Oral tolerance induction by type V collagen downregulates lung allograft rejection

Immunization with specific proteins or peptides has been used to induce immunologic tolerance to allografts other than the lung. Recently, we have reported that the immune response to lung alloantigen also involves an immune response to type V collagen [col(V)]. The purpose of the current study was to determine if oral administration of col(V) to lung allograft recipients before transplantation downregulates acute rejection episodes. The data show that, compared with controls, col(V)-fed recipients had fewer polymorphonuclear cells and lymphocytes in allograft bronchoalveolar lavage fluid, and reduced rejection pathology. Data showing that col(V)- fed allograft recipients had diminished delayed-type hypersensitivity (DTH) responses to donor alloantigens suggest that feeding col(V) prevented allograft rejection by inducing tolerance to donor antigens. Systemic production of transforming growth factor (TGF)-beta, interleukin (IL)-4, or IL-10 has been reported to be a mechanism for oral tolerance-induced suppression of immune responses. Feeding col(V) induced upregulated production of TGF-beta, but not IL-4 or IL-10 in serum. Neutralizing TGF-beta recovered the DTH response to donor antigen in tolerant allograft recipients. Collectively, these data show that oral administration of col(V) is a novel approach to induce immunologic tolerance to lung allografts, and that TGF-beta contributed to suppression of the rejection response.     

Monocyte chemoattractant protein-1 and RANTES are chemotactic for graft infiltrating lymphocytes during acute lung allograft rejection

Graft infiltrating lymphocytes (GILs) are crucial to rejection of lung allografts. However, chemotactic activities, chemokines responsible for GIL recruitment, and cells involved in chemokine production during lung allograft rejection have not been evaluated. This study determined whether chemotactic activity for GILs is upregulated, and whether the chemokines monocyte chemoattractant protein (MCP)-1 and regulated on activation, normal T cells expressed and secreted (RANTES) have roles in GIL chemotaxis during lung allograft rejection. F344 (RT1(lv1)) rat lung allografts were transplanted into WKY (RT1(l)) recipients. Chemotactic activity for GILs and quantities of MCP-1 and RANTES were determined in allograft bronchoalveolar lavage fluid 1 wk after transplantation. Data showed that during rejection, chemotactic activity for GILs is upregulated, MCP-1 and RANTES are produced locally, and both MCP-1 and RANTES are operative in GIL recruitment. Immunohistochemistry showed that alveolar macrophages (AMs) were the major source of MCP-1 and that other lung cells, including AMs, were the source of RANTES. Further, depletion of AMs in the donor lung before transplantation downregulated chemotaxis for GILs and production of MCP-1 during rejection episodes. These data show that chemotaxis for GILs is upregulated locally during lung allograft rejection, and that MCP-1 and RANTES contribute to GIL recruitment during the rejection response.     

Gerichtliche Geburtshilfe

International Journal of Legal Medicine -     

Percentage of hypochromic red blood cells as predictor of erythropoietic and iron response after i.v. iron supplementation in maintenance haemodialysis patients

Background. The percentage of hypochromic red blood cells (RBC), defined as those with a cellular haemoglobin <28 g/dl has been suggested to be a sensitive marker of functional iron deficiency in maintenance haemodialysis (HD) patients. Thus, during rHuEpo therapy an increase in hypochromic RBC to >10% would indicate that more intensive iron supplementation may be required. Methods. We investigated 70 HD patients 57.1±15.3 years old and on maintenance HD for 66.3±47.9 months without blood loss from gastrointestinal bleeding or from the vascular access, without surgery and without infectious disease or malignancy. During the study period of 12 weeks, each patient received an i.v. dose of 800 mg ferrogluconate. Haemoglobin, haematocrit, and the percentage of hypochromic RBC were measured before and every 4 weeks after the start of the study; serum ferritin, zinc protoporphyrin (ZPP) and C-reactive protein (CRP) were measured at the beginning (baseline) and end of the study. Results. At baseline the percentage of hypochromic RBC was ⩽5.0% in 28 patients, >5.0 and ⩽10.0% in 25 patients and >10.0% in 17 patients, suggesting functional iron deficiency in at least 42 patients, suggesting functional iron deficiency in at least 42 patients. Nine patients had serum ferritin values <100 &mgr;g/l; nonetheless in these patients the median percentage of hypochromic RBC was 5.9% (range 0.9-14.3%), indicating that an absolute iron deficiency can occur in the presence of normal amounts of hypochromic RBC. There was a significant correlation between serum ferritin levels and hypochromic RBC at the end, but not at the beginning, of the study. However, there was no correlation between ZPP and hypochromic RBC at any time during the study. During i.v. iron supplementation the rHuEpo dose could be reduced by 8.5% in patients with hypochromic RBC ⩽5.0%, by 11.3% in patients with hypochromic RBC>5.0 and ⩽10.0% and by 23.4% in patients with hypochromic RBC>10.0%, demonstrating the benefit of i.v. iron in patients with functional iron deficiency. In HD patients in whom serum ferritin levels remained below 290 &mgr;g/l until the end of the study, a significant reduction of the rHuEpo dosage could be obtained during i.v. iron therapy. This was not the case in patients with serum ferritin >290 &mgr;g/l after iron supplementation. We found that the percentage of hypochromic RBC is the most sensitive parameter for predicting hyporesponsiveness in CPR-positive patients. Finally our data indicate that HD patients with hypochromic RBC>6% and low to moderate increases in serum ferritin levels after i.v. iron supplementation significantly benefit from i.v. iron therapy. Conclusions. Two different aspectsshould be taken into consideration in HD patients treated with rHuEpo and concomitant i.v. iron therapy: (1) response of the erythropoietic system to rHuEpo, and (2) adequate delivery of the supplemented iron to the erythropoietic system. The patient's percentage of hypochromic RBC and increase in serum ferritin after i.v. iron supplementation should be used to decide whether or no i.v. iron should be given and to monitor this type of therapy in HD patients.     

