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Biomedical subjects

W Funk

Publications and source records attributed to W Funk.

34 records · Page 2Linked to original sources
PubMed1995

Prophylaxis of alcohol withdrawal syndrome in alcohol-dependent patients admitted to the intensive care unit after tumour resection.

Prophylaxis of alcohol withdrawal syndrome (AWS) in alcohol-dependent patients shortens the duration of stay in the intensive care unit (ICU). The objective of this study was to assess the effect of four different prophylactic regimens on the duration of ICU stay, prevention of AWS and rate of major intercurrent complications in alcohol-dependent patients admitted to the ICU after tumour resection. A total of 197 alcohol-dependent patients, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (third revised edition) with a daily ethanol intake of 60 g, were allocated randomly to one of the following regimens which were commenced on admission to the ICU: flunitrazepam-clonidine, chlormethiazole-haloperidol, flunitrazepam-haloperidol or ethanol. The duration of ICU stay, prevention of AWS, incidence of tracheobronchitis and major intercurrent complications such as pneumonia, sepsis, cardiac disorders, bleeding disorders and death were documented. On admission, patients did not differ significantly in age, APACHE II and multiple organ failure scores. ICU stay, incidence of AWS, severity of AWS (revised clinical institute withdrawal assessment for alcohol scale > 20) and major intercurrent complication rate did not differ significantly between groups. Although there was no advantage in any of the four regimens with respect to the primary outcome measures, pulmonary and cardiac patients were not included in the study. Patients in the chlormethiazole-haloperidol group had a significantly increased incidence of tracheobronchitis (P = 0.0023), probably because of an increased incidence of hypersecretion.

Adrenergic alpha-Agonists↗
PubMed1995

Microcirculatory perfusion during volume therapy. A comparative study using crystalloid or colloid in awake animals.

BACKGROUND: Because of the passage of water and salt molecules into the interstitial space, volume replacement with crystalloid solutions requires an amount at least four times that of lost blood. The resulting tissue edema may interfere with nutritive capillary perfusion and oxygen delivery. To prove this hypothesis, the effects of isovolemic hemodilution (hematocrit 30%) with Ringer's lactate solution or dextran 60 on tissue perfusion and oxygenation were investigated in awake Syrian golden hamsters. METHODS: Experiments were performed by using a chronic dorsal skinfold window giving access to skeletal muscle tissue (musculus cutaneus) with in vivo microscopy, quantitative video image analysis, and surface oxygen partial pressure electrodes. Central venous and arterial pressures were measured by means of chronically implanted jugular venous and carotid catheters. RESULTS: Isovolemic exchange of blood with dextran caused no significant changes in arterial or central venous pressure, heart rate, capillary flow velocity, functional capillary density, or surface oxygen partial pressure during the 1-h observation period. A volume of Ringer's solution equal to four times of the amount of blood lost maintained arterial pressure and heart rate when central venous pressure was kept at predilution control values. However, tissue perfusion determined by counting perfused capillaries per terminal arteriole was reduced by 62%, and mean tissue oxygen partial pressure decreased from 19 to 8 mmHg. CONCLUSIONS: In this model, volume replacement with artificial colloids yielded hemodynamic stability and adequate tissue oxygen supply, whereas administration of crystalloids alone jeopardized tissue perfusion and oxygenation.

Animals↗
PubMed1994

Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins.

Tumor-specific activation of the TAL1 gene is the most common genetic alteration seen in patients with T-cell acute lymphoblastic leukemia. The TAL1 gene products contain the basic helix-loop-helix (bHLH) domain, a protein dimerization and DNA-binding motif common to several known transcription factors. A binding-site selection procedure has now been used to evaluate the DNA recognition properties of TAL1. These studies demonstrate that TAL1 polypeptides do not have intrinsic DNA-binding activity, presumably because of their inability to form bHLH homodimers. However, TAL1 readily interacts with any of the known class A bHLH proteins (E12, E47, E2-2, and HEB) to form heterodimers that bind DNA in a sequence-specific manner. The TAL1 heterodimers preferentially recognize a subset of E-box elements (CANNTG) that can be represented by the consensus sequence AACAGATGGT. This consensus is composed of half-sites for recognition by the participating class A bHLH polypeptide (AACAG) and the TAL1 polypeptide (ATGGT). TAL1 heterodimers with DNA-binding activity are readily detected in nuclear extracts of Jurkat, a leukemic cell line derived from a patient with T-cell acute lymphoblastic leukemia. Hence, TAL1 is likely to bind and regulate the transcription of a unique subset of subordinate target genes, some of which may mediate the malignant function of TAL1 during T-cell leukemogenesis.

Amino Acid Sequence↗
PubMed1991

Cyclic amplification and selection of targets (CASTing) for the myogenin consensus binding site.

