Twenty-year follow-up on the effect of HLA matching on kidney transplant survival and prediction of future twenty-year survival

The difficulty in achieving long-term survival is demonstrated by the fact that an improvement of 30 percentage points in 1-year cadaver donor survival resulted in only a 10-percentage point improvement over 20 years. In early transplants from 1965 to 1974, the 20-year survival rate of HLA identical siblings was 46%, of parental donors 27%, and of cadaver donors 12%. More recent grafts, performed since 1987, had a projected survival of 57% for identical donors, 30% for parental donors, and 18% for cadaver donors. With respect to HLA matching for cadaver donor kidney transplants, a 0 AB-antigen mismatch produced higher graft survival than did mismatched transplants during the 20-year period from 1965 to 1984. After the introduction of HLA Class II typing in 1980 and general improvements in typing for transplants performed after 1987, the 0 ABDR-mismatched grafts have a projected 20-year survival of 40%. The projected survival rates for transplants with one or more mismatches fall progressively to 13% for transplants that have 6 ABDR mismatches. Thus, the success due to HLA matching has improved ever since the introduction of cyclosporine because of the concurrent improvements in tissue typing for Class I and Class II specificities.     

The importance of the HLA complex antigens in systemic rheumatoid diseases

The submitted paper reviews contemporary knowledge on the clinical impact of assessment of HLA-complex antigens in systemic rheumatic diseases. The authors explain the term "relative risk" and its practical importance. As to antigens of the HLA-complex class I, attention was paid in particular to the importance of HLA B 27 in ankylosing spondylitis, other spondylarthropathies and reactive arthritis; in this part the review is supplemented by results of the authors' own research. As to antigens of the HLA-complex class II, attention was paid to the sub-area DR in rheumatoid arthritis and other diffuse affections of connective tissue. The advance in knowledge of the clinical impact of investigations of selected HLA-complex antigens in systemic rheumatic diseases is that in many instances it reveals an association not only at the level of the nosological unit but frequently also sub-unit with prognostically important clinical and biochemical manifestations, a typical autoantibody profile and sometimes also with the risk of a greater organ toxicity of drugs.     

The effect of hydralazine on the development of tolerance to continuous nitroglycerin

It has been reported that nitroglycerin (GTN) tolerance can be prevented by the concurrent administration of hydralazine. Although the mechanism of this effect remains unknown, it is possible that hydralazine modifies counter-regulatory responses to nitrate administration. To address this question, we examined the impact of hydralazine therapy on the development of tolerance during sustained therapy with GTN. Twenty normal volunteers and 18 patients with chronic heart failure (mean ejection fraction 30 +/- 2%) were treated for 1 week with hydralazine or placebo in a randomized double-blind fashion. Hydralazine therapy (or placebo) was continued, and subjects then received continuous transdermal GTN for 5 to 7 days. On the first and last day of transdermal GTN therapy, standing HR, systolic blood pressure and hematocrit responses were assessed. HR and blood pressure responses to sublingual GTN (0.6 mg) were also evaluated before and during sustained transdermal GTN therapy. Significant loss of the hemodynamic effects of transdermal GTN occurred during sustained therapy in both the normal volunteer and heart failure groups. Hydralazine had no effect on the development of tolerance to the hemodynamic effect of GTN in either group. In both, transdermal GTN therapy was associated with a significant fall in hematocrit that persisted for the entire treatment period. Hydralazine had no effect on this response. These data suggest that hydralazine therapy does not prevent loss of systemic arterial effects or prevent plasma volume expansion during sustained transdermal GTN therapy.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