Role of striated sphincter muscle in urethral closure under stress conditions: an experimental study

The three-component mechanism for urethral closure under stress conditions is composed of urethral tension, passive pressure transmission and reflex pressure transmission. The reflex pressure transmission is regarded as a global result of the striated muscles of the urethra and the pelvic floor. In this experimental study, the question of what peak the reflex pressure reaches and which parts of the striated sphincter muscles produce the reflex pressure transmission is examined. The urodynamic and operative experiment was carried out on 12 female German shepherd mutts, whereby the passive and the reflex pressure transmissions were brought about by the Credé maneuver and by induced sneezing, respectively, in differentiated experimental phases. It was shown that the amount of reflex pressure transmission alone totals 89%, which is added onto the given urethral tension and passive pressure transmission. Furthermore, this animal experiment demonstrates that the reflex pressure transmission is created almost solely by the periurethral striated sphincter muscles, whereas the participation of the intraurethral striated sphincter muscles lies at a low 4%.     

The Suprapubic Arch Sling Procedure for Treatment of Stress Urinary Incontinence: A 5-Year Retrospective Study

Background

Up to now, numerous similar products concerning the surgical treatment of female stress urinary incontinence (SUI) have been developed.

Objective

To assess the long-term efficacy and safety of the suprapubic arch (SPARC) sling system in women with SUI.

Design, setting, and participants

This was a long-term retrospective study. All patients underwent a comprehensive pre- and postoperative evaluation. Forty-six women were available for clinical follow-up investigation after SPARC sling placement.

Intervention

Eighty-six women with SUI and a positive cough test underwent SPARC sling placement between June 2001 and January 2004.

Measurements

At follow-up all 46 patients underwent a cough test, a pad test, uroflowmetry, and sonographic postvoid residual volume measurement. Women rated their subjective continence status (continent, slightly incontinent, incontinent) and were asked if they would undergo the procedure again and if they would recommend it to a friend. Objective cure was defined as a pad weight 0–1 g and a negative cough test. Subjective cure was defined as no use of pads.

Results and limitations

The median follow-up was 5.2 yr. The objective cure rate was 76%; the subjective cure rate was 52%. Sixty-three percent of the patients rated themselves as continent, 33% as slightly incontinent, and 4% as severely incontinent. Most of the women (98%) would recommend the SPARC procedure to a friend and would undergo the procedure again.

Conclusions

The SPARC sling system is an effective and safe procedure for the treatment of female SUI. Patient satisfaction is independent of complete dryness.     

The natural history of lower urinary tract symptoms in females: analysis of a health screening project

OBJECTIVE: To analyse over 6.5 yr the natural history of lower urinary tract symptoms (LUTS) of continent women participating in a health investigation. METHODS: Women participating in a health screening survey in the area of Vienna in 1998-1999 underwent a detailed health investigation and completed the Bristol Female LUTS questionnaire. In 2005, all women still living in the area of Vienna were contacted by mail to complete the Bristol LUTS questionnaire again. For the current study, only women without urinary incontinence at baseline and follow-up were eligible. RESULTS: A total of 223 women (mean age, 50.3 yr; range, 21-79) were included in this 6.5-yr longitudinal study. At baseline, 80 women (35.9%) reported LUTS; this number increased to 105 (47.1%) 6.5 yr later. The calculated mean annual incidence of LUTS was 5.3% and revealed no clear dependency on age: 20-39 yr, 5.6%; 40-59 yr, 5.9%; > or =60 yr, 3.7%. The mean annual remission rate of LUTS was 4.6% without clear age dependency. Symptoms most likely to improve were "urgency"; "frequency"; "nocturia" and "feeling of incomplete bladder emptying" had the highest tendency of worsening. CONCLUSIONS: This longitudinal study on the natural history of LUTS in women without urinary incontinence provides estimates for incidence and remission rates over 6.5 yr. Compared with men, LUTS in women are a dynamic rather than a necessarily progressive disorder.