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Biomedical subjects

U Hoffmann

Publications and source records attributed to U Hoffmann.

At least 199 records · Page 11Linked to original sources

[Pulmonary embolectomy using extracorporeal circulation. An anesthesiological and intensive care viewpoint (author's transl)].

Three cases of massive pulmonary embolism are described in order to illustrate the indications for open pulmonary embolectomy with temporary cardiopulmonary bypass. Surgical treatment is mandatory in the presence of shock with systemic arterial hypotension below 90 mm Hg, arterial hypoxaemia more than 50 per cent as demonstrated by pulmonary arteriography, and pulmonary mean pressure exceeding 30 mm Hg. Additionally the prognosis of the underlying disease should be considered. The specific problems related to anesthesia are associated with the severe shock and its concomitant excessive acid base disturbances both of them being refractory to medical treatment.

Acid-Base Imbalance↗

Application of over-run thin-layer and gas-liquid chromatography in the separation of closely related C19O2 steroids.

An improved method for the separation of epimeric C19O2 steroids and their related allylic alcohols is described. In this method, the steroids are first separated by over-run thin-layer chromatography, and the unresolved groups are further analysed as free or as trimethylsilyl ether derivatives by gas-liquid chromatography. The behaviour of twenty-one C19O2 steroids was investigated by thin-layer chromatography in four systems and by gas-liquid chromatography in four liquid phases. All steroid pairs of similar polarity were resolved by the combination of these two fractionation procedures.

17-Ketosteroids↗

Metabolism of [4-14C] testosterone in the rat uterus in vitro.

In view of the uterine action of androgens we have investigated in vitro the metabolism of [4-14C]-testosterone in uterine tissue of ovariectomized rats. After purification of the extracts on Amberlite XAD-2 the metabolites have been isolated by gel. Five metabolites were isolated and identified during these incubation studies: 4-androstene 3,17-dione, 17beta-hydroxy-5alpha-androstan-3-one, 5 alpha-androstane-3alpha17beta-diol, 4-androstene-3 beta, 17beta-diol and 4-androstene-3alpha, 17beta-diol. Furthermore, two polar C19O3-metabolites and one isopolar to 5 alpha-androstane-3, 17-dione have also been detected. The metabolites were characterized by radioactive gas chromatogrphy, and determination of the relative specific activity in the eluates of Sephadex column chromatography. The identification of allylic alcohols was complemented by their oxidation to 4-androstene-3,17-dione. The present data show that activity of 17beta,3alpha- and 3beta-hydroxysteroid-oxidoreductase and 5alpha-ring-reductase are involved in the metabolism of testosterone in vitro in the rat uterus. The very low 5 alpha-reductase activity under the experimental conditions used in this work explains the formation of allylalcohols as the principal metabolites of testosterone in the rat uterus.

Androstane-3,17-diol↗

Alveolar echinococcosis of the liver: sequelae of chronic inferior vena cava obstructions in the hepatic segment.

