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Biomedical subjects

C Richter

Publications and source records attributed to C Richter.

At least 19 recordsLinked to original sources

[Long-term locally-recurrent melanoma].

Malignant melanoma is a highly malignant skin tumor with a widely variable individual course. Currently, approximately 75% of German patients can be cured of malignant melanoma by early diagnosis and excision, while more than 20% die of distant metastases of the melanoma. In contrast, there are single cases of long-term locally recurrent melanomas with neither complete cure nor development of distant metastases. We report on a female patient with a nevus-associated melanoma who was treated in 1968 with X-ray radiation (Dermopan, 100 Gy) with curative intent. In the following 31 years, the patient developed four phases of in-transit and satellite metastases in a zosteriform pattern as well as ilioinguinal lymph node metastasis. Since 1999, the patient has been free of recurrence. Besides the unusual biological features of this case, this report reflects the changes of paradigms in the therapy of melanoma over the last forty years.

Female↗

[Fibrosing mediastinitis: a rare cause of fever].

A 47-year-old woman was examined due to fever of unknown origin. She had been on holiday in Southeast Asia. Routine laboratory investigations confirmed the presence of inflammation. Serology for Hepatitis B virus, HIV, Borrelia, Cytomegalovirus, toxoplasmosis, lues, Epstein Barr virus, brucellosis, bartonellosis, histoplasmosis and auto-immune factors was negative. CT-scans of the chest and abdomen failed to reveal the cause. Finally, gallium-67 scintigraphy showed an increased uptake in the left mediastinum and the left side of the neck. This led to the discovery of an infraclavicular mass. On histological examination of the surgical excision biopsy the diagnosis 'fibrosing mediastinitis' was made. The patient was treated successfully with corticosteroids.

Adrenal Cortex Hormones↗

[The medical-psychiatric unit: added value for patients, physicians and hospitals].

Physical and mental illnesses commonly occur together. The quality of physical care in institutions for mental health in the Netherlands is not guaranteed. The cases of a 63-year-old woman with a schizoaffective disorder and diabetes mellitus who became delirious after surgery and a 76-year-old suicidal man with a psychotic disorder due to hydrocobalamine deficiency after major heart surgery show that the so-called medical-psychiatric unit, which is a part of the Psychiatric Department of a general hospital, may have several advantages in the treatment of combined physical and mental disorders. Both patients were admitted to such a unit. In this way, the internist of the first patient could continue to treat her and she could be treated with an infusion, urinary catheter and gastric intubation; in addition, laboratory investigations could be performed. The second patient, whose safety required primary attention, could also be treated for his somatic disorders and a delirium could be ruled out. His family was assisted in recovering from their traumatic life experience caused by his suicide attempt.

Aged↗

[Not all vocal cord failure following thyroid surgery is recurrent paresis due to damage during operation. Statement of the German Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery concerning recurring paresis due to intubation].

Since the phoniatrician H. Bauer described the first case of recurrent laryngeal nerve palsy most likely caused by intubation some 45 years ago, several case reports have been published. However, systematic analyses regarding the frequency of recurrent laryngeal nerve palsies due to intubation are scarce, and none of them has used the proper methods to demonstrate clearly that such a mechanism exists. Currently available data justify the assumption that not every recurrent laryngeal nerve palsy following thyroid surgery is due to the operation itself and that the damage caused by intubation, however, may only account for a minority of these cases. The differential diagnosis of postoperative recurrent laryngeal nerve palsy requires the use of specific tools which go beyond simple laryngoscopy and include stroboscopy as well as intra- and extralaryngeal electromyography. A partial palsy of recurrent laryngeal nerve due to intubation would be associated with severe dysphonia or aphonia, not with dyspnea because of the typical intermediate position of the paralyzed vocal folds with a normal electromyographic function of the cricothyroid muscle. The use of these methods to identify the nature of postoperative recurrent laryngeal nerve palsy is recommended in cases of regular intraoperative neuromonitoring but postoperatively impaired function of the vocal cords.

Diagnosis, Differential↗

[Effectiveness and results of intraoperative neuromonitoring in thyroid surgery. Statement of the Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery].

Intraoperative neuromonitoring (IONM) has yielded an increasing effect on thyroid surgery. During IONM, the recurrent laryngeal nerve is stimulated electrically and an acoustically transformed electromyographic signal is derived via either a needle electrode placed in the vocalis muscle or an electrode adjusted to the intubation tube. The IONM is used for identifying and predicting the function of the recurrent laryngeal nerve. Especially under difficult anatomic conditions, IONM has proven a valuable tool for identification of recurrent laryngeal nerves. This can lead to decreased occurrence of nerve palsy rates, as shown in numerous studies. The reliability of the IONM signal (defined as the correlation between intraoperative signal interpretation and postoperative vocal cord function) is reflected by a specificity as high as 98.2%, as shown by German multicenter studies. Thus, normal vocal cord function could be demonstrated postoperatively in over 98.2% of patients with intraoperatively unchanged neuromonitoring signals. If the neuromonitoring signal changed during operation, 39% of the patients suffered from transient vocal cord immobility and 12% had permanent loss of vocal cord function.

