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PubMed1995

Prolongation of rat islet allograft survival by treatment with monoclonal antibodies against VLA-4 and LFA-1.

In this study, we investigated the effects of treatment with monoclonal antibodies against the VLA-4 and LFA-1 adhesion molecules on rat islet allograft rejection. TA-2 and TA-3 are function-blocking mAb against rat VLA-4 and LFA-1, respectively. Lewis rats were made diabetic (plasma glucose levels > 22.2 mmol/L) with streptozotocin. One week later, 1500 freshly isolated Wistar Furth rat islets were transplanted under the left kidney capsule of each rat. Monoclonal antibodies were administered intravenously at a dosage of 2 mg on the day of islet transplantation and then intraperitoneally every second day for 3 weeks or until graft rejection. Plasma glucose levels were monitored at least 3 times a week and blood leukocyte counts were monitored every 4 days. Rejection was defined as 2 plasma glucose levels > 11.1 mmol/L. Mean graft survival times in untreated and control mAb-treated rats were 5.3 and 6.0 days, respectively. Treatment with anti-VLA-4 or anti-LFA-1 resulted in only modest prolongation of mean graft survival time (9.3 and 7.4 days, respectively). However, treatment with the combination of anti-VLA-4 plus anti-LFA-1 resulted in long-term (i.e., 60-day) graft survival in 5 of 7 rats. Graft nephrectomy and histology confirmed islet graft survival at 60 days. A second Wistar Furth rat islet graft under the opposite renal capsule after graft nephrectomy did not show full tolerance; however, the function of the second graft was significantly prolonged without any immunosuppression. Combined blockade of VLA-4 and LFA-1 also markedly prolonged islet graft survival when islets were transplanted via the portal vein. In conclusion, both VLA-4 and LFA-1 play a role in islet allograft rejection and blockade of both prevents or greatly delays graft rejection.

Animals↗
PubMed1987

Evidence that thymectomized, bone marrow-reconstituted rats do not reject their allografts.

We have investigated the reasons why thymectomized, bone marrow-reconstituted (B) rats do not reject their allografts, by comparing the structure of inflammation and functions of inflammatory cells in nonrejecting allografts to rejecting allografts in normal control recipients. The results demonstrate that B recipients mount a specific cellular response towards the graft. The response in B recipients differs from that in normal controls by a smaller intensity of inflammation, fewer blast cells, and activated mononuclear phagocytes in the inflammatory infiltrate, as well as a delay in the appearance of specific donor-directed lytic activity in the graft. B rats also have fewer blast cells and an inverted CD4/8 ratio in the spleen. There is no obvious absence of any given cell type or cellular function in the graft inflammatory infiltrate. In light of these results no cell type responsible for allograft nonrejection can be pinpointed.

Animals↗
PubMed2005

Treatment of femoral head necrosis with free vascularized fibula grafting: a preliminary report.

Since October 2000, 56 hips in 48 patients with avascular necrosis of the femoral head were treated with free vascularized fibular transplants. The average follow-up was about 16 months. The Harris hip scores of all stages were improved during follow-up. Most femoral heads showed improvement (39 hips, 69.6%) or were at least unchanged (14 hips, 25.0%) on X-rays. The results show that a free vascularized fibular graft would be a valuable procedure for femoral head necrosis. By this method, we can avoid or delay progress of the disease, and improve the function of the hip and quality of life.

Adult↗
PubMed1999

Free jejunal grafts of the pharynx: surgical methods, complications, and radiographic evaluation.

Free jejunal grafts have been used in the surgical treatment of patients with carcinoma of the pharynx and upper esophagus. Post-operative complications, including swallowing difficulty, are frequent and radiographic assessment may be required. In this pictorial paper, we describe the surgical technique of free jejunal grafting of the pharyngoesophagus, and the radiographic appearances and clinical importance of early and delayed complications following the procedure. Dysphagia after placement of a jejunal graft is a common occurrence which is often multifactorial, and may be related to functional, anatomic, or a combination of factors.

Carcinoma, Squamous Cell↗
PubMed2006

Preoperative evaluation and treatment of stable CAD in patients scheduled for major elective vascular surgery.

