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Biomedical subjects

P Kaufmann

Publications and source records attributed to P Kaufmann.

At least 91 records · Page 5Linked to original sources
PubMed1997

Preparation and gas chromatographic-mass spectrometric analysis of N-acetyl-O-trimethylsilyl derivatives of long-chain base residues of natural sphingomyelin.

A procedure for the preparation of long-chain base residues of egg yolk, bovine milk and bovine brain sphingomyelin was developed. The bases were converted to N-acetyl-O-trimethylsilyl (TMS) derivatives before being submitted to gas chromatography and mass spectrometry. The chromatographic profile of the milk sample was complex with thirteen peaks, whereas the profiles of brain and egg yolk long-chain bases were simple and remarkably similar.

Animals↗
PubMed1997

[Diuretics in the treatment of heart failure: current pathophysiological aspects].

From a pathophysiologic point of view heart failure can be divided into systolic and diastolic dysfunction. Systolic dysfunction is characterized by a decreased ejection fraction and increased chamber volume which can be typically found in young people with congestive cardiomyopathy. Diastolic dysfunction is associated with an enhanced filling pressure but with a normal systolic pump function. This disorder can be typically found in elderly patients with myocardial hypertrophy. Treatment of congestive heart failure includes. 1.) reduction of central blood volume (preload reduction) 2.) decrease of peripheral resistance afterload reduction) 3.) regression of myocardial hypertrophy (improving myocardial stiffness) 4.) maintenance of atrial contraction (atrial kick) 5.) decrease of heart rate (prolongation of diastolic filling time and increase in contractility) 6.) improvement of LV relaxation (positive lusitropic effect) and 7.) prevention of myocardial ischemia (improvement in contractility and relaxation). The primary goal of medical therapy is symptomatic improvement. Reduction in morbidity and mortality is only a secondary consideration. To achieve this goal ACE-inhibitors and in certain cases betablockers (cave: neg. inotropic action) are suited best. Additionally, digitalis-especially in the presence of atrial fibrillation- and vasodilators can be used to further improve quality of life. In the case of severe heart failure with or without atrial fibrillation oral anticoagulation is indicated to prevent systemic embolication. Diuretics are often used for symptomatic improvement but have no effect on long-term survival. Aldosterone antagonists (e.g, spironolactone) have a beneficial effect on LV remodeling and probably also on mortality. The role of endothelin antagonists and atriopeptidase inhibitors in the treatment of heart failure are not yet clear.

Adult↗
PubMed1997

Elevated plasma levels of soluble tumor necrosis factor receptor (sTNFRp60) reflect severity of acute pancreatitis.

OBJECTIVE: To investigate the role of activated leukocytes in acute pancreatitis, we measured soluble receptors of tumour necrosis factor alpha (sTNFR, p60 subtype) in plasma and evaluated the association of sTNFR with the clinical severity of the disease. DESIGN: Prospective, descriptive study. SETTING: A medical intensive care unit (ICU) in a university hospital. PATIENTS: 25 consecutive ICU admissions of adult patients with acute pancreatitis. MEASUREMENTS AND RESULTS: The clinical severity of the disease was assessed using weights for the worst 17 physiological abnormalities of the Acute Physiology and Chronic Health Evaluation III score over a 24-h period after admission. According to the sum of these weights (giving the Acute Physiology Score, APS) patients were divided into a group with mild pancreatitis (APS < 25) and into a group with severe pancreatitis (APS > or = 25). Soluble TNFR was determined in plasma using an enzyme-linked immunoadsorbent assay. In patients with clinically severe pancreatitis, plasma sTNFR concentrations of 8.8 (16) ng/ ml (median, interquartile range) were significantly higher when compared to patients with mild disease [2.7 (1.5) ng/ml; p < 0.0001]. The sensitivity and specificity of sTNFR plasma concentrations (cutoff point at 5 ng/ml) for the prediction of severe pancreatitis were 90 and 100%, respectively. A highly positive correlation between sTNFR and deviations of physiological parameters from normal (APS score) was demonstrated (r = 0.81). The development of multiple organ failure (MOF) and death was associated with significantly higher sTNFR levels when compared to patients without MOF and survivors [16.4 (17) vs 3.2 (2) ng/ml, p = 0.0014 and 16.0 (18) vs 3.3 (4) ng/ml, p = 0.016, respectively]. For evidence of necrotizing pancreatitis, plasma C-reactive protein concentrations were measured and a significant exponential regression was found with sTNFR (r = 0.77, p < 0.0001). Patients developing pancreatic necrosis, as demonstrated by contrast-enhanced computed tomography, had significantly higher sTNFR concentrations when compared to patients with edematous pancreatitis [9.1 (17) vs 3.2 (2) ng/ml, p = 0.0018). CONCLUSION: The p60 subtype of soluble TNFR is elevated in the plasma of patients with clinically severe acute pancreatitis. This elevation is positively correlated to abnormalities in physiological parameters, development of MOF, and mortality. The association with pancreatic necrosis suggests that, by mediating the effects of TNF, TNFRp60 reflects inflammatory tissue damage leading to severe systemic complications.

