The human blastocyst produces a soluble factor(s) that interferes with lymphocyte proliferation.

Animal studies have reported that the blastocyst produces immunosuppressive factors that are critical to successful implantation. The production of such factor(s) by the human blastocyst has not yet been described. To test that hypothesis, the spent media of 67 human embryos developed in vitro was evaluated using either the allogeneic one-way mixed lymphocyte response (MLR) or the concanavalin A (Con-A) stimulated lymphocyte response (SLR). Conditioned embryo media was obtained at in vitro fertilization (IVF) in aliquots of (A) the first 24 hours in vitro, (B) the second 24 hours in vitro, and (C) from 24 hours until development of the blastocyst stage. Control media consisted of Ham's F-10 medium (Gibco, Grand Island, NY) with identical maternal serum concentration to test media. Conditioned media (either A, B, or C) or control media was added to 200-microL wells containing lymphocytes in either the MLR or SLR. A significant suppressive effect of 25% to 60% was observed in seven of nine samples of blastocyst-conditioned media (P less than 0.05). No significant suppressive effect was found in the earlier embryo media (A or B) in either the MLR or the SLR. These data suggest that the human blastocyst produces a factor(s) that interferes with lymphocyte proliferation.

Re-treatment of aplastic anemia with antithymocyte globulin or antilymphocyte serum.

Twenty-two patients with aplastic anemia were treated with antilymphocyte serum or antithymocyte globulin at Vanderbilt University and affiliated hospitals from 1980 to 1986. The median age was 42 (eight to 73 years); the male:female ratio was 8:14. Nineteen patients had severe aplastic anemia, and three had moderate disease. Twenty patients received antilymphocyte serum initially while two patients received antithymocyte globulin. Fifteen patients received fluoxymesterone 10 mg by mouth three times a day with antilymphocyte serum, and all received prednisone during the course of antilymphocyte serum or antithymocyte globulin. There were seven responses (31.8 percent) to the first course with four complete responses and three partial responses. Six of 15 patients who received fluoxymesterone showed a response, compared with zero of five treated without androgens (p less than 0.05). Eight patients with no initial response and a patient who experienced a relapse after a complete response were re-treated with either antithymocyte globulin (six) or antilymphocyte serum (three), with four of nine patients (44 percent) having a response (three complete responses, one partial response). Overall, 10 of 22 patients (45 percent) had a response (six complete responses, four partial responses). Median survival for those without a response is six months. Median survival for those with a response has not been reached, with follow-up ranging from 18 to 70 months. This study shows the benefit of a second cycle of antilymphocyte serum or antithymocyte globulin and a possible role for concomitant androgens in this treatment of aplastic anemia.

Serositis with autoimmune endocrinopathy: clinical and immunogenetic features.

Twenty patients with autoimmune endocrinopathies experienced 45 episodes of pleural and/or pericardial serositis. Seventeen of these patients were women and 15 had clinical or serologic evidence of 2 or more endocrinopathies. Idiopathic primary hypoadrenalism (10 cases), Graves' disease (8 cases), Hashimoto's disease (4 cases), atrophic thyroiditis with hypothyroidism (3 cases), idiopathic primary hypogonadism (3 cases), transient thyroiditides (2 cases), and type I diabetes mellitus (1 case) were diagnosed at a mean age of 24 years. Serositis recurred after asymptomatic intervals of months to years even in patients treated for endocrine dysfunction. Fourteen of 16 Caucasians had circulating immune complexes, including all 9 patients with a C4AQ0 (C4A null) phenotype and including all 12 patients with HLA antigens B8 and DR3, antigens associated with systemic lupus and with autoimmune endocrinopathies. Serositides associated with autoimmune endocrinopathies can occur with chest pain, fever, and exudative effusions in young Caucasian women with the HLA B8 DR3 C4AQ0 phenotype. These serositides may have a common pathophysiologic mechanism.

Use of SEOPF regional crossmatch trays to share kidneys for sensitized patients. Local experience of three centers.

Regional organ procurement (ROP) crossmatch trays are used by members of the South-Eastern Organ Procurement Foundation (SEOPF) to facilitate sharing of cadaver kidneys for highly sensitized patients. ROP trays carry a single representative serum sample from over 900 patients with panel reactive antibody (PRA) levels of greater than or equal to 60%. Trays are centrally prepared periodically and distributed to member laboratories where they are used for preliminary crossmatching against locally obtained donors. Crossmatching results are used in conjunction with the SEOPF computer match program for sharing of kidneys. Proficiency testing studies by the 40-member laboratories show a greater than 90% concordance rate on results with these highly and broadly reactive sera. Data were available from 3 centers on 74 kidneys shared between SEOPF-member institutions on the basis of a remote, preliminary, negative ROP tray crossmatch. Of these, 44 (59%) crossmatched negative locally with the same and other sera, and were thus considered acceptable to be transplanted to the intended highly sensitized patients. Sixteen (22%) donors had a positive crossmatch locally, but with sera other than that present on the ROP tray used for screening. In 14 cases (19%) the same serum as on the ROP tray gave a positive crossmatch. The majority of ROP tray inconsistencies appeared to be due to use of more sensitive crossmatching techniques at the recipient center. Of the 27 patients transplanted at these 3 centers with kidneys received on the basis of ROP tray results, none experienced hyperacute or early irreversible rejection and actual graft survival at 6-48 months is 74%. These studies indicate that regional sharing of patient sera by the existing network of histocompatibility testing laboratories is an effective and reliable mechanism to identify crossmatch-negative donors for highly sensitized patients.

