaria and the data of workers compensation board show no significant decline in potassium dichromate sensitization in the German construction industry during the 1990s. In 1993, German legislation provided an Approved Code of Practice and the cement manufacturers committed themselves to reduce the level of water-soluble chromates to less than 2 ppm in bag cement. Since 2000 this agreement has also included ready-mixed concrete. It remains to be seen, if sensitization against potassium dichromate will decline in the upcoming years. Based on our data, it would be desirable if only low-chromate cement was used in the construction industry in Germany as in Scandinavia.

Adolescent↗

[Counselling versus cognitive group therapy for tinnitus. A retrospective study of their efficacy].

BACKGROUND: Both counselling and group therapy have been recommended for supporting patients with chronic tinnitus. It is unclear which of these treatments is superior. SCIENTIFIC QUESTION: This retrospective study aimed at comparing relief from tinnitus distress following counselling with that following cognitive group therapy. Distress relief was also compared to the distress level of the waiting group patients. METHOD: Tinnitus distress was assessed through the Tinnitus Questionnaire (TQ, Goebel and Hiller) at three different times: before treatment (in waiting list patients: at initial contact) and at 3 and 6 months after initial assessment. Data from 21 patients per group were included in the analysis. RESULTS: The initial tinnitus distress scores were similar in all groups (about 48 TQ points out of a maximum of 84). After 3 months, both counselling subjects and group therapy participants exhibited a significant distress reduction of 13 TQ points, which remained stable after 6 months. Patients on the waiting list experienced no distress relief over time. CONCLUSION: Results from our data demonstrate the need for a future prospective study on the comparison of efficacy of counselling vs cognitive group therapy.

Activities of Daily Living↗

[A 52-year old female patient with recurrent shock of unclear origin, hemoconcentration and hypoalbuminemia].

Systemic capillary leak syndrome is a rare life threatening condition of unknown etiology. It was firstly described by Clarkson et al in 1960. It is characterised by recurrent attacks of severe hypovolemic shock, hemoconcentration and hypalbuminemia, caused by a sudden reversible increase in capillary permeability and shift of fluid and macromolecules to the extravascular compartment. A monoclonal paraprotein is always detectable in the serum of patients, without evidence of multiple myeloma. We describe the course of a patient, who died at a severe attack despite of prophylactic treatment after 25 months of illness. Application of cytostatics should be considered if prophylactic treatment fails even if there is no evidence of progression to multiple myeloma.

Capillary Leak Syndrome↗

Reference values for cardiac troponins I and T in a goal-oriented concept of health: cardiac marker values in a series of outpatients without acute coronary syndromes.

BACKGROUND: Cardiac troponins are part of the new definition of acute myocardial infarction (AMI) by the European Society of Cardiology and the American College of Cardiology (ESC/ACC). In the new guidelines, it was suggested to establish reference values for cardiac troponins to calculate the 0.99 quantile (Q99) as cutoff for AMI diagnosis. PATIENTS AND METHODS: We run a prospective series of troponin measurements in unselected outpatients who had no suspicion of cardiac ischemia. The selection of patients as reference population is based on a "goal-oriented concept of health". One hundred and ninety-five patients agreed that 10-ml additional blood was drawn at the occasion of the venous puncture done routinely in the evaluation of their case. Cardiac troponin I was measured using a point of care (POCT) device (Stratus CS, DadeBehring, TNI-PO). Additionally, heparin-plasma was obtained and immediately deep-frozen to -80 degrees C for later batch measurement of cardiac troponin T (Elecsys 2010, Roche Diagnostics, TnT) and troponin I (Centaur, Bayer, TnI-CL). RESULTS: The Q99 values were 0.14 microg/l for TnI-PO, 0.023 microg/l for TnT and 0.07 microg/l for TnI-CL in patients with creatinine levels below 1.5 mg/dl. These values lay above those obtained from people at good health for reference study purposes. On the level of our cutoffs, CVs were 7.5%, 6.4% and 23.7% for TnI-PO, TnT and TnI-CL, respectively. CONCLUSIONS: Only the TnI-PO and TnT tests fulfilled the imprecision criteria in our study. TnI-PO values between 0.10 and 0.14 microg/l and TnT values between 0.01 and 0.03 microg/l have to be interpreted carefully. Patients presenting with chest pain will be possibly true positives, but patients without chest pain and nondiagnostic ECGs should be subjected to repetitive troponin measurements and further noninvasive investigation and maybe not directly sent to the cardiac catheter laboratory.

