Renal transplantation in the United Kingdom for patients from ethnic minorities

BACKGROUND: To investigate any differences in access to transplant and post-transplant outcomes for ethnic minority patients in the United Kingdom, national data on ethnicity of patients on the waiting list, those receiving a transplant, and deceased donors were analyzed. METHODS: Adult patients and donors were included. Ethnic origin was classified as white, Asian, black, or "other." National data were analyzed, and 2001 U.K. National census data were used for comparative purposes. Median waiting times to transplant were obtained from Kaplan-Meier estimates for patients registered 1998-2000. Transplant survival was estimated for patients transplanted from 1998 to 2003. RESULTS: A total of 92% of the U.K. population was white, compared with 77% of waiting list patients, 88% of transplant recipients, and 97% of deceased donors. Median waiting time to transplantation for white patients was 719 days (95% confidence interval 680-758) compared with 1368 (1131-1605) days for Asian patients and 1419 (1165-1673) days for black patients. The degree of human leukocyte antigen matching achieved was inferior for Asian and black patients. There is some evidence of inferior 3-year transplant survival for black patients compared with white and Asian patients (P=0.03). CONCLUSIONS: There are imbalances in the ethnic make up of the waiting list, the donor pool, and renal transplant recipients. There are significant differences in both post-transplant outcomes and time to transplantation between patients of different ethnic origin. Waiting times are influenced by allocation schemes, and the 2006 U.K. National Kidney Allocation Scheme is designed to achieve greater equity of access to transplant for all patients, regardless of geography, blood group, or ethnicity.     

Adrenomedullin and adrenomedullin-binding protein-1 downregulate inflammatory cytokines and attenuate tissue injury after gut ischemia-reperfusion

BACKGROUND: Recent studies have shown that adrenomedullin (AM) and AM-binding protein-1 (AMBP-1) possess anti-inflammatory properties in sepsis. We hypothesized that administration of AM/AMBP-1 after gut ischemia-reperfusion (I/R) downregulates inflammatory cytokines and attenuates tissue injury. METHODS: Male Sprague-Dawley rats (275-325 g) were used. Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery (SMA) for 90 minutes. Upon release of the SMA clamp, the animals were treated by AM (12 microg per kilogram of body weight) and AMBP-1 (40 microg per kilogram of body weight) in combination, or vehicle (1 mL 0.9% NaCl) over 30 minutes via a femoral vein catheter. The animals undergoing sham operation or ischemia for 90 minutes only, did not receive AM/AMBP-1 treatment. At 60 minutes after the completion of the treatment (ie, 90 minutes after reperfusion), blood samples were collected. Plasma AM and AMBP-1 were measured by radioimmunoassay and Western blot analysis, respectively. Serum levels of TNF-alpha, interleukin (IL)-1beta, IL-6, IL-10, transaminases (ie, alanine aminotransaminase, aspartate aminotransaminase), lactate, and creatinine were determined with the use of enzyme-linked immunosorbent assay and other standard methods. In additional groups of animals, the 10-day survival rate was recorded after gut I/R. RESULTS: Ischemia alone was sufficient to downregulate both AM and AMBP-1. Unlike AMBP-1 that remained decreased, AM levels increased significantly after reperfusion. I/R but not ischemia alone significantly increased serum levels of inflammatory cytokines. Moreover, I/R-induced tissue injury was evidenced by increased levels of transaminases, lactate, and creatinine. Administration of AM/AMBP-1 after ischemia, however, markedly reduced cytokine levels, attenuated tissue injury, and improved survival. CONCLUSIONS: AM/AMBP-1 may be a novel treatment to attenuate the reperfusion injury after gut ischemia.     

Duodenal- jejunal bypass sleeve: a totally endoscopic device for the treatment of morbid obesity

Morbid obesity affects over 15 million people in the United States. Nonsurgical management produces sustained weight loss in less than 5% of patients. Despite associated comorbidities, less than 1% of obese patients seek surgical intervention. Less invasive procedures have been developed with varying success. The Endobarrier( trade mark) (GI Dynamics(trade mark), Watertown, MA) duodenal-jejunal bypass sleeve is a totally endoscopically delivered device designed to produce weight loss in the morbidly obese. We describe the first placement of a duodenal-jejunal bypass sleeve in a patient in the United States. A blinded, randomized, prospective clinical trial was approved by the Food and Drug Administration to evaluate safety and efficacy of a novel device for weight loss in the obese. The first patient enrolled was a 36-year-old woman with body mass index of 45.2. After informed consent, endoscopic placement of the device under general anesthesia was performed using fluoroscopy to confirm positioning. The device was placed without complications. At conclusion of the 3-month study period, the device was removed endoscopically. Total weight lost by the patient was 9.09 kg. Described herein is the first deployment of the duodenal-jejunal bypass sleeve in North America. The device is delivered in a totally endoscopic manner in morbidly obese patients. In our patient, total weight loss at 3 months was 9.09 kg. Continued follow-up and enrollment is ongoing to demonstrate patient safety and efficacy. Additional studies are being performed to elucidate mechanism of weight loss and future clinical applications of this device.     

Identification of a novel CD56- lymphokine-activated killer cell precursor in cancer patients receiving recombinant interleukin 2.

