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Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 325 records · Page 18Linked to original sources

Oral type II collagen treatment in early rheumatoid arthritis. A double-blind, placebo-controlled, randomized trial.

OBJECTIVE: To investigate the efficacy of oral type II collagen in the treatment of early rheumatoid arthritis (RA). METHODS: Ninety patients with RA (disease duration < or = 3 years) were treated for 12 weeks with oral bovine type II collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in a double-blind randomized study. RESULTS: There were no significant difference between the 3 groups in terms of response to treatment. However, we observed a higher prevalence of responders in the type II collagen-treated groups: 7 responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4 in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group and 1 patient in the 1-mg type II group, but no patients in the placebo group, had very good response. A total of 14 patients had to be withdrawn from the study: 2 because of side effects (nausea) and 12 because of lack of efficacy. CONCLUSION: Only a minority of patients responded to treatment with oral type II collagen. These results justify further efforts to identify which patients will have good response to such therapy.

Administration, Oral↗

Sperm viability is influenced in vitro by the bovine seminal protein aSFP: effects on motility, mitochondrial activity and lipid peroxidation.

The 13 kDa acidic seminal fluid protein (aSFP) is a major component of bovine semen exerting growth factor-like activity. The influence of the pure protein on sperm viability was observed by evaluating sperm motility using computer-assisted semen analysis. Furthermore, mitochondrial dehydrogenase activity as a parameter of sperm metabolism and the integrity of sperm membranes using a metal catalyzed lipid peroxidation assay were measured. Over a wide physiological range (0.003 to 4 g/l) aSFP did not influence motility and average-path velocity of sperm, but at the highest concentration (6 g/l) a significant reduction in motility could be observed. Mitochondrial activity was significantly stimulated at medium concentrations (0.125 to 2 g/l), whereas a 40% suppression was observed at maximum levels (4 g/l). A dose-dependent inhibition of lipid peroxidation could be demonstrated for medium and high concentrations of aSFP (0.125 to 4 g/l). Compared with other reducing agents, aSFP showed the highest potency in preventing oxidative stress. Such effects might be explained by the remarkable redox behavior of the protein. We suggest that in the bull aSFP may play a role in the regulation of sperm metabolism and the protection of sperm membranes from oxidative damage.

Journal Article↗

A DNA repair abnormality specific for rearranged immunoglobulin variable genes in germinal center B cells.

The somatic hypermutation mechanism produces high-rate mutagenesis specifically targeted to rearranged immunoglobulin (Ig) variable (V) gene segments during the germinal center (GC) stage of B lymphocyte differentiation. The mechanism of this process remains uncertain, partly due to the lack of a direct assay for hypermutation activity. In this study, a gene-specific DNA repair assay was used to compare the rate and quality of DNA repair in the mantle zone (MZ) and GC B cells at rearranged and unrearranged Ig V genes. GC B cells were distinguished from MZ B cells by a retarded repair rate specific for rearranged Ig V genes. In addition, a unique feature of GC cells after DNA repair was the appearance of predominant mutations in rearranged Ig VH5 gene PCR products. These predominant mutations also occurred in natural mutants of VH5 genes. However, repair-associated mutations reflected, at least in part, "template-jumping" during amplification of the residually damaged genomic template. Overall, these findings reflect a repair abnormality associated with the hypermutation process by the criteria of sequence- and B cell stage-specificity. We conclude that locus-specific retardation of DNA repair is a component of the hypermutation mechanism. RFLP or SSCP analysis provides a simple assay to monitor this repair abnormality as a surrogate biochemical marker for hypermutation during B cell differentiation.

B-Lymphocytes↗

Endogenous retroviral long terminal repeats of the HLA-DQ region are associated with susceptibility to insulin-dependent diabetes mellitus.

