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This article features 1999-2008 trends in heart transplantation, as seen in data from the Organ Procurement and Transplantation Network (OPTN) and the Scientific Registry of Transplant Recipients (SRTR). Despite a 32% decline in actively listed candidates over the decade, there was a 20% increase from 2007 to 2008. There continues to be an increase in listed candidates diagnosed with congenital heart disease or retransplantation. The proportion of patients listed as Status 1A and 1B continues to increase, with a decrease in Status 2 listings. Waiting list mortality decreased from 2000 through 2007, but increased 18% from 2007 to 2008; despite the increase in waiting list death rates in 2008, waiting list mortality for Status 1A and Status 1B continues to decrease. Recipient numbers have varied by 10% over the past decade, with an increased proportion of transplants performed in infants and patients above 65 years of age. Despite the increase in Status 1A and Status 1B recipients at transplant, posttransplant survival has continued to improve. With the rise in infant candidates for transplantation and their high waiting list mortality, better means of supporting infants in need of transplant and allocation of organs to infant candidates is clearly needed.

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Pancreas allograft acceptance is markedly more selective than other solid organs. The number of pancreata recovered is insufficient to meet the demand for pancreas transplants (PTx), particularly for patients awaiting simultaneous kidney-pancreas (SPK) transplant. Development of a pancreas donor risk index (PDRI) to identify factors associated with an increased risk of allograft failure in the context of SPK, pancreas after kidney (PAK) or pancreas transplant alone (PTA), and to assess variation in allograft utilization by geography and center volume was undertaken. Retrospective analysis of all PTx performed from 2000 to 2006 (n = 9401) was performed using Cox regression controlling for donor and recipient characteristics. Ten donor variables and one transplant factor (ischemia time) were subsequently combined into the PDRI. Increased PDRI was associated with a significant, graded reduction in 1-year pancreas graft survival. Recipients of PTAs or PAKs whose organs came from donors with an elevated PDRI (1.57-2.11) experienced a lower rate of 1-year graft survival (77%) compared with SPK transplant recipients (88%). Pancreas allograft acceptance varied significantly by region particularly for PAK/PTA transplants (p < 0.0001). This analysis demonstrates the potential value of the PDRI to inform organ acceptance and potentially improve the utilization of higher risk organs in appropriate clinical settings.

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Although the number of candidates on the kidney transplant waiting list at year-end rose from 40 825 to 76 070 (86%) between 1998 and 2007, recent growth principally reflects increases in the number of patients in inactive status. The number of active patients increased by 'only' 4510 between 2002 and 2007, from 44 263 to 48 773. There were 6037 living donor and 10 082 deceased donor kidney transplants in 2007. Patient and allograft survival was best for recipients of living donor kidneys, least for expanded criteria donor (ECD) deceased donor kidneys, and intermediate for non-ECD deceased donor kidneys. The total number of pancreas transplants peaked at 1484 in 2004 and has since declined to 1331. Among pancreas recipients, those with simultaneous pancreas-kidney (SPK) transplants experienced the best pancreas graft survival rates: 86% at 1 year and 53% at 10 years. Between 1998 and 2006, among diabetic patients with end-stage renal disease (ESRD) who were under the age of 50 years, 23% of all and 62% of those waitlisted received a kidney-alone or SPK transplant. In contrast, 6% of diabetic patients aged 50-75 years with ESRD were transplanted, representing 46% of those waitlisted from this cohort. Access to kidney-alone or SPK transplantation varies widely by state.