One of the most controversial topics in clinical cardiology is the extent of preoperative studies that is required among patients scheduled for major elective noncardiac operations. Patients in need of an elective operation for either an expanding aortic aneurysm or lower limb ischemia have the highest risk of postoperative cardiac complications because of the high prevalence of coronary artery disease and the hemodynamic stresses associated with the vascular procedures. The decision to perform preoperative coronary angiography should be reserved for only those patients who are deemed clinically unstable or are functionally limited by cardiac symptoms. Among patients with minimal symptoms, preoperative coronary artery revascularization with either coronary artery bypass graft surgery or percutaneous coronary interventions delays the needed operation and does not improve short-term outcomes or long-term survival.

Journal Article↗
PubMed2006

Prevalence and clinical course of BK virus nephropathy in pancreas after kidney transplant patients.

The influence of BK virus nephropathy (BKVN) in pancreas after kidney (PAK) transplantation is unclear. A retrospective analysis of PAK transplants performed at our center was conducted to determine the impact of BKVN. Among 40 PAK transplants performed using sequential immunosuppression, four patients developed BKVN, as defined by a >20% rise in serum creatinine and BK viremia (BK plasma load >4 log copies/mL), at a median of 19 months following PAK. In all four patients, treatment of BKVN consisted of reduction in tacrolimus, cessation of mycophenolate mofetil, and introduction of leflunomide. With this approach, two patients experienced improvement or stabilization of renal function. The remaining two patients progressed to dialysis dependence despite treatment. Plasma BK load < or =5 log copies/mL was associated with graft preservation. Gender, age, delay between transplants, cumulative Thymoglobulin dose, and type of kidney donor were not associated with BK virus infection. Pancreas graft rejection or dysfunction was not observed with the above immunosuppression modification. Mean amylase and lipase > or =6 months following BKVN treatment remained normal. BKVN is an important cause of kidney allograft loss in PAK patients. Screening and early treatment of BKVN may enable preservation of kidney and pancreas grafts.

Antiviral Agents↗
PubMed2004

Prevalence and predictors of heart failure with preserved systolic function: community hospital admissions of a racially and gender diverse elderly population.

BACKGROUND: The reported prevalence of preserved systolic function (PSF) heart failure (HF) varies widely and has not been well-studied in nonwhite patients. To estimate the prevalence of PSF HF resulting in hospital admission, we studied admissions to a large community hospital serving a racially diverse community. METHODS: The charts of 300 consecutive patients > or =65 years old with a primary discharge diagnosis of HF were reviewed. In patients who met the Framingham criteria for HF diagnosis, an assessment of left ventricular function was obtained from review of chart data. Comparison of baseline characteristics and multivariate analysis of potential predictors of PSF HF was undertaken. RESULTS: Of the 300 patients, 247 (82%) met the Framingham criteria for diagnosis of HF. Ninety-seven patients (39%) of these had PSF. Twenty (8%) of the diagnosed HF patients had a diagnosis of severe aortic or mitral valvular disease, 9 of whom had preserved systolic functions. Thus 88 (36%) of the HF patients had PSF HF likely resulting from diastolic dysfunction. On multivariate analysis, age, hypertension at presentation, peripheral edema, normal sinus rhythm and a history of coronary artery bypass grafting or coronary angioplasty were significantly associated with PSF HF rather than HF with reduced systolic function. Left bundle branch block or other intraventricular conduction delay was independently associated with reduced systolic function HF. However, because these findings occurred in patients with and without systolic dysfunction, none were pathognomonic of PSF HF. CONCLUSION: In this racially diverse, majority nonwhite, cohort of older patients admitted for HF, the Framingham criteria for the diagnosis of HF were met in 82% of the patients. Of these, 39% had PSF HF and 36% had PSF HF in the absence of severe aortic or mitral valve disease, suggesting that diastolic dysfunction was etiologic. Although there was an independent association of PSF HF with a number of clinical characteristics, none of these characteristics was pathognomonic of preserved, versus reduced, systolic function HF.

Aged↗
PubMed2003

Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation.

