Incidence of renal artery stenosis in a population having cardiac catheterization

Patients with renovascular hypertension comprise only a small percentage of those with hypertension. In our study 102 consecutive patients who had cardiac catheterization were screened at the time of the procedure for renal artery stenosis. Only 65 (64%) of the 102 patients were hypertensive, and 14 of the total population (13.7%) had renal artery stenosis. Of these 14 patients, only five had more than 50% narrowing of the arterial lumen. By renal vein renin determination, only four of the five patients with significant renal artery stenosis had lateralizing renins. The frequency of significant renovascular hypertension does not justify the routine search for this problem during catheterization procedures, though it may be worthwhile if the patients are hypertensive. This area deserves further evaluation.     

The humoral immune response after BCG vaccination: an immunoblotting study using two purified antigens.

The specific IgG response induced by BCG vaccination was investigated in 27 adults using two purified BCG antigens in a dot immunoblotting assay. The reflectance values increased significantly after vaccination when P64 but not when P32 was used as the antigen. The values measured after vaccination were compared with those obtained when testing sera from patients with tuberculosis. We observed that the level of anti-P64 IgG reached after BCG immunization was high enough to preclude a serological differential diagnosis with tuberculosis.     

STUDIES ON PULMONARY EDEMA : II. THE PATHOGENESIS OF NEUROPATHIC PULMONARY EDEMA

1. Guinea pigs die shortly after bilateral cervical vagotomy, even when continuous artificial respiration effected through a tracheal cannula is carried out. Death is caused by severe pulmonary edema and congestion. 2. Direct observation of the lungs after bilateral vagotomy demonstrates that pulmonary edema develops gradually and increases slowly in amount and severity. Congestion precedes and accompanies the development of the edema. 3. Neuropathic pulmonary edema in the guinea pig is caused by disturbance to or abolition of the pulmonary vasomotor nerves. 4. The evidence obtained by experiments on animals suggests that neuropathic pulmonary edema in man is caused by disturbances, either central or peripheral, to the vasomotor control of the pulmonary vessels.     

Healing rates and cost efficacy of outpatient compression treatment for leg ulcers associated with venous insufficiency.

OBJECTIVE: Although newer techniques to promote the healing of leg ulcers associated with chronic venous insufficiency are promising, improved healing rates and cost effectiveness are unproven. We prospectively followed a series of patients who underwent treatment with outpatient compression for venous stasis ulcers without adjuvant techniques to determine healing rates and costs of treatment. METHODS: Two hundred fifty-two patients with clinical or duplex scan evidence of chronic venous insufficiency and active leg ulcers underwent treatment with ambulatory compression techniques. The patients were prospectively followed with wound measurements at 1-week to 2-week intervals, and the factors that were associated with delayed healing were determined. RESULTS: Of all the ulcers, 57% were healed at 10 weeks of treatment and 75% were healed at 16 weeks. Ultimately, 96% of the ulcers healed, and only 1 major amputation was necessitated (0.4%). Initial ulcer size and moderate arterial insufficiency (ankle brachial index, 0.5 to 0.8; n = 34) were factors that were independently associated with delayed healing (P <.01). Patient age, ulcer duration before treatment, and morbid obesity did not significantly affect healing times. The cost of 10 weeks of outpatient treatment with compression techniques ranged from $1444 to $2711. CONCLUSION: The treatment of venous stasis ulcers with compression techniques results in reliable, cost-effective healing in most patients. Current adjuvant techniques may prove to be useful but are likely to be cost effective only in a minority of cases, particularly in patients with large initial ulcer size or arterial insufficiency.     

In vitro studies on hirudin elimination by haemofiltration: comparison of three high-flux membranes.

BACKGROUND: Recombinant hirudin (r-hirudin) is a highly selective thrombin inhibitor used for anticoagulation in heparin-induced thrombocytopenia type II. R-hirudin is increasingly applied to patients with renal failure and on renal replacement therapy. Since kidney function impairment strongly prolongs r-hirudin elimination half-life, severe accumulation and bleeding complications may occur. Data on the r-hirudin permeability and elimination capacity of different haemofilters are limited. METHODS: Three haemofilter types were investigated: high-flux polysulphone (Fresenius), AN69 (Hospal), and polyamide (Gambro). We used two in vitro haemofiltration models: (i) an open post-dilution haemofiltration model with ultrafiltration and fluid substitution (model 1) simulating hirudin intoxication, and (ii) a closed model with ultrafiltrate reinfusion (model 2) to determine steady-state sieving coefficients (SC). Fresh human heparinized blood (2 IU unfractionated heparin/ml blood) was used. In model 2, SC obtained with human whole blood were compared with isotonic saline. RESULTS: In model 1, r-hirudin levels decreased significantly faster with polysulphone than with AN69 or polyamide (P<0.05). In accordance with this, in model 2 the observed SC in whole blood were 1.11+/-0.28 (polysulphone), 0.61+/-0.15 (AN69) and 0.33+/-0.13 (polyamide), and clearances were 28+/-7 (polysulphone), 15+/-4 (AN69) and 8+/-3 ml/min (polyamide) (P<0.001 for all comparisons). The SC in saline were slightly but significantly lower for polysulphone (0.88+/-0.12), similar for AN69 (0.59+/-0.1), and significantly improved for polyamide (0.83+/-0.1). CONCLUSIONS: Elimination of r-hirudin by haemofiltration strongly depended on the membrane material. Using human blood, we observed large differences between the three high-flux membranes. The saline experiments suggest a membrane-dependent impact of plasma proteins and pH on hirudin sieving. Our findings have implications for r-hirudin dosage in haemofiltration, for treatment of overdosage, and for future in vitro haemofiltration studies.     