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The purpose of this study was to determine the variation in relative output factors for fields shaped using a multileaf collimator (MLC) versus tray-mounted cerrobend blocks. A total of 21 different clinical fields from 16 patients were compared by casting cerrobend blocks from the same films that had generated the MLC shapes. Output measurements were made on a Varian 2300CD (26 1 cm leaves per side) in solid water for 6 and 20 MV at source-to-axis-distance (SAD = 100 cm) and at two depths, 5 cm (d5) and the clinically prescribed depth (d(clinical)). All measurements were taken under the central axis of the beam unless the shaped field was obviously skewed off axis or the beam was split. Several cases were repeated on a Varian 2100CD (40 1 cm leaves per side) MLC. For the 21 cases studied, the average overall MLC factor (MLC reading divided by the block reading) was found to be 0.9952 with a standard deviation of 0.0024. Repeat measurements performed on the 2100CD were within 0.2% of the MLC factors measured (for the same fields) on the 2300CD. When the data are broken down in terms of clinical applications (type of case at a clinically prescribed depth and energy), the resulting total clinical average is 0.9957 with a standard deviation of 0.0022. Both the overall average and the total clinical average MLC factors (0.995-0.996) agree with previous literature, which used abstract or generic field shapes. Further investigation of the data from this study may find a correlation between the MLC factor and the percent of open field.

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We developed a new two-step procedure to couple haptens to bovine serum albumin (BSA) via glutaraldehyde (GA). After activation of BSA with excess GA and removal of unreacted GA, the hapten was bound to the activated protein in a second step. This two-step procedure is easy to use, the desired molecular ratio of coupled hapten to protein is conveniently adjusted, and no visible precipitation of the conjugate is detected. Using a low peptide concentration, nearly 50% of the inserted haptens are bound to the protein, and unbound expensive peptide can be recovered after Sephadex chromatography. Antisera to neuroactive amino acids (GABA, glycine, and glutamate) and neuropeptides (Met-enkephalin) were prepared by immunization of rabbits with these conjugates. Immunological analysis of immune sera by dot-blot and ELISA techniques and subsequent removal of crossreactivities by solid-phase adsorption yielded monospecific antibodies, which were further purified by affinity chromatography. The immunocytochemical specificities of these purified antibodies were verified in adjacent sections of GA-fixed rat spinal cord. Pre-embedding staining with anti-Met-enkephalin in combination with post-embedding staining for amino acids such as GABA allowed double staining of the two antigens in a single semi-thin section.

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In the present study we developed an immunoenzymatic double staining technique allowing the simultaneous detection of two neuroactive substances with primary antibodies of the same species and their simultaneous visualization in semithin sections of epoxy-embedded material. For this purpose, primary antibodies against glutamate, GABA, and serotonin were either biotinylated or labeled with the trinitrophenyl (TNP) group. The latter was visualized by a detection system here referred to as the hapten-anti-hapten bridge (HAB) technique. The HAB technique consists of anti-TNP antibodies, serving as bridges between the TNP-ylated primary antibody, and a TNP-ylated marker enzyme, such as alkaline phosphatase. The single components of the HAB technique were optimized by use of a dot-blot assay and an "artificial tissue" system. The optimal staining sequence consisted of TNP-ylated primary antibody with a molar TNP:antibody ratio of 12:1, followed by anti-TNP antibody and TNP-ylated alkaline phosphatase (molar TNP:enzyme ratio of 20:1). No further improvement of detection sensitivity could be obtained when soluble immunocomplexes between anti-TNP antibody and TNP-ylated alkaline phosphatase on the side of phosphatase excess were prepared and used instead of simple TNP-ylated alkaline phosphatase. When compared with other established procedures, such as avidin-conjugated alkaline phosphatase or the ABC method, the HAB technique revealed a similar detection sensitivity. The TNP-ylated primary antibody, however, had to be used at higher concentration than the corresponding unlabeled primary antibody. The suitability of the HAB technique in combination with a modified three-step ABC technique for the simultaneous demonstration of glutamate-like and GABA-like immunoreactivity in the rat brain was demonstrated. The advantages of the new technique in comparison with existing double staining methods are discussed.

