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PubMed1993

Susceptibility and resistance to cyclosporin A-induced autoimmunity in rats.

Lethally irradiated Lewis (LEW) rats, reconstituted with syngeneic bone marrow and next given Cyclosporin A (CyA) for several weeks, develop disease (Cyclosporin A-induced autoimmunity; CyA-AI) after withdrawal of CyA. This disease resembles in terms of dermal changes the acute dermatitis and chronic scleroderma also seen in graft-versus-host disease (GVHD). In this study we report the relative resistance of the Brown Norway (BN) rat strain to the induction of CyA-AI. In contrast to LEW rats, in which CyA-AI was originally described, BN rats showed no acute dermatitis or scleroderma-like skin pathology in spite of comparable changes in the thymus and a maturation arrest of CD4+ T cells. The difference was also demonstrated functionally for whereas in LEW rats delayed-type hypersensitivity (DTH) reactions could not be elicited during CyA-AI, these were within normal limits in BN rats subjected to the same protocol; NK activity on the other hand was unaffected in both strains. The observation that BN rats developed very mild late disease as evidenced by a slight though significant weight loss suggests that the BN strain is susceptible to the disease but that lesser effector cell generation or, alternatively, stronger suppressor cell responses may prevent dermal disease. These observations may contribute to the elucidation of the mechanisms involved in this experimental autoimmune disease.

Animals↗
PubMed1985

The use of osteosynthesis in immediate and delayed mandibular reconstruction.

Principles of osteosynthesis utilizing dynamic compression plating have been used in immediate and delayed mandibular reconstruction in five patients. Intermaxillary fixation was not used. Follow-up ranged from eight to 14 months. Four of five patients have viable bone grafts at the present time. One bone graft has been lost due to infection. We feel mandibular reconstruction based on principles of osteosynthesis helps to rapidly restore cosmesis and function with minimal morbidity.

Bone Plates↗
PubMedDate not supplied

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

Adult↗
PubMed1997

Blockade of CD40 ligand-CD40 interaction impairs CD4+ T cell-mediated alloreactivity by inhibiting mature donor T cell expansion and function after bone marrow transplantation.

Alloreactive T cells require costimulatory signals via CD40 ligand (CD40L). The tissue-destructive properties of allogeneic CD4+ but not CD8+ T cells were inhibited by anti-CD40L mAb. Fewer CD4+ thoracic duct lymphocytes (TDL) were obtained in mAb-treated recipients. Kinetic studies revealed that CD4+ T cell expansion was reduced or delayed which may account, in part, for the partial graft-vs-host disease protective effect of anti-CD40L mAb. TDL were found to have diminished anti-host-specific proliferative responses. The frequency of donor TDL and splenocytes that expressed the Th1 cytokines IL-2, IL-12 p40, and IFN-gamma mRNA was markedly diminished in mAb-treated recipients, demonstrating that Th1-driven alloresponses were susceptible to CD40L targeting. Perforin mRNA-expressing T cells were undetectable in mAb-treated recipients, consistent with reduced in vivo lethality after the adoptive transfer of allogeneic CD4+ T cells. Similar findings were observed in both B cell-replete or -deficient recipients, indicating that allogeneic T cell expansion and priming can be sustained by a non-B cell, CD40+ host cell population. Mice receiving CD40L-deficient allogeneic CD4+ T cells had survival rates comparable to the rates of those given anti-CD40L mAb treatment. Because anti-CD40L mAb also was found to prevent host anti-donor-mediated marrow allograft rejection, in vivo blockade of CD40L-CD40 interactions may provide a highly beneficial approach to improving the outcome of allogeneic bone marrow transplantation.

Animals↗
PubMed1999

Early versus late extubation after coronary artery bypass grafting: effects on cognitive function.