Electrodes↗

Intelligent training system integrated in an echocardiography simulator.

Computer simulators play an important role in medical education. We have extended our simulator EchoComJ with an intelligent training system (ITS) to support trainees adjusting echocardiographic standard views. EchoComJ is an augmented reality application that combines real three-dimensional ultrasound data with a virtual heart model enabling one to simulate an echocardiographic examination. The ITS analyzes the image planes according to their position, orientation and the visualization of anatomical landmarks using fuzzy rules. An adaptive feedback is provided that colors the specific anatomic landmarks within the contours of the virtual model based on the quality of the image plane.

Artificial Intelligence↗

[Immunodeficiency in adult patients as the first sign of a primary underlying condition].

Three male patients, aged 56, 40 and 52 years, presented with recurrent infections and clinically suspected immunodeficiency, which was confirmed by the presence of hypogammaglobulinaemia. In one patient, no obvious underlying disease was identifiable, and primary immunodeficiency syndromes were considered in the differential diagnosis. A thorough diagnostic work-up revealed the presence of non-Hodgkin lymphoma in an iliac crest biopsy specimen. The second patient was found to have a thymoma. In the third patient, the immunodeficiency was the key to the ultimate diagnosis of multiple myeloma, which was still asymptomatic at that stage. Establishing the underlying condition had important therapeutic and prognostic consequences in these patients.

Adult↗

Compartmentation of metabolism probed by [2-13C]alanine: improved 13C NMR sensitivity using a CryoProbe detects evidence of a glial metabolon.

The labelling of metabolites with the NMR active nucleus 13C allows not only metabolite enrichments to be monitored, but also the relative fluxes through competing pathways to be delineated. [2-13C, 15N]alanine was used as a metabolic probe to investigate compartmentation in superfused cerebral slices. Perchloric acid extracts of the tissue were investigated using 13C NMR spectroscopy. The spectra were obtained using a CryoProbe optimised for 13C detection (dual CryoProbe [13C, 1H]) in which the receiver and transmitter coils are cooled to approximately 20K to reduce contributions to noise in the signal obtained. Compared with conventional inverse geometry probe, the signal-to-noise ratio (S/N) was increased by approximately 17-fold using this device. A large proportion of alanine was initially metabolised over the first 20 min by glial cells, as indicated by the relative importance of the glial, only enzyme pyruvate carboxylase to the labelling pattern of glutamate, with the ratio of pyruvate carboxylase to pyruvate dehydrogenase derived glutamate being 0.25, and exported [2-13C, 15N]aspartate. Using the increased sensitivity of the CryoProbe, [2-13C, 15N]aspartate was also detected in the extracts of cerebral tissue. This metabolite could only have been derived via the pyruvate carboxylase pathway, and given the large export of the metabolite into the superfusion buffer suggests the occurrence of a "metabolon" arrangement of enzymes within glial cells.

Alanine↗

[Three patients with African sleeping sickness following a visit to Tanzania].

Three Dutch tourists, a man aged 57 and two women aged 55 en 52 years, acquired African trypanosomiasis in the national parks of Tanzania. Two, without central nervous system involvement, were cured after treatment in the Netherlands, albeit one after having suffered a relapse. In the third patient, involvement of the central nervous system was diagnosed in Africa and she was treated with melarsoprol. After an apparently uneventful recovery she was readmitted with cerebral complaints and symptoms. While being treated with melarsoprol she lapsed into coma. She died following repatriation. An epidemic of trypanosomiasis is currently raging through Central Africa. In several western countries, trypanosomiasis has been diagnosed recently in tourists who visited Tanzania.

Africa↗

Experimental test of a trace formula for a chaotic three-dimensional microwave cavity.

We have measured resonance spectra in a superconducting microwave cavity with the shape of a three-dimensional generalized Bunimovich stadium billiard and analyzed their spectral fluctuation properties. The experimental length spectrum exhibits contributions from periodic orbits of nongeneric modes and from unstable periodic orbits of the underlying classical system. It is well reproduced by our theoretical calculations based on the trace formula derived by Balian and Duplantier for chaotic electromagnetic cavities.

Journal Article↗

Peroxovanadate inhibits Ca2+ release from mitochondria.

Mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolyzed. NAD+ hydrolysis and therefore Ca2+ release is possible when some vicinal thiols are cross-linked. Here we report that the thiol oxidant peroxovanadate inhibits the specific Ca2+ release pathway. In mitochondria, peroxovanadate causes a complete loss of reduced glutathione, which is not accompanied by formation of glutathione disulfide, and a partial loss of protein thiols. In model reactions, peroxovanadate oxidizes reduced glutathione predominantly to the sulfonate derivative, but does not react with glutathione disulfide. When the vicinal thiols relevant for Ca2+ release are cross-linked, Ca2+ release is no longer inhibited by peroxovanadate. Conversely, pretreatment of mitochondria with peroxovanadate makes them insensitive to compounds promoting the disulfide state. These results suggest that peroxovanadate inhibits the prooxidant-induced Ca2+ release from mitochondria by (i) depleting mitochondria of reduced glutathione and (ii) oxidizing the vicinal thiols relevant for Ca2+ release to a state higher than disulfide, presumably the sulfonate state. The findings provide further insight into the regulation of Ca2+ release from intact mitochondria, and may be relevant for a better understanding of the action of peroxovanadate in cells, where the compound can be insulin mimetic.

Animals↗

Development of hepatitis B virus resistance for lamivudine in chronic hepatitis B patients co-infected with the human immunodeficiency virus in a Dutch cohort.

INTRODUCTION: With the introduction of HAART, the HIV-1 has turned from a lethal into a chronic infection in the majority of patients. In homosexual populations, 20% of HIV-1 infected patients suffer from a chronic HBV infection, which may eventually lead to complications of the liver disease because of prolonged survival. Lamivudine is effective in reducing both HIV-1 and HBV viral replication. However, resistance for lamivudine may complicate the course of the HBV disease in HIV-1-infected patients. We, therefore, conducted a retrospective study in HIV-1-HBV co-infected patients on lamivudine therapy. PATIENTS AND METHODS: All HIV-1-HBV co-infected patients who were treated with lamivudine for over 6 months in five major referral clinics in The Netherlands with HBV DNA above 2.0 x 10(5) geq ml(-1) at baseline, were evaluated. Retrospectively, the course of HBV DNA in available serum samples was established. If HBV DNA was detectable with the sensitive PCR-assay, YMDD-analyses of the polymerase gene of the hepatitis B virus was executed with the INNO-LiPA-DR-strip. RESULTS: Forty-six patients were evaluated. The median level of HBV DNA at start of lamivudine therapy was 1.31 x 10(9) geq ml(-1) (range 3.5 x 10(5) - 2.0 x 10(10), n=43). Of three patients no baseline sample was available, but since HBV DNA was still above 2.0 x 10(5) geq ml(-1) at week 3, 7 and 11, these patients were included. Median duration of lamivudine therapy was 97 weeks (range 27-263). The percentage of detected mutations was 25 and 52% at 1 and 2 years, respectively. Twenty-two patients ultimately developed a mutation. Both baseline Body Mass Index (BMI) and the decrease in CD4 cell count as a time dependent factor were significantly related to the emergence of mutations. In 10 out of 12 evaluated patients, HBV DNA levels returned to baseline level or even above baseline level after the development of mutant virus. One patient (5%) developed a flare of serum transaminases (ALT>10 x ULN) 24 weeks after first detection of variant virus. CONCLUSION: There is a linear time-dependent appearance of HBV mutations for lamivudine in our population. In a minority of patients (5%), development of a mutation was followed by a significant elevation of serum transaminases. A decline in CD4 cell count, which may indicate less response to HAART, induces a faster emergence of mutations and close surveillance of HBV co-infected patients on therapy may be indicated due to the prolonged survival of HIV-1 patients.

AIDS-Related Opportunistic Infections↗

Cessation of pulmonary and coronary secretion of adrenomedullin peptides in the progression of human heart failure.

In human heart failure (CHF), adrenomedullin (AM) counteracts vasoconstriction and sodium retention. We investigated circulating levels of proadrenomedullin N-20 peptide (PAMP) and AM, and left ventricular expression of preproAM and calcitonin receptor-like receptor (CRLR) mRNA. Peptide levels were determined from the left ventricle, pulmonary artery, coronary sinus, and antecubital vein in patients demonstrating severe CHF (n = 12; mean +/- SEM cardiac index, 1.9 +/- 0.2 l/min/m(2); pulmonary wedge pressure, 32 +/- 1 mmHg), moderate CHF (n = 11; cardiac index, 2.9 +/- 0.2; pulmonary wedge pressure, 14 +/- 2), and in controls (n = 11). Left ventricular mRNA was quantified using RT-PCR and Southern blot hybridization. Depending on sites of measurement, PAMP and AM in severe CHF were 1.3 - 2.0 and 1.2 - 1.9 times as high as in moderate CHF, and 3.8 - 4.6 and 2.3 - 2.8 times as high as in controls. Only patients with moderate CHF demonstrated pulmonary and coronary net release of both peptides, that is, significant step-ups in concentrations between the pulmonary artery, left ventricle, and coronary sinus. In failing ventricles, preproAM mRNA increased 2.9 times above control, but CRLR mRNA was unchanged. Altogether, the heart and the lungs release AM peptides in moderate CHF. This secretion breaks down in severe CHF: a process that may contribute to and indicate decompensation. Unlike AM, the CRLR is not transcriptionally upregulated in severe CHF.

