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Biomedical subjects

R Lange

Publications and source records attributed to R Lange.

At least 19 recordsLinked to original sources

The cholesterol-side-chain-cleaving cytochrome P450 spin-state equilibrium. 1. Thermodynamic analysis.

We have investigated the spin-state equilibrium of adrenal mitochondrial P450scc (cholesterol-side-chain-cleaving, CYP11A1) by absorption spectroscopy in the Soret band as a function of pH and temperature. The van't Hoff plot of the high-spin/low-spin equilibrium is not linear and is shifted towards high spin by lowering the pH. This non-linearity resolves clearly into two phases when the temperature range is extended from 37 degrees C to -20 degrees C using ethylene glycol as anti-freeze cosolvent. This enabled us to measure the enthalpy and entropy changes which are delta HA = 0.7 kJ.mol-1 and delta SA = 5J.K-1.mol-1 at low temperatures and delta HB = -42 kJ.mol-1 and delta SB = -152 J.K-1.mol-1 at high temperatures. The transition temperature, Tbreak, between both phases decreases as a function of pH. The experimental data can be fitted by a minimal reactional model comprising a temperature dependent conformational transition and two ionisation steps (one for each conformation), the pK of which is 1.5 +/- 0.5 higher in the low-temperature conformation. The deduced conformational equilibrium is affected by physiological effectors: Tbreak depends on the nature of the substrate intermediate and on the presence of the physiological electron donor, adrenodoxin.

Adrenal Cortex

The cholesterol-side-chain-cleaving cytochrome P450 spin-state equilibrium. 2. Conformational analysis.

We have confirmed and characterised structurally the enzyme conformational changes deduced from the preceding thermodynamic analysis of the adrenal mitochondrial cholesterol-side-chain-cleaving cytochrome P450 spin-state equilibrium. The spin-transition kinetics following rapid pH jumps were multiphasic in aqueous buffer and biphasic in the presence of 35% ethylene glycol. The activation energy between -2 degrees C and 30 degrees C of both phases was exceptionally high (Ea = 147 kJ.mol-1), suggesting the involvement of large-scale conformational changes. The pH and temperature effects on the CD spectrum show that the enzyme is in equilibrium between at least two conformations which are predicted by the thermodynamic model, but which are not directly correlated to the spin state. The CD changes between 260 nm and 280 nm indicate that the conformation prevailing at high temperatures is characterised by a decreased polarity of the tyrosine environments; the changes between 200 nm and 250 nm suggest furthermore a 4% decreased protein helical content.

Adrenal Cortex

Cervical pheochromocytoma: a rare localization and a difficult diagnosis.

A 45-year-old hypertensive female with insulin-treated diabetes mellitus presented to our clinic with elevated urinary norepinephrine (NE) concentrations and a negative 131-metaiodobenzylguanidine (MIBG) scintigraphy, errouneously limited to the abdomen, for evaluation of a pheochromocytoma (Pheo). Despite antihypertensive medications blood pressure remained highly variable and frequently elevated. Further biochemical testing, including a glucagon provocation test and a clonidine-suppression test, revealed autonomous NE secretion. In order to avoid repeat MIBG-scintigraphy, other non invasive imaging techniques were performed, including real time sonography (7.5 MHz) of the neck which revealed a tumor. Fine needle aspiration of this tumor tissue demonstrated cells compatible with Pheo. Histology and immunohistochemistry of the excised tumor confirmed the diagnosis of Pheo. After surgical removal of the tumor, urinary and plasma NE levels normalized. Without any medication the blood pressure of the patient was now only slightly hypertensive. Only half of the daily insulin dose was needed to maintain the patient euglycemic.

Adrenal Gland Neoplasms

Pelvic phased array coil: image quality assessment for spin-echo MR imaging.

The NMR phased array coil (PA) provides improved signal-to-noise ratio (SNR) over that available with the body coil. We evaluated image quality obtained with a pelvic PA compared to that obtained with the body coil for spin-echo imaging. Thirty-three women undergoing clinical pelvic MRI were imaged with the body coil followed by imaging with the PA with the same field-of-view (FOV) in 11 patients, and with a small FOV in 23 patients. Image quality was assessed independently by two radiologists. In individual cases there was significant improvement in image quality with the PA, however the expected marked improvement in image quality was not consistently found. Two factors which may limit image quality are increased motion artifact and nonuniformity of signal with distance from the coils. Significant improvements in image quality may occur with improved techniques to decrease motion artifact.

Adult

Intraoperative transesophageal echocardiography for the evaluation of mitral, aortic and tricuspid valve repair. A tool to optimize surgical outcome.