The role of HLA antigens in predicting the active course of multiple myeloma

AIM: Detection of associations between carrying some HLA-antigens class I in patients with multiple myeloma (MM) and activity of the malignant process. MATERIALS AND METHODS: 76 MM patients received polychemotherapy. Its efficacy was assessed after one, three, six and twelve courses by reduced blood and/or urine levels of monoclonal protein, signs of bone healing, reestablishment of normal number of plasma cells in the bone marrow. Identification of HLA-antigens was made in two-stage lymphocytotoxic complement-mediated test using the standard panel of the anti-HLA sera. Data on HLA-typing of 865 blood donors served control. The findings were statistically processed. RESULTS: All the patients were divided into 3 groups: with indolent (n = 18), active (n = 25) and aggressive (n = 37) MM course. In patients with aggressive MM course high chi-square values were estimated for three HLA specificities: HLA-B13, HLA-B40, HLA-B5. Only HLA-B13 proved significant. No significant differences in carrying HLA-antigens were revealed for patients with active MM course. CONCLUSION: The survival of MM patients depends on the degree of the malignant process activity. Patients with aggressive MM course significantly more frequently carry HLA-B13, therefore it can be considered a genetic marker of MM. Its detection can serve a criterion for determination of adequate polychemotherapy.     

Effect of length of gestation on maternal cellular immunity to human trophoblast antigens

Maternal lymphocyte reactivity to human trophoblast antigens was studied in placentas of gestational ages 8 to 14 weeks and 32 to 34 weeks, respectively. Significant trophoblast lysis became apparent after 24 hours' incubation in the latter case compared with a time lag of 72 hours in the terminated gestations. Maternal cellular immunity, therefore, was not detected during the first 3 1/2 months of pregnancy, but was detectable by the time of parturition. The possible significance is discussed with respect to the antigenic stimulus and survival of the fetal allograft.     

The effect of an implantable Doppler probe on the salvage of microvascular tissue transplants

One hundred forty-seven flaps in 135 consecutive patients undergoing microvascular transplantation were monitored using a miniature Doppler ultrasonic probe. Using a modification of a technique described previously by Swartz, the probes were secured to the outflow vein of the flap with Vicryl mesh. Twenty instances of thrombosis or spasm were detected in 16 patients, and all flaps were salvaged (100 percent). There were four false positive and no false negative results. This probe allows for safe, continuous monitoring of flap blood flow, which permits the rapid detection and hence rapid treatment of postoperative complications. Our experience suggests that a significant improvement in the salvage rate of microvascular transplants may be attainable with the use of this device.     

An evaluation of vesical urodynamics before renal transplantation and its effect on renal allograft function and survival

This prospective study investigated the urodynamics of the urinary bladder prior to renal transplantation in 57 patients and related this to graft function and transplantation outcome. The study demonstrated a clear deterioration in the pretransplant urodynamic characteristics in all subgroups, with male patients in the hemodialysis group (HD) showing a more substantial decline: 1st sensation volume (ml) in male HD patients = 112 (120) vs. 171 (173) in male CAPD patients, P < 0.05; and corresponding average flow rate for same groups 3 (3) ml/sec vs. 5 (5) ml/sec, P < 0.05. Figures are median (interquartile range). We have identified a subgroup of patients with a small bladder capacity (less than 100 ml) who have a reduced graft survival (55% vs. 92% for bladders larger than 100 ml at 2 years) apparently unrelated to immunological processes.     

The effect of maternal obesity on the accuracy of fetal weight estimation

OBJECTIVE: To determine if maternal obesity affects the accuracy of either clinical or sonographic fetal weight estimations. METHODS: In a year-long study, 998 singleton pregnancies of 26-43 weeks' gestation underwent both clinical (Leopold) and sonographic (Shepard and Hadlock) fetal weight estimation within 5 days of delivery (mean 1.1, 95% confidence interval 1.0-1.3). Patients were stratified into four different groups based on increasing maternal body mass index (BMI): underweight (less than 19.8), normal weight (19.8-26.0), overweight (26.1-29.0), and obese (more than 29.0). The various estimations of fetal weight were compared with actual birth weight, and the mean absolute percent error was calculated for each specific method and analyzed among the four BMI groups. RESULTS: For each method of weight estimation, there was no difference (specifically, no increase) in the magnitude of the absolute percent error with increasing maternal obesity. Regardless of maternal size, almost half of the weight predictions were within 5% of the actual birth weight. CONCLUSION: Increasing maternal obesity does not alter or decrease the accuracy of either clinical or sonographic fetal weight estimations. Therefore, fetal weight predictions provide equally accurate and valid guidelines for determining management decisions in women, regardless of body size.     