Abrogation of recurrent autoimmunity in the NOD mouse: A critical role for host interleukin 4

BACKGROUND: We previously established a clinically relevant strategy to abrogate recurrent autoimmunity and enable long-term islet graft survival, involving antilymphocyte serum (ALS)-depletion of recipient T cells and intraportal administration of donor pancreatic lymph node cells (PLNCs) along with islet grafts. In this study, we investigated whether Th2 cytokines were required for the tolerizing ability of ALS/PLNC treatment in islet transplantation. METHODS: ALS-treated diabetic NOD recipient mice, and NOD recipient mice deficient in interleukin 4 (IL-4-/-) or 10 (IL-4/10-/-) were transplanted with NOR or NOD.scid islets intraportally along with donor PLNC. Blood glucose levels were monitored to access graft function, sections of graft-bearing livers were histologically examined, and ELISPOT assays were used to assess cytokine profile and frequency of islet-reactive CD4 T cells. RESULTS: We found that ALS/PLNC was not effective in prolonging islet graft survival in diabetic NOD hosts deficient in either IL-4 (NOD.IL-4-/-) or in IL-4 and IL-10 (NOD.IL4-/-/10-/-) (mean survival time, 36 days), contrasting the long-term survival of islet grafts in wild-type NOD mice (mean survival time, > 80 days). In contrast, PLNC deficient in IL-4 promoted long-term graft survival in wild-type NOD hosts similar to that in wild-type PLNC. In wild-type NOD recipients of either wild-type PLNC or IL-4-/- PLNC, the host autoantigen-specific CD4 T cells produced predominately IL-4 coincident with long-term graft survival, whereas, in NOD.IL-4-/- recipients with rejected grafts, the autoreactive T cells produced interferon gamma and low amounts of IL-4. CONCLUSIONS: These data demonstrate that abrogation of recurrent autoimmunity requires host IL-4 and that manipulation of the autoreactive cytokine profile in long-term diabetes may be an effective strategy for islet transplant therapies.     

Overexpression of the focal adhesion kinase (p125FAK) in the vascular smooth muscle cells of intimal hyperplasia

PURPOSE: The migration and proliferation of vascular smooth muscle cells (VSMCs) are important events in the development of intimal hyperplasia (IH). The focal adhesion kinase (FAK) gene encodes a protein tyrosine kinase (p125FAK) involved in signal transduction pathways used in cell adhesion, motility, and proliferation. Because alterations in these cellular processes are thought to occur in VSMCs during IH, we studied FAK expression in healthy arteries and veins in comparison with that in pathologic vessels containing IH. METHODS: To determine p125FAK expression at the cellular level, we developed a monoclonal antibody that specifically detected FAK in formalin-fixed, paraffin-embedded tissue sections (5 microm) and analyzed the levels of FAK expression in human arteries and veins. Specificity of monoclonal antibody 4.47 was demonstrated by means of immunofluorescence microscopy showing FAK-specific staining at focal adhesions of healthy human vascular smooth muscle cells (AoSMCs). By using immunohistochemistry techniques, we analyzed the expression of p125FAK in 25 adult human vascular tissue samples from individual patients, which contained a histologically confirmed healthy artery, vein, or IH. RESULTS: FAK expression in healthy and pathologic human vascular tissue was localized predominantly within VSMC cytoplasm. In healthy human artery and vein, borderline FAK expression was detected in the media of seven of 17 vessels and undetectable in the remainder of specimens. However, in vessels containing IH, FAK was overexpressed in the pathologic VSMC populations at moderate-to-strong levels in eight of eight specimens. The levels of FAK expression were directly correlated with structures containing IH, and the results of FAK staining intensity and the percentage of positive cells in these samples were significantly increased compared with normal vascular tissue levels (P <.05, Student t test). CONCLUSION: These results provide the first evidence that FAK is overexpressed in VSMCs involved in IH and suggest that FAK upregulation may be part of a mechanism for migration and proliferation of VSMCs during this process. Furthermore, the dramatic upregulation of FAK in IH and the relative lack of expression in healthy vessels suggest that FAK may be a rational target for controlling IH.     

Sharing Heterogeneous Data: The National Database for Autism Research

The National Database for Autism Research (NDAR) is a secure research data repository designed to promote scientific data sharing and collaboration among autism spectrum disorder investigators. The goal of the project is to accelerate scientific discovery through data sharing, data harmonization, and the reporting of research results. Data from over 25,000 research participants are available to qualified investigators through the NDAR portal. Summary information about the available data is available to everyone through that portal.