The present study reviews the clinical applicability and usefulness of intraoperative transesophageal echocardiography (TEE) during valve repair. Intraoperative TEE was performed in 48 consecutive patients, who were divided into three groups: 1. mitral valve repair (MVR), 2. aortic valve repair (AVR), 3. tricuspid valve repair (TVR). Residual valve regurgitation was assessed by color Doppler echocardiography on a scale from 0 to 4. The ratios of the jet area (JA) to the left- and right-atrial areas (JA/LAA and JA/RAA) were analyzed before and after cardiopulmonary bypass (CPB). In group 1, 14 patients were scheduled for MVR, of which 4 patients underwent valve replacement and 10 MVR. Post-repair TEE studies showed a significant decrease of mitral regurgitation. In 2 of the 10 patients, TEE demonstrated severe residual regurgitation requiring valve replacement during the same thoracotomy. In group 2, 11 patients underwent aortic commissurotomy. Post-repair TEE showed an increase in the systolic opening diameter and opening area of the aortic valve. One patient underwent valve substitution because of severe aortic regurgitation. In group 3, 23 patients were scheduled for TVR. In 3 of them TEE showed no significant regurgitation thus rendering tricuspid valve surgery unnecessary. Twenty patients underwent TVR of whom two showed unacceptable post-repair regurgitation requiring further surgery. Eighteen patients showed a significant reduction of valve regurgitation after TVR, and a further reduction was achieved by adjusting the tricuspid annuloplasty under TEE guidance.

Adult

Superiority of endocardial versus epicardial implantation of the implantable cardioverter defibrillator (ICD).

The implantable cardioverter-defibrillator (ICD) has proved to be an efficient device for the treatment of severe ventricular tachyarrhythmias (VT). From May 1985 to August 1991, the ICD was implanted in 107 patients of whom 72% suffered from coronary artery disease, 17% from cardiomyopathy, 5% from long QT-syndrome and 6% from other heart disease. All patients had a life threatening episode of VT or at least one episode of ventricular fibrillation. Of 107 implants, 12% were combined with other heart surgery, 55% were isolated epicardial implantations (epi I) and in 33%, the novel endocardial (endo I) approach was chosen. Between epi I and endo I we found no difference in operation time, but time for ICU and in-hospital stay was significantly shorter using the transvenous approach. In addition, sensing and pacing capability of the endocardial screw-in electrode was superior and the need for thoracotomy was avoided, a particular advantage in patients with previous heart surgery. Complications after epi I were: temporary low cardiac output, 1; perioperative death, 2; infection, 3, and after endo I: electrode dislocation, 2. Hence, endo I may become the method of choice for patients without concomitant surgery.

Adult

Prevalence of antibodies to Borrelia burgdorferi in serum and cerebrospinal fluid samples from patients with neurological disorders in Berlin.

Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological department were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by Western blotting a method for confirmation. 65 patients (8.1%) had serum IgG antibodies in ELISA and 22 of these patients (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titres in CSF by ELISA and 12 (1.5%) reacted in the Western blot. Clinical features of Bannwarth's syndrome were present in 12 patients (1.5%) and 4 patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were seropositive by both methods and 10 had elevated antibody activity in the CSF proved by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduced the number of false positive results but kept its standard in detecting antibodies in patients with active disease.

Adult

Inflammatory signs, antibody response and antigen detection in cerebrospinal fluid over the course of neuroborreliosis.

CSF and serum specimens were consecutively obtained from three patients with neuroborreliosis (stage I, II and III), CSF protein content, cell counts and differential, IgG index, oligoclonal bands and anti-B. burgdorferi antibodies were measured. Cerebrospinal fluid (CSF) was tested for Borrelia-DNA being present prior to and after antibiotic treatment. While DNA could be identified before ceftriaxone was administered, there were no more amplification products afterwards. The goal of this study was to compare the usefulness of serodiagnostic methods and the detection of Borrelia burgdorferi-DNA in patients with clinically confirmed neuroborreliosis to test the efficiency of antibiotic therapy.

Aged

Lactic acidosis from thiamine deficiency during parenteral nutrition in a two-year-old boy.

This is a case report of a two-year-old boy who was operated electively for a blind-loop syndrome of the proximal jejunum. Because of the appearance of chylous ascites, parenteral nutrition was carried out postoperatively. The boy developed a severe uncompensated acidosis and paralytic ileus. Relaparotomy on suspicion of ischemic bowel did not explain the cause of the acidosis and ileus. Postoperatively, the child's condition worsened, requiring intensive care. The drastically elevated lactate levels corroborated the eventually suspected diagnosis of a vitamin B1 deficiency syndrome. The administration of thiamine within two hours produced correction of the acidosis without further bicarbonate therapy. In 24 hours circulation was stabilized. Two months post-operatively the boy had completely recovered from the sequelae of his shock event.

Acidosis, Lactic

Prognostic B-cell epitopes on the flagellar protein of Borrelia burgdorferi.

Overlapping decapeptides based on the flagellin sequence of Borrelia burgdorferi B31 (G. S. Gassmann, M. Kramer, U. B. Göbel, and R. Wallich, Nucleic Acids Res. 17:3590, 1989) were used to identify immunologically reactive regions of flagellin. Five serum specimens from patients with late manifestations of Lyme disease and borrelia-specific monoclonal antibody H9724 reacted with an epitope in the central region of the flagellar protein (amino acids 205 to 226), which is heterologous to the amino acid sequences of other bacterial flagellins. This epitope was not recognized by human sera with antibodies to Treponema pallidum, sera of healthy individuals, or sera from patients with stage I or II of Lyme disease.