OBJECTIVE: To compare the effects of a short period of mechanical ventilation and sedation and a longer one on cognitive functioning of patients exposed to cardiopulmonary bypass (CPB). DESIGN: A randomized, prospective study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Forty-eight adult patients with surgical coronary artery disease. INTERVENTION: Elective coronary artery bypass surgery. MEASUREMENT AND MAIN RESULTS: Patients (n = 48; mean age, 60.12+/-9.30 years) were randomized to either group I (mean delay, 3.49+/-2.21 hours) or group II (mean delay, 10.32+/-1.75 hours). Cognitive functioning was evaluated before surgery, postoperatively, and at the 8-week follow-up. Tests included measures of central nervous system integrity, attention/concentration and psychomotor performance, verbal fluency, visual scanning speed, mental flexibility, auditory and visual attention, and verbal memory. Covariance analyses were used for group comparisons. Covariates were age, education, and baseline or postoperative performance. No differences in cognitive functioning were found between the two groups. Globally, performance deteriorated for 34.1% of the patients at the posttest evaluation, whereas 2.3% improved and 63.6% remained unchanged. At follow-up, nearly 40.5% of the patients showed an improvement from baseline, 2.4% still had deficits, and 57.1% had no change. None of the cognitive functions appeared to be more affected than others. CONCLUSION: Early extubation and a shortened period of anesthesia/analgesia do not appear to positively or negatively affect cognitive functioning at 3 to 5 days and 8 weeks postoperatively. Early extubation is suggested because it has no deleterious effect (besides the low risk for reintubation) and it may facilitate patients' care in the intensive care unit.

Adult↗
PubMed1987

[Functional results following complicated injuries of the extremities--how can they be improved?].

This study evaluates the critical points in the management of 48 patients with injured arteries of the lower limb between 1980 and 1986. 77% of the traumas were resultant from blunt vehicular traffic mishaps. 13 patients were treated within 6 h, 8 patients later than 6 h, 21 patients later than 24 h post injury. Delays in diagnosis occurred due to lack of or no indication for vascular trauma. Careful physical examination and aggressive use of angiography is essential in improving limb salvage rates, while doppler investigation may lead to improper diagnosis. Overall limb salvage was 69%, however, no reconstruction was possible in 6 cases (13%). 38 of the 42 arterial reconstructions required interposition of venous bypass grafts, four end to end anastomoses. Eleven patients had associated venous injuries, which in nine cases were repaired. Venous ligation in three cases was attributed with increased complication. In three cases ischemia time was shortened by the use of temporary javid shunts for rapid restoration of arterial flow. 50% of the patients were found to require fasciotomy, either pre- or postvascular repair. Early fasciotomy, however was found to be most beneficial. Fractures were treated in 15 cases with the external fixator, in 21 cases with internal fixation. Delayed revascularization after 24 h combined with aggressive debriding of muscle necrosis and the employment of vascularized muscular and skin flaps resulted in a decline in amputation rates and improved functional results.

Adult↗
PubMed2005

Role of poly (ADP-ribose) polymerase in kidney transplant and its relationship with delayed renal function: multivariate analysis.

UNLABELLED: Kidney allografts undergo pretransplant cold ischemia and consequent ischemia-reperfusion injury (IR). Poly (ADP-Ribose) polymerase (PARP-1) overactivation leads to massive NAD+ consumption and ATP depletion with induction of cellular necrosis under ischemic conditions, which may lead to an increase in acute tubular necrosis (ATN) and a delay in total recovery of renal function (RFR) of the transplanted organ. MATERIALS AND METHODS: Nuclear PARP-1 immunohistochemical expression (clone: PARP01) was studied in 155 paraffin-embedded renal biopsies from suboptimal donors and 95 kidney allograft biopsies with histopathological diagnosis of ATN. RESULTS: In 50% of ATN biopsies, more than 50% of tubular nuclei were immunostained for PARP-1. PARP-1 expression was higher in ATN biopsies than in those from suboptimal donors (2.40 +/- 0.74 vs 0.92 +/- 1.13, P = 0.0001 Mann-Whitney). PARP-1 showed a statistically significant relationship with the time required to achieve effective diuresis (Rho:0.779), with serum creatinine, and with duration of cold ischemia (Rho:0.803). These relationships were stronger in the biopsies with ATN. In conclusion, multivariate analysis demonstrated that PARP-1 expression and cold ischemia duration in kidney biopsies with ATN predicted the short-term delay in total recovery of renal function and serum creatinine in the first month.

Adult↗
PubMed1998

Baseline glomerular size as a predictor of function in human renal transplantation.