The effect of HLA alleles on response to interferon therapy in patients with chronic hepatitis C

The objective of this study was to determine the degree of leukocyte activation, as measured by cytokine release, in circulating blood during experimental extracorporeal circulation. Complete in vitro extracorporeal membrane oxygenation (ECMO) circuits were used, and 9 experiments were performed. Whole blood stored at 37 degrees C was used as the control. Blood samples were withdrawn before the start of perfusion and at 24 h of perfusion. Statistically significant releases of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist were observed in the perfusion circuits compared to both the control blood and baseline values. Also, increases in plasma tumor necrosis factor (TNF)alpha and IL-6 were seen after 24 h of perfusion although these changes did not reach statistical significance. These results indicate that extracorporeal circulation induced leukocyte activation and cytokine release. These reactions might, as an additional trauma, deteriorate the situation in an already severely ill patient. A search for methods to counteract this untoward activation seems warranted.     

Molecular and immunologic aspects of the nonclassical HLA class I antigen HLA-G: evidence for an important role in the maternal tolerance of the fetal allograft

To support collaborative engineering, it is important not only to share information, but also to manage that information in a manner that actively promotes integration. This paper describes the central models underlying the COMMIT (construction modeling and methodologies for intelligent integration of information) project, which is defining mechanisms to handle a number of issues relating to the management of information to support decision-making in collaborative projects. Examples are given to illustrate the implementation of the COMMIT information management concepts. The project is being carried out in consultation with a well-established steering group comprising standardization bodies, industries, and researchers. The COMMIT project is supported by the Engineering and Physical Sciences Research Council, United Kingdom.     

The replacement of the fantasied oedipal child: A disruptive effect of sibling loss on the mother-infant relationship.

Presents the case of a 30-yr-old woman whose sibling had died during adolescence and who experienced her own child, almost 2 decades later, as a replacement for the lost sibling. This process was facilitated by the oedipal meaning of her sibling and by the interference in her family's ability to mourn the death of the child. The case illustrates the manner in which these conflicts were activated during the patient's pregnancy and how they subsequently interfered in the developing mother–infant relationship prior to intervention. (13 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of infant colic on maternal self-perceptions and mother-infant attachment

The 5-HT2A and 5-HT2C antagonists MDL 100,907 and SER-082 were tested with the 5-HT2A/C agonist DOI and the 5-HT1A/2A/2C agonist LSD in the Behavioral Pattern Monitor, which provides multiple measures of locomotor and investigatory activity. Previous investigations have shown that these measures load onto three independent behavioral factors: amount of activity, exploratory behavior, and behavioral organization. Rats pretreated with saline, MDL 100,907 (0.25-2.0 mg/kg), or SER-082 (0.5-1.0 mg/kg) were treated with saline, 0.25 mg/kg DOI, or 60 micrograms/kg LSD. All effects of DOI were blocked by all doses of MDL 100,907, but only by the highest dose of SER-082. While the effects of LSD on activity and exploratory behavior were largely unaffected, either pretreatment antagonized the effects of LSD on behavioral organization. Thus, all of these effects of DOI were attributable to 5-HT2A receptors, whereas the effect of LSD on behavioral organization was influenced by both 5-HT2A and 5-HT2C receptors.     

The effect of oral ritodrine on maternal and fetal carbohydrate metabolism

The reported growth-promoting effects of the beta-sympathomimetic compound, ritodrine, have been investigated. The carbohydrate tolerance of eight pregnant women was found to be unaffected by treatment with oral ritodrine over a ten-week period. A further observation that the carbohydrate metabolism of the newborn infants of these women was within normal limits tends to discount possibility that any growth-promoting action ritodrine may have on the fetus is mediated through a diabetogenic effect on the mother.