Case report: transthoracic retrograde venous bullet embolization.

The embolism of bullets in the venous system is an uncommon complication of penetrating missile injuries. Retrograde transthoracic venous bullet embolization is exceedingly rare. This report describes embolization of a small-caliber bullet from the left subclavian vein to a branch of the right popliteal vein. The patient was treated successfully without surgery.

The status of rehabilitation, morbidity, and mortality of long-term survivors of pediatric kidney transplants.

The long-term survivors of pediatric renal transplantation show, in our early experience, an excellent status of rehabilitation. The majority of the survivors are enjoying good health and lead active lives. Skin lesions constituted significant morbidity, requiring a better understanding and preventive strategy. Cardiovascular disease appearing in such a young age group is another disturbing problem. The problem of mental health is surprisingly small in these hardy survivors.

Nonpenetrating vascular injury to the subclavian artery.

Blunt subclavian artery injury has been uncommonly reported in the literature. Recent encounter with three such injuries prompted us to review our experience over the past 10 years uncovering only one additional case. These four cases and a review of pertinent literature form the basis for this article. Key clinical issues include a high index of suspicion in patients sustaining major blunt deceleration and rotational or direct injuries to the neck, thorax, and/or upper extremities. Prompt diagnosis remains obscured by the presence of severe associated injuries, the treatment of which requires prioritization. Arteriography is invaluable to elucidate injury because prompt vascular control is dictated by various approaches depending on the location. Expeditious surgical repair is indicated to prevent complications of hemorrhage, pseudoaneurysm, thromboembolism, and/or arteriovenous fistula. Long-term results appear to be good with major morbidity related to associated neurologic, soft tissue, and bony injuries.

Use of the Greenfield filter in adolescents for deep vein thrombosis and pulmonary embolism.

Serious venous thromboembolic disease is now recognized more frequently in the pediatric age group. Caval interruption is indicated most commonly for prophylaxis against life-threatening or recurrent pulmonary embolism (PE) when anticoagulation is ineffective or contraindicated. Greenfield vena caval filters have been utilized locally in 415 adult patients with 97% long-term patency and 5% recurrent embolization. Its application in adolescents is reported herein. Standard adult (30-mm) vena caval filters were placed in ten patients, ages 13 to 18. Four filters were required following PE, six were used for deep venous thrombosis (DVT) when anticoagulation was contraindicated, and one was inserted prophylactically. In eight patients, filter insertion was accomplished with local anesthesia, while two underwent filter placement under general anesthesia administered for other procedures. One filter was misplaced into the right renal vein, requiring a second filter insertion. All patients have been followed from 1 to 11 years with yearly vascular duplex imaging and radionuclide venograms documenting caval patency without clinical embolic sequelae. This duplicates the adult experience in safety and efficacy. As recognition of venous thromboembolism becomes more frequent in the pediatric age group, safe caval interruption may be necessary for those excluded from or not responsive to anticoagulation. This technique may be extended to smaller patients with miniaturization of both filter and carrier.

Antiidiotypic antibodies to human major histocompatibility complex class I and II antibodies in hepatic transplantation and their role in allograft survival.

In order to evaluate the role of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, serial serum samples obtained from 10 liver recipients both pre- and posttransplantation were analyzed for the development of HLA alloantisera inhibitory activity by a microcytotoxicity inhibition assay. Seven of the 10 recipients developed strong anti-anti-HLA activity during the immediate posttransplant period, which was able to block killing of a specific alloantiserum to class I MHC antigens (44-100%). Recipients' sera were also able to block class II alloantisera (HLA-DR8) cytotoxicity of B-lymphocytes. The inhibitory activity developed 10-15 days posttransplantation, was cyclical, and was present in the immunoglobulin fraction of the serum. One patient developed specific antibodies to anti-HLA-B7 and had no inhibition for alloantisera to HLA-B8,B17,B49 and B13. Another developed antibodies capable of blocking anti-HLA B44 (mismatched donor antigen) and also cytotoxicity of HLA-B17,B49 (crossreactive group), but showed no significant inhibition of HLA-B13,B8 and B7. One recipient, transplanted across strong (1:500 titer) antilymphocyte crossmatch, rejected the graft within 1 month and failed to develop any inhibitory antibodies to anti-HLA. Two other patients who lost their grafts within 2 months posttransplantation developed only minimal (11% and 16%) and transient inhibition. Immunoprecipitation of surface-labeled, mixed lymphocyte culture stimulated lymphocytes, with sera containing inhibitory antibodies, identified membrane components of approximate molecular weights of 54,43 and 17,000, suggesting T cell clonotypic structures. Thus, these studies provide support for the development of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, which may play a regulatory role in the tolerance of allograft.