BACKGROUND: Nonimmune mechanisms have been implicated in chronic renal allograft injury. In experimental studies, a strong correlation exists between glomerular size and the degree of glomerular sclerosis that develops after subtotal nephrectomy. Therefore, we assessed the impact of glomerular maximal planar area (MPA) in baseline biopsy specimens of human renal allografts on later graft function. METHODS: The MPA was measured, by point counting and by computer planimetry, in postperfusion biopsy specimens from 96 allograft kidneys from nonhypertensive donors that had functioned for at least 2 years. Clinical data were analyzed throughout a follow-up period averaging 7.46+/-2.46 years. RESULTS: Both methods produced equivalent estimates of MPA. MPA proved to be a strong predictor of late renal allograft function, with a significant correlation (P = 0.02 to P < 0.01) between MPA at baseline and later serum creatinine level and creatinine clearance, beginning at 6 months after transplantation and persisting through follow-up. Creatinine level at discharge and occurrence of rejection were also independent predictors, whereas donor age, gender and race, cold ischemia time, cadaveric versus living donor, delay in initial function, and HLA mismatch did not predict clinical outcome. CONCLUSION: Larger glomeruli at baseline, measured by a simple point-counting technique, provide an early predictor of risk for late allograft dysfunction and may identify a subpopulation of patients in whom treatment to prevent/ameliorate glomerular enlargement and/or hypertension may be efficacious.

Adolescent↗
PubMed1994

The quinoline-3-carboxamide linomide inhibits angiogenesis in vivo.

Linomide (Roquinimex) has antitumor activity when given in vivo (but not when applied in vitro) that has been attributed to immune host mechanisms. Recent studies, however, suggest that Linomide may also possess antiangiogenic properties. The aim of the present study was to evaluate the antiangiogenic effect of Linomide using an intravital microscopic technique. Syngeneic pancreatic islets were isolated and implanted into the dorsal skinfold chamber of Syrian golden hamsters. This model allows detailed repeated in vivo observations and quantitative analysis of revascularization of pancreatic islet grafts. The neovascularization process of the islets is a highly reproducible phenomenon that is completed within about 2 weeks, resulting in a microvascular network very similar to that of islets in situ. The plasma concentration profile of Linomide following a single oral dose of the compound was determined. The elimination of Linomide was fast, the half-life being 2.6 +/- 0.2 h. Due to the short half-life, the hamsters were given Linomide twice a day. One group of animals (n = 9) was force-fed Linomide (100 mg/kg per day) from the day of implantation throughout the 2-week observation period, and the results were compared with those obtained in a nontreated control group (n = 7). At days 6, 10, and 14 after implantation, the neo-vasculature of the islets was examined. In the control group, 91% +/- 4% (mean +/- SEM) of the islets showed the first signs of angiogenesis at day 6, whereas in the Linomide-treated group the corresponding value was 48% +/- 12%. At days 10 and 14, the "take-rate" in the control group increased to 94% +/- 3% for day 0 and to 94% +/- 4% (n = 6) for day 14, whereas in the treated group the corresponding take-rate was 67% +/- 11% and 72% +/- 12%, respectively. The functional capillary density in the control group at days 6, 10, and 14 was 223 +/- 17,348 +/- 29, and 495 +/- 29 cm-1, respectively, and that in the Linomide treated group was 91 +/- 28, 181 +/- 43, and 229 +/- 47 cm-1, respectively. These results demonstrate that Linomide suppresses the neovascularization of the islet grafts by both delaying the onset of and reducing the percentage of islets displaying angiogenesis as well as by decreasing the rate of proliferation of capillary endothelium of the revascularized islets.

Animals↗
PubMed1984

Immunologic effects of nonsteroidal anti-inflammatory drugs.

Recent studies of the immunoregulatory effects of prostaglandin and the immunomodulating actions of nonsteroidal anti-inflammatory drugs reveal that earlier reports of inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs cannot alone fully explain the anti-inflammatory properties of these agents. Data defining the complex inter-relationship of prostaglandin, the immune response, and nonsteroidal anti-inflammatory drugs are reviewed, and possible mechanisms of anti-inflammatory action of these agents are considered. The effects of nonsteroidal anti-inflammatory drugs on cellular immune function and humoral immune response suggest that anti-inflammatory activity may be related to altered suppressor cell function, inhibition of monocyte collagenase release, or inhibition of neutrophil migration and activation. Further elucidation is awaited.

Animals↗
PubMed1976

Seven years' experience with antilymphoblast globulin for renal transplantation from cadaver donors.