Acute Disease↗
PubMed1997

[Function of the residual myocardium after infarct and prognostic significance].

Changes of the left ventricle after myocardial infarction are characterized by geometric, structural, and vascular alterations, which have been summarized under the term "remodeling". This process takes place in the infarct region as well as in the surviving myocardium. Depending on to the size of infarction and the degree of neurohumoral activation, the left ventricle demonstrates diastolic dysfunction which may finally lead to systolic failure. The residual myocardium develops progressive myocyte hypertrophy and interstitial fibrosis. These structural alterations are due to changes in loading conditions and stimulation of the neurohumoral system with an activation of local paracrine and autocrine factors. Myocardial function can be assessed by different non-invasive (echocardiography, radionuclide ventriculography, magnetic resonance imaging, etc.) or invasive methods (e.g., simultaneous pressure-volume measurements). "Myocardial tagging" based on magnetic resonance imaging allows the assessment of 3D-motion of the left ventricle by labelling specific myocardial regions with a rectangular grid. A systolic "wringing" motion with clock-wise rotation at the base and counter-clockwise rotation at the apex has been described in normal subjects. In the ischemic myocardium, delayed relaxation with a prolonged back-rotation (untwisting) has been reported during early diastole, whereas decreased systolic contraction with delayed diastolic rotation has been observed in non-Q-wave infarction. In patients with anterolateral aneurysms, a complete loss of systolic rotation has been demonstrated. The prognostic significance of LV "remodeling" has been emphasized by several authors: The size of infarction, LV volume, LV ejection fraction, as well as the degree of neurohumoral activation have been identified as being associated with an unfavorable clinical outcome. Yearly mortality rates have been reported to range between 15 and 17% in patients with large infarcts and marked LV dilatation and between 3 and 7% in patients with small to medium-sized infarcts.

Diagnostic Imaging↗
PubMed1997

Oxygen and placental villous development: origins of fetal hypoxia.

The increasing practice of preterm delivery in the fetal interest for conditions such as pre-eclampsia or intrauterine growth restriction (IUGR) has provided an opportunity to study placental structure in pregnancies with prenatal evidence of fetal compromise. These data suggest that the origin of fetal hypoxia in IUGR with absent end-diastolic flow in the umbilical arteries is due to a failure of oxygen transport from intervillous space to umbilical vein. Failure of the fetoplacental circulation to extract oxygen from the intervillous space under such circumstances means intervillous PO2 is closer to maternal arterial values than under physiological conditions. Correspondingly the placental villi are chronically exposed to a higher oxygen tension than under normal circumstances--the term ¿hyperoxia', relative to normal intraplacental oxygenation, is proposed to describe this situation. Both the trophoblast and villous core react to increased oxygen despite fetal hypoxia. These results challenge the generally accepted concept of ¿placental hypoxia' in all circumstances where fetal hypoxia might arise. Therefore three categories are proposed for the origins of fetal hypoxia: (1) preplacental hypoxia; (2) uteroplacental hypoxia; and (3) postplacental hypoxia. Examples for these three disease states are listed in this review and the structural reaction patterns of placental villi to these differences in oxygenation are discussed.

Animals↗
PubMed1997

Stromal differentiation and architecture of the human umbilical cord.

In order to assess the characteristics of its stromal cells and the distribution of extracellular matrix proteins, we investigated, immunohistochemically and ultrastructurally, term, first and second trimester human umbilical cords. A differential distribution pattern of the various cytoskeletal proteins of stromal cells and extracellular matrix proteins was observed in different zones of the stroma, the subamniotic stroma, Wharton's jelly, and the vessels' adventitia. All three zones showed immunoreactivities for collagen types I, III and VI and for basement membrane molecules such as collagen type IV, laminin and heparan sulphate proteoglycan. Immunoreactivities for these extracellular matrix molecules were observed around cleft-like territories (stromal clefts) in the Wharton's jelly which were occupied by homogeneous ground substance but void of collagen fibrils and basal lamina molecules. Moreover, between the stromal clefts, slender cells were found which immunohistochemically and ultrastructurally corresponded to various stages of myofibroblastic differentiation. In earlier stages of gestation, stromal cells with a less complex expression pattern prevailed. The stromal clefts and the contractile cells together might serve as a system regulating the turgor of the cord.