BACKGROUND: The clinical pattern and long-term course of chronic inferior vena cava (IVC) obstructions are variable and depend on the underlying cause, the segment involved, and the extension of secondary thrombosis. Pertinent data on IVC obstructions in well-defined series of patients are lacking. We report the sequelae of chronic IVC obstructions in the hepatic segment in 11 consecutive patients derived from a cohort of 104 patients with alveolar echinococcosis of the liver. METHODS: Based on the results of computed tomography scans, 11 patients (7 men, 4 women; mean age, 53.4 years) with IVC obstructions were selected from an ongoing prospective long-term chemotherapy trial comprising 104 patients with alveolar echinococcosis studied at yearly intervals according to a protocol. Obstruction of the IVC in the 11 patients existed for a mean duration of 8.6 years. In these patients, magnetic resonance imaging was performed to assess the morphologic features and extension of the IVC obstruction, as well as the collateral venous pathways. Patency and valvular function of the femoropopliteal veins were analyzed by color-coded duplex ultrasonography. RESULTS: Total occlusions of the IVC were evident in 8 patients (73%) and subtotal stenoses in 3 patients (27%). Only 4 patients (36%) exhibited signs and symptoms of chronic venous insufficiency of the lower extremities; 2 (18%) of the 4 had a history of swelling in the lower extremity. Seven patients (64%) had no lower extremity symptoms. One patient had a history of pulmonary embolism. Abdominal collateral veins were documented in 5 patients (45%) by using magnetic resonance imaging; however, they were clinically evident in only 3 patients (27%). In the 8 patients with IVC occlusion, thrombosis ended at the confluence of the hepatic veins. Obstruction of the IVC was limited to the hepatic segment in 2 patients (18%) and extended to the distal IVC or the iliofemoral veins in 6 patients (54%). Chronic venous insufficiency was present only if the femoropopliteal veins had been involved in the thrombotic process, showing residual venous obstruction, valvular incompetence, or both. Bilateral renal vein thrombosis with moderate proteinuria was observed in 2 patients (18%). The main collateral drainage was achieved through the ascending lumbar, azygos, and hemiazygos veins. CONCLUSIONS: In patients with alveolar echinococcosis, obstruction of the IVC in the hepatic segment often develops asymptomatically and rarely leads to the impairment of renal function. The collateral circulation fully compensates for obstruction of the IVC. Thrombotic involvement and valvular incompetence of the femoropopliteal veins seems to determine the development of chronic venous insufficiency of the lower extremities.

Adult↗

Pharmacokinetic MRI for assessment of malignant glioma response to stereotactic radiotherapy: initial results.

The purpose of this study was to assess the value of dynamic, contrast-enhanced MRI in patients with malignant glioma (a) to predict before stereotactic radiotherapy local tumor control, (b) to investigate temporal changes in tumor microcirculation after stereotactic radiotherapy, and (c) to analyze whether malignant glioma response may be predicted earlier by alterations in the tissue pharmacokinetics rather than in terms of tumor volume. Ninety MRI studies were performed of 18 patients with malignant glioma before and 6, 18, 26, 52, and 72 weeks after the end of stereotactic radiotherapy. The signal time courses of the contrast-enhanced tumors were analyzed using a pharmacokinetic two-compartment model that calculates for the parameter A, reflecting the degree of MRI signal enhancement [no units] and the exchange rate constant k21 [min(-1)]. Before radiotherapy, the amplitude A was significantly (P < .05) lower in patients with subsequent local tumor control (n = 8; mean A = .34 +/- .15) compared to patients without subsequent local tumor control (n = 10; mean A = .94 +/- .71). In the local tumor control group, early after stereotactic radiotherapy (at 6-18 weeks), there was a significant (P < .05) time-dependent decrease in the parameter k21, whereas there was still no alteration in the tumor volume. A low amplitude A before radiotherapy, combined with an early drop of k21 after stereotactic radiotherapy, reliably characterized the group of patients with subsequent tumor volume decrease. Our preliminary results suggest that two contrast-enhanced dynamic MR studies, one before and one early after stereotactic radiotherapy, offer important information on local tumor control within the first 6 to 18 weeks after stereotactic radiotherapy. Moreover, this response may be evidenced before tumor volume changes and provides a therapeutic window to broaden treatment options and to improve treatment outcome.

Brain↗

Glycolytic ATP production estimated from 31P magnetic resonance spectroscopy measurements during ischemic exercise in vivo.

In an oxygen-depleted muscle, glycolytically produced ATP is inversely related to the ([ATP]+ creatine phosphate [PCr]) decrease because ATP, PCr, and glycolysis are virtually the only energy sources under these conditions. In particular, the onset of glycolysis or any appreciable increase in the rate of glycolytic ATP production will lead to a slower rate of ([ATP]+ [PCr]) breakdown at a given energy consumption. To quantify this relationship, endurance athletes performed isometric foot plantar flexion (20% of a test force [TF], n = 10; 50% TF, n = 5) during local arterial occlusion. Parameters of energy metabolism were measured with 31P magnetic resonance spectroscopy (31P-MRS). During exercise, [PCr] decreased to 80 +/- 10 (20% TF) and 11 +/- 4% (50% TF) of its resting concentration, and pH dropped from 7.04 +/- 0.01 to 6.98 +/- 0.10 (20% TF) and from 7.03 +/- 0.02 to 6.70 +/- 0.10 (50% TF). In both experiments, two phases of ([ATP]+ [PCr]) decrease were observed: an initial faster decrease was followed by a slower decline. The latter phase started at about the time when the pH began to drop. The difference between a line extrapolated from the slope of the initial phase and the measured ([ATP]+[PCr]) decrease was used as an estimate for glycolytically produced ATP. This estimate and pH were significantly correlated with r = -0.97 (20% TF) and r = -0.99 (50% TF). These results indicate that glycolytically produced ATP can be estimated from the ([ATP]+ [PCr]) decrease during exercise.