Long-term survivors of kidney transplantation, mortality, rehabilitation, and immunologic reactivities.

1. The overall patient and graft survival rates (83.6% and 82% respectively) up to 23 years posttransplant of the group who survived a minimum of 10 years is reasonably good regardless of the donor source. 2. The primary grafts that survived a minimum of 10 years and were lost during the subsequent 12 years (17.7%) were equally due to rejection and the death of the patient. 3. Rehabilitation of the long-term survivor has been very good. Cardiovascular disease is becoming a significant morbidity among pediatric-aged recipients reaching the thirties. 4. The causes of death after 10-year survival are evenly distributed among infection, cardiovascular disease, neoplasms, dialysis, and hepatic failure. 5. The selected studies of immunologic reactivities in the long-term survivors show their failure to generate significant killing against donor-specific antigens while displaying normal MLR response against donor and third party. Significant depressions in their ability to respond in vitro to soluble antigens was also demonstrated.

Peritoneal dialysis in chronic renal failure in children: a six year study.

A six year study was conducted to evaluate the long-term use of chronic peritoneal dialysis in children with end-stage renal failure at a single center. All patients maintained satisfactory clinical status and achieved good biochemical control. No significant changes in developmental continuum as measured by weight and length/height were observed in these patients upon institution and maintenance on peritoneal dialysis. The incidence of peritonitis was one episode every 12.3 patient-months. The overall incidence of catheter replacement was one change every 15 patient-months. Our results serve to underscore the effectiveness of long-term peritoneal dialysis in children.

Characterization of ethanol-inducible human liver N-nitrosodimethylamine demethylase.

Through the use of monospecific antibodies directed against hepatic cytochrome P-450j, an enzyme induced in rats treated with ethanol or isoniazid, we have purified from human liver the related cytochrome P-450 termed HLj. HLj resembles rat P-450j and P-450 LM3a, the homologous cytochrome in rabbit liver, in its NH2-terminal amino acid sequence, in being in highest concentration in liver microsome samples prepared from two patients intoxicated by ethanol and one patient given isoniazid, and in catalyzing the metabolic activation of the procarcinogen N-nitrosodimethylamine. Furthermore, each of nine human liver RNA samples contained a species of mRNA hybridizable to a cloned HLj cDNA. We conclude that HLj is related by structure, function, and some regulatory characteristics to rat P-450j and rabbit P-450 LM3a, cytochromes critical for metabolism of several clinically relevant cytotoxic and carcinogenic agents.

Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver.