Circulating lymphokine-activated killer (LAK) cell activity in cancer patients receiving recombinant interleukin 2 (rIL-2) therapy is confined to cells expressing the CD56- surface marker. However, CD56- cells from these patients but not normal individuals have been reported to exhibit LAK cytotoxicity only following in vitro activation with rIL-2. Studies were performed to document the existence of CD56- LAK precursor cells and to phenotypically characterize this population in patients receiving rIL-2 therapy using fluorescence-activated cell sorter-purified CD56- cell subsets. Initial studies confirmed that CD56- cells exhibit NK activity [20 +/- 7 (SE) LU/10(6) cells] but not LAK activity (0 +/- 0 LU/10(6) cells) when evaluated directly from peripheral blood of patients receiving rIL-2. CD56- cells from patients but not normal individuals developed significant LAK cytolytic activity against NK-resistant COLO 205 targets (16 +/- 3 LU/10(6) cells) when cultured for 3 days with 1500 units/ml rIL-2. The CD56- LAK precursor activity was confined to cells expressing a CD56-CD16+ phenotype and a large granular lymphocyte morphology; little or no NK or LAK precursor activity was detectable in CD56-CD5+ T-cells from patients. Phenotypic characterization of CD16+CD56- cells revealed that this population is uniformly CD11a+,CD18+, and CD38+ and is heterogeneous in its expression of CD11b, CD11c, and CD16/Leu 11c. These results indicate that rIL-2 administration induces enhanced LAK precursor activity in a novel population of CD5-CD16+CD56- cells.     

Biochemistry of the induction and prevention of lipoperoxidative damage in human spermatozoa

Lipid peroxidation occurs in human sperm cells with damage to the cell plasma membrane, leading to loss of cytosolic components and hence to cell 'death'. The peroxidation may be induced at high rates in the presence of Fe2+ and ascorbate. It occurs at slower rates under physiological conditions as spontaneous lipid peroxidation, which has the following characteristics. The rate is constant over the time required for complete loss of motility in the cells of the sperm sample; one can thus use the time to complete loss of motility (TLM) as a ready measure of the rate. Loss of motility occurs at a characteristic extent of lipid peroxidation, assayed in terms of production of the peroxidative breakdown product, malonaldehyde (MA), that is independent of peroxidation rate. For human sperm, this extent corresponds to 0.1 nmol MA/10(8) cells. Human spermatozoa possess the anti-lipoperoxidative defence enzymes, superoxide dismutase (SOD) and glutathione peroxidase plus glutathione reductase (GPX/GRD). The SOD activity is highly variable between human sperm samples while the activities of GPX and GRD are rather more constant. The rates of production of superoxide anion, O2-, and hydrogen peroxide, H2O2, from human spermatozoa are variable, but their sum calculated in O2- equivalents as O2- + 2H2O2 is quite constant. The variability arises from the variability in SOD activity: all H2O2 produced is from O2- due to the action of SOD. The essential role of SOD as defence enzyme is inferred from the observation that TLM of a given sperm sample is directly proportional to the SOD activity of that sample. The essential role of GPX/GRD is inferred from the observation that inhibition of GPX, either with mercaptosuccinate or with complete oxidation of intracellular reduced glutathione, results in a 20-fold increase in peroxidation rate. The capacity of the GPX/GRD system appears to be limited by the glucose-6-phosphate dehydrogenase-catalysed rate of production of NADPH, the required reductive substrate for GRD. Human spermatozoa appear to have enough anti-lipoperoxidative defensive capacity for lifetimes long enough for fertilization but still short enough for ready removal from the female reproductive tract in good time. Too low a defence capacity could lead to male infertility.      

Hypocalcemia during sepsis. Relationship to resuscitation and hemodynamics.

The ionized calcium (IC) and parathyroid hormone response to polymicrobial intra-abdominal sepsis and the relationship between IC and hemodynamic alterations with and without crystalloid resuscitation were investigated. Thirty swine underwent cecal ligation and incision (n = 19) or sham laparotomy (n = 11), with seven animals that had cecal ligation and incision administered Ringer's solution (50 mL/kg) after each set of measurements recorded on days 0, 1, 2, 4, and 8. An early decrease in mean arterial pressure and cardiac index in animals that had cecal ligation and incision reversed with resuscitation. The IC also fell early and parathyroid hormone level increased in both the unresuscitated and resuscitated septic groups. However, correlation coefficients of mean arterial pressure and cardiac index with IC ranged from .034 to .287 in the septic animals and were lower in the group that had sham laparotomy. We conclude that polymicrobial intra-abdominal sepsis results in decreased IC and an elevated parathyroid hormone level. Hemodynamics do not correlate with IC levels, and resuscitation can be achieved without calcium administration.     

Transport of IgA antibody-antigen complexes by the rat liver

MOPC 315 IgA polymers with antibody activity to TNP were complexed with TNP-HSA and added to a perfusion of an isolated rat liver. Soluble IgA antibody-antigen complexes were transported from blood to bile with similar kinetics to that of IgA alone. TNP-HSA antigen was not transported by itself. In addition, little or no IgG antibody-antigen complex was transported.