The consensus binding site for the muscle regulatory factor myogenin was determined from an unbiased set of degenerate oligonucleotides using CASTing (cyclic amplification and selection of targets). Stretches of totally random sequence flanked by polymerase chain reaction priming sequences were mixed with purified myogenin or myotube nuclear extracts, DNA-protein complexes were immunoprecipitated with an antimyogenin antibody, and the DNA was amplified by polymerase chain reaction. Specific binding was obtained after four to six cycles of CASTing. The population of selected binding sites was then cloned, and a consensus was determined from sequencing individual isolates. Starting from a pool with 14 random bases, purified myogenin yielded a consensus binding site of AACAG[T/C]TGTT, while nuclear extracts retrieved the sequence TTGCACCTGTTNNTT from a pool containing 35 random bases. The latter sequence is consistent with that predicted from combining an E12/E47 half-site (N[not T]CAC) with the purified myogenin half-site ([T/C] TGTT). The presence of paired E boxes in many of the sequences isolated following CASTing with nuclear extracts proves that myogenin can bind cooperatively with other E-box-binding factors.

Animals↗
PubMed1987

Thin-layer chromatography--the forgotten alternative for the quantitative determination of steroids.

We have developed a high performance thin layer chromatography (HPTLC) system for quantitative determination of androgens, corticosteroids, mineralocorticoids and gestagens on silicagel KG-60 HPTLC-plates with different solvent systems. A complete separation of androgens, gestagens and metabolites was achieved with dichlormethane/cyclohexane/acetone (70:25:5). Corticosteroids, mineralocorticoids and their derivatives were completely separated with diethylether/isooctane/isopropanol (70:25:5). The quantitative in situ fluorescence determination was carried out after post-chromatographic derivatization with cinnamic aldehyde, 4-dimethylaminobenzaldehyde and sulfuric acid. The sensitivity of detection was found between 500 pg and 1 ng per spot. The steroid metabolism as catalysed by rat liver microsomal oxidoreductases was measured by these procedures, and was compared with determination of steroids by gas chromatography (GC). According to HPTLC, steroids were reduced by NADPH-5 alpha-reductase (EC 1.3.1.4) in the order progesterone greater than testosterone greater than aldosterone greater than cortisol greater than corticosterone. The enzyme activities as measured by HPTLC agree well with those obtained by GC (r = 0.94). When turnover of enzyme assays, speed of determination, detection limit, application to labile steroids and costs of steroid determination are considered, all points speak in favour of HPTLC.

Adrenal Cortex Hormones↗
PubMed1987

[Direct observation of microcirculation in isoflurane anesthesia].

The effects of anaesthesia with 1.0 vol% isoflurane or 0.7 vol% halothane on the microcirculation were studied in the dorsal skin fold chamber of 15 awake Syrian Golden hamsters. To avoid relative hypovolaemia hydroxyethyl starch (HES 450/0.7) was infused to keep the CVP at baseline level. Arterial blood gas values did not change with either of the anaesthetic agents. Mean arterial pressure decreased significantly with isoflurane to 79% of baseline. Small arteries (25-100 micron) did not exhibit any alterations of diameters in both groups, whereas arterioles (less than 25 micron) constricted with isoflurane from 15.5 to 13.3 micron (15 min) and to 12.0 micron (60 min). 10 min after stopping isoflurane further vasoconstriction was regularly noticed (from 51.0 resp. 15.5 micron to 36.6 resp. 9.7 micron) which did not occur after halothane. Spontaneous arteriolar vasomotion was abolished by halothane, but not by isoflurane; in two animals its amplitude increased. Capillary density rose with both anaesthetics: 9.1% (15 min) resp. 9.0% (60 min) with halothane, 14.0% resp. 17.3% with isoflurane. Local tissue pO2 measured in 6 additional hamsters increased during isoflurane from 16.4 to 22.8 mmHg (15 min) and 19.8 mmHg (60 min). It is concluded that isoflurane is less detrimental to local perfusion control than halothane. The preserved regulatory capacity results in a redistribution of microvascular flow and an improvement of oxygen supply to the dorsal skin fold chamber despite arterial hypotension.

Anesthesia, Inhalation↗
PubMed1986

A novel method for follow-up studies of the microcirculation in non-malignant tissue implants.

Specimens of syngeneic spleen, myocardium, and spongious bone as well as lyophilized dura were implanted into a dorsal skinfold chamber of hamsters. Using intravital microscopy and quantitative video-image analysis, the formation of the implants microcirculation was observed for 2 weeks. The steps of revascularization were similar for spleen, myocardium, and spongiosa: After initial bleeding into the implants (12-54 h), the specimens cleared up and revealed small channels devoid of blood cells (diameter 2-5 microns) 3-4 days after implantation. After 3-5 days blood flow could be observed throughout the specimens. Despite these similarities, the evolving angioarchitecture was specific for each tissue. In contrast, dura specimens were not vascularized. Histology of the implants revealed characteristic structures of the original organs 10-15 days after implantation. It is concluded that the hamster dorsal skinfold chamber provides a suitable host tissue for syngeneic implants. By this procedure, the study of the microcirculation of remote or unpredictably moving organs becomes possible over prolonged periods of time.

Animals↗
PubMed1986

[Transvenous DSA of the extracranial cerebral arteries. Causes of reduced image quality based on a critical analysis of 1000 patients].