HLp is a human liver cytochrome P-450 that is immunochemically related to the glucocorticoid-inducible liver cytochrome P-450p in the rat and its homologue in the rabbit, P-450 LM3c. To investigate the structure and regulation of HLp, we used a monoclonal antibody that recognizes purified HLp to screen a human liver cDNA library in lambda gt11. We isolated and sequenced two overlapping cDNA clones that span the entire 2011 bases of an mRNA that codes for a protein of 504 amino acids. The predicted amino-terminal amino acid sequence of this protein is identical to the first 20 residues determined from purified HLp. HLp mRNA shares more than 70% sequence homology with related proteins from the rat and rabbit but less than 40% homology with other published cytochrome P-450 genes. Moreover, Southern blot analysis of human and rat genomic DNA revealed 50 and 60 kilobases of DNA, respectively, hybridizable to the HLp cDNAs. Blot analysis of human liver RNA from five patients revealed major (2.2 kilobase) and minor (3.0 kilobase) bands that hybridized to HLp cDNAs. The apparent concentration of these hybridizable mRNAs as well as the amounts of immunoreactive HLp protein in microsomes from the same liver were increased in a dose-dependent relationship in three patients who received dexamethasone, a potent glucocorticoid. Furthermore, in samples of RNA and of microsomes isolated from cultures of a human hepatoma cell line (Hep G2) incubated for 120 hr in medium containing dexamethasone, there was a 6-fold induction of the two mRNA species hybridizable to HLp cDNAs and a 3-fold induction of immunoreactive HLp protein as compared to the values for cultures incubated in steroid-free medium. We conclude that HLp is a human representative of a conserved glucocorticoid-inducible cytochrome P-450 gene family whose mechanism of induction involves accumulation of HLp mRNA.

Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat.

The rat 3-methylcholanthrene-inducible family of liver cytochromes P-450 contains two proteins (P-450c and P-450d) that are immunochemically related, possess 68% total sequence homology, and are induced by a number of toxic or carcinogenic compounds. To determine whether equivalent isozymes of hepatic cytochrome P-450 are expressed in humans, as they are in several mammalian species, we performed immunoblot analyses on microsomes prepared from 14 human liver specimens and found that each one contained a 52.5-kDa protein (termed HLd) that reacted with antibodies specific for rat P-450d. In addition, one specimen contained a 54-kDa protein (termed HLc) that reacted with antibodies specific for rat P-450c. HLd was purified through the use of immunoaffinity chromatography and was found to be 56% homologous to rat P-450d and 61% homologous to the equivalent isozyme in the rabbit (P-450 LM4) through their first 18 NH2-terminal amino acids. Finally, levels of immunoreactive HLd varied more than 10-fold among these patients but were unrelated to the patients' drug treatments, smoking habits, or amount of immunoreactive HLp, a human liver cytochrome P-450 related to the glucocorticoid-inducible family of rat cytochromes P-450. We conclude that, in man, there is a cytochrome P-450 family composed of two isozymes (HLc and HLd) that are immunochemically and structurally related to the 3-methylcholanthrene-inducible family observed in several other species.

The importance of the Lewis system in cadaver renal transplantation.

Previous reports have suggested that Lewis (Le) antigens may exert a significant effect on cadaver renal allograft (CRA) survival, especially in black recipients in whom there is a higher frequency of Le-negative phenotypes. We review our experience with this problem in 70 donor-recipient pairs of CRA who underwent prospective Le typing and received conventional immunosuppression between 1980 and 1983. Recipient typing alone yielded the following graft survival (GS) and patient survival (PS) at 2 years by life table analysis: (a+,b;-) (n = 12) 51% GS, 93% PS; (a-, b+) (n = 44) 57% GS, 88% PS; and (a-,b-) (n = 14) 51% GS, 93% PS(P-ns for GS, PS). Recipient racial characteristics did not effect ultimate graft survival, as whites and blacks had similar two-year GS in all phenotypic groups. When Le matching was considered, no significant differences in one-year graft survivals could be ascertained between Le-matched and Le-mismatched donor-recipient pairs, and this effect persisted despite stratification for race and HLA-A,B and DR histoincompatibilities. In light of these results, we do not recommend using Lewis compatibility as a criterion for donor selection in cadaver renal allografting, as this substantially increases the difficulty in finding suitable matches, especially in the (a-,b-) recipient group.

The effect of delayed function on long term survival of renal allografts.