Renal transplantation. A 20-year experience in a Veterans Administration Medical Center.

Between March 1963 and December 1983, 324 renal transplants were performed in 273 veteran patients at the Veterans Administration Medical Center, Nashville, Tenn. Cadaver donors were used in 273 transplants, with an overall one-year patient survival of 72.5% and one-year functional graft survival of 50%. Twenty-four living-related transplants were performed, with an overall one-year patient survival of 89% and one-year functional graft survival of 75%. For analytical purposes the 20-year transplant experience was divided into five eras. One-year patient survival increased from 45% in era 1 to 84% in era 5, while functional graft survival increased from 45% to 70%. Death has occurred in 139 patients, with sepsis being responsible for the largest number of early deaths. Cardiovascular disease was responsible for most late deaths.

Bilateral nephrectomy concomitantly with renal transplantation.

During a 2-year interval 206 patients underwent renal transplantation at a single center, 38 of whom underwent bilateral nephrectomy and other adjuvant operations as part of the transplant procedure. The indications for this type of procedure were reviewed, with special emphasis on the control of hypertension. The morbidity and mortality (16 per cent) in this group were compared in detail to those in patients not undergoing a concomitant adjuvant operation. The results with regard to renal function were similar to the group as a whole and the indications for appropriate patient selection are discussed.

Factors influencing the outcome of kidney transplants.

This study is a multifactorial analysis of 389 transplants performed from June 1977 to December 1981. Analysis of the effects of transfusions antilymphocyte serum (ALS), histocompatibility testing, gender, and patient risk factors (presence of concomitant disease, greater than 50 years of age, etc.) was done. Two-hundred fifty-three patients received cadaver kidneys and 136 patients obtained kidneys from a relative. Two-hundred eighty-three (73%) patients received blood transfusions prior to transplantation. Our data showed that recipients receiving transfusions prior to transplantation had a significantly higher graft survival than those who were not transfused in both cadaveric and related graft recipients. Two-hundred twenty-one (56%) patients received ALS following the transplant. This group had a 15% higher graft survival than a comparable group. Analysis of histocompatibility testing data shows approximately 5% higher functional graft survival between each match grade. Surprisingly, female patients receiving kidneys from living related donors had a 16% higher graft survival than male patients. In cadaver recipients female patients had a 10% higher patient survival as compared to male patients. The risk factor status of recipients affected not only graft survival but patient survival, which probably is due to the consequences of immunotherapy. The authors' conclusion is that the above mentioned factors may be additive in nature. Further, multivariable analysis is necessary in order to correctly transplant data.

Ovarian development in 46,XY gonadal dysgenesis.

In humans the XY ovary is degenerative, there being scant evidence of persistence of that organ beyond the perinatal period. Here we describe indications of functional ovarian tissue in a 17-year-old female with male karyotype, H-Y+ cellular phenotype, and some signs of the Turner syndrome. Her gonads were removed after the onset of secondary amenorrhea. Histological examination revealed a degenerative right ovary devoid of germ cells and follicles, and a left streak gonad. There was no trace of testicular development in either side.

Transport of apolipoproteins A-I and A-II by human thoracic duct lymph.

The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in two subjects before and three subjects after renal transplantation. Lymph triglyceride transport was approximately 83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659+/-578 mg/d for apolipoprotein A-I and 109+/-59 mg/d for apolipoprotein A-II among the five subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine. Lymph high density lipoprotein particles are mostly high density lipoprotein(2b) and high density lipoprotein(2a) and have a greater overall relative triglyceride content and a smaller relative cholesteryl ester content when compared with homologous plasma high density lipoproteins. The major quantity of both lymph apolipoprotein A-I (81+/-8%) and apolipoprotein A-II (90+/-11%) was found within high density lipoproteins with almost all of the remainder found in chylomicrons and very low density lipoproteins. The combined results are consistent with a major contribution of the intestine to total body synthesis of apolipoprotein A-I and apolipoprotein A-II. An important role of lymph in returning filtered apolipoprotein to plasma in association with high density lipoproteins is proposed. Accompanying the return of filtered apolipoprotein to the plasma is a probable transformation, both in size and composition, of at least some of the lymph high density lipoprotein(2b) and high density lipoprotein(2a) particles into high density lipoprotein(3).