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Biomedical subjects

R Lange

Publications and source records attributed to R Lange.

At least 217 records · Page 12Linked to original sources
PubMed1995

Treatment of dilated cardiomyopathy with dynamic cardiomyoplasty: the Heidelberg experience.

BACKGROUND: Data concerning the efficacy of dynamic cardiomyoplasty are still inconsistent, especially in terms of improvement of left ventricular function. METHODS: Between August 1990 and February 1994, eight isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (ejection fraction, 0.14 to 0.32; New York Heart Association class III) and contraindications to heart transplantation. RESULTS: Follow-up was 41.1 +/- 14.1 months. One patient died 2 months and another 3 years after operation. Considerable symptomatic improvement was found in 6 of 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. Mean New York Heart Association-class decreased from 3.0 to 1.9 (p < 0.001). Echocardiography showed an increase in fractional shortening and in peak aortic flow velocity in all patients. Left ventricular ejection fraction increased from 0.21 +/- 0.05 to 0.38 +/- 0.16 (n = 7, p < 0.015) at 1 year, to 0.37 +/- 0.18 (n = 6, p < 0.05) at 2 years, and to 0.36 +/- 0.19 (n = 5, not significant) at 3 years. Pulmonary artery pressure tended to decrease over time. No significant change in exercise level or maximal oxygen consumption during treadmill testing was observed. CONCLUSIONS: Our preliminary results show that patients may exhibit an impressive clinical improvement after cardiomyoplasty, with only moderate changes in objective hemodynamic indices. We do not consider cardiomyoplasty an alternative to heart transplantation, but reserve it for patients with contraindications to heart transplantation.

Cardiomyopathy, Dilated↗
PubMed1995

Atrioventricular valve insufficiency and atrial geometry after orthotopic heart transplantation.

BACKGROUND: The etiology of tricuspid and mitral valve regurgitation (TR and MR) after heart transplantation is still controversial. METHODS: We studied 25 patients undergoing transplantation and intraoperative transesophageal echocardiography to evaluate the incidence, the degree, and the cause of TR and MR. The degree of valve regurgitation was assessed by color Doppler echocardiography. Cross-sectional areas of the recipient (R) and donor (D) portions of the atria and their ratio (R/D) were measured to assess the distortion of atrial geometry. Tricuspid and mitral valve annuli, their systolic shortening, and hemodynamic indices were measured preoperatively and perioperatively. RESULTS: Tricuspid valve regurgitation was found in 21 of 25 patients (84%) and MR in 12 of 25 (48%). The degree of MR was mild, whereas TR was mild to moderate. Mitral valve regurgitation did not show any correlation with the studied indices; TR showed no correlation with the hemodynamic indices but a significant correlation with R/D ratio (r = 0.90; standard error of the estimate = 0.2). An inverse correlation was found between the degree of TR and systolic shortening of tricuspid annulus (r = -0.88; standard error of the estimate = 0.03) and between R/D ratio and systolic shortening of tricuspid annulus (r = -0.85; standard error of the estimate = 0.04). CONCLUSIONS: Tricuspid valve regurgitation has a higher incidence than MR and occurs immediately after transplantation; MR is mild and correlates with neither hemodynamic indices nor atrial distortion. An increased R/D ratio, and hence distortion of right atrial geometry, may lead to a reduction in systolic annulus shortening, which in turn causes TR. Surgical attempts to reduce the R/D ratio may decrease the incidence and the degree of TR after heart transplantation.

Echocardiography, Doppler, Color↗
PubMed1995

Modified surgical concept for fulminant pulmonary embolism.