Adenosine Triphosphate↗

Atrial and ventricular myosins from human hearts. I. Isoenzyme distribution during development and in the adult.

Two distinct types of native isomyosins, referred to as human fetal HF and human ventricular myosin HV-3, have been identified in the human fetal heart during two different periods of gestation and in the neonatal state, whose relative parts change with development. In the adult ventricle, only HV-3 was found. Two myosin isoforms designated as HA-3 and HA-1 occur in the atrial myocardium of the normal human heart, which are electrophoretically distinct from the fetal isoenzymes. In fetal tissue, the myosin light chain complement is composed of atrial and ventricular light chains. In support of recent results, we also found identical spots from the atrial ALC-1 and the fetal light chain FLC, suggesting a homology between them. Apart from the light chains typical for this tissue, the atrial myocardium also contains ventricular light chains. Therefore we hypothesize that atrial myosin consists of two atrial isoenzymes and presumably of a ventricular type, too. Differences between atrial and ventricular myosin from human hearts were demonstrated by measuring the temperature dependence of the Ca2+-ATPase.

Adenosine Triphosphatases↗

Atrial and ventricular myosins from human hearts. II. Isoenzyme distribution after myocardial infarction.

Human atrial and ventricular myosins were prepared from autopsy specimens from subjects with coronary heart disease. Cardiac myosin light chain isotypes were resolved using two-dimensional gel electrophoresis, whereas myosin isozymes were detected by pyrophosphate gel electrophoresis. Myocardial infarction and associated work overload cause a transition in the light chain complements of the myosins. Thus ventricular myosin light chains were found in pressure overloaded atria and atrial light chains have also been identified in the infarct ventricle of the human heart. Two molecular isoenzymes of the human atrial myosin, the relative proportions of which are changed after infarction, were separated under non-dissociating conditions by gel electrophoresis. A decrease in HA-3 and a corresponding increase in HA-1 were observed. Ventricular hypertrophy in patients with coronary insufficiency induces a second ventricle isomyosin, called HV-1, with the same electrophoretic mobility as HA-1. The relative part of this myosin type amounts to 20%. Comparative peptide mapping studies were carried out on myosin subfragment-1 preparations from normal and infarct ventricles. In the primary structures, the chymotrypsic digestions produced slight differences. These data demonstrate the heterogeneity of human atrial and ventricular myosins in patients with coronary heart disease.

Aged↗

Can MR measurement of renal artery flow and renal volume predict the outcome of percutaneous transluminal renal angioplasty?

