The alternative-splice isoforms of the PDGF A-chain differ in their ability to associate with the extracellular matrix and to bind heparin in vitro. Platelet-derived growth factor (PDGF) consists of disulfide-linked homo- or heterodimers of A and B chains. mRNA encoding the A chain (PDGF-A) occurs in two versions that differ by the presence or absence of a single short exon. These alternatively-spliced mRNAs encode polypeptides that differ in length by fifteen amino acids. The longer isoform (PDGF-AL) possesses a highly basic carboxy-terminal extension that is responsible for retaining PDGF-AL homodomers at the cell surface after secretion, while homodimers of the shorter isoform (PDGF-AS) are released into the extracellular medium. We have investigated the mechanism by which PDGF-AL remains in association with the cells that produce it. We expressed epitope-tagged versions of PDGF-AL and PDGF-AS in Cos cells and compared their intra- and extracellular distributions by immunofluorescence microscopy. PDGF-AL, but not PDGF-AS, was detected on and around cells in a diffuse pattern suggesting associated with the extracellular matrix (ECM). Metabolically radiolabelled PDGF-AL, but not PDGF-AS, could be eluted from ECM preparations by washing in high salt. Moreover, PDGF-AL bound reversibly to heparin-Sepharose in vitro at physiological salt concentrations, eluting at a salt concentration around 0.5 M. PDGF-AS did not bind to heparin under the same conditions. Thus, PDGF dimers that contain PDGF-AL may remain immobilized near the cells that secrete them by virtue of binding to heparin-like constituents of the ECM.


Recombinant PDGF from lower vertebrates: receptor binding and immunochemical analysis with metabolically labeled growth factor. We used a baculovirus vector/insect host cell system to express cDNA clones of PDGF A genes from mouse and frog (Xenopus laevis). The insect host cells process PDGF A subunits from either frogs or mice into biologically active AA homodimers with yields in the range of 0.5-1.0 mg/liter of culture medium. The recombinant PDGFs can be metabolically labeled with 35S-cysteine for use in radioreceptor and radioimmunoassays. Neutralizing polyclonal antisera can be raised against the mouse and frog PDGFs. These antisera are markedly species-specific in action. However, in radioreceptor binding assays and bioassays for mitogenic activity, human, mouse and frog PDGF AA homodimers occupy and activate murine PDGF receptors with equal efficiency.


Interaction of heparin-binding EGF-like growth factor (HB-EGF) with the epidermal growth factor receptor: modulation by heparin, heparinase, or synthetic heparin-binding HB-EGF fragments. The binding of heparin-binding EGF-like growth factor (HB-EGF) to the epidermal growth factor (EGF) receptor of human endometrial carcinoma cells was compared to that of EGF using an 125I-EGF radioreceptor assay. The inhibitory effect of HB-EGF on 125I-EGF binding was reversed either in the presence of heparin (but not by chondroitin sulfate) or by pre-treating the cells with heparinase. These treatments did not affect the binding of EGF to its receptor. To map potential regions in the HB-EGF molecule that mediate its heparin-dependent interaction with the EGF receptor, HB-EGF peptides were synthesized that were non-homologous to EGF. Accordingly residues 20-25 and 36-41, but not residues 8-19, of HB-EGF were found to be (i) heparin-binding and (ii) modulators of HB-EGF (but not of EGF) binding to the EGF receptor.


Interleukin 2 and tumor necrosis factor alpha are complementary for proliferation of the hematopoietic stem cell line LyD9. We have shown that tumor necrosis factor alpha (TNF alpha) and interleukin 2 (IL-2) are complementary for stimulation of growth of the hematopoietic stem cell line, LyD9. Neither TNF alpha nor IL-2 alone could stimulate the proliferation of LyD9 cells even after pre-incubation with these growth factors. The number of high-affinity IL-2 receptors on LyD9 cells did not increase after incubation with IL-2 and TNF alpha. These results suggest that the proliferative response of LyD9 by TNF alpha and IL-2 is not mediated by receptor inducing activities. We used the induction of the proto-oncogenes c-myc and c-pim to characterize the proliferative stimulation by IL-2 and TNF alpha. Northern blot analysis revealed that the simultaneous addition of IL-2 and TNF alpha was more efficient than IL-2 alone for c-myc mRNA induction. However, the addition of TNF alpha and IL-2 could not increase c-pim mRNA more than the level induced by IL-2 alone. The results indicate that the two growth factors complement each other by transducing different types of growth signal.


The interaction of amphiregulin with nuclei and putative nuclear localization sequence binding proteins. Amphiregulin (AR) is a 23 kDa, bifunctional growth modulating glycoprotein belonging to the epidermal growth factor (EGF) family of polypeptide growth regulators. AR possesses two putative nuclear localization sequences (NLS), binds to DNA sepharose, and localizes to the nucleoli of human ovarian surface epithelial carcinoma cells suggesting that AR has a direct nuclear role. We have found that 125I-labeled AR, when exogenously applied to several carcinoma cell lines, associated with nuclei in a time, temperature, and concentration dependent fashion. The control peptide, EGF, also associated with these fractions but at approximately 20% of the efficiency of AR. Cross-linking experiments with 125I-labeled AR and nuclear fractions derived from various carcinoma and normal cell lines demonstrated that AR binds two proteins of molecular mass 205 and 120 kDa. AR binding to these nuclear fraction proteins was specific and saturable as shown by competition experiments utilizing both SV-40 large T antigen NLS and an AR derived peptide encompassing both putative AR NLS. The combined results suggest that nuclear interactions may play a significant role in AR induced growth responses.


Never ending growth and a growth factor. I. Immunocytochemical evidence for the presence of basic fibroblast growth factor in a tapeworm. Basic fibroblast growth factor immunoreactivity (bFGF-IR) was detected in a specific set of nerve cells in the central nervous system of the gull-tapeworm Diphyllobothrium dendriticum (Cestoda)--an obligatory endoparasite. The long varicose processes of the bFGF-IR neurons extend along the two main nerve cords, which contain an actively growing population of nerve cells. A neurotrophic function for the bFGF-like material is proposed. The adult tapeworm lives in the intestine of a homeothermic host and has a pattern of very active and never ending growth. The larval stages live in poikilothermic hosts and grow very slowly. The bFGF-IR nerve cells occur both in II stage larvae and in adult worms. Thus, no correlation between the presence of bFGF-IR and the general growth rate of the worm was found. Western blot analysis revealed the presence of an anti-bFGF immunoreactive peptide with a molecular mass of 47 kDa in both larval and adult worms.


The UNOS Scientific Renal Transplant Registry. 1. One-year graft survival rates were 80%, 74%, and 66% for recipients of first (27,755), second (4,263), and multiple (914) cadaveric renal transplants, respectively. The 1-year patient survival rate was 94% for recipients of first or second grafts and 92% for multiply retransplanted patients. Half-lives projected for all cadaver transplants surviving the first year were approximately 8 years. 2. One-year graft survival rates were 95% for recipients of HLA-identical sibling-donor transplants (1,493), 91%, 90%, and 89% for recipients of 1-haplotype-matched sibling (1,787), parent (2,118), and offspring (715) donor grafts, respectively. One-year patient survival was 94% for parents receiving transplants from their children and 98% for all other recipients of kidneys from immediate family members. Projected half-lives were 26 years for HLA-identical grafts and 12-14 years for 1-haplotype-mismatched transplants from living related donors. 3. There were 181 transplants between spouses, with a 1-year graft survival rate of 92% and 99% patient survival. There were also 369 transplants from distant relatives or unrelated living donors with a 1-year graft survival rate of 86% and 95% patient survival. Projected half-lives for these transplants were 13 years. 4. Rejection episodes that occurred during the initial transplant hospitalization were reported in 24% of first and 33% of retransplanted recipients (p < 0.001). Rejection-free patients had an 85% 1-year graft survival rate compared with 67% and 58% in recipients of first or regrafts after early rejection (p < 0.001). Rejection episodes were strongly associated with histoincompatibilities. Among HLA-identical sibling transplants, 6% had early rejection compared with 12% of HLA-A,B,DR-matched cadaver transplants, 25% of parent-donor transplants and 28% of HLA-DR-mismatched cadaveric transplants. 5. The serum creatinine level (SCr) reported at the time of discharge was predictive of graft survival in both the short and long term. Recipients of first cadaver transplants discharged with SCr below 1.6 mg/dl (8,960) had a 91% 1-year graft survival rate and a projected half-life of 12 years, while those with SCr above 3.5 mg/dl had 49% 1-year graft survival and 5.3-year projected half-life (p < 0.001). Discharge SCr was significantly influenced by the recipient's weight, the donor's age, and the cold ischemia time.(ABSTRACT TRUNCATED AT 400 WORDS)


Organ donation in the United States: 1988 through 1991. 1. During 1988 through 1991, the total number of cadaveric donors increased by 11% and the number of living donors increased by 25%. 2. During 1991, at least 1 kidney per donor was recovered from 94% of cadaveric donors. Livers were recovered from 70% of cadaveric donors; hearts from 47%, pancreases from 24%, lungs from 8%, and heart-lung combinations from 1%. The percentage of cadaveric donors from whom multiple organs were recovered increased by 23% between 1988 and 1991. 3. During 1988 through 1991, the largest group of cadaveric donors was White, male, age 19-35, with blood group O. During 1991, the primary cause of cadaveric-donor death was cerebrovascular. The largest group of living donors was also White and age 19-35; however, most donors were female. 4. Between 1988 and 1991, the percentage of cadaveric donors age 50-64 increased by 36% (from 11% in 1988 to 15% in 1991) and the percentage of cadaveric donors 65 years old or older increased by 200% (from 1% to 3%). 5. The percentage of White cadaveric donors declined by 4% between 1988 and 1991, while the percentage of Black donors increased by 16%. The percentage of Hispanic donors increased by 25% and that of Asian donors increased by 29%. 6. Throughout 1988 to 1991, the percentage of cadaveric hearts transplanted locally increased by 18% (from 55% to 65%). Interregional cadaveric kidney sharing also increased by 70% (from almost 10% to 17%). Local cadaveric liver transplantation increased by 80% (from 25% to 45%), resulting in a smaller percentage of livers shared interregionally. Local transplantation of cadaveric lungs increased by 173% (from 15% to 41%), reducing the lung discard/research rate by 69%, from 42% to 13%.


Heart transplantation: update.