The experience at a single center with 297 consecutive cadaver renal transplants over the past 12 years is reviewed with special attention to acute post-transplant ischemic renal injury (ATN). Sixty-seven patients received kidneys which failed to function immediately (22.5 per cent). Twenty-five (8.4 per cent) never showed any function (NF), and 42 (14.1 per cent) developed delayed function (ATN). The over-all incidence of this complication has exhibited a downward trend in the past 12 years and the possible reasons for this are discussed. The overall rate of patient survival and functional grafts observed for to 12 years by actuarial methods were found to be no different by statistical analysis (ATN versus IF). When patients were subgrouped according to quality of renal function attained by four months post-transplantation, ATN patients with good renal function (serum creatinine levels of less than 2 milligrams per deciliters) demonstrated similar patient and functional graft survival rates when compared with IF patients with similarly good renal function. Thirty-eight per cent of patients with ATN never achieved good renal function (serum creatinine levels of more than 2.0 milligrams per deciliters) and were compared with 8 per cent of IF patients who likewise never achieved good renal function. These two groups were also found to be statistically similar with regard to the rates of patient survival and functional grafts. Thus, it is likely that, although the presence of ATN may predispose a patient to a higher risk of never achieving good renal function, the eventual long term outlook is similar for patients with ATN and those with IF. The most important determining factor in terms of ultimate functional graft survival appears to be relative to the quality of renal function in the early post-transplantation period.

Identification of an inducible form of cytochrome P-450 in human liver.

It has not yet been determined whether human liver contains inducible cytochromes P-450 similar to those that catalyze the oxidative metabolism of foreign substances in animals. We carried out immunoblot analyses of liver microsomes isolated from eight patients and found that each contained a cytochrome P-450, termed HLp, that reacted with antibodies directed against P-450p, a rat liver cytochrome that is inducible by the anti-glucocorticoid pregnenolone-16 alpha-carbonitrile, by glucocorticoids, by anti-seizure drugs, and by such macrolide antibiotics as triacetyloleandomycin. In the two patients who received dexamethasone and anti-seizure medications and in the one patient who was given triacetyloleandomycin, the concentrations of immunoreactive HLp and the ability to demethylate erythromycin and/or to convert triacetyloleandomycin to a metabolite that forms a spectral complex with cytochrome P-450 heme (catalytic properties unique to P-450p in rat liver) were significantly higher as compared to the values for patients who received no inducing drugs. We purified HLp to homogeneity and found that it was immunochemically related to P-450p and to its homologue in the rabbit (LM3c), actively demethylated erythromycin in a reconstituted system, exhibited electrophoretic mobility identical to that of P-450p, and shared 57% homology in its NH2-terminal amino acid sequence with that of a pregnenolone-16 alpha-carbonitrile-inducible rat cytochrome P-450. We conclude that HLp is a human representative of the multigene family of the glucocorticoid-inducible cytochromes P-450.

Pretransplant warm B cell antibodies in recipients of primary and retransplanted cadaver renal allografts.

Eighty-four recipients of cadaveric renal allografts were retrospectively crossmatched for donor-specific pretransplant B cell antibody. Of these, 28 were found to be positive for the antibody and 56 were negative. Actuarial survival analysis over six years revealed a slightly better graft survival overall in the B-cell-negative group as compared with the B-cell-positive group (P less than 0.07). These patients were further subgrouped into those who received primary transplants and those who were retransplanted. Fifty-four percent of the B-cell-positive group (15/28) consisted of retransplants, and only 13% (7/56) of the B-cell-negative group were retransplants. When considering primary transplants only, B-cell-negative and B-cell-positive groups had similar graft survival rates (P less than 0.25). When retransplants only were considered, the graft survivals of the B-cell-positive and B-cell-negative groups were comparable (P less than 0.32). The most significant differences were observed when comparing the B-cell-positive primary transplant group with the B-cell-positive retransplanted group. The primary transplants fared consistently better at all time intervals (P less than .007). Conversely, when primary and retransplants in the B-cell-negative group were compared, no differences were noted (P less than 0.29). Our results suggest that the identification of pretransplant B-cell antibodies may be indicative of a poorer allograft survival prognosis in patients who have been previously transplanted.