John R Montgomery

Outcomes of ABO-Incompatible Kidney Transplantation in the United States

Background. ABO incompatible (ABOi) kidney transplantation is an important modality to facilitate living donor transplant for incompatible pairs. To date, reports of the outcomes from this practice in the United States have been limited to single-center studies. Methods. Using the Scientific Registry of Transplant Recipients, we identified 738 patients who underwent live-donor ABOi kidney transplantation between January 1, 1995, and March 31, 2010. These were compared with matched controls that underwent ABO compatible live-donor kidney transplantation. Subgroup analyses among ABOi recipients were performed according to donor blood type, recipient blood type, and transplant center ABOi volume. Results. When compared with ABO compatible-matched controls, long-term patient survival of ABOi recipients was not significantly different between the cohorts (P=0.2). However, graft loss was significantly higher, particularly in the first 14 days posttransplant (subhazard ratio, 2.34; 95% confidence interval, 1.43–3.84; P=0.001), with little to no difference beyond day 14 (subhazard ratio, 1.28; 95% confidence interval, 0.99–1.54; P=0.058). In subgroup analyses among ABOi recipients, no differences in survival were seen by donor blood type, recipient blood type, or transplant center ABOi volume. Conclusions. These results support the use and dissemination of ABOi transplantation when a compatible live donor is not available, but caution that the highest period of risk is immediately posttransplant.

A Special Report: Four-year Study of a Boy with Combined Immune Deficiency Maintained in Strict Reverse Isolation from Birth