Heart transplantation: update. Clinical application of heart transplantation goes beyond 25 years experience. The main indications for cardiac transplantation remain idiopathic cardiomyopathies and ischemic diseases. To obtain a suitable donor has become progressively more difficult due to the increase of transplants performed and the shortage of donors. Advances in the detection of early rejection, improved organ preservation procedures, and the introduction of new immunosuppressive therapy protocols have produced dramatic results in heart transplantation. Late graft atherosclerosis remains a serious threat despite retransplantation and, in some cases, mechanical cardiac support.


Heart transplantation at the Heart Center North Rhine-Westphalia. Since 1989, 427 heart transplants were performed at our center, limited only by donor availability, not by moderating donor criteria. Therefore, an increasing number of possible recipients was bridged with mechanical circulatory support systems. Immunosuppression was based on double-drug therapy (CsA, Aza) without steroid maintenance if possible and without mono- or polyclonal antibody prophylaxis. Monitoring adult transplant patients was based on endomyocardial biopsies only during the first 12 months posttransplant. In the pediatric group, only noninvasive diagnostic procedures were performed. Our present 1- and 3-year survival rates for heart transplant patients are 85% and 78%, respectively. We believe that only centers performing approximately 1,000 routine open-heart surgery procedures per year should be allowed to perform heart transplantation, with a minimum of 25 procedures per year (5). Our goal is to start our heart-lung and lung transplant programs in the near future. Our research interests are mainly in the field of postoperative monitoring, induction of immune tolerance, and in establishing a method to determine an individual immunosuppression protocol for each patient (6).


Lung transplantation at the University of Pittsburgh. Lung transplantation appears to be a therapeutic alternative for selected patients with end-stage pulmonary vascular and/or parenchymal disease. The greatest impediment to transplantation remains the availability of donor organs. This has become more significant as additional transplant centers become operational. The primary cause of death has been infection, and this most frequently occurs in the early post-transplant period. Significant progress has been made in curbing the morbidity and mortality from bacterial pneumonia and CMV infection, and this is the primary reason for improved survival rates. If the recipient survives the initial hospital stay, the likelihood of survival at 5 years is approximately 80%. The primary long-term complication is obliterative bronchiolitis which is poorly understood and difficult to treat. Nevertheless, the improvement in survival provides impetus to refine and improve the procedure so that survival can reach that attained by recipients of other major organ allografts.


Liver transplantation at the University of Nebraska Medical Center from 1985 to 1992. Based on our 7 and one-half-year experience with liver transplantation at the University of Nebraska Medical Center: 1. Success and growth of the program has been, in part, the result of close interaction and support of the various specialists involved. 2. We have demonstrated that outstanding patient and graft survival rates can be obtained with cyclosporine/prednisone immunosuppression. 3. Few, if any, technical contraindications exist to liver transplantation. 4. Surgical advances have allowed allografts to be salvaged which would otherwise require replacement. 5. Routine donor-liver biopsy prior to implantation has reduced the rate of primary nonfunction. 6. New strategies to improve survival for patients with hepatitis-B-related liver disease and hepatic malignancies undergoing liver transplantation need to be developed. 7. The management of patients with fulminant hepatic failure is evolving and now includes innovative approaches such as the use of ECLS and auxiliary transplants.


The Pitt-UNOS Liver Transplant Registry. Since the establishment of the scientific LTR, the frequency of OLTX has been increasing. Between 1988 and 1991, the number of procedures performed on pediatric patients increased by 28.2%, and among adult patients OLTX increased 84.8%. During this same period, the number of transplant centers performing OLTX rose 62.5% for children, and 54.7% for adult recipients. In 1991 there was a larger proportion of recipients under 1 year of age than in previous years. The effect was to lower the median age at transplantation from over 2 to between 1 and 2. In pediatric recipients of initial transplantation in 1991, compared with earlier recipients, the functional status at time of liver transplantation was improved. Fewer children were in the ICU while awaiting transplantation, and more were able to wait at home. Multiorgan transplantations in pediatric patients remained relatively rare, but a larger portion of these procedures in 1991 than was seen previously included the small intestine. Biliary atresia remained the most common indication for liver transplantation among children, accounting for over 55% of all OLTX procedures in 1991. There was a significant change in the racial distribution among adult recipients. Compared with previous years, there were greater proportions of Hispanic and Asian recipients in 1991. Adult recipients were older in 1991 than previously, and the median age increased from 46 to 49. As with pediatric recipients, adult recipients had better functional status in 1991 than earlier recipients. The increase in positive CMV serology was likely to be a function of older age. Among multiorgan recipients, the combination of liver and pancreas only was much less common in 1991 than previously. As was found previously (1), alcoholic cirrhosis continued to be the most common reason for OLTX, with the proportion of patients diagnosed with this condition increasing in 1991. Twice as many patients with cystic fibrosis were recipients in 1991 as in the prior 3 years. There were decreases in the proportion of patients receiving OLTX due to fulminant liver failure, metabolic disease, and malignant neoplasms. The cumulative probability of surviving (without retransplantation) 4 years after initial transplantation was 0.74 (0.61) for pediatric recipients. Univariate (unadjusted) analyses detected significant differences in survival for age (the youngest recipients had the worst survival), UNOS description (poorer functional status just prior to transplantation led to poorer survival), and primary liver disease (survival was worst for recipients transplanted due to fulminant liver failure, and best for patients with alpha-1 antitrypsin deficiency).(ABSTRACT TRUNCATED AT 400 WORDS)


Pediatric liver transplantation at the University of Chicago Hospitals. The concept of graft-reduction surgery in liver transplantation has revolutionized pediatric transplantation and soon may carry over into adult transplantation. Reduced-size liver transplants have virtually eliminated patient deaths while waiting for donor organs to become available by increasing the potential donor pool. This has shifted the distribution of pediatric liver transplant recipients to a younger age which more closely matches the needs of pediatric patients with end-stage liver disease. Split-liver transplants can create new grafts without increasing the donor supply. Living-donor liver transplantation not only increases the supply of organs but also creates uniformly good quality grafts that can be used electively in stable patients. The result is patient and graft survival rates that are better than those seen with cadaveric organs. Orthotopic auxiliary liver transplantation offers children with metabolic disorders the opportunity to correct their diseases without the risks associated with whole-organ replacement.


Combined kidney/pancreas transplantation at the Ohio State University Hospitals. We conclude that combined kidney and pancreas transplantation is a safe and effective procedure to treat complicated Type I diabetic patients. It does carry significant potential for morbidity; therefore, it is essential that potential recipients understand these details prior to considering the procedure. Adequate preoperative screening for coronary artery disease is essential. The most difficult problem is dealing with early posttransplant dehydration and acidosis. More sensitive tools are needed to diagnose acute rejection in both combined kidney/pancreas recipients, as well as pancreas-alone grafts. Infectious complications are frequent, but most pose little morbidity. Currently, the incidence of early thrombosis is negligible. Even with these complications, overall excellent patient outcome demonstrates that kidney and pancreas transplantation should be the procedure of choice in well-selected Type 1 diabetics with end-stage renal disease.


The current status of the University of Tennessee, Memphis, experience in pancreas transplantation. SPK transplantation is associated with excellent rehabilitation and greater improvement in posttransplant functional status than is KTA transplantation. This improvement is not just a function of the magnitude of the improvement experienced by a few patients but was seen in the majority of patients and the majority of our study parameters. Since pancreatic transplantation adds to the morbidity of kidney transplantation for the uremic patient, longitudinal evaluation which demonstrates added benefits from the restoration of euglycemia by pancreas transplantation is important. Such evidence generated by us (14) and others (15, 16) now provides the justification for continuing pancreas transplantation.


Results of the National Kidney Transplantation Program in Norway. 1. Of 2,003 patients starting renal replacement therapy for end-stage renal disease in Norway from 1983 through 1991, 83% were candidates for transplantation. The need for transplantations increased to 58 (50 first and 8 repeat) grafts PMP per year as the number of elderly patients increased. 2. There were 1,528 transplants performed at a rate increasing to 46 grafts PMP per year. The grafts were procured from LDs in 44% and CDs in 56%. Eighty percent of all patients in need were transplanted and 65% of all patients requiring replacement therapy for end-stage renal disease were treated by transplantation. The national waiting list and dialysis population remained almost stable. 3. Graft survival rates in recipients of first LD grafts (n = 593) were 91% and 77% at 1 and 5 years, respectively. One-year graft survival was 98% in HLA-identical grafts (n = 73), 91% in haploidentical grafts (n = 411), 89% in 2 haplotype-mismatched related grafts (n = 38), and 85% in spousal donor grafts (n = 71). Higher rates were observed in younger (< 55 yrs) patients. 4. Graft survival rates in recipients of first CD grafts (n = 688) were 78% and 59% at 1 and 5 years, respectively. The rates were 84% and 66% in younger (n = 342) versus 72% and 52% in older (> 55 years) (n = 346) patients. Death with a functioning graft caused approximately 45% and 75% of all graft losses in younger and older patients, respectively. Cardiovascular disease was the major cause of death.(ABSTRACT TRUNCATED AT 250 WORDS)


Renal transplantation at the University of Pennsylvania Medical Center: an update of results in the cyclosporine era. This chapter presents a summary of living-related, living-unrelated, and cadaver renal transplantation performed at the University of Pennsylvania Medical Center between January 1984 and October 1992. Over the past 9 years, 895 patients (557 males, 338 females, mean age 42 yrs) received 942 renal transplants; 599 patients received kidneys from cadaver donors (n = 627) and 296 patients received kidneys (n = 315) from living donors of all types. During this period, 151 patients were retransplanted, sometimes more than once (159 total retransplants, 124 secondary grafts, and 35 third or more transplants). An analysis of patient ant graft survival rates (calculated by actuarial methods) for different categories of transplant recipients was performed. Black recipients, as a racial subcategory, had the poorest graft outcome, especially when followed over the long term. Graft survival rates for Black recipients who were retransplanted with cadaver grafts were even worse and were noted to be similar to the diabetic population that received cadaver retransplants (66% vs 62% at 1 yr and 32% vs 25% at 5 yrs). Diabetic recipients of living-donor transplants had excellent graft survival results, similar to nondiabetic, living-donor recipients (patient survival rates 98% and 92% vs 97% and 92% at 1 and 5 yrs; graft survival rates 92% and 82% vs 92% and 82% at 1 and 5 yrs). HLA-identical recipients of first cadaver grafts demonstrated the best outcome in the entire cadaver series (graft survival rates 91% and 83% at 1 and 5 yrs, respectively). HLA-identical recipients of second or more cadaver grafts had poorer results than expected (50% graft survival at 1 yr) despite a 100% patient survival rate. HLA-identical recipients of living-related grafts had the best graft survival rates (96% at 1 yr and 94% at 5 yrs) and superior graft survival rates for retransplanted grafts as well (100% at 1 and 5 yrs). We conclude that in the last decade, patient and graft survival rates for cadaveric and living-donor renal transplants have improved dramatically relative to the results obtained in the pre-CsA era. Long-term graft survival in Black recipients remains lower than in other races, suggesting the need to analyze other factors to explain poorer graft survival in this recipient population. Results in diabetic recipients continue to be excellent at our center, encouraging the continuation of our aggressive approach to try to transplant diabetics as early as possible, particularly when a living donor is available.


