An interview with professor Henk Schmidt. Interview by Jan van Dalen.
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Interview↗
Biomedical subjects
H Schmidt
Publications and source records attributed to H Schmidt.
Psychomotor recovery in very old patients after total intravenous or balanced anaesthesia for cataract surgery.
We compared psychomotor recovery after total intravenous anaesthesia (TIVA) with remifentanil/propofol and balanced anaesthesia (BAL) with etomidate/fentanyl/isoflurane in 40 patients, ASA I-III, aged > or =80 yr undergoing elective cataract surgery. Recovery times were recorded and psychomotor recovery was assessed according to simple reaction time, critical flicker fusion frequency (CFF) and short-term memory 30 min, 2 h and 1 day after surgery. Physical characteristics of patients in the two groups (19 in the TIVA group and 21 in the BAL group) were comparable. The TIVA group recovered significantly more quickly. Both groups showed a poorer psychomotor performance 30 min after surgery than at baseline assessment, but simple reaction time and short-term memory were close to baseline values 2 h after surgery. Only performance in the CFF test remained below baseline at this point. No deficits in psychomotor performance were noted on the first day after surgery. We conclude that there is only a minor deficit in psychomotor function in elderly patients 2 h after cataract surgery under general anaesthesia and that psychomotor function recovers completely by 24 h after surgery.
Aged↗
Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-kappaB.
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Animals↗
The transfer half-life of morphine-6-glucuronide from plasma to effect site assessed by pupil size measurement in healthy volunteers.
BACKGROUND: Clinical and experimental data suggested a long delay between the plasma concentration versus time course of morphine-6-glucuronide and the time course of its central opioid effects. This study was aimed at the quantification of the transfer half-life (t(1/2,ke0)) of this delay. METHODS: Pupil size was used as a measure of central opioid effect. Eight healthy volunteers (four men, four women) participated in that single-blind randomized crossover study. Median dosages administered intravenously were 0.5 mg morphine as loading dose followed by 10.7 mg given as infusion over a period of 4.7 h, and 10.2 mg M6G as loading dose followed by 39.1 mg M6G given over a period of 3.7 h. The duration of the infusion was tailored to achieve submaximum pupil constriction. The pupil diameter was assessed every 20 min for approximately 18 h. Values of t(1/2,ke0) were obtained by semiparametric pharmacokinetic-pharmacodynamic modeling. RESULTS: The estimated median t(1/2,ke0) of M6G was 6.4 h (range, 2.9-16.2 h), and that of morphine was 2.8 h (range, 1.8-4.4 h). The individual t(1/2,ke0) of M6G was always longer than that of morphine. Judged by the concentration at half-maximun effect (EC50) values of the sigmoid pupil size at maximum constriction (Emax) model describing concentration-response relation, M6G was apparently 22 times less potent than morphine (EC50 = 740.5 nm [range, 500-1,520 nm] for M6G and 36.2 nm [range, 19.7-43.3 nm] for morphine). The steepness of the sigmoid Emax model did not significantly differ between morphine and M6G (gamma = 1.9 and 2.6, respectively). To produce similar pupil effects, the M6G dose had to be 2.8 times greater than the morphine dose. CONCLUSIONS: The reported numerical value of the t(1/2,ke0) of M6G in humans obtained after direct administration of M6G is a step toward a complete modeling approach to the prediction of the clinical effects of morphine. The study raises questions about the high interindividual variability of the transfer half-life between plasma and effect site (ke0) values and the apparent low potency of M6G.
Adult↗
Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimental endotoxemia: an intravital microscopic study in the rat.
OBJECTIVE: To test the effects of dobutamine and dopexamine on hepatic portal and sinusoidal blood flow in a model of normodynamic endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats (250-350 g). INTERVENTIONS: A total of 40 male Wistar rats were randomized into four groups: a control group, which only received Ringer's solution; an endotoxin group, which received a continuous infusion of 2 mg/kg body weight (bw)/hr of endotoxin; a dobutamine group, which received endotoxin and a continuous infusion of dobutamine (3 microg/kg bw/min); and a dopexamine group, which received endotoxin and dopexamine (2 microg/kg bw/min). The experimental period was 120 min. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) were detected. Portal blood flow was measured using an ultrasonic flow probe positioned around the portal vein, and sinusoidal blood flow was detected in the left liver lobe using intravital microscopy. All detected variables remained stable in the control group. In the endotoxin group, HR increased significantly and MAP decreased significantly from 111 +/- 10 mm Hg to 95 +/- 8 mm Hg at 120 mins, whereas CO remained unchanged. Both in the dobutamine and the dopexamine group HR increased and MAP decreased more than in the endotoxin group. CO increased in both groups significantly. Portal blood flow (23 +/- 4 mL/min to 16 +/- 3 mL/min) and sinusoidal blood flow (38.6 +/- 2.5 to 22.8 +/- 1.2 10(3) microm(3)/sec) decreased significantly in the endotoxin group. In the dobutamine and the dopexamine group portal and sinusoidal blood flow remained at baseline values. CONCLUSIONS: In our model of endotoxemia, dobutamine and dopexamine preserved systemic and hepatic blood flow. These preservations of hepatic blood flow during endotoxemia could portend beneficial effects but need to be studied further.