Antibody of the IgGab type can be isolated from horses immunized with cultured human lymphoblasts plus complete Freund's adjuvant. The essential steps for the production of a safe, potent anti-human lymphoblast globulin (ALG) are: A) the use of early bleedings after immunization to reduce the titer of antibodies which react with red blood cells and platelets; B) careful absorption with human red blood cell stroma and platelets; C) stabilization with non-crystalline silica dioxide; D) chromatography through QAE sephadex to remove pyrogens, microaggregates and possible inhibitors of ALG activity; E) careful safety testing in animals for toxicity and pyrogenicity; and F) testing in vitro for sterility. Such a purified horse ALG (IgGab) can be administered safely intravenously to patients to supplement a standardized immunosuppressive regimen incorporating azathioprine and prednisone. Under these circumstances, allergic reactions are very rare, antibodies to horse IgG do not develop, skin tests to horse IgG remain negative, and immune elimination of circulating horse IgG from the human circulation cannot be demonstrated. The overall results of ALG patient survival and transplant function after 184 consecutive first cadaver transplants at the University of Minnesota demonstrate a statistically significant improvement in both parameters accompanying increases in ALG dose while rigidly utilizing standardized doses of azathioprine and prednisone. There is a significant reduction in the number of grafts lost to rejection; significant reduction in the number of rejection episodes; significant delay in the onset of rejection episodes; but there is no increase in septic loss of patients or kidneys. These efforts could be seen in the gross data or when subgroups controlling for patient age, tissue typing were analyzed. Excluding patients at high risk did not alter the results. The beneficial effects of ALG were particularly striking in good matches. In the highest doses, ALG may be dangerous for older patients with poor matches who develop an increased incidence of septic loss of kidney and/or life. Thus, ALG appears to be a useful adjunct in the early management of cadaver transplants by reducing the incidence and frequency of rejection episodes. The dose should probably be reduced in the older patients who receive kidneys from badly mismatched donors. One cannot conclude from this study that ALG manufactured in other centers by this or other techniques, will accomplish the same results since the multiplicity of factors involved in the success and failure of transplants must be controlled so that the influence of intravening variables in the assessment of ALG effectiveness can be assessed.

Age Factors↗
PubMed1982

Prolongation of islet xenograft survival by in vitro culture of rat megaislets in 95% O2.

Individual rat islets could be aggregated into single megaislets in vitro and the megaislets remained morphologically and functionally intact after a 7-day period of culture in the presence of 95% O2 and 5% CO2. Cultured rat megaislets transplanted beneath the renal capsule of diabetic mice produced normoglycemia in the recipients and the survival of the xenografts was markedly prolonged by the 7-day exposure of a high oxygen tension. A single injection of antilymphocyte sera to mouse and rat lymphocytes into the recipients receiving cultured megaislets did not produce a further increase in the percentage of survival of the grafts at 70 days after transplantation. Lymphoid aggregates were present around xenografts of cultured negaislets at 60 and 90 days after transplantation. This lymphoid reaction did not interfere with the function of the xenografts since the recipients were normoglycemic and removal of the grafts resulted in a rapid return to a diabetic state. Intraportal and intrasplenic transplants of cultured rat megaislets did not survive as long as the xenografts of megaislets transplanted beneath the renal capsule. The renal subcapsule site apparently provided some immunological advantage for delaying acute rejection since transplants of individual, fresh rat islets survived for twice as long under the renal capsule as compared wtih intraportal transplants of fresh rat islets.

Animals↗
PubMed1987

Autogenous parathyroid grafts for generalized primary parathyroid hyperplasia: contrasting outcome in sporadic hyperplasia versus multiple endocrine neoplasia type I.

Sixteen patients with generalized primary parathyroid hyperplasia were treated with attempted total parathyroidectomy and placement of an autogenous parathyroid graft in the forearm musculature; these patients have been followed for up to 79 months. We assessed completeness of parathyroidectomy on the basis of the background immunoreactive parathyroid hormone (iPTH) value 3 to 7 days after surgery, which predicted the chance of a graft-independent recurrence or persistence of hyperparathyroidism (0/8 if undetectable versus 4/5 if normal or high). Total parathyroidectomy was sometimes difficult to achieve because of the presence of supernumerary or ectopic parathyroid glands; to enhance the success rate of total parathyroidectomy, we suggest both the use of preoperative ultrasonography to locate intrathyroidal parathyroids and a routine search for supernumerary parathyroids that includes transcervical thymectomy. Graft function was monitored by measuring the secretory gradient for iPTH (the difference between the two antecubital fossae). Gradients on postoperative days 3 to 7 were barely detectable, but by 3 weeks, larger iPTH gradients were noted in every case. By 4 months, the graft could maintain normal serum calcium levels in all but one case. Autonomous graft function has evolved in four of six evaluable patients with type I multiple endocrine neoplasia (MEN I), but in none of the nine patients with sporadic hyperplasia (p = 0.043). A prospective study is needed to determine whether the use of a smaller number of parathyroid fragments for the autogenous graft in known MEN I patients might delay recurrence.