Surgical intervention in fulminant pulmonary embolism (PE) is still associated with an overall 30% fatal outcome which increases to about 60% when cardiopulmonary resuscitation (CPR) is necessary. Despite unfavorable conditions like hemodynamic instability, failed lysis or CPR, the surgical strategy might have a certain impact on the patient's outcome since 30-40% of the surgical mortality is related to persistent right heart failure and early thromboembolic recurrence. From 1/88 to 8/94 a total of 25 patients (15 females, 10 men, mean age 57 [25-78]) years underwent emergency pulmonary embolectomy with the use of the heart-lung machine. Seventeen patients were operated upon between 1988 and 1992. A standard approach by central pulmonary artery incision with extraction of adjacent pulmonary emboli using forceps, suction of Fogarty catheters was used. Six of these patients (35%) died, with four out of six operated upon under CPR. Since 1993 we have used a modified surgical strategy in eight patients. Five patients (63%) were operated on after or under CPR. In these cases, left and right pulmonary arteries were incised peripherally and all segmental arteries were desobliterated selectively using small suction devices. Thereafter the right atrium was opened and inspected. After removal of the inferior caval vein cannula all inferior body blood was taken with cardiotomy suction while both legs and the abdomen were massaged centripetally to mobilize additional fresh thrombotic material. In three cases up to 50 cm long thrombi could be delivered. All patients have survived to date with two patients receiving a LGM caval filter placed percutaneously after bilateral postoperative phlebography had revealed ongoing thrombotic disease. We conclude that selective desobliteration of every segmental pulmonary artery in combination with simultaneous clearance of major body veins from additional thrombotic material will probably lower surgical mortality in these critically ill patients.

Adult↗
PubMed1995

Dynamic cardiomyoplasty: indication, surgical technique, and results.

The efficacy of dynamic cardiomyoplasty is still controversial. To date more than 400 patients have been operated worldwide. In recent years the indication and the surgical technique have become more uniform, which makes results from different centers eligible for comparison. We performed cardiomyoplasty exclusively in patients with contraindications for heart transplantation, such as chronic and recurrent infections or severe, irreversible sequelae of diabetes. Between August 1990 and October 1994, 8 isolated cardiomyoplasty procedures were performed in patients with cardiomyopathy (EF 14-32%, all in NYHA III). One patient died 2 months after surgery. Reported are the results of 7 patients after a mean follow-up of 41.1 +/- 14.1 months. Considerable symptomatic improvement was found in 6 or 7 patients, 3 of whom went back to work. One patient with severe pulmonary hypertension exhibited no improvement. In the others NYHA class improved by at least one. Echocardiography showed an increase in fractional shortening in all patients. LVEF increased from 21.2 +/- 5.2% to 38.1 +/- 15.9% (n = 7, p < 0.015) at 1 year, to 36.6 +/- 17.6% (n = 6, p < 0.05) at two years, and to 36.4 +/- 18.9% (n = 5, NS) at three years. Pulmonary artery pressure tended to decrease at rest over time. Resting lung function showed no change of vital capacity and FEV1. No significant change in exercise level and maximal O2-consumption during treadmill testing was observed. One patient died 34 months after the operation from sudden death. Our preliminary results show that patients after cardiomyoplasty may exhibit an impressive clinical improvement with less striking changes of objective hemodynamic parameters. This data is in agreement with the results of all other investigators. Some possible mechanisms of action are discussed and a risk profile suggested. According to the current state of experience with cardiomyoplasty, we do not consider this method an alternative to heart transplantation, but reserve it for patients with contraindications for heart transplantation.

Cardiomyopathies↗
PubMed1995

[Anesthesiologic management in cardiomyoplasty].

Dynamic cardiomyoplasty is a therapeutic possibility in irreversible cardiac insufficiency. With this operation, the latissimus dorsi muscle is mobilised and drawn into the thorax where it is placed around the heart. Lateral and supine positioning as well as thoracotomy and direct manipulation of the heart are associated with particular risks during surgery. Eight patients with the diagnosis of cardiomyopathy underwent cardiomyoplasty. The patients were classified as NYHA III-IV. Continuous dobutamine infusions were routinely started after induction of anaesthesia. All patients were intubated with single-lumen tubes. After sternotomy, lidocaine was administered. Monitoring included Swan-Ganz catheterisation and invasive blood pressure measurement. With early use of inotropic and vasodilatator agents the cardiac index and peripheral vascular resistance were adequately maintained. Double-lumen intubation seems to be unnecessary during cardiomyoplasty and only increases patient risk. Prophylactic lidocaine infusions are effective in preventing ventricular tachycardia and fibrillation. We conclude that adequate intraoperative management can improve the haemodynamic status of these patients so that cardiomyoplasty may be performed without significant morbidity.

Adult↗
PubMed1995

Developmentally regulated mouse gene NK10 encodes a zinc finger repressor protein with differential DNA-binding domains.