Kidney transplantation in patients with type I diabetes: 26-year experience at the University of Minnesota. With current immunosuppressive protocols, 1- and 6-year graft survival is similar in diabetic and nondiabetic kidney transplant recipients. Living-donor transplant recipients have significantly better outcome. Death with function and chronic rejection remain the 2 predominant causes of graft loss for diabetic recipients. Compared with national statistics on diabetic patient survival on dialysis, our data suggest that transplantation is the treatment of choice for diabetic patients with end-stage renal disease.


Immunosuppression without prophylactic antilymphocyte preparations. 1. Triple-drug immunosuppression following third party transfusion can result in graft survival equal to protocols that employ prophylactic antilymphocyte preparations. 2. T1/2 was statistically improved in cadaveric and living-related donor grafts in the CsA era. 3. Patients 65 years and older had an excessive death rate. Younger groups were admixed. Extreme youth was not a risk factor. 4. Black recipients had excessive late graft loss. 5. Diabetic recipients had only a slight decline in graft and patient survival rates. 6. First and multiple graft recipients had similar transplant survival rates. 7. Delayed graft function remains costly in this immunosuppressive scheme.


Single-center experience of unrelated living-donor renal transplantation in the cyclosporine era. Renal transplantation from the unrelated living-donor might be an alternative when the cadaveric or related donor is not available, because graft and patient survival rates are superior to those of kidneys from cadaveric donors and even comparable to those from related donors. Among the many factors that might contribute to these excellent results, we believe that the good quality of kidneys (lacking preservation or ischemic injury) is the most important one. In addition, our criteria for patient selection requiring well-matched HLA typing might partially contribute to our success. For the successful renal transplantation program using unrelated-living donors, high ethical standards, accumulated experience from living-related donor transplantation, and dedicated professionalism are strongly recommended.


Factors influencing long-term outcome of living-donor kidney transplantation in the cyclosporine era. To evaluate the effect that CsA has had on the weight of some factors previously considered influential on kidney graft survival rates in conventionally immunosuppressed recipients, we analyzed patient and graft survival rates for 524 consecutive living-donor first kidney transplants. All patients were transplanted at the Catholic Medical Center between 1984 and 1991 and treated with CsA. The data were stratified to reflect differences in a) HLA matching; b) acute graft rejection within 3 months posttransplant; c) donor sources; d) age; e) sex; f) graft number; g) diabetics; h) HBV status; i) DST; and j) number of pretransplant transfusions. Overall actuarial 5-year patient and graft survival rates were 86% and 77%. The actuarial 5-year graft survival rates for the HLA-identical, haploidentical, and mismatched groups were 93%, 75% and 80% (p = 0.3858), respectively. The actuarial 5-year graft survival rates in recipients with acute graft rejection (< 3 months) and without acute graft rejection were 55% and 80% (p = 0.0001). The actuarial 5-year graft survival rates for the HBV-positive and -negative groups were 55% and 80% (p = 0.0048). The actuarial 5-year graft survival rates according to the number of pretransplant blood transfusions--0, 1-4, and over 5 units groups--were 65%, 80%, and 81% (p = 0.0026), respectively. We conclude that a) acute graft rejection within 3 months, b) HBV-positive, and c) pretransplant nontransfusion had a significant negative influence on long-term graft survival, whereas little or no effect was attributable to HLA matching, donor source, age, sex, graft number, diabetes, and DST.


Perioperative fluid and drug therapy during cadaver kidney transplantation. 1. For all outcome measures associated with delayed onset of urine output and the need for posttransplant dialysis, the prognosis is poor. Low 1-year graft survival of 49% and patient mortality of 13% associated with delayed function make it exceedingly important to identify measures that induce immediate posttransplant kidney function. 2. Intraoperative blood volume expansion with albumin improves short- and long-term posttransplant function at every level of analysis, including earlier urine onset, larger urine volumes, improved kidney function, decreased incidence of delayed and no function, and greater graft and patient survival. 3. Aggressive intraoperative blood volume expansion during cadaver renal transplantation enables the safe use of intraoperative verapamil without inducing hypotensive complications. 4. Intraoperative verapamil improves the decreased renal blood flow associated with poor function as seen after organ procurement and cold ischemia. 5. Clinical studies confirm previous animal research demonstrating that verapamil and other calcium antagonists prevent CsA-induced deterioration of renal blood flow. 6. Several studies have demonstrated elevated CsA blood concentrations during concomitant treatment with verapamil and diltiazem but not with the dihydropyridine class of calcium antagonists. 7. Despite the higher CsA blood levels, kidney function, as determined by serum creatinine and glomerular filtration rate, improves with verapamil. 8. Verapamil given intraoperatively into the renal artery after revascularization improves renal function and reduces the need for posttransplant hemodialysis. 9. The combination of intraoperative verapamil and blood volume expansion acts synergistically, resulting in larger urine volumes, improved renal function, and decreased incidence of delayed function. 10. Most importantly, perioperative administration of albumin and verapamil independent of each other, significantly improves graft survival. 11. The beneficial effects of albumin are probably due to improved hemodynamics from increased blood and plasma volumes leading to better renal perfusion and prompt oxygenation. Secondly, blood volume expansion provides a safeguard against the intraoperative use of verapamil. The beneficial effects of verapamil on posttransplant outcome may be related to cellular protection from ischemia, selected vasodilation of the afferent arteriole, inherent immunosuppressive properties, and elevated CsA blood levels.


Multifactorial analysis of renal transplants reported to the United Network for Organ Sharing Registry. 1. From a multivariate log-linear analysis of 35,625 renal transplants between 1988 and 1991, center effects accounted for 28%, 45%, and 27% of all assignable variation in 3-month, 1-year, and 2-year outcomes, respectively. Although center variation dominated 22 other variables, most factors were relatively independent of transplant center (ie, a percent of factor variation due center less than 10%). Recipient race and health status were notable exceptions; both highly influenced by center affiliation. Centers also differed in the age mix of recipients and racial mix of donors in some epochs. Again, we found only extremely weak correlations among a center's 3-month, 1-year, and 2-year graft survival rates. 2. In order of 3-month accountability, the other important factors were PRA, donor age, recipient working status, year of transplant, HLA-A,B mismatching, previous transplant, donor's death, donor relationship, recipient race, body mass, recipient age, cold ischemia time, donor race, donor kidney mode (ie, left/right kidney), original disease, and HLA-DR mismatching. Regarding 1-year outcome, the important factors were recipient race, donor age, donor's death, donor relationship, HLA-A,B mismatching, previous transplant, and recipient sex. Finally at 2 years, the important factors were recipient race, donor age, year of transplant, donor relationship, recipient sex, working status, donor's death, recipient age, CMV status, body mass, and donor sex. 3. Body mass, donor kidney mode, and CMV status were novel factors in our own multifactorial analyses of the UNOS Registry file. An elevated body-mass index (> 30 kg/m2) had a negative impact on short- and long-term graft survival. Recipients receiving left kidneys had nominal improvement in 3-month graft survival, but no impact thereafter. Survival rates over the 4 combinations of donor/recipient CMV statuses, suggest that this covariate was principally long-term and donor related. 4. It is noteworthy that graft failures in the 2 most recent transplant years, 1990 and 1991, have shown both short- and long-term declines, breaking stationary patterns previously reported in this series on clinical transplants. 5. The transitory nature of most transplantation factors was confirmed in this study, implying that future multifactorial studies in renal transplantation must include some mechanism for varying risks.(ABSTRACT TRUNCATED AT 400 WORDS)


Long-term kidney graft survival.

Long-term kidney graft survival. 1. More than 90% of long-term grafts were first transplants. 2. The percentage of long-term transplants from living-related donors decreased from 78% in the years prior to 1968 to 42% in the 1973-1977 period. 3. More than 60% of living-related long-term grafts were from sibling donors. 4. Among long-term survivors, there was no difference from the expected rates in the percentage of red blood cell groups. 5. HLA-A,B matching resulted in significant improvement in graft survival rates for both cadaver donor and related transplants.


Thoracic organ transplants in the United States from October 1987 through December 1991: a report from the UNOS Scientific Registry for Organ Transplants. 1. In 1991 there were 2,127 heart, 402 lung, and 51 heart-lung transplants performed in the United States. These numbers reflect increases of 27% for heart, over 1000% for lung, and a decrease of 31% for heart-lung transplants since 1988. 2. The number of programs performing heart transplants has increased by 16% since 1988, whereas the number of programs performing lung transplants has tripled over that time. 3. The most frequent primary indications for thoracic transplantation were: cardiomyopathy (45%) and coronary artery disease (41%) for heart; primary pulmonary hypertension (43%) and congenital/Eisenmenger's for heart-lung; and emphysema/chronic obstructive pulmonary disease (28%) and Alpha-1 antitrypsin deficiency (20%) for lung. 4. Average cold ischemic time increased gradually between 1988 and 1991: 2.7 hours for hearts transplanted in 1991 compared with 3.3 hours for heart-lungs, and 4.3 for lungs. 5. Between 1988 and December 1991, the following percentages increased significantly: pediatric heart and lung transplantations; non-White thoracic transplant recipients and donors; the use of thoracic organs from younger (< or = 5 yrs) as well as older (> or = 45 yrs) donors; and local utilization of thoracic organs. 6. For the entire period covered by this report, 1-year recipient survival rates were: heart 81.6%, heart-lung 55.4%, and lung 67.2%. Patient survival was significantly lower in heart retransplants or when the primary indication for transplantation was the treatment of congenital disease. Between 1988 and 1991, 1-year survival appeared to have increased significantly for heart-lung and lung recipients.


