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Biomedical subjects

A Krause

Publications and source records attributed to A Krause.

At least 73 records · Page 4Linked to original sources

Interactions of autonomic nervous, neuroendocrine, and immune systems in rheumatoid arthritis.

In general, it is assumed that the two pathways (i.e., HPA axis and sympathetic nervous system) probably act cooperatively to maintain homeostasis. The previously mentioned studies clearly point to a disturbance in the interaction between the ANS, the HPA axis, and the immune system in chronic rheumatic diseases (Fig. 2). Even early on in the course of RA, these changes can be observed. Along with the results obtained in animal models, an important role of neuroendocrine interactions in the pathogenesis of RA is proposed. Further studies are required to establish the exact contribution of the ANS in the initiation and perpetuation of RA. To date, it is quite obvious that neuropeptides play a part in the orchestration of the various molecules (e.g., cytokines) exerting modulatory effects on immune cells. One can speculate that therapeutic implications are likely to result from investigations on the ANS-immune interactions. Based on early observations that blocking catecholamine actions ameliorate symptoms of RA, it is quite promising to follow this avenue in investigating ANS-immune interactions of various time points of the disease. Conversely, further studies are required to determine the contribution of the HPA axis to the onset of RA. Results from ongoing studies are eagerly awaited so as to establish new therapeutic options. In the future,it may be possible to interfere with the inflammatory process in RA by an exactly timed neuroendocrine intervention right at or even before the onset of disease. Therapy with steroids in RA might be better planned based on the genetically determined reactivity of an individual's HPA axis. In this respect, a recent report by Masi et al is of special interest. Based on the current literature on the disturbances in the neuroendocrine, immune, and microvascular systems found in early RA, the authors hypothesize that an imbalance in the interactive homeostasis of these systems develops during a long preclinical phase and eventually leads to the outbreak of the disease in genetically predisposed individuals. This interesting hypothesis includes the perspective that individuals prone to develop RA may be identified in a preclinical phase and treated prophylactically. In any event, results from all these studies are promising in two ways: to gain more insight in the pathogenic process of RA and to establish novel therapies to help the patients bear their burden of a chronic rheumatic disease.

Arthritis, Rheumatoid↗

Ultrafiltration profiling and measurement of relative blood volume as strategies to reduce hemodialysis-related side effects.

Hemodialysis (HD) side effects, such as hypotension and muscle cramps, may be related to excessive ultrafiltration (UF) in relation to refilling of fluids from the extravascular space, resulting in hemoconcentration and reduction of relative blood volume (RBV). This study examines the suitability of RBV measurements and UF modeling to reduce the incidence of dialysis side effects. We followed up 188 dialysis sessions in 53 patients. RBV and incidence of side effects were evaluated. Six treatment regimens were examined: UF profile 0, with a constant UF rate; UF profile 1, with a linear decreasing UF rate; UF profile 2, with a stepwise decreasing UF rate; and UF profiles 3 through 5, with intermittent high UF rates interrupted by UF pauses. During dialyses with a constant UF rate (UF profile 0), 10.6% of the treatments were associated with symptomatic hypotension. UF profiles 2 through 5, intermittently using high UF rates, caused a marked increase in hypotensive episodes (18.4%). In contrast, UF profile 1, providing a continuously decreasing UF rate, showed a reduced incidence of hypotension at only 5.7%. Symptomatic hypotension occurred in 13 of 53 patients during one or more dialysis sessions. With the help of RBV measurements, a subgroup of 8 patients with hypovolemia-induced hypotension could be identified. In these patients, an individual threshold of RBV could be defined, below which 92.3% of all hypotensive episodes occurred. In the remaining 5 hypotension-prone patients, there was no correlation between the occurrence of symptomatic hypotension and low RBV during HD treatments. In conclusion, UF profiles intermittently using high UF pulses cannot be recommended. RBV measurements help define a subgroup of patients at risk for hypovolemia-induced hypotension. Only these patients may benefit from blood volume-controlled UF. The incidence of symptomatic hypotension can likely be reduced if an individual threshold of RBV is avoided during HD treatments, eg, using lower UF rates in these patients.