Cell Differentiation↗
PubMed1997

Influence of a novel amino acid solution (enriched with the dipeptide glycyl-tyrosine) on plasma amino acid concentration of patients with acute renal failure.

In this randomized, double-blind controlled study we compared the effect of parenteralnutrition with two different amino acid solutions on the plasma concentration of amino acids in 27 patients with acute renal failure. Fourteen patients received the new dipeptide-containing (glycyl-tyrosine) amino acid solution (AADI) in combination with glucose (60%) and fat (10%) as an 'all-in-one' solution over 120 h continuously via a central venous catheter. In the control group (AAST), parenteral nutrition with a standard amino acid solution in isonitrogenous and isocaloric form (0.7 g amino acids/kg BW/day and 25 kcal/kg BW/day) was administered to 13 patients over the same period of time. The administration of the dipeptide-containing amino acid solution caused a return to within the normal range of most of the amino acid concentrations which were decreased at the onset. A significant difference could be found between the AADI and AAST group for the achieved plasma concentrations of threonine (P < 0.01), phenylalanine (P<0.05), isoleucine (P<0.05), tryptophan (P<0.01) and ornithine (P<0.05), The phenylalanine/tyrosine ratio, did not change in the AADI group, while a marked increase was observed in the AAST group. (152.7 +/- 23.5 - 159.8 +/- 37.6 vs 172.6 +/- 24.6 - 310.6 +/- 136.7, respectively). The plasma concentration of glycyl-tyrosine was at the limit of detectability indicating rapid hydrolysis of the dipeptide in acute renal failure. These data suggest that the new dipeptide-containing amino acid solution offers a clear advantage over a standard amino acid formulation in correcting the amino acid imbalances in plasma of patients with ARF and is able to maintain normal tyrosine concentrations and phenylalanine/tyrosine ratio.

Journal Article↗
PubMed1997

Coronary vasomotion after percutaneous transluminal coronary angioplasty depends on the severity of the culprit lesion.

OBJECTIVES: This study sought to evaluate coronary vasomotor response to percutaneous transluminal coronary angioplasty (PTCA) and its influence on proximal and distal vessel diameters with regard to stenosis severity and coronary blood flow. BACKGROUND: Coronary vasoconstriction of the distal vessel segment has been reported after PTCA. This vasoconstrictive effect was thought to be due to balloon-induced injury of the vessel wall, with release of local vasoconstrictors or stimulation of the sympathetic system with release of catecholamines, or both. METHODS: Thirty-nine patients were prospectively studied before and after PTCA. Patients were classified into two groups according to the severity of the culprit lesion: group 1 = > or = 70% to < or = 85% diameter stenosis (n = 23); and group 2 = > 85% to < or = 95% diameter stenosis (n = 16). The coronary vessel diameter of the proximal and distal vessel segments as well as the minimal lumen diameter were determined by quantitative coronary angiography. In a subgroup of 16 patients, basal and maximal coronary flow velocity was measured before and after PTCA with the Doppler FloWire system. RESULTS: The groups were comparable with regard to age, gender, serum cholesterol levels and medical therapy. The proximal vessel segment remained unchanged after PTCA in group 1 ([mean +/- SD] 0.9 +/- 3.5%, p = 0.8) but showed vasodilation in group 2 (+13.7 +/- 3.6%, p < 0.05). However, the distal segment showed vasoconstriction in group 1 (-6.7 +/- 2.0%, p < 0.01) and vasodilation in group 2 (+31 +/- 8.0%, p < 0.01). A significant correlation was found between the change in distal vessel diameter after PTCA and stenosis severity (r = 0.61, p < 0.0001). Changes in blood flow were directly correlated to stenosis severity (r = 0.85, p < 0.002); that is, rest flow increased after PTCA in narrow lesions but remained unchanged in moderate lesions. The diameter changes in the distal vessel segment after PTCA were significantly related to flow changes (r = 0.90, p < 0.0001). Coronary distending pressure of the distal vessel segment increased significantly in both groups; however, this increase was significantly greater in group 2 than in group 1 (55 +/- 4 vs. 14 +/- 3 mm Hg, p < 0.0001). CONCLUSIONS: Coronary vasomotion of the proximal and distal vessel segments after PTCA depends on the severity of the culprit lesion; that is, vasoconstriction of the distal segment is found in patients with moderate lesions and vasodilation in those with severe lesions. Thus, vasomotion of the post-stenotic vessel segment depends on the severity of the culprit lesion and is influenced by changes in coronary flow or distending pressure, or both.