PURPOSE: Predicting therapeutic benefit from percutaneous transluminal renal angioplasty (PTRA) in patients with renal artery stenosis (RAS) remains difficult. This study investigates whether magnetic resonance (MR)-based renal artery flow measurements relative to renal parenchymal volume can predict clinical outcome following PTRA. METHODS: The data on 23 patients (13 men, 10 women; age range 47-82 years, mean age 64 years) were analyzed. The indication for treatment was hypertension (n = 18) or renal insufficiency (n = 5). Thirty-four cases of RAS were identified: bilateral disease was manifest in 11 and unilateral disease in 12 patients. The MR imaging protocol included a breath-hold, cardiac-gated cine phase-contrast sequence for renal flow measurement and a fast multiplanar spoiled gradient-echo sequence for renal volume measurement. MR measurements were performed on the day prior to and the day following PTRA. Clinical success was defined as (a) a reduction in diastolic blood pressure > 15% or (b) a reduction in serum creatinine > 20%. Kidneys were categorized as normal volume or low volume. A renal flow index (RFI) was calculated by dividing the renal flow (ml/min) by the renal volume (cm3). RESULTS: Clinical success was observed in patients. Twelve patients did not benefit from angioplasty. Normal kidney volume was seen in 10 of 11 responders and in 8 of 12 nonresponders, resulting in a sensitivity of 91%, specificity of 33%, a positive predictive value (PPV) of 56% and a negative predictive value (NPV) of 80%. A RFI below a threshold of 1.5 ml/min/cm3 predicted successful outcome with 100% sensitivity, 33% specificity, 58% PPV, and 100% NPV. The combination of normal renal volume and a RFI below 1.5 ml/min/cm3 identified PTRA responders with a sensitivity of 91%, a specificity of 67%, a PPV of 71%, and a NPV of 89%. PTRA resulted in a greater increase in renal flow in responders compared with nonresponders (p < 0.001). CONCLUSION: A combination of cine phase-contrast MR renal flow and parenchymal volume measurements enables identification of patients benefiting from PTRA with a high sensitivity and NPV, but only moderate specificity and PPV.

Aged↗

Cardiovascular responses to apnea during dynamic exercise.

Breath holding maneuvers induce hypoxia, hypercapnia, and various cardiovascular responses typically including increases in total peripheral resistance, mean arterial pressure (MAP) and decreases in heart rate (HR). During dynamic exercise these responses may have a generally negative impact on performance. Moreover, they deserve particular attention in cardiovascular risk subjects. In 26 healthy sport students we studied the HR and MAP effects induced by the combination of dynamic exercise (cycle ergometry, 30 W and 250 W) with 20 s of either respiratory arrest (mouth piece pressure held constant at 20 mm Hg), free breathing, or rebreathing, i. e. periods of unimpeded breathing leading to similar levels of hypercapnia and hypoxia as the respiratory arrest. The measurements yielded no major differences between the conditions of rebreathing and free breathing. In contrast, 20 s of apnea led to a marked increase in MAP and a HR depression at both levels of exercise intensity. Additionally, there was a delayed MAP recovery after this stimulus. The present findings show that breath holding has marked effects on MAP and HR during dynamic exercise, which are essentially independent of the resulting hypoxia and of increases in intrathoracic pressure. The key factor seems to be an increase in total peripheral resistance, probably including a vasoconstriction in the exercising muscles.

Adult↗

[Heparin-induced thrombocytopenia after elective hip joint replacement with postoperative prevention of thromboembolism with low-molecular-weight heparin].

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe side effect of the prophylaxis of venous thromboembolism with unfractionated heparin. The aim of the present study is to gain more information on the incidence of HIT during prophylaxis of venous thromboembolism with low-molecular-weight heparin in elective hip surgery. METHODS: 586 consecutive patients were included into the prospective study, who were admitted to hospital for elective hip replacement. The incidence of thrombocytopenia, clinically manifest venous thromboembolism and of the heparin-induced IgG antibodies were analysed during prophylaxis with low molecular-weight heparin. Patients received once daily subcutaneously low molecular-weight heparin for a mean of 28 days postoperatively. Platelet counts and clinical examinations for the presence of venous thromboembolism were done at days 0, 2, 7 (+/- 1) and 12 (+/- 2). Heparin-induced IgG antibodies were determined before and after a 12 (+/- 2) days prophylaxis with low molecular-weight heparin in 265 of 586 patients randomly. Patients were reexamined for thromboembolic complications after 3 and 6 months. The clinical suspicion of thromboembolic complication was documented objectively. RESULTS: None of the patients developed a decrease of platelets of < 50% of the initial value. Ten of 265 patients had elevated IgG antibodies against heparin/platelet factor 4 before prophylaxis (3.8%). After the 12 (+/- 2) days prophylaxis 13 of 265 patients had elevated IgG antibodies (4.9%). C14 serotonin assay was positive in 0 of 10 patients before treatment and in 3 of 19 patients at day 12 (+/- 2). Ten patients developed venous thromboembolism postoperatively (8 x deep venous thrombosis, 2 x pulmonary embolism, no fatal embolism). Only 1/19 patients with elevated antiheparin IgG titres developed venous thromboembolism. The C14 serotonin assay was negative in this patient. Two patients died in the postoperative phase due to underlying cardiovascular diseases. CONCLUSIONS: In patients with elective hip replacement prophylaxis of venous thromboembolism with low molecular-weight heparin was associated with a very low incidence of HIT, and hence screening for HIT antibodies is not required.