HLA-DQ genes are the main inherited factors predisposing to IDDM. This gene region harbors long terminal repeat (DQ LTR) elements of the human endogenous retrovirus HER V-K, which we analyzed for a possible association with disease. We first investigated whether LTR segregate with DQ alleles in families. Members (n = 110) of 29 families with at least one diabetic child, unrelated patients with IDDM (n = 159), and healthy controls (n = 173) were analyzed. Genomic DNA was amplified for DQ LTR3 by a nested primer approach as well as for DQA1 and DQB1 second exons, to assign DQA1 and DQB1 alleles. DQ LTR segregated in 24 families along with DQ alleles. Of the 29 families, 20 index patients were positive for DQ LTR. The DQ LTR was in all patients on the haplotype carrying the DQA1 *0301 and DQB1 *0302 alleles. A majority of patients had DQ LTR (62%) compared with controls (38%) (p < 1.3 x 10(-5)), even after matching for the high-risk alleles DQA1 *0501, DQB1 *0201-DQA1 *0301, and DQB1 *0302 (79% of patients and 48% of controls; p < 0.02). Subtyping for DRB1 *04 alleles in all DQB1 *0302+ individuals showed 56% DRB1 *0401, DQB1 *0302 [LTR' patients vs. 29% controls with the same haplotype (p < 0.002)]. In conclusion, these data demonstrate the segregation of DQ LTR with DQA1, DQB1 alleles on HLA haplotypes. Furthermore their presence on DRB1 *0401-, DQA1 *0301-, and DQB1 *0302-positive haplotypes suggest that they contribute to DQ-related susceptibility for IDDM.

Diabetes Mellitus, Type 1↗

Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients.

The purpose of this study was to assess the value of electron beam computed tomography in the detection of cardiac calcifications in coronaries and valves of dialysis patients and to determine the rate at which calcification progresses. Forty-nine chronic hemodialysis patients aged 28 to 74 years were compared with 102 non-dialysis patients aged 32 to 73 years with documented or suspected coronary artery disease, all of whom underwent coronary angiography. We used high-resolution electron beam computed tomography scanning to make 30 axial slices with a distance of 3 mm between each slice. The number of calcifications, the surface area, and the average and highest density values were measured. We calculated a quantitative coronary artery calcium score and assessed calcification of mitral and aortic valves. In dialysis patients, the measurements were repeated after 12 months. The coronary artery calcium score was from 2.5-fold to fivefold higher in the dialysis patients than in the non-dialysis patients. Hypertensive dialysis patients had higher calcium scores than non-hypertensive dialysis patients (P < 0.05). A stepwise, multiple regression analysis confirmed the importance of age and hypertension. No correlation between calcium, phosphate, or parathyroid hormone values and the coronary calcium score was identified; however, the calcium score was inversely correlated with bone mass in the dialysis patients (r = 0.47, P < 0.05). The mitral valve was calcified in 59% of dialysis patients, while the aortic valve was calcified in 55%. The coronary artery calcium score was correlated with aortic valvular, but not mitral valvular calcification. A repeat examination of the dialysis patients at an interval of 1 year showed a disturbing tendency for progression. Our data under-score the frequency and severity of coronary and valvular calcifications in dialysis patients, and illustrate the rapid progression of this calcification. Finally, they draw attention to hypertension as an important risk factor in this process.

Adult↗

Towards the neuronal correlate of visual awareness.

Several encouraging developments towards identifying the neuronal correlate of visual awareness have emerged recently. Increasingly sophisticated behavioral paradigms permit the study of visual awareness in humans as well as in non-human primates. In patients with anatomically restricted lesions in striate and extrastriate cortex, highly informative deficits of visual awareness are observed. Similar deficits can be obtained in normal observers with a novel class of psychophysical displays. Taken together, these results suggest that the contents of visual awareness reflect neuronal activity in certain extrastriate, but not in striate, visual cortical areas.

Animals↗

Genetic markers in diagnosis and prediction of relapse in Graves' disease.