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To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P = 0.00097) and in 79% of patients with active liver cirrhosis (P = 0.0126) but not in patients with chronic persistent hepatitis (P = 0.06). Serum concentrations (medians) of HA were increased (P = 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P less than 6 x 10(-7)). The difference of HA serum concentrations but not that of P-III-NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P-III-NP serum concentrations were significantly elevated in 22 patients with acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

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The concentrations of the Sm, RNP, La and Ro antigens of thymus glands from rats were determined depending on the developmental stage of the animals. It was found that lupus antigens strongly decrease after birth. Parallel with this change, the activities of the enzymes DNA polymerase alpha and terminal nucleotidyl transferase in the thymus glands drop during maturation and ageing. These biochemical analyses were supported by immunofluorescence studies using human thymus glands. Moreover, it is documented that a redistribution of Sm and Ro occurs during development. Focusing on Sm, fetal thymus glands contain this antigen predominantly in the cytoplasm, while in immature, mature or old animals Sm is found almost exclusively in the nucleus. From these data we conclude that the amounts of the lupus antigens are additional parameters for the age-correlated function of thymocytes.

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The effect of prednisone (15 mg/day) or azathioprine (2 mg/kg daily) or a combination of prednisone (10 mg/day) and azathioprine (2 mg/kg daily) was assessed in a controlled multi-centre trial of chronic-active hepatitis. Since 1st January, 1972, a total of 162 patients were registered, 81 previously untreated. Fifty-two of them (30 HBs-antigen negative and 22 positive) fulfilled the criteria for admission to the treatment trial. 27 of 29 patients not fulfilling the criteria had HBs-antigen positive chronic-active hepatitis. All 29 untreated patients had slight active non-progressive chronic-active hepatitis over an observation period of one to four years by clinical, biochemical and histological criteria. Taking into account clinical, biochemical and histological findings, a treatment effect independent of treatment form was noted in 23 of 30 of the HBs-antigen negative patients. In 18 of the 23 successfully treated patients auto-antibodies were demonstrable. In contrast, in 18 of 22 patients with HBs-antigen positive chronic-active hepatitis no objective improvement or influence on the clinical course was observed, independent of form of treatment, and three died. It is concluded that HBs-antigen negative, auto-antibody positive chronic-active hepatitis is an indication for immunosuppressive treatment with prednisone or azathioprine or the two combined.

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Using monospecific antisera against human liver specific protein (LSP) it could be demonstrated that Chang liver cells bear LSP on their membranes. Chang liver cells can therefore be used as in vitro system to study immune reactions against LSP in human inflammatory liver diseases.

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In this paper we report on anti-HBc-titers, HBcAg, DNApolymerase activity in the serum and intracellular HBsAg in healthy HBsAg-carriers and patients with HBsAg-positive inflammatory liver diseases. 32/44 patients with acure virus-B-hepatitis were negative for anti-HBc in the first week of the disease. Anti-HBc-titers in healthy HBsAg-carriers varied between 1:10 and 1:32,000 (medium titer 1:4,000). In HBsAg-positive CAH we found a medium titer between 1:32,000 and 1:64,000, in cases with CPH of about 1:16,000. All autoimmune type CAH showed anti-HBc-titers less than 1:10. By immunofluorescence we could demonstrate in a group of 71 asymptomatic HBsAg-carriers in none of the healthy HBsAg-carriers HBcAg in the liver cell nuclei. In contrast HBcAg could only be found in 4/5 HBsAg positive CAH- and 6/9 CPH patients. No elevated DNApolymerase activity could be demonstrated in healthy HBsAg-carriers. Out of 44 patients with virus-B-hepatitis only 3 showed elevated DNApolymerase activity. On the other hand DNApolymerase elevation was demonstrable in 17/37 cases with CAH and 9/15 with CPH. The investigations showed a strong correlation between the demonstration of HBcAg in the serum and the DNApolymerase activity. The characteristic findings enabled us to differentiate between "healthy" HBsAg-carriers and HBsAg-carriers with inflammatory liver diseases.