Adult↗
PubMed1983

Immunologic reactivity in marrow graft recipients receiving cyclosporine to prevent graft-versus-host disease.

In vitro and in vivo immunologic parameters were determined in 26 patients treated continuously with cyclosporine to prevent graft-versus-host-disease (GVHD) after allogeneic bone marrow transplantation (BMT) for acute and chronic leukemia and for aplastic anemia. A group of 18 patients was tested 6 months after BMT and another group of 10 patients was tested after one year. At 6 months after BMT, 94% of the patients had normal serum IgG and IgM levels, whereas at one year 29% of them had low IgA levels. The proportion of patients with normal lymphocyte responses in vitro at 6 months after BMT was 69% and 76% for the responses to concanavalin A and to soluble antigens; 75% and 53% for the responses to allogeneic cells and pokeweed mitogen, respectively; and 89% for the response to phytohemagglutinin. All but one were able to generate suppressor cells upon con A stimulation. At one year after the graft, only one patient had demonstrable multiple abnormalities in in vitro tests. Skin test reactivity at one year was comparable to pre-graft reactivity. After BMT a lymphopenia persisted for 6 months. The rate of infectious complications was high during the first 3 months after BMT, and it diminished progressively as immune functions returned to normal. Infection was the cause of death in two cases (one disseminated cytomegalovirus infection and one septicemia). GHVD occurred in 12 patients; in nine of them the disease was transient and mild, only 1 patient developed severe chronic GVHD. Acute GVHD did not influence the tempo of immunologic reconstitution. In comparison to other studies, it seems that cyclosporine does not delay immune restoration, or increase morbidity from infection, while preventing GVHD and its complications efficiently.

Anemia, Aplastic↗
PubMed1998

Humanized IgG1 and IgG4 anti-CD4 monoclonal antibodies: effects on lymphocytes in the blood, lymph nodes, and renal allografts in cynomolgus monkeys.

BACKGROUND: Optimizing therapeutic monoclonal antibody (mAb) depends on the incorporation of the necessary effector functions and the development of hypoantigenic "humanized" antibodies by genetic engineering, which then need to be tested in appropriate preclinical trials. METHODS: Constructs of humanized OKT4A containing the complementarity-determining region (CDR) of murine OKT4A and the framework and constant regions of human light (kappa) and heavy chains (IgG1 and IgG4) were prepared and tested in cynomolgus monkeys who received a renal allograft. A prophylactic course of CDR-OKT4A/human (h) IgG1 or CDR-OKT4A/ hIgG4, either as high-dose single bolus (10 mg/kg) or as low-dose multiple infusion (1 mg/kg for 12 days) was given, and the effects on graft survival, immunohistology, circulating cells, and lymph node cells were assessed. RESULTS: The IgG1 isotype induced coating of T cells, modulation of surface CD4 molecules, and profound depletion of CD4+ lymphocytes in peripheral blood, which persisted as long as the animals were followed (up to 7 weeks). The IgG4 isotype induced only cell coating without cell clearance or modulation. In lymph nodes, coating of lymphocytes (approximately 60%) was seen with both isotypes in the earliest sample (6 hr). After 2 days, significant depletion of lymph node CD4 cells was evident, with a decrease in the CD4 to CD8 ratio in the IgG1-treated group; no depletion occurred in the IgG4 group. The emigration of CD4+ cells into the allograft was significantly delayed in the CDR-OKT4A/hIgG1-treated animals when compared with the CDR-OKT4A/hIgG4 group as judged by immunocytochemistry (23.8+/-13.2 days vs. 7.4+/-1.5 days, P<0.001) or interleukin-2-promoted T-cell outgrowth from allograft biopsies (22.2+/-11.0 days vs. 6.3+/-0.5 days, P<0.01). CONCLUSIONS: This study demonstrates that the in vivo effects of CDR-grafted OKT4A are dependent on its isotype. The depleting mAb CDR-OKT4A/hIgG1 significantly delays the entry of CD4+ cells into the graft, inhibiting the early phase of rejection. However, graft rejection occurs when CD4+ cells eventually infiltrate the graft, even in the presence of depressed levels of circulating CD4+ cells. Both isotypes demonstrated therapeutic efficacy: graft survival was prolonged over controls. In the case of CDR-OKT4A/hIgG4, neither lymphocyte depletion, antigenic modulation, nor prevention of infiltration is necessary for a beneficial effect, which indicates that this mAb blocks CD4 function or renders the CD4+ cell less responsive. The lack of depletion is a feature of potential clinical advantage in minimizing the risk of excessive immunosuppression.