Aged↗

Severe intoxication with the veterinary tranquilizer xylazine in humans.

Xylazine (Rompun, Proxylaz) is a veterinary tranquilizing agent. A case of self-injection of 1.5 g xylazine by a 27-year-old farmer is reported. He subsequently became comatose, hypotensive, bradycardic, and mildly glycemic. An intensive supportive therapy including intubation and ventilation was required. The patient made a full recovery over the next 30 h. The largest concentrations measured were 4.6 mg/L in plasma, 446 mg/L in gastric fluid, and 194 mg/L in urine. The calculated plasma half-life was 4.9 h. Kinetic data correlated with clinical symptoms. Qualitative and quantitative analyses of xylazine were done by thin-layer chromatography, gas chromatography-mass spectrometry, and high-performance liquid chromatography. These methods allow the detection of small amounts substance in stomach, plasma, and urine. Liquid-liquid extraction was used for the isolation of drug. The sensitvity is high, and with these methods, a rapid analysis is possible. Xylazine intoxications in humans are rare. We describe the management of acute poisoning and present a review of xylazine toxicity in humans.

Adrenergic alpha-Agonists↗

SDF-1 expression is elevated in chronic human renal allograft rejection.

The exact mechanism of acute and chronic allograft rejection still remains unclear. The chemokine SDF-1 as mediator of allograft rejection has been under intensive investigation in liver, cardiac and bone marrow transplantation, whereas in renal transplantation, there are no reports about SDF-1 to date. This study was performed to evaluate if SDF-1 might also play an important role in human renal graft biopsies. One hundred and ninety formalin-fixed, paraffin-embedded renal allograft biopsies were included in the analysis from patients with normal renal graft morphology (according to Banff 97 classification grade 1, n = 84), with acute interstitial rejection (Banff grade 4 type I, n = 10), with acute vascular rejection (Banff grade 4 type II, n = 21), with chronic allograft nephropathy (CAN, Banff grade 5, n = 23), and without rejection but with various other lesions (Banff grade 6, n = 42). SDF-1 was localized by immunohistochemistry. In biopsies with CAN, SDF-1 expression was significantly elevated in interstitial infiltrates and infiltrating neointimal cells of arteries compared with biopsies with normal renal graft morphology. This is the first study describing a role of SDF-1 in human renal allograft rejection. We were able to demonstrate in a large number of biopsies an upregulation of SDF-1 in patients with CAN. Whether SDF-1 has pro-inflammatory or protective properties in this setting has to be evaluated in further trials.

Biomarkers↗

Measurement of the lymphatic clearance of the human skin using a fluorescent tracer.

The lymphatic clearance of the human skin at the instep of the foot was measured in 20 healthy volunteers (mean age +/- SD 33.8 +/- 10.5 years). Ten microliters of fluorescein isothiocyanate-dextran 150,000 were injected intradermally and the fluorescent light intensity of the deposit was measured 10 min and 24 h after injection by window densitometry. Fluorescent light intensity decreased by 31.2 +/- 13.5 arbitrary units (p < 0.0001) or by a factor of 4.1 +/- 3.9. Reproducibility was tested 2-6 weeks later in 7 subjects and an intraclass reliability of 0.76 was found. These are the first measurements of the lymphatic clearance of the human skin using a fluorescent tracer. The method is easier and safer than the isotope clearance technique and small areas of the human skin can be investigated. The data found form a basis with which to compare measurements made in patients with different forms of edema.

Adult↗