Hyperthyroidism of Graves' disease takes an unpredictable clinical course in the long-term follow-up. Whereas roughly 30-60% of patients relapse after their first antithyroid drug treatment, the likelihood of remission in the remaining group can not be foreseen. We have analysed-retrospectively-patients with Graves' disease that had been on antithyroid drug treatment for one year and were followed up thereafter. Patients were investigated for a variety of clinical parameters like ophthalmopathy status and relapse or remission as well as gene polymorphisms of the HLA and other regions. Of the 259 patients analysed so far, patients with ophthalmopathy did not differ from those without for HLA DQA1 and CTLA4 alleles tested. Also, the subgroup of patients with relapses after antithyroid drug treatment showed no different distribution of those alleles from the group with long-term remission. This study also confirms that the allele HLA DQA1* 0501 confers susceptibility to Graves' disease, furthermore, that the CTLA4-alanine 17 allele is an additional predisposing factor.

Abatacept↗

The sacroiliac joint in the spondyloarthropathies.

The term spondyloarthropathy (SpA) describes and defines a group of related inflammatory joint disease that share characteristic clinical features and a unique association with the major histocompatibility complex class I molecule HLA-B27. Five subgroups can be differentiated: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The sacroiliac joints are centrally involved in the SpA, most clearly and pathognomonic in ankylosing spondylitis, in which most patients are affected early in the disease. Overcoming some of the diagnostic difficulties of early sacroiliitis, dynamic magnetic resonance imaging was shown to visualize both acute and chronic changes in the sacroiliac joints. The inflammation in the sacroiliac joints in patients with SpA was recently examined in more detail; using immunohistology and in situ hybridrization, T cells, macrophages, and various cytokines were found in infiltrates. Biopsy specimens were obtained under guided computed tomography, and in the same study, intra-articular corticosteroid treatment was successfully undertaken. Further investigation of such biopsy specimens showed the absence of DNA of reactive arthritis-associated bacteria. The pathogenesis of the SpA and the reason for the tropism for the sacroiliac joints is still obscure. The nature of the relation of the genetic background of SpA to initially triggering bacterial infections remains to be established. In chronic disease, autoimmune mechanisms might be more important.

Humans↗

Is zinc protoporphyrin an indicator of iron-deficient erythropoiesis in maintenance haemodialysis patients?

BACKGROUND: Zinc protoporphyrin (ZPP), a metabolic intermediate generated in the red blood cell by incorporation of zinc instead of iron, has been suggested to be a sensitive and specific parameter of absolute iron deficiency in haemodialysis (HD) patients. METHODS: We studied 62 HD patients, 29-86 years old, with ZPP levels > 50 mumol/mol haeme (normal value of ZPP < 40 mumol/mol haeme) assessing the value of ZPP as a marker of functional iron deficiency at different cut-off points of ZPP. None of the patients had apparent inflammatory disease, infectious disease, or malignancy. ZPP, haemoglobin, iron and ferritin levels were determined before, and after a 24-week period of once-weekly i.v. administration of 40 mg iron, to determine whether ZPP levels return to normal during adequate iron supplementation (960 mg iron/ patient). RESULTS: There was no significant change in ZPP levels after iron supplementation in patients with a ZPP > 50 mumol/mol haeme (96.7 +/- 49.8 versus 88.4 +/- 43.5 mumol/mol haeme before and after iron administration respectively, P = n.s.). However, in patients with a ZPP > 90 mumol/mol haeme, there was a significant reduction in ZPP levels (141.2 +/- 54.5 versus 108.0 +/- 48.8 mumol/mol haeme, P < 0.001). Serum ferritin increased significantly in both groups. There was no correlation between ZPP and serum ferritin at any time during the study. There was also no correlation between serum aluminium levels and ZPP and no significant difference in changes in ZPP in patients receiving desferrioxamine therapy compared to those not receiving desferrioxamine therapy. We did find a significant correlation between moderately elevated total blood lead concentrations and ZPP levels at the end of the study. The ZPP levels were not significantly different in the range from 50-110 mumol/mol haeme before and after i.v. iron supplementation in the responders (10% increase of haemoglobin or 20% decrease of the recombinant human erythropoietin dose) compared with the non-responders. CONCLUSIONS: Our data indicate that ZPP cannot be used to predict the erythropoietic response to iron supplementation. However, ZPP levels may be an indicator of functional iron deficiency due to blockade of the reticuloendothelial iron release in haemodialysis patients.