Animals↗
PubMed2000

Cardiac surgery in patients with end-stage renal disease: 10-year experience.

BACKGROUND: End-stage renal disease is known to be an important risk factor complex for cardiac operations performed with cardiopulmonary bypass. METHODS: To investigate the influence of preoperative status on perioperative mortality and morbidity, we retrospectively analyzed data from 65 patients (20 women and 45 men with a mean age of 58.8+/-10.0 years [+/-standard deviation]) with end-stage renal disease who were on dialysis and who underwent a cardiac surgical procedure between 1988 and 1998. RESULTS: Fifty-one percent of the patients had isolated coronary artery bypass grafting, 35% had replacement or reconstruction of one valve or two valves, and 14% underwent combined coronary artery bypass grafting and valve replacement. The perioperative mortality rate was 13.8% with 78% (7 of 9) of deaths occurring in patients having a valve procedure. Six of the 9 patients who died had compromised left ventricular function preoperatively, and all 9 were in New York Heart Association class III or IV. Mean preoperative duration of dialysis was longer (80+/-70 months) in the 9 patients who died compared with that in the surviving 56 patients (45+/-49 months) (p = 0.05). We found dyspnea at rest, duration of dialysis of 60 months or more, combined procedures (coronary artery bypass grafting and valve operation), and New York Heart Association class IV to be associated with a higher relative risk for perioperative death. Neither angina pectoris nor isolated coronary artery bypass grafting was associated with increased relative risk for perioperative death. However, after a cardiac operation, mortality in patients with end-stage renal disease was substantially higher than in those with normal renal function. CONCLUSIONS: These data are comparable with those in the literature and possibly suggest that both indications and referral for surgical intervention have been delayed in patients who have end-stage renal disease combined with coronary artery disease, valve disease, or both. The delay may contribute to the relatively high perioperative mortality.

Adult↗
PubMed1977

Deficiency in the thymus-dependent immunity in "lethargic" mutant mice.

T cell function of "lethargic" mutant mice which exhibit spontaneous thymic involution was evaluated by skin transplantation and graft-versus-host reaction tests. At 15 to 30 days of age, the mutant mice did not reject skin allografts, but by 45 days of age their response was normal. Spleen cells from 24-day-old mutant donors demonstrated delayed appearance of graft-versus-host induced splenomegaly in F1 recipients. Implications of these results in understanding the immunological status of lethargic mice were considered.

Animals↗
PubMed2004

Locking compression plates for osteoporotic nonunions of the diaphyseal humerus.

Poor bone quality increases the technical difficulty and complications of operative treatment of nonunions and delayed unions of the diaphyseal humerus in older patients. Plates with screws that lock to the plate (transforming each screw into a fixed blade) are intended to improve the fixation of poor quality bone. Twenty-four patients (20 women, four men) with an average age of 72 years (range, 52-86 years) were followed up for a minimum of 12 months after locking compression plate fixation of an osteopenic delayed union (nine patients) or nonunion (15 patients) of the diaphyseal humerus. Twelve patients had iliac crest cancellous bone grafts, two patients had local graft, and 13 patients had demineralized bone applied to the fracture site. All the fractures eventually healed; two healed after a second procedure for autogenous bone grafting in patients who initially received demineralized bone. Using a modification of the Constant and Murley shoulder score, the results were good or excellent in 22 patients, and fair in two patients. Locking compression plates provide stable fixation of poor quality bone in patients with delayed union or nonunion of the humerus. Successful union and restoration of function are achieved in most patients. We no longer consider osteoporosis a contraindication to operative fixation of an ununited fracture of the humeral diaphysis.

Aged↗