Adrenergic beta-Agonists↗
The gastrointestinal tract in critical illness.
The gut has often been suggested to be one of the essential factors in the pathogenesis of many nosocomial infections and possibly multi-organ failure. In the light of several recent studies, the importance of normal gut bacterial flora and the role of the gastrointestinal tract in human immune function are now better understood. It now seems clear that stimulation of gut-associated lymphoid tissue through enteral feeding is the key to the preservation of mucosal-derived immunity; however, the role of this native gastrointestinal immune function in the subsequent development of sepsis and multi-organ dysfunction syndrome remains the subject of ongoing study.
Critical Illness↗
Identification and characterization of a novel genomic island integrated at selC in locus of enterocyte effacement-negative, Shiga toxin-producing Escherichia coli.
The selC tRNA gene is a common site for the insertion of pathogenicity islands in a variety of bacterial enteric pathogens. We demonstrate here that Escherichia coli that produces Shiga toxin 2d and does not harbor the locus of enterocyte effacement (LEE) contains, instead, a novel genomic island. In one representative strain (E. coli O91:H(-) strain 4797/97), this island is 33,014 bp long and, like LEE in E. coli O157:H7, is integrated 15 bp downstream of selC. This E. coli O91:H(-) island contains genes encoding a novel serine protease, termed EspI; an adherence-associated locus, similar to iha of E. coli O157:H7; an E. coli vitamin B12 receptor (BtuB); an AraC-type regulatory module; and four homologues of E. coli phosphotransferase proteins. The remaining sequence consists largely of complete and incomplete insertion sequences, prophage sequences, and an intact phage integrase gene that is located directly downstream of the chromosomal selC. Recombinant EspI demonstrates serine protease activity using pepsin A and human apolipoprotein A-I as substrates. We also detected Iha-reactive protein in outer membranes of a recombinant clone and 10 LEE-negative, Shiga toxin-producing E. coli (STEC) strains by immunoblot analysis. Using PCR analysis of various STEC, enteropathogenic E. coli, enterotoxigenic E. coli, enteroaggregative E. coli, uropathogenic E. coli, and enteroinvasive E. coli strains, we detected the iha homologue in 59 (62%) of 95 strains tested. In contrast, espI and btuB were present in only two (2%) and none of these strains, respectively. We conclude that the newly described island occurs exclusively in a subgroup of STEC strains that are eae negative and contain the variant stx(2d )gene.
Amino Acid Sequence↗
Genetic characterisation of invasive breast cancer: a comparison of CGH and PCR based multiplex microsatellite analysis.
AIMS: Comparative genomic hybridisation (CGH) is a reliable tool to gain an overview of all unbalanced chromosomal alterations within a tumour. Nevertheless, the high numbers of tumour cells required and the comparatively low resolution are drawbacks of this technique. Polymerase chain reaction (PCR) based multiplex microsatellite analysis represents a semi-automated, highly reproducible method, which requires small amounts of tumour cells. This is a comparative study of CGH and microsatellite analysis. METHODS: Eighty one samples of invasive breast cancer were investigated by two sensitive multiplex PCRs containing three microsatellites each of six markers (D6S261, D11S907, D6S300, D11S927, D8S272, and D11S925), and two additional microsatellite markers located within intron 1 of the epidermal growth factor receptor gene (egfr) and p53 (p53CA). RESULTS: At least one example of loss of heterozygosity was detectable in all breast cancer tissues. However, the overall rate of accordance between the two methods tested was only 61%. An increasing rate of the number of genetic alterations in each case was mirrored by a constantly increasing fractional allelic loss index. CONCLUSIONS: PCR based multiplex microsatellite analysis using this panel of eight microsatellite markers not only enables the characterisation of cells that have malignant potential in a high frequency of patients with breast cancer, but can also give an estimate of the degree of genetic progression.
Breast Neoplasms↗
Angiotensinogen polymorphism M235T, carotid atherosclerosis, and small-vessel disease-related cerebral abnormalities.