Adult↗

[Differentiated surgical therapy of diffuse peritonitis--a prospective study].

PATIENTS AND METHODS: In a prospective protocol 86 consecutive patients with a diffuse peritonitis were treated in the Surgical Clinic of the RWT-University in Aachen (FRG) from January 1992 to June, 1994. According to the "Mannheim Peritonitis-Score" three different stages were treated with different procedures. Stage-I-peritonitis (mild forms, MPS 0-20) was treated with the so-called standard procedure, Stage-II-cases (MPS: 21-29) with the closed postoperative lavage and severe stage-III-cases (MPS > 29) with the so-called "Etappenlavage" (multiple reexplorations and intraoperative lavage). RESULTS: 36 patients showed stage-I-, 29 stage-II-, and 21 stage-III-peritonitis. Mortality was 3% (1/36) in stage-I-, 24% (7/29) in stage-II-, and 33% (7/21) in stage-III-groups. The overall mortality of the whole group was 17% (15/86). The statistically expected mortality was 38% according to the MPS and 33% related to the APACHE-II-Score.

APACHE↗

Computed tomography guided corticosteroid injection of the sacroiliac joint in patients with spondyloarthropathy with sacroiliitis: clinical outcome and followup by dynamic magnetic resonance imaging.

OBJECTIVE: To evaluate computed tomography (CT) guided corticosteroid injections of inflamed sacroiliac (SI) joints in patients with spondyloarthropathies (SpA), and to evaluate dynamic magnetic resonance imaging (DMRI) of the SI joints in serial examinations of these patients, who had different degrees of inflammatory back pain. METHODS: We examined and treated 30 patients with ankylosing spondylitis (n = 9) or undifferentiated SpA (n = 11) (14 women and 16 men, mean age 36.5 +/- 13.4 years, mean disease duration 5.4 +/- 4.0 years) who had severe inflammatory back pain for more than 3 months. All patients had DMRI of the SI joints before and 4-6 months after a CT guided injection of 40 mg triamcinolone acetonide into SI joints (n = 54; 24 patients received injections in both joints). Enhancement of the contrast agent gadolinium-DTPA was quantified by calculating the enhancement of the contrast agent gadolinium-DTPA was quantified by calculating the enhancement gradient Fenh. A subjective index with a visual analog scale (0 = no pain, 10 = very severe pain) was used for assessment of back pain. Followup visits were done every 3 months for a maximum of 18 months. RESULTS: There was significant improvement of inflammatory back pain and sacroiliitis at 5.2 +/- 1.3 months after therapy in 25/30 patients (83.3%). The differences between the Fenh values before (98.2 +/ 56.1) and after (44.3 +/- 31.2) therapy and of the subjective pain index (8.5 +/- 1.5 and 3.0 +/- 2.3, respectively) were statistically significant. Subjective improvement lasted a mean of 8.9 +/- 5.3 months. CONCLUSION: CT guided corticosteroid injection of inflamed SI joints is a useful option in therapy for sacroiliitis in patients with SpA. Different degrees of inflammation in the SI joints can be quantitatively assessed by DMRI.

Adult↗

[Intersphincteric rectum resection with radical mesorectum excision and colo-anal anastomosis].