Blood Volume↗

[Detection of atypical site of "sentinel lymph nodes" by lymph drainage scintigraphy in patients with breast carcinoma].

OBJECTIVE: Sentinel lymph node (SLN) localization in breast cancer allows biopsy of directly tumor drained lymph nodes. The objective was to study the association of tumor and SLN localization. PATIENTS AND METHODS: SLN was identified in 39 (81%) of 48 patients with histologically proven breast cancer, clinically and sonographically unsuspected axillary lymph nodes after peritumoral application of 40-50 Mbq 99mTc-Nanocolloid. Patients age, tumor size and localization, histology and localization of the SLN as well as removed axillary lymph nodes were analyzed. RESULTS: Axillary lymph node metastases were found in 11 (28%) of 39 patients. Involvement of the SLN was confirmed by intraoperative frozen sections (n = 9) and paraffin embedded histology (n = 1). One (9%) patient with a positive node revealed a false-negative SLN. In 24 patients with a tumor in the lateral hemisphere of the breast the SLN were identified in the ipsilateral axilla. In 6 (40%) of 15 patients with a central or medial localized tumor the SLN was observed infraclavicular (n = 3), parasternal (n = 2) or in the contralateral axilla (n = 1). In the latter one the SLN of the contralateral axilla showed metastases, whereas the simultaneous SLN and all removed lymph nodes of the ipsilateral axilla were not involved. More than one SLN were found in 12 (31%) of the 39 cases. CONCLUSION: A correlation between tumor localization and localization of the SLN is suggested, but the lymph drainage seems more variable in cases of medial tumor size. Using blue dye for map of extraaxillary SLN seems inappropriate. Currently the diagnostic and therapeutic impact of the detection of extraaxillary SLN is still unclear.

Adult↗

[Skin sparing mastectomy with autologous immediate reconstruction: oncological risks and aesthetic results].

OBJECTIVE: Is the oncological safety of skin sparing mastectomy (SSM) with immediate autologous reconstruction and improved aesthetic results comparable to postoperative findings in patients treated with modified radical mastectomy (MRM)? MATERIAL AND METHODS: Sixty patients with T1-2 breast carcinomas and contraindications for breast conserving therapy were treated by SSM and compared to 81 patients of the same age groups and MRM with regard to oncological and aesthetic data. In 33 (55%) patients the nipple areola complex (NAC) could be spared. For autologous tissue TRAM- and Latissimus dorsi-flaps were used. The mean follow-up was 40 (range 20-71) months. RESULTS: The observed local recurrence rates were not significantly different (p = 0.443) after SSM (n = 3; 5.0%) or MRM (n = 5; 6.2%). Distant metastases and death were seen in 26.7% and 15.0% (SSM), respectively, and in 25.9% and 13.5% (MRM), respectively. Body mass index, operation time and postoperative haemoglobin concentration differed between both groups significantly (p < 0.001) but not the rate of complications (p = 0.232). Aesthetic results of SSM were judged as excellent or good in 90.0% of patients and in 83.4% of surgeons. Nine patients (11.1%) underwent a secondary breast reconstruction after MRM. Furthermore, 12 (14.8%) patients with MRM would prefer a SSM with immediate reconstruction in a similar situation. CONCLUSION: Skin-sparing mastectomy improves aesthetic results to a high degree without increasing of local or distant recurrence rates. Skin-sparing mastectomy should be offered to selected patients with breast cancer as an alternative to modified radical mastectomy.

Adult↗

[Retinopathia centralis serosa--stomach ulcer of ophthalmology?].