The angiotensinogen M235T polymorphism has been linked to hypertension and cardiovascular disease. We studied the role of this polymorphism as a risk factor for carotid atherosclerosis and small-vessel disease-related brain abnormalities. A total of 431 randomly selected community-dwelling subjects without clinical evidence for strokes underwent angiotensinogen genotyping and carotid Duplex scanning; 1.5-T brain magnetic resonance imaging (MRI) was done in 396 individuals. At 3-year follow-up, we reexamined 343 and 267 study participants by ultrasound and brain MRI, respectively. Carotid atherosclerosis was graded on a 5-point scale. Small-vessel disease-related brain abnormalities were deep or subcortical white matter lesions or lacunes. Progression of carotid atherosclerosis and MRI findings was rated by direct imaging comparison by 3 independent raters. The M/M, M/T, and T/T genotypes were seen in 20.9%, 52.9%, and 18.1% of subjects, respectively. The M235T polymorphism was neither associated with baseline carotid findings nor with progression of carotid atherosclerosis. There was a trend toward more frequent small-vessel disease-related MRI abnormalities in the T/T than in the other genotypes at the baseline examination. Progression of brain lesions occurred significantly more commonly in T/T than in M/M and M/T carriers (P<0.001). Logistic regression analysis identified the T/T genotype (odds ratio, 3.19; P=0.002) and arterial hypertension (odds ratio, 3.06; P=0.03) as significant independent predictors of lesion progression. These data suggest that the angiotensinogen T/T genotype at position 235 is a genetic marker for brain lesions from and progression of small vessel disease but not for extracranial carotid atherosclerosis.
Angiotensinogen↗
Angiotensinogen gene promoter haplotype and microangiopathy-related cerebral damage: results of the Austrian Stroke Prevention Study.
BACKGROUND AND PURPOSE: Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the most important risk factors. We assessed the association between MARCD and sequence alterations in the promoter region of the angiotensinogen (AGT) gene. METHODS: We studied 410 randomly selected community-dwelling individuals aged 50 to 75 years. MARCD was defined as early confluent or confluent white matter hyperintensities or lacunes on a 1.5-T MRI. The AGT promoter was analyzed by temporal temperature gradient gel electrophoresis and automated sequencing. RESULTS: We detected 4 polymorphic sites, at positions -6, -20, -153, and -218. They created 5 haplotypes, which we coded as A (-6:g, -20:a, -153:g, -218g), B (-6:a, -20:c, -153:g, -218:g), C (-6:a, -20:c, -153:a, -218:g), D (-6:a, -20:a, -153:g, -218:g), and E (-6:a, -20:a, -153:g, -218:a). MARCD was seen in 7 subjects (63.6%) carrying 2 copies of the B haplotype (B/B), in 12 subjects (38.7%) carrying 1 copy of the B haplotype in the absence of the A haplotype (B+/A-), but in only 70 subjects (19.0%) in the remaining cohort (P:<0.001). The odds ratios for the B/B and the B+/A- genotypes were 8.0 (95% CI, 2.1 to 31.1; P:=0.003) and 1.8 (95% CI, 0.8 to 4.2; P:=0.14) after adjustment for possible confounders. CONCLUSIONS: The B haplotype of the AGT promoter in the absence of the wild-type A haplotype might represent a genetic susceptibility factor for MARCD.
Age Distribution↗
Persistent papilledema in Ullrich-Turner syndrome treated with growth hormone.
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Child↗
Dietary intervention in the first four years prevents abnormal weight gain but negatively affects height development in Prader-Willi syndrome.
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Body Height↗
Psychiatric referrals. In primary care and general hospitals in Qassim Region, Saudi Arabia.
OBJECTIVE: From different perspectives, psychiatric symptoms have special significance in psychiatry. This study comparatively describes the psychopathological symptoms as noted in primary care (402) and general hospital (138) referrals. METHODS: Five hundred and forty psychiatric referrals, retrieved randomly, were reviewed extensively for collecting relevant data. RESULTS: Both hospital and primary care referrals were observed to have a variety of psychological and somatic symptoms of variable frequencies, which were suggestive of several psychopathological domains. Functional psychotic (19.5% versus 10%), mood (27.5% versus 23%) and psychosomatic (7% versus 2%) symptoms were significantly noted in hospital referrals as compared to primary care referrals while the later were observed to have significantly more somatic (34.5% versus 22.5%) and neurological (8% versus 4%) symptoms. Only a small proportion of primary care referrals (33/402, 8%] have symptoms of childhood psychiatric disorders. CONCLUSION: Psychiatric symptomatology differs in primary care and general hospital referrals. Both the general practitioners and clinicians are expected to record psychiatric symptoms in a comprehensive manner. Hence, they need condensed training courses on psychiatric symptomatology.
Hospitals, General↗
Validation of the first automated chemiluminescence protein-binding assay for the detection of 25-hydroxycalciferol.