Using oligonucleotides complementary to the conserved inter-finger region of a variety of previously described zinc finger-encoding genes, a novel mouse gene was cloned and characterized. The gene is localized on chromosome 8 and comprises five exons. Its corresponding mRNA is developmentally regulated in various tissues and includes an open reading frame encoding a protein of 72,422 daltons. It shares amino-terminal homologies with human KRAB (or FPB) boxes, and contains 13 zinc fingers of the C2-H2 type. The NK10 KRAB domains exhibit repressing activity when tested in GAL4 fusion protein assays. Cloning of putative target sequences revealed that the individual domains differentially contribute to zinc-dependent target DNA binding.

Amino Acid Sequence↗
PubMed1995

Identification of transcriptional start sites and the role of ppGpp in the expression of rpoS, the structural gene for the sigma S subunit of RNA polymerase in Escherichia coli.

rpoS is the structural gene for the sigma S subunit of RNA polymerase which controls the expression of a large number of genes in Escherichia coli that are induced during entry into stationary phase or in response to increased medium osmolarity. Using a combination of primer extension experiments and a 5' deletion analysis of the region upstream of rpoS, we show that rpoS transcription is mainly driven by a single promoter (rpoSp1) located within the nlpD gene upstream of rpoS (the two relatively weak nlpD promoters contribute to the low level of rpoS expression during early exponential phase). In addition, we demonstrate that the expression of both transcriptional and translational rpoS::lacZ fusions as well as the level of rpoS mRNA originating at rpoSp1 is strongly reduced in ppGpp-deficient relA spoT mutants. However, experiments with the 5' deletion constructs indicate that a lack of ppGpp does affect transcriptional elongation rather than initiation.

Bacterial Proteins↗
PubMed1995

Central adiposity and its metabolic correlates in obese adolescent girls.

To establish whether alterations in insulin action and secretion and their relationship to body fat distribution occur early in the course of developing obesity, we studied 14 obese adolescent girls [13.2 +/- 0.7 yr, body mass index (BMI) 32 +/- 1.4], 16 nonobese young women (24.0 +/- 0.6 yr, BMI 21.0 +/- 0.9). Insulin action was assessed by a sequential two-step (8 and 40 mU,m-2.min-1) euglycemic insulin clamp in combination with [1-13C]glucose and indirect calorimetry. Insulin secretion was determined by the hyperglycemic clamp technique (6.9 mmol/l). Magnetic resonance imaging was used to quantify visceral and subcutaneous abdominal fat depots. In obese girls, an impairment in glucose disposal was present with both insulin doses; at the higher dose, rates of glucose uptake were reduced by 30% in nonobese girls (240 +/- 30 vs. 340 +/- 19 mg.m-2.min-1, P < 0.05) and by an additional 29% (170 +/- 17 mg.m-2.min-1, P < 0.05) in obese girls. Insulin infusion failed to stimulate glucose oxidation and to suppress lipid oxidation only in obese girls. Suppression of free fatty acid levels, but not hepatic glucose production, was decreased in obese girls compared with controls. Fasting and glucose-stimulated insulin responses were greater in obese than in nonobese adolescents, who, in turn, had greater responses than lean women. In obese girls, visceral fat, but neither waist-to-hip circumference ratio nor subcutaneous fat, was highly correlated with basal insulin secretion (r = 0.89, P < 0.001), stimulated insulin secretion (r = 0.61, P < 0.05), and insulin resistance (r = -0.87, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle.