Centralis serosa retinopathy is regarded in ophthalmology as a psychosomatic disease, although this assumption has not been satisfactorily proven so far. With the use of the Freiburg Personality Inventory (FIP, [4]), the questionnaire for the evaluation of psychosomatic pathological processes [10], and by recording the affliction undergone by stressful events in the patients' lives, the question as to whether a psychogenic contributory cause existed was examined with a control group study (n = 11), parallelised according to age and sex. The results proved significantly that there was a psychosomatic connection, specifically a tendency to somatisation in patients with centralis serosa retinopathy. However, it was not possible to compile a typical personality profile, although it was possible to describe some conspicuous personality features. As a conclusion, the consequences for a subsequent study are being discussed.

Adult↗

Human chorionic gonadotrophin-beta transcripts correlate with progesterone receptor values in breast carcinomas.

The pathophysiological role for the expression of human chorionic gonadotrophin (hCG) in malignant neoplasms is currently speculative. We investigated the overall expression of genes hCG-beta 5, 3, 8 and 7 in breast carcinoma (n=214), fibroadenoma (n=37) and macromastia (n=10) by quantitative reverse transcriptase-PCR. Eighty (37.4%) of the breast cancer samples revealed positive hCG-beta mRNA expression and the mean value was 67. 9 copies per 200 ng total RNA (range: 0-1743; 95% confidence interval (CI) for mean: 44-92). Fibroadenomas had more frequently detected (56.8%) and greater hCG-beta copy numbers (mean 86.9; range: 0-845; 95% CI for mean: 35-138). Macromastia probes yielded no positive hCG-beta mRNA. The hCG-beta mRNA expression was significantly different in the three histological subgroups (P=0. 006). Among breast carcinomas, a positive correlation was detected between hCG-beta mRNA copy numbers and progesterone receptor (PgR) values (P<0.001). No significant differences were seen regarding disease-free (P=0.87) and overall survival (P=0.20) depending on hCG-beta mRNA status. Finally, our findings do not support a role for hCG-beta in malignant transformation of human breast cells and indicate a possible involvement of hCG-beta in benign breast disease. The relationship with PgR expression may suggest that progestins regulate the expression of hCG in breast epithelial cells.

Adult↗

Studies on the pathogenesis and treatment of Lyme arthritis.

Lyme arthritis is one of the most common clinical manifestations of Lyme borreliosis. It is caused by an intraarticular infection with Borrelia (B.) burgdorferi. A small number of bacteria are liable to provoke severe arthritis by inducing mechanisms (including the induction of cytokines and chemokines) that amplify the inflammatory response. The cellular immune response against B. burgdorferi is characterised by a predominant T helper cell type 1 (Th1) pattern that appears to be inadequate to overcome the infection. In most cases, Lyme arthritis may be cured by antibiotic therapy. A brief summary of current recommendations for the treatment of Lyme arthritis in adults and children is given in this article. However, about 10% of Lyme arthritis patients do not respond sufficiently to antibiotic treatment. Two not mutually exclusive pathogenetic concepts of these treatment-resistant cases will be discussed in the present study: persistent infection and infection-induced immunopathology.

Adult↗

Different molecular basis for spinal muscular atrophy in South African black patients.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder occurring at a rate of between 1/5,000 and 1/10,000 births in most European countries. The phenotype results from the degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical muscle weakness and wasting. The disorder can be classified according to the severity of the disease and the age of onset into three major types. Two candidate SMA genes, NAIP and SMN, isolated from the 5q13 region, have been reported to be homozygously deleted in approximately 30% and >95% of SMA patients, respectively. Black SMA patients have been reported to have facial muscle weakness more commonly. This study aimed to determine the molecular basis of SMA in South African black SMA patients. The SMN gene was found to be homozygously deleted in 65.5% (19/29) of patients, significantly less frequently than in previous studies. Similarly, the NAIP gene was homozygously deleted in a smaller number, 14% (4/29) of patients; 47% (9/19) of SMN deletion patients appeared to have deletions of telomeric exon 7, but not exon 8. In at least six of these patients a gene conversion event has occurred. No detectable deletions were found in 35% (10/29) of patients. Haplotype analysis in the nondeletion patients, using six closely linked markers, provided no evidence for a founder mutation. No mutations were found in exons 3 and intron 6 through exon 8 by sequence analysis of these nondeletion patients. It is proposed that the differences in the SMA phenotype observed in black patients may in part be explained by a different molecular basis.