Center effect in the UNOS Renal Transplant Registry. Based upon univariate and multivariate analyses of transplant center effects: 1. Among the 115 centers selected for these analyses, there was no correlation between 6-month graft survival rates and half-lives projected for grafts surviving 6 months. 2. There was no significant center effect for living-related donor transplantations. 3. Centers that had the poorest short- and long-term survival performed more cadaveric transplants with patients in poor health at the time of transplant, more often transplanted a recipient other than the one originally identified for a particular kidney, and more often transplanted kidneys with prolonged cold ischemia, and kidneys from pediatric (age 0-11) donors, older (ages over 50) donors, Black donors, or donors who died with cerebrovascular accidents. 4. After adjusting for 17 potentially confounding variables, the difference between the best and worst center groups was the second most detrimental factor (following broad sensitization) in the first 6 months and was the factor ranked ninth in long-term survival. 5. The transplant year has emerged as a significant factor in long-term survival. This suggests that the late loss rate for transplants performed after 1988 may be diminishing. 6. The health status of the patient at the time of transplant was the dominant factor affecting long-term survival. 7. The choice of outcome variable and the selection criteria used in center classification affect the magnitude of the center effect and its relationship to other significant variables that influence graft outcome.


Regrafts.

Regrafts. 1. Retransplant survival rates have been increasing at a much faster rate than those of first transplants. The difference between first and second transplant 1-year survival rates has decreased from 8% in 1988 to 2% in 1991. 2. Second transplant recipients given 1-20 pretransplant transfusions had 3-5% higher graft survival rates than nontransfused patients or those given more than 20 transfusions. Transfusions for first or multirenal transplants had no significant impact on survival and in some cases, nontransfused patients had higher graft survival rates. 3. The duration of previous graft survival remains one of the best indicators of how subsequent grafts will survive. The 1-year regraft survival rate for second transplant recipients was 77% when the first transplant had survived longer than 1 year, 69% when first graft survival was 6 months to 1 year, and 60% when first graft survival was less than 3 months (p < 0.005, each comparison). 4. The HLA-DR1 phenotype was associated with higher graft survival than patients lacking HLA-DR1. The difference was 8% at 1 year for second graft recipients (p < 0.001) and 15% for multiply retransplanted patients (p = NS). 5. Repeating an HLA-A or -B locus antigen mismatch from a previous graft had no apparent effect on regraft survival rates. Repeating an HLA-DR locus antigen mismatch, either alone or in combination with other antigens, resulted in a 5-8% decrease in 1-year regraft survival. Although the difference was not statistically significant at 1 year, survival was significantly lower at 2 and 3 years for recipients with repeated HLA-DR antigen mismatches.


Sensitization.

Sensitization. 1. The transfusion effect, which had its greatest impact in 1985, disappeared in 1989. Since then, transfused and nontransfused groups have had identical 1-year graft survival rates. 2. The percentage of nontransfused recipients reached nearly 50% in 1992. The amount of pretransplant transfusion blood has dropped from 7 units in 1982 to below 5 units in 1992. Whole blood and packed red cells were the preferred products, comprising 98% of total transfusions in 1992. 3. The transfusion effect was observed in both sensitized and nonsensitized transfused recipients until 1988, although the effect was greater in the nonsensitized group. Since 1989, the sensitized group of transfused recipients had an even lower 1-year graft survival rate, while the nonsensitized group had a slightly better survival rate than those with no pretransplant transfusions. 4. Although washed red cells, frozen red cells, and frozen plasma constituted only a small percentage of total transfusions, any pretransplant transfusion of these blood products still produced a transfusion effect. Since 1982, patients who received washed red cells, frozen red cells, or frozen plasma had 8% higher 1-year graft survival rates since 1982 than those who had no transfusions, a difference still patient in 1990. 5. The percentages of broadly sensitized recipients decreased significantly in the last decade. Even recipients who had very specific antibodies (PRA 1-10%) had significantly lower graft survival rates than those with no antibodies (PRA = 0). Patients with PRA 1-10% and those with PRA 11-50% had almost identical graft survival curves and the same half-life, whether first or regrafted recipients. Only 0-PRA patients could be distinguished as "nonsensitized." 6. Once patients were sensitized, any time pretransplant, the current PRA values had less meaning for predicting graft survival than the peak (historical) PRA values. Those with peak PRA 51-100% had the same graft survival rates regardless of their current PRA values. Peak PRA was more important than current PRA for predicting graft status. 7. The deleterious effect of a positive flow cytometry crossmatch (FCXM) was obvious in both first and regrafted recipients. The positive group had about a 10% lower 1-year graft survival rate than the FCXM-negative group. 8. The significance of the positive FCXM outweighed the current PRA values, especially in regrafted recipients and first transplant recipients with peak PRA values. 9. FCXM seemed to work only on patients who had a chance of being sensitized by HLA stimulation. There was no positive FCXM effect in nontransfused recipients.(ABSTRACT TRUNCATED AT 400 WORDS)


Disease effects and associations.

Disease effects and associations. 1. The most common disease leading to end-stage renal disease were IDDM for Whites (36%), hypertensive NS for Blacks (26%), and CGN for Hispanics (35%) and Asians (47%). These racial differences should be taken into account in analyzing outcomes with respect to disease. 2. Differences in graft survival associated with different primary diseases were more apparent among Whites than Blacks. Race, rather than disease, was the dominant factor. 3. One-year graft survival was consistently highest for patients with IgA nephropathy (87%) and poorest for patients with SLE (78%). The difference across the spectrum of original diseases was significant (p < 0.001). 4. About 84% of White diabetics and 90% of those under age 50 had an HLA-DR3 or 4 tissue type compared with 50% of White donors (p < 0.001). The 1-year graft survival rate was 80% for DR3 or 4 IDDM patients and 74% for non-DR3/4 patients (p < 0.001). Black IDDM patients also had a significantly increased frequency of DR3 and 4 compared with Black donors (46% vs 32%, p < 0.001) and a similar trend toward higher graft survival, although the difference was not significant. 5. Of Whites transplanted with SLE, 60% had HLA-DR2 or 3 compared with 47% of donors (p < 0.001) and those with DR2 or 3 had significantly higher 1-year graft survival rates. Similar trends were noted for Blacks with SLE. 6. HLA-DR2 was present in 46 of 72 patients (64%) transplanted for Goodpasture's syndrome, compared with 28% of donors. Despite the small numbers, 1-year grafts survival was significantly better in the HLA-DR2 group (p = 0.006). 7. Significantly higher graft survival rates were observed among patients with HLA-DR1 in non-HLA-DR-associated diseases (CGN, IN, NS, or PC) but not in HLA-DR-associated diseases such as IDDM and SLE. 8. There were significant differences in recipient age and sex distributions in the major disease groups. Blacks under age 50 had significantly poorer outcomes than comparable Whites. 9. Pretransplantation health status influenced graft outcome in all disease groups. Patients with IDDM or NS were generally less healthy and correspondingly more debilitated than patients with other diseases. 10. Diabetic given a simultaneous kidney-pancreas transplant had 83% 1-year graft survival compared with 78% for those given a kidney alone (p < 0.001).


Preservation.

Preservation. 1. There were no significant differences in 1-year graft survival rates comparing kidneys stored with 3 commonly used cold storage solutions (Collins', EuroCollins, and University of Wisconsin) over the past 12 years, even though preferences have changed sharply. 2. No significant differences in 1-year graft survival rates were noted when comparing kidneys preserved by pump perfusion and those maintained by simple cold storage. The lower incidence of delayed graft function for pump-preserved kidneys was at least partly attributable to a center effect. 3. Prolonged cold ischemia time (CIT) was associated with an increase in delayed onset of function. Of 2,718 kidneys transplanted within 24 hours, 21% did not function well within the first week. The fraction increased to 28% and 33% of kidneys transplanted between 25 and 36 hours (n = 1,858) and after 36 hours (n = 955), respectively (p < 0.01). One-year graft survival rates were 82%, 78%, and 76% for kidneys transplanted within 24 hours, between 25 and 36 hours, and after 36 hours, respectively (p < 0.01, each comparison). 4. HLA matching neutralized the impact of prolonged CIT completely. One-year graft survival was more than 86% in 715 recipients of 0 HLA-mismatched kidneys, regardless of CIT. For recipients of mismatched transplants, survival decreased by 5-6% as CIT increased from less than 24 to more than 36 hours (p < 0.01). Of the mis-matched kidneys with less than 24 hours CIT, up to 83% survived at 1 year compared with 87% of matched kidneys with more than 36 hours CIT (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


Rejection episodes.

Rejection episodes. Based upon analyses of 40,671 kidney transplants reported to the UNOS Scientific Renal Transplant Registry between October 1987 and August 1992: 1. Twenty-four percent of the 21,923 recipients of first cadaver grafts experienced one or more rejection episodes during their transplant hospitalization, 52% during the first 6 months. At 12 months, only 40% of patients remained rejection-free. Patients who experienced any rejection during the first 6 months had a 72% 1-year graft survival rate compared with 95% for those who remained rejection-free (p < 0.001). 2. Recipients of transplants from living donors had a significantly lower incidence of rejection episodes. There was a clear effect of histocompatibility in comparing the incidence of rejection in HLA-identical sibling transplants (8% at discharge and 32% at 1 year) with that in 1-haplotype disparate transplants (22% at discharge and 52% at 1 year, p < 0.01 at each time point). Rejections were reported for 25% of transplants from other living donors at discharge and for 56% at 1 year, similar to the figures for cadaver transplants. 3. Histocompatibility also influenced the incidence of rejection in first cadaver-donor transplants. Only 15% of recipients of 0-HLA-A,B mismatched kidneys had rejection episodes reported at discharge, compared with 26% of those who received kidneys completely mismatched for HLA-A,B antigens (p < 0.01). At 1 year, 56% of HLA-A,B matched patients remained rejection-free, whereas only 35% of those mismatched for 4 antigens had no reported rejection through the first year (p < 0.01). Considering HLA-DR antigen mismatches, 19% of the 0-antigen mismatched group had rejection episodes at discharge, versus 28% for those with 2 HLA-DR mismatches (p < 0.01), and at 1 year, the percentage who were rejection-free decreased from 48% to 40% and 34% with 0, 1, and 2 HLA-DR mismatches, respectively. 4. The incidence of rejection episodes decreased as the recipient's age increased. Patients under age 16 had the highest incidence prior to discharge (28%) and at 1 year (70%) compared with 17% and 47% at the same intervals in patients over age 60 (p < 0.01). 5. The donor's age also had a significant effect on rejection episodes. Transplants from pediatric and older donors had a higher incidence of reported rejections than those from donors aged 16-30, especially after hospital discharge.(ABSTRACT TRUNCATED AT 400 WORDS)