In this study images of 1000 patients examined via transvenous DSA were analysed and the image quality scrutinised for each vascular region while determining the causes of image quality reduction. The results show that the diagnostic image quality was 98% (excellent/good 79%, fair: 19%) for a. carotis communis, 94% (69 and 25%, respectively) for carotid bifurcation, 84% (54%, 30%) for distal int. carotid arteries, 91% (65%, 26%) for vertebral arteries and 74% (45%, 29%) for basilar artery. Reasons for image quality reduction were artifacts due to movements by the patients, and were also due to vascular superposition. Reduced left ventricular function resulting in prolonged circulation time and dilution of contrast material was frequently combined with an advanced age of the patients (greater than 75 years). Our studies suggest that transvenous DSA is not useful in patients with significantly reduced cardiac output who do not cooperate properly and are of advanced age. It may, therefore, be omitted to avoid unnecessary stress and high cost. In such cases intraarterial DSA or conventional angiography is indicated.

Aged↗
PubMed1984

Prognostic classification of malignant melanoma by clinical criteria.

In a retrospective study of 503 well-documented cases of primary malignant melanoma (stage I) clinical criteria were analysed for their prognostic relevance. The maximum elevation (in mm) of the tumour was found to be the most important single prognostic factor. There was a close association with tumour thickness, measured histologically by the method of Breslow (correlation coefficient = 0.73). A combination of elevation and three additional clinical criteria (site, nodule- or lesion-diameter, and surface defects such as erosion, ulceration or bleeding) allowed a further improvement in prognostic accuracy. This clinical classification into low-risk and high-risk melanomas was as effective as the use of tumour thickness measured histologically, and can therefore be used for the preoperative planning of treatment.

Adult↗
PubMed1983

Spontaneous arteriolar vasomotion as a determinant of peripheral vascular resistance.

Spontaneous changes of diameter in small arteries and arterioles were studied in the hamster skin fold chamber preparation, which allows to observe the microcirculation without acute exposure and anesthesia. Continuous measurements of diameter were made when the preparation appeared to be physiologically normal according to preset criteria. 89% of the arterial vessels studied showed spontaneous changes in diameter. The activity was prevalently periodic with 29% of the vessels exhibiting random changes in diameter. The amplitude of the periodic activity expressed as a percentage of the mean diameter increases in proportion to the vessel size, arterial vessels in the 40-100 micron diameter range exhibit amplitudes of the order of 10-20%. The smallest arterioles show changes as large as 100% of mean diameter, which cause these vessels to become temporarily occluded. This phenomenon is analyzed in terms of its effect on peripheral vascular resistance by means of an analytical model that assumes vasomotion to be a periodic phenomenon. It is shown that the presence of time dependent changes in vessels diameter similar to those observed, has an important effect on peripheral vascular resistance.

Animals↗
PubMed1980

[Regional blood flow in splanchnic organs during positive end-expiratory pressure ventilation (author's transl)].

An experimental study was performed on 10 dogs to evaluate the effect of positive end-expiratory pressure ventilation (PEEP) on hemodynamics and regional blood flow (RBF). The following conclusions can be drawn from the results of this study: 1) PEEP leads to a significant reduction of cardiac output (CO). 2) Total blood flow to the preportal splanchnic organs, and consequently the portal venous flow, decreases in proportion to the reduction of CO. Within the splanchnic area, there is a redistribution of RBF in favour of the small and large intestines, at the expense of stomach and pancreas. 3) The arterial blood flow to the liver is only moderately affected. 4) The observed changes of RBF may in part contribute to the complications of the splanchnic organs occurring in PEEP-ventilated patients. 5) PEEP should be used only when strictly indicated; close monitoring of organ function appears mandatory in these patients.

Animals↗
PubMedDate not supplied

Human embryonic stem cells: culture, differentiation, and genetic modification for regenerative medicine applications.

Human embryonic stem (hES) cells can proliferate extensively in culture and can differentiate into representatives of all three embryonic germ layers in vitro and in vivo. The undifferentiated hES cells have now been cultured for more than 50 passages in vitro, yet maintain a normal karyotype. The hES cells express a series of specific surface antigens, as well as OCT-4 and human telomerase, proteins associated with a pluripotent and immortal phenotype. On differentiation, OCT-4 and human telomerase expression decreases with the emergence of a maturing population of cells. During hES cell differentiation, modulation of the expression of many genes has been evaluated using microarray analysis. To improve the ease, reproducibility, and scalability of hES culture, methods have been developed to propagate the cells in the absence of mouse embryonic cell feeders. hES cells maintained in culture using extracellular matrix factors together with mouse embryonic cell conditioned medium proliferate indefinitely while maintaining a normal karyotype, proliferation rate, and complement of undifferentiated cell markers. hES cells cultured without feeder layers retain their capacity to differentiate into cells of all three germ layers in vitro and in teratomas. The hES cells can also be genetically modified transiently or stably using both plasmid and viral gene transfer agents. These analyses and technological developments will aid in the realization of the full potential of hES cells for both research and therapeutic applications.

Animals↗