Angioplasty, Balloon, Coronary↗
PubMed1997

Identification and quantification of Bifidobacterium species isolated from food with genus-specific 16S rRNA-targeted probes by colony hybridization and PCR.

A Bifidobacterium genus-specific target sequence in the V9 variable region of the 16S rRNA has been elaborated and was used to develop a hybridization probe. The specificity of this probe, named lm3 (5'-CGGGTGCTI*CCCACTTTCATG-3'), was used to identify all known type strains and distinguish them from other bacteria. All of the 30 type strains of Bifidobacterium which are available at the German culture collection Deutsche Sammlung von Mikroorganismen und Zellkulturen, 6 commercially available production strains, and 34 closely related relevant strains (as negative controls) were tested. All tested bifidobacteria showed distinct positive signals by colony hybridization, whereas all negative controls showed no distinct dots except Gardnerella vaginalis DSM4944 and Propionibacterium freudenreichii subsp. shermanii DSM4902, which gave slight signals. Furthermore, we established a method for isolation and identification of bifidobacteria from food by using a PCR assay without prior isolation of DNA but breaking the cells with proteinase K. By this method, all Bifidobacterium strains lead to a DNA product of the expected size. We also established a quick assay to quantitatively measure Bifidobacterium counts in food and feces by dilution plating and colony hybridization. We were able to demonstrate that 2.1 x 10(6) to 2.3 x 10(7) colonies/g of sour milk containing bifidobacteria hybridized with the specific nucleotide probe. With these two methods, genus-specific colony hybridization and genus-specific PCR, it is now possible to readily and accurately detect any bifidobacteria in food and fecal samples and to discriminate between them and members of other genera.

Bacterial Typing Techniques↗
PubMed1997

Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy.

Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of 20 affected individuals 16 months after an initial evaluation. The optic features were painless symmetric vision loss with poor visual acuity, color vision loss, central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop-out. The neurologic symptoms included stocking-glove sensory changes, hearing loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had received multivitamin therapy. We performed comparisons using the paired two-tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a decline in vision. In patients not harboring mtDNA mutations, overall visual acuity, color vision, and peripheral neuropathy manifestations improved significantly (p < 0.001 for each manifestation). Most of the patients with Cuban ON and PN improved on multivitamin therapy. The significance of the mtDNA mutations is unclear. In the 2 LHON patients, manifestation of the disease may have been precipitated by nutritional deficiency. Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses.

Adult↗
PubMed1997

Carnitine palmitoyltransferase II deficiency: diagnosis by molecular analysis of blood.

Four missense mutations have been reported to be associated with the typical, adult form of carnitine palmitoyltransferase II (CPT II) deficiency: Three amino acid substitutions (R631C. P50H and D553N) appear to be rare, while the S113L mutation was found to be common in a group of European patients with CPT II deficiency. We analyzed genomic DNA from 20 American patients with recurrent episodes of myoglobinuria as well as DNA from 10 normal controls in order to determine the frequency of the reported missense mutations in our patient population. The three previously described rare mutations were not found in our group of patients. The S113L mutation was found in 19 of our patients: 5 patients were homozygous, 14 patients were heterozygous. Given the high frequency of this mutation in our series of patients we concluded that the clinical diagnosis of CPT II deficiency can be confirmed by a 'blood test' without resorting to a muscle biopsy.

Adult↗
PubMed1996

Cloning of choriocarcinoma cells shows that invasion correlates with expression and activation of gelatinase A.