To determine the relationship between circulating metabolic fuels and their local concentrations in peripheral tissues we measured glycerol, glucose, and amino acids by microdialysis in muscle and adipose interstitium of 10 fasted, nonobese human subjects during (a) baseline, (b) euglycemic hyperinsulinemia (3 mU/kg per min for 3 h) and, (c) local norepinephrine reuptake blockade (NOR). At baseline, interstitial glycerol was strikingly higher (P < 0.0001) in muscle (3710 microM) and adipose tissue (2760 microM) compared with plasma (87 microM), whereas interstitial glucose (muscle 3.3, fat 3.6 mM) was lower (P < 0.01) than plasma levels (4.8 mM). Taurine, glutamine, and alanine levels were higher in muscle than in adipose or plasma (P < 0.05). Euglycemic hyperinsulinemia did not affect interstitial glucose, but induced a fall in plasma glycerol and amino acids paralleled by similar changes in the interstitium of both tissues. Local NOR provoked a fivefold increase in glycerol (P < 0.001) and twofold increase in norepinephrine (P < 0.01) in both muscle and adipose tissues. To conclude, interstitial substrate levels in human skeletal muscle and adipose tissue differ substantially from those in the circulation and this disparity is most pronounced for glycerol which is raised in muscle as well as adipose tissue. In muscle, insulin suppressed and NOR increased interstitial glycerol concentrations. Our data suggest unexpectedly high rates of intramuscular lipolysis in humans that may play an important role in fuel metabolism.

Adipose Tissue↗
PubMed1995

Comparison ketoprofen, ibuprofen and naproxen sodium in the treatment of tension-type headache.

The safety and efficacy of treatment of tension-type headache with either ketoprofen or ibuprofen and naproxen sodium were evaluated in a prospective, randomized, double-blind parallel-group-study in 345 subjects. All patients were valid for evaluation of efficacy and safety. Headache pain intensity and pain relief were measured on categorical verbal scales 30, 45, 60, 120, 180 and 240 min after ingestion of a single dose of 12.5 mg or 25 mg ketoprofen, 200 mg ibuprofen and 275 mg naproxen sodium. At no time in four hours observation the efficacy of the four treatments differed, neither in pain intensity difference nor in the pain relief scale. A statistical comparison test was performed only once analysing the primary efficacy variable, the sum of pain intensity differences. There was no statistically significant difference among all treatments in this respect. The results of this clearly indicate that ketoprofen in a dosage of 12.5 or 25 mg, compared to 200 mg ibuprofen and 275 mg naproxen sodium, is an effective and safe treatment in tension-type headache.

Adolescent↗
PubMed1995

Pharmacokinetics and relative bioavailability after single dose administration of 25 mg ketoprofen solution as compared to tablets.

The relative bioavailability of ketoprofen from a liquid formulation as compared to a tablet formulation as reference after single oral dose administration was investigated in 16 healthy male subjects. The subjects received in a randomized, crossover design during one study period of 5 days 2.5 mg of ketoprofen as tablet or liquid formulation administered as single dose with a washout interval of 48 h. The plasma concentrations of S(+)- and R(-)-ketoprofen were determined before and up to 24 h post-administration. S(+)- and R(-)-ketoprofen in the collected plasma samples was determined using an internally standardized validated HPLC method. Regarding the geometric mean concentration-time courses there were no relevant differences between the two ketoprofen enantiomers for both formulations. Remarkable differences in the shape of concentration-time courses between the two formulations were found with higher Cmax (by about 70%) and earlier tmax (by 15 min) values for the ketoprofen solution. The treatments were widely equivalent with regard to AUC. The quotients of geometric means as well as 90% confidence intervals for AUC of R(-)-ketoprofen were 95.72% (92.55-99.00%) and for S(+)-ketoprofen 94.23% (89.91-98.76%). The administration of the ketoprofen solution resulted earlier in higher concentrations (by about 70%) for both enantiomers, whereas the extent of absorption expressed by AUC was nearly the same (about 95%) as compared to the equimolar tablet formulation. The differences between the two formulations for Cmax,norm and tmax were statistically significant.

Adolescent↗
PubMed1995

[Surgical therapy of acute tricuspid valve endocarditis: indications, technique and results].