Summary: A 4-year study of a boy with combined immune deficiency is presented, and the impact of this disease on various aspects of his growth and development is examined. There is no evidence of immune deficiency in either parent or in the genetic background on the maternal side. Three children of a brother of the mothers father may have had immune deficiencies but two have grown to be teenagers with no problems. Another died. At autopsy, however, lymph nodes appeared normal. The deceased older brother had severe combined immune deficiency (SCID). The autopsy findings showed Pneumocystis carinii pneumonia to be the direct cause of death and these findings contributed to the diagnosis of SCID. After a successful germ-free birth, the male infant (DV) was placed in the isolator. Laboratory tests were normal except that the x-rays showed no thymic shadow, his absolute lymphocyte count ranged from 399–440/mm, and the lymphocytes showed no proliferative response to phytohemagglutinin (PHA). Specific tests showed the antibody-producing immune system and the cell-mediated immune system to be severely defective. The patients lymphocytes elicited positive responses by lymphocytes from father, mother, and sister. Subsequent search in national and international tissue-typing laboratories has shown four HLA matches but none has been nonreactive in mixed lymphocyte culture (MLC). therefore, this patient has remained in isolation to the present; now he is 4 years old.Approximately 35 species of microorganisms, mostly transient contaminants, have been isolated, taking into account that the same organism may have been identified under different names in different laboratories. Those isolated frequently and in sufficiently high concentration to indicate colonization have been speciated as follows: anaerobes—Propionibacterium acnes, Lactobacillus catenaforme (disappeared spontaneously), Bacteroides oralis ss. elongatus, Clostridium (perenne, hastiforme, bifermentans), Bacteroides clostridiiformis ss. clostridiiformis; aerobes—Alcaligenes faecalis (eradicated by antibiotics), Staphylococcus epidermidis, Enterobacter agglomerans, Micrococcus sp. subgroup 1, Bacillus pulvifaciens (disappeared spontaneously); yeasts—Candida (tropicalis, parapsilosis). Seven are considered to be probable components of the current autoflora: P. acnes, C. bifermentans, B. clostridiiformis ss. clostridiiformis, S. epidermidis, Micrococcus sp. subgroup 1, E. agglomerans, C. parapsilosis. No viruses or protozoa have been isolated. At age 3 years, the mean quantitation of anaerobic cells was 7.9 × 107 viable cells/g feces; this falls short of the mean anaerobic load from normal children. The mean aerobic concentration was 1.2 × 108 viable cells/g feces, not unlike normal children. Qualitatively his flora has abnormally few species and lacks those most common in normal subjects. This child has had no evidence of infection and has always been in excellent health even though some organisms which could be pathogenic under some circumstances have been isolated.Phagocytic functions, adenosine deaminase (ADA) levels, and serum complement levels were normal except that C1q was 30% of normal. Thymosin assays showed adult control subject 1/4, 10-year control subject 1/128, this patient 0. To age 47 months serum immunoglobulin (Ig) M levels were generally low and IgG was not detected. No serum IgA was detected until, at 39 months, assays indicated IgA at the lowest range of sensitivity of the agar plates. Ultracentrifugal analysis of serum revealed no 19s material at 24 months but at 36 months both 7s and 19s materials were present. At 44 months these fractions were still present and an abnormal 4s component had disappeared. Radial immunodiffusion assay at 44 months indicated the presence of IgD and at that time an IgM component of normal electrophoretic mobility was detected for the first time. Before injection of keyhole limpet hemocyanin (KLH) at 1 month antibody liter was 0–0. Antibody titers and skin tests after injection were negative and remained so after further antigen injections. At 11 months, on the fifth rechallenge, the patient had an erythematous reaction of 5 mm diameter but no significant antibody responses. Two typhoid antigen injections elicited no antibody response. Using the isolated leukocyte technique, lymphocytes showed minimal or no blastogenesis in response to PHA, poke-weed mitogen (PWM), or in MLC. Using the whole blood technique, transient, low positive responses (stimulation index (SI) range 4.1–9.7) to PHA were observed but not consistently maintained. At 3 years, purified T cells showed a notable response (SI 17.4) to PHA, but this was not obtained in subsequent experiments. Transfer factor (TF) was given to this patient between 10 and 16 months of age. In skin tests to C. albicans, purified protein derivative (PPD) and streptokinase-streptodornase (SK-SD) administered a day after TF injection, small areas of redness appeared early and faded rapidly. Addition of TF to lymphocyte cultures obtained before administration of TF caused them to respond to C. albicans and PPD (SI 8 for each); after injection of TF and skin tests to these antigens, similar responsiveness could not be induced by addition of TF. After a second dose of TF, before skin test to SK-SD, the lymphocytes responded to SK-SD in vitro with TF (SI 13) and without TF (SI 8) added to the cultures; after SK-SD skin tests, responses were no longer elicited under the same circumstances. During the first 2 years membrane-bound immunoglobulin (SmIg), bearing lymphocytes ranged from 50–100% of the total lymphocytes whereas the percentage of lymphocytes with cells forming rosettes with sheep erythrocytes (E-RFC) markers was low, about 3–12%. Between 2.5 and 4 years striking changes occurred, representing a shift toward a normal distribution (20–40% SmIg and 19–60% E-RFC). In electron microscopic studies, new type lymphocytes which appeared at 15 months increased in number until at 4 years they represented 93% of the lymphocytes. In contrast to cells from normal donors, complement (C3) receptor-bearing cells of this patient did not express significant direct cytotoxicity; however, lymphotoxin (LT) levels 3–4 times those of E-RFC either from patient or normal donors were detected. Consistent with the positive responses, C3 receptor-stimulated cells also produced leukocyte migration inhibition factor (MIF) activity (40 * 16%) greater than background (15%) level. No correlation was evident between fluctuations in absolute numbers of C3 receptor-bearing cells in peripheral blood and the presence of LT and MIF responses. The expression of LT and MIF indicated that this patient was capable of nonspecific host responses. The findings suggest an impairment of the ability of this SCID patient to expand or sustain functional subpopulations essential to immunologic responsiveness.Hematologic surveillance revealed no dramatic differences from other children with SCID. Absence of complicating infections indicated that the changes were probably attributable to the natural disorder. Thrombocytopenia appears to be related to the basic disease because occurrence and recovery did not relate in a consistent pattern with antibiotic therapy, other therapy, or bacterial contamination. Peri~heral blood counts followed a pattern consistent with previously described cases. At 3 months of age the patient showed scalp changes, loss of hair, and rough skin. He was placed on an iron-fortified formula and vitamins. The scalp problems soon cleared up. Another episode of hair loss and dry skin occurred at 15 months. He had not been given his vitamin supplements. Vitamins were given again. Subsequently scalp problems improved. This is a child who has been on low cholesterol intake from birth, yet there is no malfunction of the nervous system or delay in myelinization. At age 2 years he was excreting a larger percentage of primary bile acids (70%) than control subjects (30%). This indicated a reduced activity of bacterial flora. DV excreted 99.4% of his neutral lipids as cholesterol with a trace of coprostanol whereas control subjects of 1.5 years or less showed 95% cholesterdl~with about 5% coprostanol.When he was 5 months, 24 days of age, using the BayleyScales of Infant Development, the Mental Index was 116 (6.5- 7.5 months) and the Psychomotor Index was 112 (6.5-7.5 months). When he was 3 years old, potential intellectual endowment was estimated to be 1-2 years above his chronologic age. He showed unusual ability in the discrimination and recognition of geometrical shapes of objects in his environment. Evaluation of general ego functioning showed rejection of some popular responses, a healthy awareness of color nuances, a rather low prdductivity relative to his intellectual potential, but no apparent idiosyncratic or dereistic quality in his ideation or concept formation. At age 12 months, the child showed a marked deficit in receptive and expressive language skills. Implementation of a program of language stimulation resulted in rapid and consistent improvement. Recent objective testing revealed above average speech and language abilities, except for a mild, persistent deficit in receptive and expressive vocabulary which was related to his atypicai environment.Psychiatric evaluation in this patient demonstrates that it is possible to rear a child, under conditions of strict reverse isola tion, who can respond with normal affective, cognitive, and intellectual ability to age 4 years.Speculation: The continued maintenance of this patient in a gnotobiotic state has provided opportunity for serial studies in an uncomplicated disease state.Although he has not remained germ free, this technology has been successful in preventing infection for 4 years in a child who, otherwise, would have been overwhelmed with infection. In addition, the studies have shown that the significantly simpler microflora in the early part