Kidney allocation under the UNOS point system: an update. 1. The 1,480 patients awaiting cadaveric renal transplants at 14 Southern California transplant centers as of December 3, 1992, were compared with patients transplanted using a point system for one kidney and a hospital-based allocation for the second, or the current system allocating all locally procured kidneys by the point system with regard to several demographic parameters. 2. Of 1,472 waiting patients with sensitization data, 8.5% were broadly sensitized (> 80% PRA). Of the 737 kidneys allocated by the point system, 7% went to broadly sensitized patients, compared with 3% of 438 kidneys allocated by the hospitals (p < 0.001). 3. Of 1,470 waiting patients with information available, 23% were awaiting a repeat transplant. Under the point system, 18% of kidneys were used for repeat transplants compared with 9% of hospital-allocated kidneys (p < 0.001). 4. Of 1,434 waiting patients where the time waiting was available, 26% had waited 1-2 years, 12% 2-3 years, and 6% more than 3 years. Under the point system, patients waiting longer received significantly more kidneys than those recently added to the list: 35% had waited 1-2 years, 21% 2-3 years and 14% more than 3 years (p < 0.001). Kidneys allocated by the hospitals were transplanted to patients in approximately the same proportions as the waiting list: 29% to those waiting 1-2 years, 10% 2-3 years, and 3% more than 3 years. 5. Racial distribution of recipients was not significantly different under either allocation system from that of the waiting list. Whites comprised 39% of waiting patients, the same as the population of Los Angeles County.(ABSTRACT TRUNCATED AT 250 WORDS)


Crossmatch prediction of highly sensitized patients. 1. A subset of negative reactions of sera from highly sensitized patients to donor lymphocytes are predicted with high accuracy (96.5% negative correct). 2. The prediction is performed by a hybrid expert system (HES) which uses multiple knowledge of stochastic (SCORES), artificial neural net (ANN), and genetic algorithm (GA) techniques. 3. All knowledge for the T-cell predictions is derived from serological reactions of the investigated sera (93) to a large panel (284). 4. When analyzing 5 HLA Class I typing sera controls, HES performs better than a standard serum analysis method in 3 measurement categories: r value; percent correct; and percent negative correct. 5. SCORES and ANN produce the strongest complementary association. SCORES is the best method with low PRA sera, while ANN is better at predicting high PRA sera. GA performs very poorly with high PRA sera. 6. HES can acquire knowledge from any of the various methods used for serum screening and crossmatch testing. Therefore, there is no need for method standardization as each laboratory will produce its own program incorporating its patients' data. High standardization of HLA Class I typing is necessary. 7. Most recipients for whom donors are never selected by HES are in the PRA range of 97-100%. 8. Certainty level categorization of a crossmatch gives clinical flexibility in judgement of potential donors. 9. All programs are written in the C language and are portable to numerous platforms. HES is implemented on an inexpensive IBM-PC compatible computer and can calculate predictions quickly. 10. HES predicts negative crossmatches with enough accuracy to initiate an organ sharing protocol to increase the chance for highly sensitized patients to obtain a transplant.


Analysis of United Network for Organ Sharing (UNOS) United States of America (USA) Pancreas Transplant Registry data according to multiple variables. As of 1992, more than 4,200 pancreas transplants were reported to the International Pancreas Transplant Registry. Of these, more than 2,600 were performed in the United States, and of these, more than 2,100 have been transplanted since the inception of the UNOS Registry in October 1987. The analyses here are only of the UNOS data. Pancreas transplants performed in conjunction with a liver (either cluster or noncluster) or a heart were excluded from the analysis, and only those performed as a solitary procedure or in conjunction with a kidney were included. Emphasis was placed on those performed with the bladder drainage (BD) technique (96%). In the overall analysis of BD cadaveric pancreas transplants (n = 1,879), 1-year patient survival and pancreas graft function survival rates were 91% and 71%, respectively, 87% and 66% at 2 years, and 81% and 59% at 3 years. There were no differences according to gender, but 1-year graft survival rates were significantly higher in recipients 45 years or younger (72%) (n = 1,679) than in those older than 45 (64%) (n = 200). There were no significant differences according to graft preservation times of less than 12 (n = 749), 12-24 (n = 940), 24-30 (n = 79), and more than 30 (n = 9) hours, function rates at 1 year being 71%, 72%, 72%, and 44%, respectively. When analyzed according to the 3 major recipient categories (simultaneous pancreas/kidney transplants [SPK] [n = 1604]; pancreas after kidney transplants [PAK] [n = 166]; and pancreas transplants alone [PTA] [n = 109]), patient survival rates were no different (91%, 92%, and 92% at 1 year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (75%, 48%, and 49%, at 1 year, respectively). In the SPK group, kidney graft survival rates at 1 year were 84%. Outcomes were also compared according to whether induction immunotherapy included ALG, OKT3, or neither. In the SPK category, there was no difference among the protocols, with 1-year graft survival rates being 76% in the ALG (n = 838), 76% in the OKT3 (n = 416), and 72% in the Neither (n = 299) group.(ABSTRACT TRUNCATED AT 400 WORDS)


International Cell Exchange: 1992.

International Cell Exchange: 1992. 1. This is a review of 1992 typing of 40 cells for Class I antigens and 18 cultured cell lines for Class II antigens through the International Cell Exchange. Serological typings were compared with DNA typing reports for Class II specificities. Presently, 290 laboratories participate in the monthly Class I exchange. Class II results were received monthly from 166 serology laboratories and from 36 DNA laboratories. 2. In 1992, 11 of the 16 A-locus antigens attained 95% or greater average detection. Nine of the 27 B-locus antigens showed 95% or better mean agreement levels. Antigens such as B46 and B70 continued to show improvement in detection in a 5-year period. 3. We compared discrepancy rates of 7 A-locus and 8 B-locus antigens typed 3 times or more. The rates for the B-locus specificities, especially for percentages of false negatives (ie, how often the antigen assignment was missed), continued to be greater than those for the A-locus antigens. Nevertheless, the discrepancy rates of B35 and B70 decreased dramatically during the last 5 years. 4. We showed the number of laboratories with the total of false negatives and false positives. Nine laboratories achieved perfect records (0 false negatives and false positives) for all analyzed antigens in 1992. 5. Results of retyping of 3 donors over several years were shown to indicate improved antigen detection. 6. Recently recognized HLA-specificities, such as A2403 and B5102, were shown as cell variants studied in previous cell exchanges. Variants of B15, B16, and B40 families were presented, as well as several new A-locus antigens. 7. The low and high rates, in addition to the average detection levels, were indicated for a total of 27 (18 DR and 9 DQ) Class II specificities by serology and by DNA typings. Eight of the 15 DR/DRB1 specificities attained 90% or better average agreement by both serology and DNA. Three of the 9 DQ antigens achieved 90% or better average detection by both methods. 8. Confirmation by DNA typings was demonstrated for 8 Class II specificities with 60% or lower detection levels by serology; the average detection levels by DNA typing was 80% or greater. Confirmation of 2 splits of Class II antigens by DNA typing was shown in 3 cells. 9. The percent detection levels were calculated for 17 DRB1 alleles and 11 DQB1 alleles. Variation in agreement was observed for the Class II alleles. Two DRB1 and 3 DQB1 alleles had average detection levels of 80% or higher.(ABSTRACT TRUNCATED AT 400 WORDS)


Phenotype frequencies of the class II (DR, DQ) DNA alleles by the patterns of sequence-specific primer mixtures (SSPM) in four different populations and the probable haplotypes between DRB1 allele and DQB1 allele. From this study, it is clear that: 1. Most alleles of DRB1, DRB3, DRB4, DRB5, and DQB1 can be identified by 19 combinations of primers. 2. Among a total of 81 alleles, 54 of 64 were contained in the DRB1, B3, B4 and B5 loci, and all 17 DQB1-locus alleles were identified by this method. From this extensive population study and past serological experience, it is clear that: 3. SSPM, which uses only primers, not probes, is another tool that can be utilized to detect polymorphisms or microvariations in DNA sequence within the same locus.


The UNOS OPTN (Organ Procurement and Transplantation Network) waiting list: 1988 through November 30, 1992. Based on data from the OPTN Waiting List and the Scientific Registry between 1988 and 1992: 1. The number of registrations on the overall waiting list increased by 81% between December 31, 1988 and November 30, 1992. On November 30, 1992, there were 29,047 registrations for a transplant in the United States. Organ-specific waiting lists showing strong increases during the period were lung (1,277%), liver (262%), and heart (162%). The number of heart-lung registrants decreased during the period. 2. Overall, Whites comprised the largest percentage of waiting-list registrants, followed by Blacks and Hispanics. This frequency distribution remained relatively constant between 1988 and 1991. On the organ-specific waiting lists, the percentage of Whites ranged from 80% on the liver waiting list to 90% on the pancreas waiting list. Blacks make up about 12% of the United States population, but about 32% of the kidney waiting list, due to the high incidence of end-stage renal disease among Blacks in the United States. 3. The frequency distribution of age on the waiting lists is shifting toward a greater proportion of potential recipients age 45 or older. This trend was especially true for the liver, lung, and pancreas waiting lists. 4. The percentage of highly sensitized registrants (PRA > or = 80%) on the kidney waiting list decreased by 8% between 1988 and 1991. The percentage of registrants with PRA less than 20% increased by 11.3%, probably as a result of longer waiting times for low-PRA registrants. 5. A result of the growth of the waiting lists was an increase in the median waiting time to transplant during the period. This effect was observed on every waiting list except the heart-lung. The wait for a liver transplant was the shortest (67 days in 1991), whereas the wait for a heart-lung transplant was the longest (543 days in 1990). 6. The overall death rate remained relatively stable, but was up slightly in 1991, when 6.1% of registrants died while waiting for a transplant (compared with 5.6% in 1990). The death rate on the heart-lung waiting list fell from 23.5% in 1988 to 14.8% in 1991, probably because of fewer heart-lung registrations. In 1991, the death rates were highest on the thoracic waiting lists (11.7-14.8%), followed by liver (9.3%), kidney (3.7%), and pancreas (3.0%). 7. The percentage of patients in the most urgent medical status categories remained stable on the heart waiting list and has decreased on the liver waiting list.