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After a short historical retrospect and a comment on the nomenclature and on the notion of chronic hepatitis and liver cirrhosis the diagnostic criteria and immunopathological peculiarities of virus-induced HBsAg-positive, non-virus-induced autoimmune, drug-induced and finally cryptogenic chronically progressing liver diseases are discussed. Immunoserology and immunohistology are nowadays to be regarded as the most important enrichments in the diagnostic spectre for the differentiation of chronic inflammatory liver diseases. In order to complete the diagnostic programme and to understand the pathogenesis of cryptogenic chronic hepatitides as soon as possible an establishment of the hepatitis-A- and C-serology is necessary. Apart from a further analysis of the group of the non-B-hepatitides the diagnostic use of other markers of virus hepatitides will be able to adopt a definite attitude to the unclarified question of virus-induced autoimmunopathies in liver diseases. The primary biliary cirrhosis with the morphologic findings of a chronically destructing, non-purulent cholangitis is an immunologically conditioned liver diseases of unknown etiology, which in contrast to the autoimmune chronic active hepatitides and liver cirrhoses is not to be influenced in the course by therapeutic measures.

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129 blood donors found to be HBsAg-positive on routine testing were studied for evidence of hepatic disease. Twelve had already lost the antigen from the serum when histologically examined. None of these has had clinical or histological evidence of inflammatory liver disease. Two of the 129 patients showed mild icteric hepatitis, cleared the antigen during the follow up and became anti-HBs positive. The remaining 115 patients who appeared clinically healthy and who had no history of previous icteric liver disease remained HBsAg positive during a mean follow up period of 17.3 +/- 3.0 months. Forty patients from these had a normal liver histology and 37 mild to distinct steatosis but no signs of inflammatory liver disease. 11 patients a mild nonspecific mesenchymal activity but no focal necrosis, 16 patients had mild infiltration in portal tracts and a few necrotic parenchymal cells with mesenchymal reaction, 6 patients had chronic persistent hepatitis, 4 chronic aggressive hepatitis, and 1 definite posthepatic cirrhosis.

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Endogeneous fatty acid biosynthesis in the two yeast species, Saccharomyces cerevisiae and Candida lipolytica is completely repressed by the addition of long-chain fatty acids to the growth medium. In Candida lipolytica, this repression is accompanied by a corresponding loss of fatty acid synthetase activity in the cell homogenate, when the cells were grown on fatty acids as the sole carbon source. The activity of the Saccharomyces cerevisiae fatty acid synthetase, however, remains unaffected by the addition of fatty acids to a glucose-containing growth medium. From fatty-acid-grown Candida lipolytica cells no fatty acid synthetase complex can be isolated, nor is there any immunologically cross-reacting fatty acid synthetase protein detectable in the crude cell extract. From this it is concluded that Candida lipolytica, but not Saccharomyces cerevisiae, is able to adapt to the growth on fatty acids either by repression of fatty acid synthetase biosynthesis or by a fatty-acid-induced proteolytic degradation of the multienzyme complex. Similarly, the fatty acid synthetase complex disappears rapidly from stationary phase Candida lipolytica cells even after growth in fatty-acid-free medium. Finally, it was found that the fatty acid synthetase complexes from Saccharomyces cerevisiae and Candida lipolytica, though very similar in size and subunit composition, were immunologically different and had no common antigenic determinants.

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Reports on 102 patients suffering from IgD-myeloma are reviewed and analyzed. Patients with IgD-myeloma are younger than patients with myeloma producing IgG or IgA myeloma proteins. Males are affected by this disease 3 times as often as females and 11 times as often as female patients in the group producing kappa light chain type of IgD myeloma protein. Hyperproteinaemia and extreme spikes of the monoclonal immunoglobulin occur less often. Approximately 90% of the patients have a lambda light chain myeloma protein and almost all patients excrete Bence-Jones protein. Renal insufficiency, amyloidosis, and plasma-cell leukemia are found more frequently than in other types of multiple myeloma. IgD-multiple myeloma carries a poorer prognosis, possibly related to the frequent finding of renal insufficiency.

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