Black People↗

Toward the gene catalogue of sea urchin development: the construction and analysis of an unfertilized egg cDNA library highly normalized by oligonucleotide fingerprinting.

We describe the use of oligonucleotide fingerprinting for the generation of a normalized cDNA library from unfertilized sea urchin eggs and report the preliminary analysis of this library, which resulted in the establishment of a partial gene catalogue of the sea urchin egg. In an analysis of 21,925 cDNA clones by hybridization with 217 oligonucleotide probes, we were able to identify 6291 clusters corresponding to different transcripts, ranging in size from 1 to 265 clones. This corresponds to an average 3.5-fold normalization of the starting library. The normalized library represents about one-third of all genes expressed in the sea urchin egg. To generate sequence information for the transcripts represented by the clusters, representative clones selected from 711 clusters were sequenced. The construction and preliminary analysis of the normalized library are the first steps in the assembly of an increasingly complete collection of maternal genes expressed in the sea urchin egg, which will provide a number of insights into the early development of this well-characterized model organism.

Animals↗

Disease activity related catecholamine response of lymphocytes from patients with rheumatoid arthritis.

In patients with chronic rheumatic diseases, a decreased density of beta 2-adrenergic receptors (beta 2R) on peripheral blood mononuclear cells (PBMC) could be demonstrated negatively correlating with various disease activity parameters. The aim of the present study was to determine the impact of this decrease on catecholamine response of PBMC from patients with rheumatoid arthritis (RA) in vitro. PBMC from 17 patients with RA and 6 healthy blood donors (HD) were investigated. The effects of epinephrine (E) and norepinephrine (NE) on PBMC proliferation were studied using cells activated with phytohemagglutinin (PHA) and monoclonal anti-CD3-antibodies (OKT3), respectively. The results revealed that lymphocytes of patients with RA showed a significantly reduced influence of catecholamines on PBMC function. In RA patients with high disease activity only, a shift to alpha 1-adrenergic-mediated catecholamine effects upon PBMC reactivity could be observed. The study demonstrates the intricate relationship between PBMC reactivity and catecholamine effects that is mediated via alpha- and beta-adrenergic receptors due to disease activity. In this respect the altered catecholamine response of PBMC from patients with RA may contribute to the pathogenic process of RA.

Adrenergic alpha-Agonists↗

Targetability of novel immunoliposomes prepared by a new antibody conjugation technique.

In order to develop long-circulating immunoliposomes (IL), which combine sterical stabilization with a superior targetability, we have introduced a new methodology for attaching monoclonal antibodies directly onto the distal ends of liposome-grafted polyethylene glycol (PEG) chains. Therefore, we have synthesized a new PEG-PE derivative, which had been endgroup-functionalized with cyanuric chloride. Antibodies can simply be coupled to this membrane anchor in mild basic conditions (pH 8.8) without the need for previous antibody derivatizations. The coupling results have been determined with consideration to various liposome parameters and have been compared to several established antibody coupling procedures, where antibodies had been linked directly to the liposome surface in the presence of PEG (conventional IL). To investigate the targetability of the resulting new IL, anti E-selectin mAb have been coupled and the degree of binding selectin-containing cells has been analyzed. The terminal coupled antibodies show a 1.8-fold higher degree of in vitro cell binding compared to conventional IL, which has been attributed to the antibody position being more easy accessible at the PEG termini. Furthermore, we have illustrated the liposome surface topology and the coupled antibodies by atomic force microscopy, which for such fluid IL has been used first. These images have finely corresponded to the cell binding results, and have been discussed in terms of antibody position and flexibility at the liposome surface.