Potentials of spleen, lymph node, and Peyer's patches to reconstitute lymphoid tissue and produce graft-versus-host reaction.

The capabilities of cells from parental or isogeneic spleen, lymph node, or Peyers patches to repopulate the spleens of sublethally irradiated (C57 X A) F1 hybrid mice were determined. The ability of A cells from the various organs to produce graft-ver-sus-host reaction was assessed. Spleen cell suspensions expressed the capacity to restore -all the spleen components; lymph node suspensions were not competent in restoration of the hematopoietic components, but did restore the lymphoid components. Both the spleen and the lymph node cells from parental strain donors produced severe graft-ver-sus-host reactions. Peyers patch cells from either isogeneic donors or parental strain donors specifically restored the thymus-independent components of lymphoid tissue but did not produce graft-versus-host reactions. These findings are discussed in relation to the thymus-independent nature of the Peyers patches and to the concept of the Peyers patches as the mammalian equivalent to the fowl bursa of Fabricius.

Surgical management of early and late ureteral complications after renal transplantation: Techniques and outcomes

In this study, we present our experience with ureteral complications requiring revision surgery after renal transplantation and compare our results to a matched control population.

The Use of the Nitroblue Tetrazolium Reduction (NBT) Test in Diagnosis and Treatment of Bacterial Endocarditis

Despite the recent advances in the diagnostic and therapeutic armamentarium, the bacterial endocarditis remains one of the most challenging clinical endocarditis remains one of the most challenging clinical problems. The conventional diagnostic methods for bacterial endocarditis often either fail or delay in the diagnosis and treatment of this disease. A new diagnostic test for the bacterial endocarditis is urgently needed in order to initiate the antibiotic therapy promptly. We have found the NBT test [PARK et al., Lancet ii: 532, 1968] to be a useful diagnostic aid in these clinical situations. Patients with proven bacterial endocarditis and those with presenting symptoms suggestive of bacterial endocarditis were studied with the NBT test. The results were compared with those of controls. The absolute number and percentage of the NBT positive neutrophils were found to be regularly increased in seventeen patients with bacterial endocarditis (means: 3,150/mm3, 24.5%) as compared with normal control and patients with non-bacterial disease (439±187/mm3, 6.86±2.87%). Furthermore, the clinical response to the antibiotics therapy was well correlated with the results of the NBT test. The simplicity and instant results are other advantages of NBT test as a diagnostic aid in bacterial endocarditis.

Germ-free delivery. The initiation of management of infants with a high probability of congenital immune deficiency states

Abstract Germ-free delivery of an infant with a high probability of congenital severe combined immune deficiency disease was accomplished by cesarean section without major modification of routine medical and nursing procedures. The male sex of the infant had been determined by karyotype on amniotic fluid cells, thus the risk of being affected by an X-linked disease was established. Intensification of ordinary methods for preparation of operating area and personnel resulted in successful germ-free delivery. Highly technical equipment and specially trained people with attendant high cost were not required. The infant was placed in a sterile plastic flexible film isolator where he has been maintained in a gnotobiotic state for twelve months (to date) free of infection in spite of continued immune incompetence. With the likelihood that lesser forms of this disease may be more common than heretofore expected and with the advent of new obstetric and immunologic diagnostic techniques, sterile delivery may assume more importance in the future.