Current status of lung transplantation--report of the St. Louis International Lung Transplant Registry. There were 1,536 lung transplants reported to the St. Louis International Lung Transplant Registry as of September 1, 1992. The number of centers performing lung transplants increased each year. The 1- and 2-year actuarial survival statistics for all transplants were 68% and 60%, respectively. The most common indication for transplantation was chronic obstructive pulmonary disease, followed by idiopathic pulmonary fibrosis, emphysema secondary to alpha-1 antitrypsin deficiency, and cystic fibrosis. Among the total of 492 deaths reported (34%), sepsis was the leading cause of death.


Report from the International Bone Marrow Transplant Registry. The number of allogeneic BMTs performed worldwide continues to increase. In addition, the characteristics of patients, donors, and selected treatments are changing. In BMT for leukemia during the 1980s there was a marked increase in transplants for early disease, the use of unrelated donors, and utilization of preparative regimens without radiation. Although treatment-related mortality declined during this period, there was only a modest decrease in relapse rates, indicating the need for more effective antileukemia strategies. The IBMTR collects data from many centers, and, as a consequence, it is uniquely suited to examine clinical situations in which patient accrual at a single institution would be insufficient for a study to be performed. In such analyses, BMT was shown to be an effective treatment for Ph1-positive ALL. Patients tended to have earlier relapses and lower probabilities of LFS than Ph1-negative ALL but the differences were not statistically significant. BMT was also shown to be effective in patients with acute leukemia failing to ever go into remission, most of whom would die within the first 6 months following diagnosis. The IBMTR is a premier example of international scientific collaboration. Its success is a consequence of the desire of investigators throughout the world to combine their clinical data for statistical analysis in order to accelerate and improve patient care.


Current status of unrelated-donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study. 1. The International Marrow Unrelated Search and Transplant (IMUST) Study 1 provides novel prognostic data on outcome of unrelated-donor (UD) searches for patients with well-defined clinical characteristics. Case-types analyzed by multifactorial methods reveal the importance of HLA phenotype, ethnic mismatching, and stage of disease at search request, in predicting search outcome. White patients, with common HLA types and early disease, were least likely to suffer search failure. In contrast, searches for non-White patients with unusual HLA phenotypes and advanced disease were most likely to fail. Of importance, 70% of patients had HLA phenotypes defined as uncommon. 2. Overall donor yield at the 2 UK registries between 1989 and 1991 was 7%, significantly below expectations. Reasons for this shortfall are that theoretical predictions did not consider ethnic mismatch and logistical delays incurred by outdated UD search routines and most importantly HLA-typing inaccuracies. 3. IMUST Study 2 is a prospective multicenter-controlled cohort study comparing HLA-identical sibling donor (ID) and UD-bone marrow transplantation (BMT) for factors affecting BMT outcome. Generous support was provided by 83 BMT centers worldwide. An interim analysis of 165 UD- and 368 ID-BMT, with at least 6 months follow-up after BMT, is described. Unifactorial analysis showed a probability of engraftment at day 100 of 89% after UD- compared with 98% after ID-BMT (p < 0.001). Probability of Grades II-IV acute graft-versus-host disease (AGvHD) at 100 days was 52% after UD- compared with 42% after ID-BMT (p < 0.01). Probability of overall survival at day 400 was 42% after UD- compared with 63% after ID-BMT (p < 0.001). Survival on day 400 of those patients receiving UD-BMT for early disease was encouraging at 52%. 4. Multifactorial analysis was performed on combined data from UD- and ID-BMT cohorts to identify various factors predicting engraftment, AGvHD, and overall survival. Survival after UD-BMT was increased by center experience of UD-BMT and the use of additional pretransplant immunosuppression. Survival was decreased in UD- compared with ID-BMT, by female donor to male recipient and poor-risk disease. Engraftment was improved in ID- compared with UD-BMT, and after UD-BMT at centers experienced in UD-BMT. Engraftment worsened with the use of ex-vivo T-cell depletion for GvHD prophylaxis, in chronic myeloid leukemia, and in male recipients of female marrow.(ABSTRACT TRUNCATED AT 400 WORDS)


Oral infection as a reason for febrile episodes in lymphoma patients receiving cytostatic drugs. 56 patients receiving chemotherapy for non-Hodgkin lymphoma or Hodgkin's disease with curative intent were monitored for up to one year after initiation of treatment. During chemotherapy (mean duration 5.2 months), 26 of the patients (46%) suffered from 38 febrile episodes. In only 16 instances was an extraoral cause for the septicaemia found. However, severe dental infection, reflected in an elevated radiological index for the jaws, was found more frequently in patients suffering febrile episodes than in those without (P = 0.02). Moderate to severe gingival inflammation was observed during 22 (58%) of episodes. During 71% of the episodes various pathological findings were also recorded in the oral mucosa. No source of infection other than an oral one was found in 42% of the patients. Our results emphasise the importance of oral foci as the possible infection source in patients receiving intensive chemotherapy.


Comparison of oral squamous cell carcinoma in younger and older patients in India. This study examines the demographic, aetiological and clinico-pathological features of 37 patients with oral squamous cell carcinoma (SCC) who were less than 35 years old and a comparable number of patients who were greater than 60 years old. The study was undertaken at the Regional Cancer Centre, Trivandrum, India, between 1988 and 1990. In patients younger than 35 years old, oral SCC occurred more commonly in females, was apparent in all social classes and was associated with fewer aetiological factors. The tumours manifested predominantly as invasive lesions affecting the tongue and there was early spread to lymph nodes. By contrast, in patients older than 60 years of age, oral SCC was more common in males, occurred more frequently in social classes III and IV and was always seen in association with smoking, alcohol or pan chewing. These latter tumours presented as exophytic lesions of the buccal mucosa or gingivae and spread late to lymph nodes. The results indicate that the biological behaviour of oral SCC in young patients may be distinct from that occurring in older patients.


Progressive 13-cis-retinoic acid dosage in the treatment of oral leukoplakia. 16 patients with oral leukoplakia were treated with oral 13-cis-retinoic acid. The initial dose, given for 3 months, was 0.2 mg/kg/day, increasing by a further 0.2 mg/kg/day in successive 3 month cycles. The maximum dosage reached at 1.0 mg/kg/day, was given to only 2 patients (who received a total of 15 months treatment). However, 10 patients completed the cycle at 0.8 mg/kg/day (12 months treatment in total), but treatment could not continue due to toxicity (grade I and II), which was cutaneous, mucosal, and haematological (hypertriglyceridemia and hypercholesterolemia). There was grade III toxicity in the skin and mucosa in only 1 case, a patient treated at a dose of 1.0 mg/kg/day. The toxicity was reversible in all cases. 14 of the patients completed the trial. In 4 there were improvements graded as partial responses (PR) obtained at 0.2 mg/kg/day (3PR) and 0.6 (1PR) and there was one complete response (CR) obtained at 0.4 mg/kg/day. Overall there was thus an objective response rate of 36% who showed 50% or more reduction in lesion size. After the retinoic acid treatment was stopped, patients were followed-up for 12 months; 2 patients showed regression of the responses obtained after 6 and 9 months. This study shows that oral treatment with 13-cis-retinoic acid at low dosages is efficacious and with minimal toxicity. It also shows that it is not feasible to treat these patients at doses above 0.8 mg/kg/day for long periods--mainly due to poor compliance.


The prognostic value of cytometric DNA analysis in early stage tongue cancer. In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies.


Amplification and overexpression of epidermal growth factor receptor gene in human oropharyngeal cancer. The presence of epidermal growth factor receptor (EGF-R) gene was determined in 84 patients with squamous cell carcinoma (SCC) of the oropharyngeal region--a highly prevalent, chewing-tobacco associated malignancy in India, using Southern hybridisation analysis of DNA extracted from primary tumor tissues. We observed a 3- to 8-fold amplification of EGF-R gene in 19/66 (29%) of the SCCs of the oral cavity, and about 30-fold EGF-R amplification in 2/18 (11%) hypopharyngeal cancers. Dot blot analysis of total RNA from several tumour tissues, revealed overexpression of the EGF-R gene in the examined patients, with the EGF-R gene amplified. 4 patients with single copy EGF-R gene, did not exhibit overexpression of the gene. Within our sample set, no correlation was evident between EGF-R gene amplification and clinico-pathological parameters of the malignancy. The amplification and overexpression of the EGF-R gene observed in the primary tumour tissues of 25% (21/84) of the human oropharyngeal cancers, indicate possible involvement of the gene in the pathogenesis of these cancers.


Amalgam fillings, diagnostic dental x-rays and tumours of the brain and meninges. A population-based case-control study of incident brain tumours in adults in Adelaide, South Australia considered possible associations of exposures to amalgam fillings and diagnostic dental X-rays with subsequent development of glioma and meningioma. The study, conducted in 1987-1990, recorded data from 110 subjects with glioma, 60 with meningioma and 417 controls. Principal findings were unexplained decreased risks for glioma associated with both exposure to amalgam fillings (age- and sex adjusted relative risk = 0.47, 95% confidence interval: 0.25-0.91; P = 0.02) and to diagnostic dental X-rays (adjusted relative risk = 0.42; 95% confidence interval: 0.24-0.76; P = 0.004), and a possible increased risk for meningioma in males exposed to dental X-rays. The choice of the unexposed comparison group is important in determining if an increased risk is associated with panoramic or full-mouth X-rays in glioma.


Prevention of local relapses and new localisations of oral leukoplakias with the synthetic retinoid fenretinide (4-HPR). Preliminary results. This paper analyses preliminary results of a randomised chemoprevention trial in patients surgically treated for oral leukoplakia started in 1988 at the Istituto Nazionale Tumori of Milan with the synthetic retinoid N-(4-hydroxyphenyl)-retinamide (4-HPR). To date 115 patients have been randomised, after surgical excision of oral leukoplakia, to receive 200 mg 4-HPR daily for 52 weeks versus no intervention. 80 patients completed the 1-year intervention, 41 in the control group and 39 in the 4-HPR group. During this period 12 local relapses or new lesions occurred in the control group and three in the 4-HPR group. Only 5 patients interrupted the intervention because of toxicity. No impaired dark adaptation was observed. It is concluded that 4-HPR is well tolerated and seems efficacious in preventing relapses and new localisations during the treatment period. This promising trend needs further confirmation.