Animals↗

Differential diagnosis of peri- and postmenopausal ovarian cysts.

OBJECTIVES: To test the value of preoperative and intracystic parameters in the differential diagnosis of ovarian cysts. METHODS: Criteria for admission of 58 patients were age > 47 years, complete history, detection of CA 125 serum level, and ultrasound findings. Tumor markers (CA 125, cancer-associated serum antigen (CASA), CA 72-4), hormones (estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH)), epidermal growth factor (EGF) receptor and c-erb B-2 amplification rate were detected in cyst fluid. RESULTS: Of the 58 subjects, 9 (15.4%) had functional cysts, 37 (63.8%) had benign tumors and 12 (20.8%) had malignant tumors. No functional ovarian cyst presented as echoic or multilocular cyst sonographically. The serum CA 125 values demonstrated significant differences between the non-malignant and malignant patient groups (P < 0.0005). The majority (63.8%, n = 37) of ovarian cysts were obtained at laparotomy, whereas only 36.2% (n = 21) were laparoscopically operated. The cyst fluid levels of FSH (P < 0.005) and LH (P < 0.05) were significantly lower in the functional group than in the benign or malignant group. Malignant cysts were significantly different from non-malignant cysts regarding low E2 (P < 0.01), high FSH (P < 0.05) and CASA (P < 0.02) values. There were no significant correlations between EGF receptor (P = 0.14) and c-erb B-2 (P = 0.06) gene amplification rates and malignant histology. CONCLUSIONS: Simple ovarian cysts combined with normal serum CA 125 levels are candidates for conservative follow-up or laparoscopy. The serum CA 125 is a powerful marker for prediction of histology in postmenopausal ovarian cyst. Laparoscopic surgery may be considered in patients with multilocular sonographic findings and normal CA 125 serum level. Combining serum CA 125 levels with cyst fluid parameters (E2, FSH, CASA) improves the sensitivity and specificity in predicting malignancy.

Age Distribution↗

[Corneal astigmatism as a special complication after lid-loading in patients with lagophthalmos].

UNLABELLED: Lid-loading with precious metals, described by Illig in 1958, has become increasingly important. because of its good functional and cosmetic results this method is superior to tarsorrhaphy. Furthermore, lid-loading can be combined with additional surgical techniques to achieve more dynamic lid-closure. In a prospective study we examined the results after lid-loading and discuss postoperative changes of the cornea. PATIENTS AND METHODS: Between May 1994 and June 1998, 36 patients with peripheral facial paresis and lagophthalmos were treated with a pretarsally fixed upper-lid implant. We used 99.99% gold for the implants with a weight of 1.5 g on average. RESULTS: In all cases we obtained sufficient postoperative lid closure which resulted in a statistically significant reduction in lagophthalmos and improved keratopathy. Postoperative complications were: pseudoptosis, remaining lagophthalmos, bulge, extrusion, migration and corneal astigmatism. Depending on the implant pressure, an astigmatism of 1-2 D developed in the vertical meridian. In all cases the initial visual acuity was reached by an ordination of cylindrical glasses. CONCLUSIONS: So far, corneal astigmatism as a complication after lid-loading has not received much attention in the literature. In our opinion, the development of astigmatism is caused by implants that are too heavy, an incorrect implant radius and individual cofactors (consistency of lid and cornea). There has been no need for an explantation in any case.

Adult↗

Prosthetic heart valve endocarditis caused by Bacillus circulans.

We report a case of prosthetic valve endocarditis due to Bacillus circulans in a 56-year-old woman. Pre-operative blood cultures were negative and the organism was only recovered on culture of the explanted mechanical valve. We discuss the reasons for the late clinical presentation of this case, 15 months post valve replacement, caused by an organism which is conventionally regarded as 'early' pathogen. The patient recovered well post surgery on a 6 week course of trimethoprim and ciprofloxacin.

Anti-Bacterial Agents↗