Tricuspid valve endocarditis is treated by antibiotics alone in the majority of the cases. However, intractable infection or hemodynamic compromise may warrant surgery. In those cases total valve-excision or valve-replacement had been the most common surgical procedures. Both are controversial in regards to the hemodynamic consequences and to the long-term prognosis. In the following, results of tricuspid valve repair in acute infective endocarditis are reported and discussed as an additional treatment option. Between January 1988 and December 1993, 118 patients were operated for acute valve endocarditis at our institution. Eleven of these patients had tricuspid valve endocarditis, isolated (n = 7) or combined with endocarditis of a left-sided valve (n = 4). In the cases with isolated tricuspid valve endocarditis, the indication for surgery was intractable infection in 6 and hemodynamically relevant tricuspid-insufficiency in 1 out of 7 patients, respectively. In all patients with associated left-sided endocarditis, the indication was hemodynamic deterioration. In 8 patients the tricuspid valve endocarditis was treated as follows: Debridement, vegectomy, patch-reconstruction of the cusps, bicuspidalization. In 3 patients reconstruction was not possible because of extended involvement of all parts of the valve, including the valve ring and the papillary muscles. In these patients, primary valve-replacement (n = 1) or valve-excision with secondary replacement (n = 2) was performed. In 4 patients tricuspid-reconstruction was combined with mitral- (n = 1), aortic- (n = 1) or double-valve replacement (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Interaction of tryptophan residues of cytochrome P450scc with a highly specific fluorescence quencher, a substrate analogue, compared to acrylamide and iodide.

The cytochrome P450scc tryptophan fluorescence was studied by the use of the three quenchers acrylamide, 25-doxyl-27-nor-cholesterol (CNO) and potassium iodide (KI). All the nine tryptophan residues were accessible to acrylamide. Whereas a strong interaction (static quenching) between acrylamide and tryptophan in the active site had been found previously for cytochrome P450c21 [Narasimhulu, S. (1988) Biochemistry 27, 1147-1153], in the case of P450scc the temperature dependence of the slope of the linear Stern-Volmer plots indicated a dynamic quenching mechanism. This mechanism was confirmed by fluorescence lifetime measurements. Of the three observed life-times tau 1 = 3.1 +/- 0.5 ns, tau 2 = 0.7 +/- 0.25 ns and tau 3 = 20 +/- 10 ps, tau 1 decreased noticeably as a function of the acrylamide concentration. CNO, a spin-labeled substrate which is known to bind tightly to the substrate-binding site of P450scc, quenched 15.5% of the total fluorescence. The Lehrer plot of this compound indicated a static quenching process with a reciprocal quenching constant of 1/Ks = 4 microM, a value which is in accord with the dissociation constant. Our data indicate that CNO quenches selectively one or two tryptophan residue(s) in the active site. The fluorescence spectrum of the residue(s) accessible to CNO was characterized by a red-shifted emission maximum (from 332 nm to 336 nm). The same residue(s) appeared to be quenched by potassium iodide, although much less effectively (1/Ks = 0.12 M). The most probable candidate for a complex formation with CNO is Trp417, which is rather close to Cys422 (the fifth heme ligand). Four arginine residues (Arg411, Arg420, Arg425 and Arg426) in the heme peptide may constitute the iodide-binding site.

Acrylamide↗
PubMed1994

Conformational analysis of mitochondrial and microsomal cytochrome P-450 by resonance Raman spectroscopy.

Mitochondrial and microsomal cytochromes P-450SCC and P-450LM2 in the ferric substrate-free and substrate-bound states were studied by resonance Raman spectroscopy. In the spectra of cytochrome P-450SCC two conformational states (A and B) were detected, each of them constituting an equilibrium between a six-coordinated low-spin and a high-spin form. Both the conformational and the spin equilibria are pH- and temperature-dependent, which is in line with previously published results [Lange, R., Larroque, C., & Anzenbacher, P. (1992) Eur. J. Biochem. 207, 69-73)]. On the basis of well-resolved resonance Raman spectra, measured at different pH and temperatures, these equilibria were analyzed quantitatively. Both low-spin configurations of A and B exhibit different band patterns in the spin state marker band region, indicating differences in the active-site structures. While in the high-spin configuration of state A the heme iron remains weakly bound by a sixth ligand, the high-spin form of state B is five-coordinated. Binding of cholesterol to cytochrome P-450SCC causes a significant population of the high-spin forms, particularly of state A (62%). On the other hand, binding of 22R-hydroxycholesterol to the substrate-free enzyme leaves the overall spin equilibrium largely unchanged, i.e., six-coordinated low spin (76% A and 24% B). In both substrate-bound complexes, interactions between the substrate and the heme lead to small but distinct differences in the resonance Raman spectra of the low-spin form of state A. In contrast to cytochrome P-450SCC, the resonance Raman spectra of microsomal cytochrome P-450LM2 provide no indications for multiple conformers at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