Fitting accuracy of indirect restorations: a review of methods of assessment. The current interest in indirectly manufactured, tooth-coloured restorations has highlighted a need to identify factors pertinent to the success of both these and other indirect restorations. Although restoration longevity is limited by the degree of adaptation to the prepared tooth, there exists no standard method for either the assessment of marginal adaptation or the overall accuracy of fit. This review examines methods of assessment of both of these important parameters, and considers the problems associated with existing in vivo and in vitro techniques.


Attachment and orientation of human periodontal ligament fibroblasts to lipopolysaccharide-coated and pathologically altered cementum in vitro. Previous studies have suggested that bacterial lipopolysaccharides (LPS) may inhibit fibroblast attachment to root surfaces affected by periodontal disease. This study was carried out to investigate the effects of pathologically altered cementum and cementum coated with LPS on the attachment and orientation of periodontal ligament fibroblasts in vitro. LPS caused a maximum reduction of cell orientation of 26% after 5 days' culture compared with controls. However cells did not become attached and orientated to pathologically altered root surfaces. It was concluded that as yet unidentified factors other than LPS may have greater significance when considering optimal methods for the preparation of root surfaces for new attachment procedures.


Mandibular guidance prostheses following resection procedures: three case reports. Unilateral loss of mandibular continuity creates problems in prosthetic reconstruction. For dentate patients, palatal guide ramps or mandibular guide flange prostheses are indicated. Edentulous patients are much more difficult to retrain in mandibular movements, but complete dentures designed with stabilising occlusal contacts can be successful in compensating for the deviation. Three case reports are presented.


Early in vitro marginal microleakage associated with different lining materials under Class II amalgam restorations. The aim of this study was to determine which dental cavity lining material exhibited least microleakage when used under amalgam. Extracted premolar teeth, prepared with Class II cavities, had one of three lining materials (cavity varnish, zinc oxide-eugenol or light-cured glass-ionomer) placed. Following restoration the teeth were immersed in eosin and sectioned. Sections were subjected to image analysis measuring the linear leakage and area of spread into coronal dentine. Percentages in relation to restoration length and the area of crown dentine were calculated. Light-cured glass-ionomer cement liner significantly (P < 0.05) reduced all aspects of the microleakage parameters studied.


Dental stone and improved dental stone surface hardness: the effect of the addition of potassium salts. Changes in dental stone and improved dental stone surface hardness observed when prepared with aqueous solutions of potassium salts (K2SO4, KCl, KF, KBr, KNO4, KMnO4, K2Cr2O7) in concentrations of 0.5-5.0% were investigated. Parallel studies were carried out on dental stone and improved dental stone prepared with distilled water and crystallised in contact with alginate impression material, previously immersed in the above solutions for 2 minutes. Vicker's hardness tests were performed 3 hours and 24 hours after the initial set. The surface hardness of dental stone and improved dental stone is increased significantly by either method. The most effective hardening solution is potassium sulphate in concentrations of 0.5-5.0%. The degree of increase in surface hardness is directly proportional to the concentration of the solutions and proportionately greater at a shorter time (3 hours after the initial set).


A comparative study of the attitude of dental students towards the elderly. The aim of this study was to assess the attitudes of dental students towards the elderly in the two dental schools in Israel. The study population comprised 180 dental students currently enrolled in the two dental schools in Israel. The response rate was 59% and 92% for the students in Tel Aviv and Hebrew University respectively. The self-administered questionnaire measured attitudes using the Rosencranz and McNevin Aging Semantic Differential Scales. Students' attitudes were observed to be more or less neutral. No differences of significance were observed between the students of the two schools. Social contact with and experience in treating the elderly did not seem to change students' attitudes and their desire to work with elderly patients in the future. Further development of the curriculum should be implemented in order to try to change students' attitudes towards the elderly from neutral to positive for the benefit of the provider and society.


Dental needs of residents and carers in elderly peoples' homes and carers' attitudes to oral health. The dental needs of elderly people in residential homes and of their carers were investigated. Also, the carers' attitudes to oral health for themselves and the elderly residents were explored. Professionally diagnosed or normative need was greater than lay persons' perceived need in both groups. Overall, carers' attitudes towards their own and the residents' oral health were positive. However, carers had experienced a lack of formal training opportunities for mouth care and 93% requested education in oral hygiene procedures. It is recommended that the dental team develops and provides oral care programmes which will enable carers to provide routine hygiene support for the residents.


[The contractile properties of the frog muscle fiber in the intact and the skinned states]. The comparison of force-velocity (p-V) relation was made for live and chemically skinned frog skeletal muscle fibers. The latter fibers revealed steeper p-V curves. Maximal isometric tension in these fibers was 27 per cent less. The maximal velocity of unloaded shortening was 15 per cent greater.


[The contractile activity of the lymphatic microvessels and the role of opioid peptides in its regulation]. The lymphatic microvessels of the rat mesentery do not contract rhythmically. Adrenaline and naloxone modulate the lymph-activating effect of opioid peptides (leu-enkephalin and dalargin).


[The characteristics of the bile-secreting function of the liver and its regulatory mechanisms in ruminants]. The function of gall secretion and the latter's composition were found to be regulated by the hypothalamic nuclei, amygdala and hippocampus in goats. The liver function was studied in starvation, feeding and repletion.


[The temperature changes in different organs during immersion hypothermia]. Precise thermometry of the brain, liver, rectum, muscles and skin surface was performed in white rats in conditions of immersion of the body in water with the temperature 1 degree C. Breathing arrested within 15-18 min after immersion, their brain temperature being 16.7-18.2 degrees C, liver temperature 12.7-15.2 degrees C, rectum--10.4-15.5 degrees C, muscle 8.3-12.0 degrees C, skin surface--1.6-5.0 degrees C.


[Oxygen transport and gas exchange in rats under immersion hypothermia]. Changes of the oxygen consumption and the main parameters of the blood respiratory function as well as oxygen transport, were studied in Wistar rats under conditions of immersion hypothermia (with rectal temperature 15-13 degrees C). From the viewpoint of the oxygen exchange, the rectal temperature 20 degrees C was found to be the critical level of the hypothermia.


[Changes in the water-salt composition of alveolar and ductal milk in the white mouse when accumulated in the mammary gland]. The ion and water contents revealed a 25-41% lower Na level in the duct than in alveolar secret in lactating albino mice through 1 to 7 and 24th hour of suckling. The data obtained suggests dynamic properties of alveolar and duct epithelium in mice.


[The biological mechanisms of a congenital predisposition to alcoholism]. In descendants of white rats with chronic alcoholic intoxication, the contents of DA in the brain and blood plasma, characteristics of GABA and opiate brain receptors, the contents of cAMP and other substances were studied as well as the c-fos gene expression. The data obtained suggest a considerable role of the changes in the DA system functions in the genesis of pathology in these descendants.


[The uncoupling of the functioning of the force generation and ATP hydrolysis centers in the myocardial myofibrils in experimental informational disease]. Active and rigor force generation under the effect of electrostatic charge, the temperature and pCa, was significantly decreased in informational experimental disease. Other significant changes on the molecular level occurred in cardiomyocyte contractile apparatus in conditions of experimental informational disease.


[An improvement in the cognitive characteristics of monkeys induced by an antioxidant: the neurophysiological correlates in the visual cortex]. Administration of oximetacyl considerably improved the cognitive characteristics of the processes of delayed visual recognition, increased auto- and cross-correlation coefficients in the responses of groups of neurons. The data obtained suggests nootropic properties of oximetacyl and participation of visual cortex of the monkey brain in realisation of these properties for improvement of the cognitive characteristics.


Advances in nutritional care of medical-surgical patients. Malnutrition and its related complications occur at an alarming rate in medical-surgical patients. New technology and other advances in clinical nutrition can now significantly enhance the nutritional care that medical-surgical nurses provide to their patients.


Standards of clinical nursing practice: a link to quality of care. The impact of nursing care on client outcomes must be visible if nursing is to obtain its share of the health care dollar. The first step in substantiating nursing's input on health care is to describe the responsibilities for which nurses are accountable. The ANA Standards of Clinical Nursing Practice (1991a) identify those responsibilities, setting the stage for implementing practice guidelines.


Effectiveness of glove barriers used in clinical settings. Gloves are the most common barrier used to prevent the transmission of microorganisms between patients and nurses, and clinicians should be familiar with factors that affect glove choice, including the type of unit, exposure to bloodborne pathogens, tasks performed, and personal safety. In addition to selecting the proper gloves for clinical practice, nurses can play an important role in the evaluation, quality control, and development of new effective barriers for hand protection.


A nursing perspective on advance directives. The nurse's role in implementing the Patient Self-Determination Act is often unclear. This article describes the clinical use of advance directives, discusses related ethical concepts, and identifies methods nurses could use for initiating discussions about advance directives.


Clinical scholarship: publishing clinical excellence. Clinical scholarship is an important professional responsibility for clinically excellent nurses. Nurses with publication goals should develop publishable ideas for a target journal, adhere to the basics of good writing, consider the special requirements of clinical journals, and address issues of authorship and professional goals.


Implementing nurse case management in a community hospital. A nursing case management system was implemented on the medical-surgical unit of an 86-bed community hospital using a four-phase process. The development and implementation processes are described. Program evaluation indicated that the application of the model resulted in benefits for patients, care providers, and the institution.


[Effect of insulin therapy on abnormal bone and mineral metabolism in chronic streptozotocin-induced diabetic rat]. By use of histomorphometry and photon and physical, calcium homeostasis, bone morphology, bone mass and bone growth were studied in freely fed control, streptozotocin-induced diabetic, long-term and short-term insulin treated diabetic rats 14 weeks after the induction of diabetes. We conclude that untreated chronic streptozotocin-induced diabetic rat could result in abnormal bone and mineral metabolism, which is characterized by hypercalciuria, hyperphosphaturia and hyperphosphatemia, significant bone loss and growth arrest. The extent of bone loss correlated with the duration of the disease process. The anatomical basis of bone mass reduction is the diminution of osteoblasts activity which results in reduction of bone formation and insufficient bone calcification and relative increment of osteoclasts activity. Thus, bone resorption overweight bone formation leading to a negative balance of bone remodeling. The effect of PTH and CT on bone changes in diabetic rats can't be affirmed in our experiments. It is probable that metabolic disorder and/or insulin deficiency has a direct effect on bone changes. Insulin therapy started earlier in the course can prevent and somewhat later can completely normalize the altered skeletal morphology of diabetic rats. Whether this result is due to direct effect of insulin on skeletal tissue or through the correction of metabolic disorder remains to be resolved.