Amino Acid Sequence

Ovalbumin blocking improves sensitivity and specificity of immunoglobulin M immunoblotting for serodiagnosis of patients with erythema migrans.

To improve the serodiagnosis of erythema migrans, we evaluated how sensitivity and specificity of immunoblotting are influenced by antigen concentration and blocking conditions. We found that an antigen concentration of 0.5 micrograms per lane in concert with ovalbumin blocking of the nitrocellulose provided the best results. In this case, 81% of the erythema migrans had positive immunoglobulin M tests, whereas only 33% were positive in a flagellum enzyme-linked immunosorbent assay (ELISA) and 28% were positive in a sonicate ELISA.

Antibody Specificity

[Correlation between neurologic disease and Borrelia burgdorferi antibodies in 800 paired serum/cerebrospinal fluid samples].

Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological clinic were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by a Western blot, a method for confirmation. 65 patients (8.1%) had serum IgG antibodies on ELISA screening and 22 of these (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titers in CSF by ELISA and 12 of these (1.5%) reacted to the Western blot. Clinical features of Bannwarth's syndrome (BS) were present in 12 patients (1.5%) and four patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were positive in serum by both methods and 10 had elevated antibody activity in the CSF proven by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduces the number of positive results but is sensitive in detecting active disease.

Antibodies, Bacterial

Gastric tolerance of single dose unbuffered and buffered acetylsalicylic acid: a randomized comparative endoscopic study in 24 volunteers.

A randomized, three-way crossover study by gastroscopic examination in 24 healthy male volunteers was performed to compare the gastric tolerance of a single dose of buffered or unbuffered acetylsalicylic acid. Gastroscopic assessment was made two hours after administration of the buffered (800 mg ASA) or unbuffered (500 mg ASA) tablets taken with 200 ml of water. Mucosal changes were rare and of a minor nature. Only two volunteers in the unbuffered ASA group presented minor changes (erythema and oedema). No pathological changes were observed after the buffered ASA. Subjective adverse reactions, e.g. epigastric complaints, were reported by four volunteers in the unbuffered group and by two in the buffered group. Based on the limited number and the minor extent of visible changes, statistical tests did not appear to be warranted. The results indicate that buffered ASA is better tolerated.

Adult

[Intraoperative evaluation of tricuspid valve annuloplasty with transesophageal echocardiography].

The present study shows a new application of transesophageal echocardiography (TEE) to optimize tricuspid valve annuloplasty. Eighteen patients with tricuspid regurgitation (TR) underwent De Vega tricuspid annuloplasty. After cardiopulmonary bypass the tension on the suture was adjusted until the surgeon could not feel any regurgitant jet by intraatrial palpation; subsequently, the tension was further adjusted on the basis of TEE. The post-pump residual tricuspid regurgitation was assessed by semiquantitative grading of tricuspid regurgitation (0 to 4+), area of regurgitant jet and percentage of right atrial area subtended by jet area. The data obtained by intraatrial palpation were compared with the data obtained by TEE. A significant reduction of residual tricuspid regurgitation was shown by TEE when compared to intraatrial palpation. After a follow-up period of 2 weeks, no significant changes in the grade of TR were observed. The results showed that the use of TEE was able to optimize the De Vega's tricuspid annuloplasty.

Adult

Gastric emptying in childhood inflammatory bowel disease: nutritional and pathologic correlates.

To determine the incidence of gastric emptying abnormalities in children with inflammatory bowel disease, we performed dual liquid/solid-emptying studies on 25 children with ulcerative colitis (UC) and on 45 with Crohn's disease (CD) over a 6-yr period. Nutritional parameters were evaluated initially and at the time of repeat study in those with abnormal emptying after a period of nutritional rehabilitation. All UC patients and 30 of 45 with CD (67%) had normal emptying of both liquid and solid components of the meal. Fifteen children with CD had delayed emptying of the solid liquid. Fourteen of these had preceding weight loss and one had no weight gain for 3 months prior to the study. Twelve complained of upper gastrointestinal symptoms (nausea, early satiety, postprandial epigastric pain, and anorexia), and five had evidence of growth retardation. The group averaged 4.8 abnormal nutritional parameters, compared with an average of 2.2 in those with CD and normal gastric emptying. Twelve of the 15 with abnormal emptying had abnormal gastric and/or duodenal biopsies: 10 were treated with sulfasalazine and prednisone, whereas five were taking only sulfasalazine. Studies repeated 6-15 months later after establishment of weight gain by caloric supplementation showed significant improvements in gastric emptying, nutritional status, and disease activity for the group, despite persistence of upper gastrointestinal disease documented in eight patients who underwent reexamination.

Adolescent