Adrenomedullin↗

Flow-induced pressure differentially regulates endothelin-1, urotensin II, adrenomedullin, and relaxin in pulmonary vascular endothelium.

We hypothesized that increased pulmonary vascular pressure--one of the characteristics of congestive heart failure--directly regulates pulmonary endothelial vasoconstrictors (endothelin-1, urotensin II) and vasodilators (adrenomedullin, relaxin). To this end, we subjected pulmonary artery endothelial cells in a novel flow-chamber model to different shear stresses (17, 29, and 46 dyn/cm(2)) at low and elevated levels of downstream pressure (10 and 30 mm Hg). Application of elevated pressure over 16 h increased gene expression and peptide secretion of endothelin-1 at all shear levels, whereas secretion of adrenomedullin rose via decreased expression of its clearance receptor. In contrast, preprourotensin II mRNA and urotensin II peptide decreased in response to elevated pressure, and relaxin remained unaffected. This is the first study to identify pressure as key regulator of mediator synthesis by pulmonary vascular endothelium. Pressure-induced mediator regulation may represent an early event in the development of secondary pulmonary hypertension.

Adrenomedullin↗

Replacing ritonavir by nelfinavir or nelfinavir/saquinavir as part of highly active antiretroviral therapy leads to an improvement of triglyceride levels.

In a randomized, parallel arm, open-label study, the effect of switching from ritonavir to either nelfinavir or nelfinavir plus saquinavir as part of a triple antiretroviral regimen was investigated in 16 patients with undetectable HIV-1 loads. Patients continued to use the same nucleoside reverse transcriptase inhibitors as before the switch of protease inhibitor. The period of follow-up was 48 weeks. In all patients HIV-1 load remained undetectable, whereas CD4 cell counts remained stable. Furthermore, lipid markers improved after the switch.

Adolescent↗

Endoscopic exploration of Red Sea coral reefs reveals dense populations of cavity-dwelling sponges.

Framework cavities are the largest but least explored coral reef habitat. Previous dive studies of caverns, spaces below plate corals, rubble and artificial cavities suggest that cavity-dwelling (coelobite) filter-feeders are important in the trophodynamics of reefs. Quantitative community data are lacking, however, as the bulk of the narrow crevices interlacing the reef framework are inaccessible to conventional analysis methods. Here we have developed endoscopic techniques to explore Red Sea framework crevices up to 4 m into the carbonate rock, revealing a large internal surface (2.5-7.4 m2 per projected m2 reef) dominated by encrusting filter-feeders. Sponges alone provided up to 60% of coelobite cover, outweighing epi-reefal filter-feeder biomass by two orders of magnitude. Coelobite community filtration removed more than 60% of the phytoplankton in the course of its less than 5-minute passage through the crevices, corresponding to an uptake of roughly 0.9 g carbon m-2 d-1. Mineralization of the largely allochthonous organic material is a principal source of nutrients supporting coral and algal growth. The supply of new material by coelobites may provide a key to understanding the 'coral reef paradox'-a rich ecosystem thriving in nutrient-poor water.

Animals↗

Cytochrome c oxidase inhibition by N-retinyl-N-retinylidene ethanolamine, a compound suspected to cause age-related macula degeneration.

The endogenous lipophilic and cationic compound N-retinyl-N-retinylidene ethanolamine (A2E) is suspected to cause age-related macula degeneration. It inhibits cytochrome c oxidase, detaches proapoptotic proteins from mitochondria, and induces apoptosis in mammalian retinal pigment epithelial cells (M. Suter, C. E. Remé, C. Grimm, A. Wenzel, M. Jäättela, P. Esser, N. Kociok, M. Leist, and C. Richter, 2000, J. Biol. Chem. 275, 39625-39630). The inhibition of cytochrome c oxidase is highly specific for A2E and is observed with the solubilized and reconstituted enzyme. In the dark, inhibition is overcome by cardiolipin or other acidic phospholipids. With illumination, inhibition is stronger, becomes complete with prolonged exposure, and is then no longer abrogated by cardiolipin. Cardiolipin effectively displaces A2E from cytochrome c oxidase, suggesting noncovalent binding of A2E to the enzyme. We conclude that A2E is a potent cytochrome c oxidase-specific inhibitor which interferes with the binding of cytochrome c to cytochrome c oxidase and, in the light, causes persistent modifications of the enzyme.

Animals↗