[The relationship between plasma atrial natriuretic peptide (ANP) and glomerular ANP receptors in 5/6 nephrectomized rats]. Chronic renal failure was induced in male Wistar rats with 5/6 nephrectomy (group I) and sham-operation was carried in the controls (group II). The results showed that in group I, plasma ANP levels increased progressively as Scr elevated. The plasma levels of renin and angiotensin raised simultaneously as compared with the controls (P < 0.001). At the 20th week after operation, urine volume and Na decreased significantly (P < 0.05) and the number of glomerular ANP receptors decreased significantly at the 12th week (P < 0.05) and 20th week (P < 0.01). Our data suggest that in 5/6 nephrectomized rats: 1. The elevation of plasma ANP level might be partly caused by damage of glomerular receptors. 2. The elevated plasma ANP could not cause its diuretic, natriuretic, blood pressure depression and R-A inhibition effect due to the damage of kidney ANP receptors.


[Metabolism of serum lipoprotein in hypothyroidism]. The changes of serum lipids concentrations in 15 patients with primary hypothyroidism were studied. 9 euthyroid persons in the similar age group with patients were selected as a control group. The serum levels of total and LDL cholesterol, TG, ApoAI, ApoB and ApoCII in patients before treatment were all higher than those of the control group. They decreased to normal level after treatment. The mean values of total cholesterol decreased from 6.7 mmol/L to 4.1 mmol/L, TG decreased from 2.5 mmol/L to 1.0 mmol/L, LDI-ch from 3.9 mmol/L to 2.4 mmol/L, ApoAI from 1.9 g/L, to 1.3g/L, ApoB from 1.2 g/L to 0.7 g/L and ApoCII decreased from 6.9 mg/dl to 3.9 mg/dl. There were no differences of HDI-ch level between patients before treatment and normal controls, HDI-ch level of patients only slightly decreased after treatment. Soon after the thyroid hormone treatment, all parameters of serum lipids, not including HDI-ch, were improved, as TT, level became normal, although the levels of TT4 was still not reached to normal level.


[Factors influencing carboxyhemoglobin kinetics in inhalation lung injury]. Anesthetized dogs were ventilated with 1% carbon monoxide (CO) in air for 10 minutes to produce CO poisoning and then with room air (n = 5) or pure oxygen (n = 5) for 3 hours as control. Acute lung injury was produced by intratracheal injection of 0.1 N HCl (2 ml/kg) 30 minutes before CO poisoning in another 10 experimental dogs. Arterial blood gas and carboxyhemoglobin (COHb) were monitored before and after CO poisoning. Pharmacokinetic analysis was used to find the half-time of COHb elimination (T 1/2 beta). Pulmonary shunt was measured before CO poisoning in the injured dogs. Half-time of COHb elimination was prolonged in the injured dogs resuscitated with air as compared with dogs in the control group (275% +/- 28 vs. 203 +/- 24 min., P < 0.05); Oxygen accelerated COHb excretion in both injured and control animals. No significant correlation was found between T 1/2 beta and Qs/Qt in the injured dogs ventilated with air or oxygen. A negative linear relationship was found between T 1/2 beta of COHb elimination and the pre-CO-poisoning PaO2 (r = -0.98, P < 0.005) in the injured dogs treated with oxygen. The data suggest that hypoxemia may represent the underlying mechanism of altered COHb kinetics in acute inhalation lung injury.


[Reaction of serum growth hormone in patients with endemic cretinism to arginine and clonidine in continuous excitement tests]. Reaction of serum growth hormone in cretins whose pituitary and thyroid function have returned to normal in IDD-control by using iodized salt to arginine and clonidine in continuous excitement tests ws observed. The result is that during the phase of clonidine excitement, serum growth hormone in cretins was obviously lower than that in normal controls and the reaction peak value, maximum increase value and reaction time all markedly lower than those of the normal controls. 3 cases (18.8%) had no excitement reaction during the phase of arginine excitement, 8 cases (50.0%) no reaction during the phase of clonidine excitement and 2 cases (12.5%) no reaction in the entire process of continuous tests. The results indicate that patients with cretinism suffer from low reserve function of pituitary growth hormone and insufficiency of synthesis even after ther thyroid function has returned to normal.


[Endoscopic injection sclerotherapy for esophageal varices: studies on methodology and complication]. From November 1985 to February 1991, sixty patients were randomized to three groups of intravariceal sclerotherapy: (1) many punctures of low quantity sclerosant, (2) one puncture of large quantity sclerosant, and (3) one puncture of large quantity sclerosant with transendoscopic balloon. The early effects and complications were investigated. Varices eradication was reached 91.2% in group 1, significantly higher than group 2 (58.3%) (P < 0.05), similar to group 3(89.9%). However, balloon group (group 3) required shorter duration than group 1 (12.6 vs. 21.7 days) (P < 0.05). There were no significant differences in complications, but all 6 esophageal stenosis were in group 1, recurrent bleeding was 11.4% in group 1.35.7% in group 2 and 0 in group 3 during sclerotherapy sessions. Further more, we found though attempted to inject into variceal veins, accurate intravariceal injection reached only 46.8% in accordance with venographic findings. We conclude that sclerotherapy with transendoscopic balloon seems to be more simple, safer, and required short time to produce successful variceal sclerosis.


[Factors predicting mortality in idiopathic dilated cardiomyopathy]. A study of factors predicting mortality was performed in 69 patients with idiopathic dilated cardiomyopathy by analyzing 14 parameters according to clinical, electrocardiographic and echocardiographic findings. On admission 64% of the patients were in NYHA functional class 3 or 4. During a mean follow-up period of 18 months 43 patients died; 31 of refractory heart failure and 12 suddenly. 1 year survival was 58%. Multivariate analysis (Cox model) revealed that the independent predictors for mortality due to refractory heart failure were left ventricular enddiastolic diameter, NYHA functional class and systolic blood pressure; the presence of tricuspid regurgitation predicted mortality due to sudden death.


[Allergen-stimulated release of prostaglandin E, F2 alpha by alveolar macrophages from patients with allergic asthma]. Bronchoalveolar lavage (BAL) was performed in healthy subjects (n = 12) and patients with bronchial asthma (n = 11). Between the two groups there was no significant difference in the total number of cells and the percentage of alveolar macrophages (AM), lymphocytes (L), neutrophils (N) and eosinophils (E) in BAL fluids. When AM were cultured in vitro and stimulated with dermatophagoides farinae (DPF) antigen, the amount of PGE released by AM was significantly increased in the asthmatics. When the asthmatics, AM were sensitized with specific IgE positive serum and stimulated with DPF, they released more PGE and PGF2 alpha than those when specific IgE negative serum was used (P < 0.01). The PGE/PGF2 alpha ratio was significantly decreased. There was positive correlation between the decreased value of PGE/PGF2 alpha and patients, MCH-PC20. The increase in the amount of PGE and PGF2 alpha released and the decrease of PGE/PGF2 alpha ratio might play an important role in the pathogenesis of allergic asthma.


[Immunoenzymatic labeling of monoclonal antibodies for surface antigens of T-cells using immune complexes of APAAP in patients with interstitial lung disease]. The use of unlabeled antibody bridging technique with alkaline phosphatase monoclonal anti-alkaline phosphatase (APAAP) complexes makes it possible to solve the problem of short durability of immunofluorescent staining and the problem of nonspecific endogenous enzyme interference of blood cells with immunoperoxidase method. The technique of APAAP allows satisfactorily to demonstrate the cytoplasmic and surface membrane antigens of T-cells both in peripheral blood and bronchoalveolar lavage fluid (BALF). With the technique studied, the subsets of T-lymphocytes simultaneously in both peripheral blood and BALF of 26 patients with interstitial lung disease and of 16 apparently healthy subjects. The results showed: (1) In patients with interstitial pulmonary fibrosis (IPF) CD8 cells in BALF were higher in number than those in peripheral blood and BALF of normal subjects (P < 0.01). It is suggested that abnormalities of T-Lymphocytes might also play a role in the pathogenesis of IPF. (2) CD4 cells in BALF of patients with sarcoidosis were significantly higher in number than those in other groups (P < 0.01). However, CD8 cells in BALF of patients with sarcoidosis were lower in number than those in others (P < 0.01). The higher ratio of CD4/CD8 was found in sarcoidosis patients during active stage. The findings suggested that change of the ratio of CD4/CD8, as an immunoregulatory abnormalities in lung, could be regarded as one of parameters in assessing the activity in patients with sarcoidosis.


[The use of thoracoscopy in the diagnosis and treatment of chest diseases]. The procedure and results of thoracoscopy by using a fiberoptic bronchoscope and rigid cold-light thoracoscope in 76 cases with chest diseases of unknown causes were reported. The positive diagnostic rate was 89.5% (68/76). The histologic diagnosis following thoracoscopic biopsy in 65 patients was compared with the findings at follow-up, the results showed the sensitivity being 87.7%, specificity 100% and diagnostic accuracy 89.2%. 3 cases with persistent or recurrent spontaneous pneumothorax were cured by Nd-YAG laser transendoscopically. 5 patients with malignant pleural effusion were treated with intrapleural talcum powder under thoracoscopic control, 4 of them obtained complete pleurodesis. There were only minor complications: transient fever in 40 cases and local subcutaneous emphysema in 7. It was concluded that thoracoscopy is simple, safe, reliable and practical in the diagnosis and treatment of chest diseases. It should be popularized clinically.


[Dynamic changes in the platelet granule membrane glycoprotein level in patients with acute myocardial infarction]. Platelet granule membrane glycoprotein (GMP-140) level was measured by using 125I labelled monoclonal antibody (SZ-51) in 20 patients with acute myocardial infarction in the first three days and at the first three weekends. The correlation of severe arrhythmia and administration of aspirin with platelet GMP-140 in AMI were studied respectively. It is shown that platelet GMP-140 increased significantly in the first three days after AMI, then it dropped quickly, but remained at high level as compared with the controlled group till the third weekend (P < 0.01). Platelet GMP-140 level was higher in the first three days than at the first three weekends (P < 0.01). The changes of platelet GMP-140 have not been shown to be related with severe arrhythmia or administration of aspirin (P > 0.05). The results indicated that the platelets in AMI are activated continuously in the first three weeks after infarction; it might be thought as an important index of coronary artery thrombus formation.