BACKGROUND: Measurement of 25-hydroxyvitamin D, 25(OH)D is the ideal parameter to indicate the access of the organism to vitamin D. Numerous studies have shown that serum levels of 25(OH)D are the best markers of vitamin D deficiency, normal vitamin D supply or vitamin D intoxication. The aim of the study was to validate a beta-site version of the first fully automated chemiluminescence protein-binding assay (CLPBA) for the detection of 25-hydroxycalciferol. METHODS: The newly developed CLPBA run on the Nichols Advantage Specialty Systems was compared to an inhouse radioimmunoassay (RIA), focussing on the major assay features such as imprecision, functional sensitivity, linearity, method comparison and suitability of serum or EDTA-plasma as well as establishing a preliminary reference range. RESULTS: Within-run imprecision is approximately 4.5% and total imprecision approximately 6% respectively (NCCLS protocol), functional sensitivity 6.8 microg/l. With mean recovery values of 96.9% and 98.7% for two diluted serum samples linearity is given over the measuring range. Due to different calibrations used for RIA and CLPBA the CLPBA reads approximately 70% lower (CLPBA = 0.321xRIA + 0.571, n = 469) but correlates well with the RIA (r = 0.9045). Method comparison with HPLC reveals a regression line of CLPBA = 0.8921xHPLC + 0.1358 (n = 54, r = 0.9117). Serum or EDTA-plasma is not equally suitable. Plasma samples read on average 5 microg/l higher than serum samples. The preliminary reference range is 11 microg/l to 84 microg/l (95% of all values). CONCLUSION: The validated 25(OH)D CLPBA is a very promising alternative to established commercially available 25(OH)D measurements and will, with its use on a fully automated platform, simplify the reliable quantification of 25-hydroxycalciferol significantly.
25-Hydroxyvitamin D 2↗
[Anastomotic insufficiencies of the esophagus--early surgical endoscopy and endoscopic therapy].
Therapeutic value of flexible endoscopy regarding treatment of esophagoenteric anastomotic leakage was retrospectively analyzed in 56 patients (female n = 13, male n = 43, age 60 years, 1/1992-4/2000). Endoscopic treatment was performed in 44 patients (self-expanding metal stent n = 38, fibrin glue n = 16, feeding tube/decompression tube n = 20, endoscopic percutaneous jejunostomy n = 8), interventional radiological technique in 4 patients and surgical treatment in 11 patients. All patients with open surgical reintervention developed reinsufficiency of the anastomosis. Successful endoscopic therapy was achieved in 75% with a mortality of 21.4%. Endoscopic treatment of esophageal anastomotic insufficiency is an effective alternative to conventional re-thoracotomy. The appropriate endoscopic intervention needs to be decided individually depending on diagnosis and location.
Adult↗
[A concept of nursing care relations: the roles play a role].
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Adaptation, Psychological↗
Enoximone maintains intestinal villus blood flow during endotoxemia.
BACKGROUND: The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase inhibitor enoximone on mucosal villus blood flow in a normotensive model of endotoxemia. METHODS: Twenty-four anesthetized and ventilated rats underwent laparotomy and a ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with enoximone pretreatment (10 microg x kg(-1) x min(-1), start 30 min before LPS infusion, enoximone group), or infusion of an eqivalent volume of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = DA, and mean erythrocyte velocity within the arterioles = VE) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from DA and VE. RESULTS: In this normotensive endotoxemia model MAP remained stable in the control and the LPS group but significantly decreased in the enoximone group. The endotoxin-induced decrease of VE and DE of central arterioles of mucosal villi could be prevented. Thus, mucosal villus blood flow did not decrease compared to the LPS group. CONCLUSIONS: Our results indicate that enoximone during an early stage of sepsis contributes to systemic hypotension but prevents mucosal hypoperfusion.
Analysis of Variance↗
A MboII polymorphism in exon 11 of the human MDM2 gene occuring in normal blood donors and in soft tissue sarcoma patients: an indication for an increased cancer susceptibility?
The human MDM2 oncogene, well known as the tumor suppressor gene p53's partner, plays an important role in tumorigenesis whether it is dependent on or independent of TP53. In this study, we investigated in a PCR-sequencing analysis the exon 11 of the human MDM2 gene for gene alterations. A MboII polymorphism occurs in 8% of normal blood donors (8 out of 100 probands) and in 13% of the soft tissue sarcoma patients (11 out of 82 patients). Of note was that two STS patients carried the gene alteration only in the tumor specimens heterozygously but not in normal tissue. In a Kaplan-Meier analysis, patients without the polymorphism, indicated a median survival rate of 57 months, whereas, patients with the polymorphism survived on average only 38 months. We suggest that this polymorphism might be associated with an increased cancer susceptibility.
Base Sequence↗