Adult↗

Endoluminal stent-graft placement for acute rupture of the descending thoracic aorta.

AIMS: To investigate the results of endovascular stent-graft placement for the treatment of acute perforating lesions of the descending thoracic aorta. METHODS AND RESULTS: A total of 31 consecutive patients underwent interventional treatment for perforating lesions of the descending aorta. In 21 cases (group A), the aortic perforation was due to rupture of a descending thoracic aneurysm or dissection, whereas 10 patients (group B) were treated for traumatic transection of the descending aorta. A total of 42 endoprostheses were implanted. The implantation procedure was successful in all cases without peri-interventional complications. In one case, implantation of a second endoprosthesis became necessary due to type I endoleak. Overall, the 30-day mortality was 9.7%. As all three deaths occurred in group A, the mortality rate in this group was 14.3% versus 0% in group B. Similarly, postinterventional complications were more prevalent, with 28.6% in group A (renal failure n = 4; stroke n = 2) versus 10.0% in group B (renal failure n = 1). No paraplegia and no further deaths or ruptures occurred during follow-up (mean 17 months). CONCLUSION: Interventional stent-graft placement is an effective treatment option for the emergency repair of descending aortic perforations.

Acute Kidney Injury↗

First clinical experiences with an endovascular clamping system for neuroprotection during carotid stenting.

OBJECTIVES: This report evaluates the feasibility and efficacy of an endovascular blood flow blockage technique to prevent intracerebral embolization of plaque debris during carotid artery stenting. METHODS: Forty-two patients were enrolled in five clinical sites in Germany and Italy with either an asymptomatic internal carotid artery stenosis > or =75% (mean 87%) or a symptomatic stenosis > or =60% (mean 85%). Cerebral protection during the stenting procedure was achieved using an endovascular clamping technique, obtained by occlusion of the external and common carotid artery via two independently inflatable balloons integrated in the Mo.Ma system. Blood with particulate plaque debris was aspirated before flow was restored. The patient's clinical and the neurological status were assessed during intervention, at discharge, and at 3 months follow-up. RESULTS: Stenting was performed in all but one patient. The mean flow occlusion time was 10.6+/-6.5 min. Transient clamping intolerance was observed in five patients (12%). In two patients, neurological deficits persisted for 2 and 12 h, respectively. Two minor strokes (4,7%) occurred at 5 and 72 h after the procedure. No major strokes or deaths were observed at 3 months follow-up. CONCLUSIONS: This first clinical experience with the Mo.Ma device substantiates the feasibility of endovascular clamping in preventing cerebral embolization during carotid artery stenting.

Carotid Artery, Internal↗

Partial agonist/antagonist properties of androstenedione and 4-androsten-3beta,17beta-diol.

Androgens play important endocrine roles in development and physiology. Here, we characterize activities of two "Andro" prohormones, androstenedione (A-dione) and 4-androsten-3beta,17beta-diol (A-diol) in MDA-MB-453 (MDA) and LNCaP cells. A-dione and A-diol, like cyproterone acetate, were partial agonists of transfected mouse mammary tumor virus (MMTV) and endogenous prostate-specific antigen (PSA) promoters. Different from bicalutamide but similar to CPA, both are inducers of LNCaP cell proliferation with only mild suppression of 5alpha-dihydrotestosterone (DHT)-enhanced cell growth. Like bicalutamide and cyproterone acetate, A-dione and A-diol significantly antagonized DHT/R1881-induced PSA expression by up to 30% in LNCaP cells. Meanwhile, in MDA cells, EC(50)s for the MMTV promoter were between 10 and 100nM. Co-factor studies showed GRIP1 as most active for endogenous androgen receptor (AR), increasing MMTV transcription by up to five-fold, without substantially altering EC(50)s of DHT, A-dione or A-diol. Consistent with their transcriptional activities, A-dione and A-diol bound full-length endogenous AR from MDA or LNCaP cells with affinities of 30-70nM, although binding to expressed ligand-binding domain (LBD) was >20-fold weaker. In contrast, DHT, R1881, and bicalutamide bound similarly to LBD or aporeceptor. Together, these data suggest that A-dione and A-diol are ligands for AR with partial agonist/antagonist activities in cell-based transcription assays. Binding affinities for both are most accurately assessed by AR aporeceptor complex. In addition to being testosterone precursors in vivo, either may impart its own transcriptional regulation of AR.

Adaptor Proteins, Signal Transducing↗