The tendency toward sphincter-preserving resection for distal rectal cancers has led in recent years to a revival of the technique of coloanal anastomosis (CAA). Our experience with intersphincteric resection in combination with CAA was reviewed with the aim of assessing morbidity, functional outcome, and cancer treatment results. A total of 119 patients treated for primary rectal cancer by CAA between 1978 and 1994 were studied retrospectively. Seventy-six percent of the tumors were located in the lower third of the rectum. There were 4 (3.3%) deaths. The most common postoperative complications were urinary retention (13.5%) and sexual dysfunction (17%). There were 10 patients (8.4%) with clinical anastomic leaks and 3 patients (2.5%) with symptomatic stricture. General complications occured in 33 patients (28%). The mean stool frequency was 2.2 per day. Twenty-three percent of patients reported 4 or more stools per day. Fecal continence was complete in 69%, incontinence to gas in 10%, minor leak in 17% and major soiling in 4%. Urgency occurred in 14% and incomplete evacuation was present in 27%. The cumulative local recurrence rate was 8.7%, 5-year survival was 71% (Dukes A 100%, Dukes B 89%, Dukes C 48%). Interspincteric resection combined with CAA provides excellent treatment for low rectal cancers with long-term preservation of sphincter function and satisfactory local and distant tumor control.

Adult↗

[Surgical therapy of severe colitis].

Severe colitis, eventually complicated by toxic megacolon, perforation or massive hemorrhage still represents a potentially life threatening complication during the course of inflammatory bowel disease reaching a mortality of almost 40% if not operated in time. From 1.1.1973 until 30.4.1994 22 patients (13 men, 9 women, mean age 29 years) with either ulcerative colitis or Crohn's disease of the colon were operated on for severe colitis. Indications for operative treatment were as follows: 7 patients relapsed conservative medical treatment, 8 developed toxic megacolon and in 7 patients perforation occurred. Diagnosis was based on the clinical criterias first described by Turnbull. In 11 (50%) cases subtotal colectomy with an ileostomy and intrapelvic Hartmann's pouch was performed, in 4 (18%) patients a Turnbull's procedure was carried out with loop ileostomy and colostomies and in 3 (14%) cases a left hemicolectomy and transversostomy was applied. In two patients with Crohn's disease an ileocolic resection was done because of perforation, one received a subtotal colectomy and ileorectal anastomosis and one patient was operated by a right hemicolectomy and ileostomy. One patient with ulcerative colitis died, reaching a post-operative mortality of 4.5%. After an intervall of approximately 18 months in the 16 surviving patients with ulcerative colitis an ileal pouch-anal procedure could be done. Of the 5 patients with Crohn's disease one had to be operated on for recurrence, the other patients have been free of recurrent Crohn's disease for a follow-up time between 3 and 11 years. We conclude, provided early operative treatment is intended, that subtotal colectomy with Hartmann's pouch and ileostomy is the procedure of choice in patients with severe colitis.

Adult↗

[The effect of the season and sexual stress on the concentration of testosterone and estradiol-17beta in the seminal plasma of stallions].

Semen from three stallions was collected weekly for six months (December through May) to determine semen parameters and hormones (testosterone and estradiol-17 beta) in seminal plasma. Once a month three ejaculates were collected at intervals of one hour and examined accordingly. Testosterone and estradiol-17 beta were also determined in peripheral blood plasma (V. jugularis) collected twice a week. Semen parameters (volume, gel-free volume and sperm concentration) were clearly influenced by season. The testosterone concentration in peripheral blood plasma was lowest during December whereas in seminal plasma testosterone concentration gradually increased throughout the experimental period. Testosterone concentrations in seminal plasma were only one tenth of those in peripheral blood. Estradiol-17 beta in blood plasma was highest in April and May whereas no significant differences occurred in seminal plasma. Average monthly concentrations of estradiol-17 beta in blood and seminal plasma were in the range of 27.4 pg/ml to 45.3 pg/ml. Collection of three successive ejaculations led to a significant decrease of ejaculate volume as well as sperm concentration. Ejaculation frequency did not influence testosterone in seminal plasma whereas the concentration of estradiol-17 beta decreased significantly in the second and third ejaculate. The results indicate that estradiol-17 beta in the stallion's semen may be bound to spermatozoa or is accumulated in seminal plasma.

Animals↗