Implantation and placental development are dependent upon trophoblast invasion of the endometrium. While the villous trophoblast does not display invasive behavior, the extravillous cytotrophoblast is highly invasive. By cloning BeWo choriocarcinoma cells, we have isolated two distinct clones that share similarities with villous and extravillous cytotrophoblasts. When cultured at the surface of a type I collagen gel, BeWo MC-1 cells were not invasive, whereas BeWo MC-2 cells rapidly invaded this matrix. When injected subcutaneously in nude mice, BeWo MC-1 cells developed a localized tumor and BeWo MC-2 cells developed larger tumors with micrometastases. Gelatinase A expression and minute amounts of gelatinase B were detected in the parental cell line and in both clones. However, the parental and the BeWo MC-2 cells secreted 5-to 10-fold more gelatinase A than the BeWo MC-1 cells. Laminin and matrigel stimulated the production of gelatinase A in BeWo MC-2 cells. Type I collagen promoted the conversion of the 72-kDa progelatinase A in an active enzyme only in parental BeWo and in BeWo MC-2 cells. These clones provide an interesting model for studying the complex mechanisms regulating implantation as well as the controlled invasiveness during implantation compared to tumor invasion.

Animals↗
PubMed1996

Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension.

BACKGROUND: Endothelial dysfunction with a loss of endothelium-dependent vasodilation has been reported in patients with arterial hypertension. The purpose of the present study was to evaluate coronary vasomotor response to dynamic exercise in patients with coronary artery disease with and without arterial hypertension and to determine the effect of calcium antagonists on coronary vasomotion. METHODS AND RESULTS: Cross-sectional areas of a normal and a stenotic coronary vessel segment were examined in 79 patients with coronary artery disease at rest and during supine bicycle exercise (Ex). Change in luminal area after acute administration of a calcium antagonist (diltiazem or nicardipine), during exercise, and after sublingual nitroglycerin (percent change compared with rest = 100%) was assessed by biplane quantitative coronary arteriography. Patients were divided into two groups: Group 1 (control) consisted of 48 patients without (normotensive subjects, n = 30; hypertensive subjects, n = 18) and group 2 of 31 patients with (normotensive subjects, n = 15; hypertensive subjects, n = 16) pretreatment with a calcium antagonist immediately before exercise. The groups did not differ with regard to clinical characteristics or hemodynamic data measured during exercise. Mean aortic pressure at rest, however, was significantly increased in hypertensive patients compared with normotensive subjects in group 1 (103 mm Hg versus 92 mm Hg, P < .01) and group 2 (110 mm Hg versus 98 mm Hg, P < .025). In group 1, exercise-induced vasomotor response was significantly different between normotensive and hypertensive patients in normal (+20% versus +1%, P < .003) and stenotic vessels (-5% versus -20%, P < .025). However, in group 2 there was coronary vasodilation in normotensive and hypertensive patients for both normal (delta Ex +23% versus +21%, P = NS) and stenotic vessel segments (+24% versus +26%, P = NS). CONCLUSIONS: Abnormal coronary vasomotion during exercise can be observed in hypertensive patients with reduced vasodilator response in normal arteries and enhanced vasoconstrictor response in stenotic arteries. Calcium antagonists prevent the abnormal response of normal and stenotic coronary arteries to exercise in hypertensive patients and thus may compensate for endothelial dysfunction with reduced vasodilator response to exercise.

Calcium Channel Blockers↗
PubMed1996

Erb's explanation for the tendon reflexes. Links between science and the clinic.

OBJECTIVE: To determine whether 19th-century experimental neurophysiological concepts directly influenced Erb's initial explanation for the deep tendon reflexes (DTRs). BACKGROUND: There is extensive literature on the discovery of the clinical utility of the DTRs on the one hand and on the development of 19th-century experimental neurophysiological concepts and early scientific concepts of reflexology on the other. While it seems logical to assume that Erb's 1875 discovery of the clinical utility of the DTRs and his initial interpretation of the physiological meaning of heightened DTRs were grounded in some of these scientific concepts, the important link between the clinical and scientific realm has not, to our knowledge, been the subject of previous analysis. METHODS: Review of the 19th-century neurophysiological literature and translation of seminal manuscripts written by Erb in the years 1875 and 1876. RESULTS: The concepts of spinal inhibition and reflex action arose from 19th-century neurophysiological experimentation. Erb first described the term Patel-larsehnenreflex (patellar tendon reflex) in 1875, and his publications reveal clear insight into several fundamental scientific concepts, including spinal inhibition, the reflex arc, distinct motor and sensory neurons, and an excitomotor system in the spinal gray matter. CONCLUSION: While Erb's initial description and interpretation of the DTRs may be regarded as a fortuitous discovery by a keen clinical observer, on another level his observations were not made in isolation, but were based on his knowledge of the physiological work of the preceding decades.

History, 19th Century↗