Polyclonal anti-thymocyte globulin (ATG) administered before allogeneic blood hematopoietic progenitor cell transplantation reduces the risks of graft rejection and graft-versus-host disease, but may delay posttransplant immune reconstitution caused by delayed clearance of ATG from the blood. We studied graft-versus-host disease, infections, and the kinetics of immune reconstitution in 28 patients with very poor-risk hematologic malignancies who received lymphocyte-depleted, CD34(+) cell-enriched hematopoietic progenitor cell grafts from partially HLA-matched related donors (PMRD). The incidence of these clinical events was correlated with blood ATG levels in 19 transplant recipients who received rabbit ATG (r-ATG, thymoglobulin) during conditioning. Total r-ATG and the fraction of ATG antibodies that bind human cells (active ATG) were measured for up to 45 days posttransplantation using enzyme-linked immunosorbent assay and flow cytometry assays. Three patients received equine ATG (e-ATG; total dose of 60 mg/kg/day), 3 patients received 10 mg/kg r-ATG, and 22 patients received 6 mg/kg r-ATG during conditioning. All evaluable patients engrafted. Median numbers of blood CD4(+) and CD8(+) T cells at 100 days posttransplantation were 15 and 8 cells/microL, respectively. Acute graft-versus-host disease developed in 3 of 3 recipients of e-ATG and 1 of 25 recipients of r-ATG. Rapid T-cell reconstitution was seen only in younger patients. Overall mortality was 93% (26/28 patients) with poor immune reconstitution contributing to death in 21 of 28 patients. Recipients of 6 mg/kg r-ATG had peak levels of total and active r-ATG of 64+/-20 microg/mL and 9.2+/-5.8 microg/mL, respectively, with clearance of active r-ATG (t(1/2)6 days) to sub-therapeutic levels (<1 microg/mL) by a median of 15 days posttransplantation (range, 8-38 days). Delayed immune reconstitution is likely a consequence of ex vivo and in vivo purging of donor T cells in the graft coupled with inadequate thymic function rather than persistence of active r-ATG in the blood for months posttransplantation.

Adult↗
PubMed1989

Further studies on the mechanism of radiation induced thymic lymphoma prevention by bone marrow transplantation in C57BL mice.

Whole body fractionated irradiation induces thymic lymphomas in C57BL/Ka mice after a latent period during which intrathymic lymphopoiesis is modified; thymocyte numbers are subnormal and the epithelial component of thymic nurse cells (TNCs) is altered as estimated by the number of TNCs in vivo and by its ability to interact with immature thymocytes in vitro. A graft of normal bone marrow cells immediately after the last irradiation prevents the development of lymphomas; but when such a graft is performed 1 month later, it does not inhibit the emergence of tumors. In both cases the grafted precursors home and repopulate the thymus. However, the delayed graft does not exert any effect upon the altered epithelial component of TNCs, whereas the early one restores the numbers of TNCs and the function of their epithelial component. The results thus demonstrate that lymphoid thymic repopulation by a bone marrow graft is not sufficient to prevent the development of lymphomas and that there is an intimate relationship between tumor development and alterations of nurse cells microenvironment.

Animals↗
PubMed1995

Prefabricated flaps: experimental and clinical review.

Prefabricated flaps are a useful tool for the reconstructive surgeon and present a number of advantages: 1. Specific preferred tissue composites, regardless of their native vascular origin, can be transferred as free or pedicled flaps. 2. Larger flaps of specialized tissue may be transferred safely. 3. Donor-site morbidity is reduced. 4. The functional outcome for the patients may be more satisfactory. The various methods of flap prefabrication include vascular induction through stage transfer; pretransfer delay, expansion, and grafting; the use of alloplastic materials; and tissue bioengineering. We have reviewed both the experimental and clinical research on flap prefabrication, describing the theory, technique, and advantages of each method.

Animals↗
PubMed1995

Pathology and biopsy diagnosis of the transplanted liver.

Over the past 30 years, liver transplantation has evolved from an experimental therapy to a routine procedure and most pathology textbooks have now a section dedicated to the pathology of liver transplant. Although there remain problems of biopsy interpretation due to the numerous post-transplant complications which can occur singly or in association, the major changes have been well characterized and are reviewed here, a particular attention being given to those features which are unique to or distinctive of the liver allograft. These include the outcome of donor fatty liver, reperfusion damage, massive haemorrhagic necrosis and the patterns of rejections, in particular the rarity and delayed onset of hyperacute rejection and the selective involvement of the small interlobular bile ducts and vascular endothelia in both acute and chronic graft rejection. "Functional" cholestasis with hepatocyte ballooning, cholangiolar cholestasis associated with sepsis and lesions of the larger bile ducts which may result from preservation, immune and/or ischaemic injury and closely resemble the changes observed in primary sclerosing cholangitis are also considered. Later in the post-transplant course, changes due to de novo or recurrent hepatitis have to be distinguished from those of late cellular rejection, protracted biliary complications, lymphoproliferative disorders, disease recurrence, in particular autoimmune chronic hepatitis, primary biliary cirrhosis and sclerosing cholangitis, differential diagnoses which often require interpretation of allograft changes in conjunction with all laboratory and clinical data available.

Bile Ducts↗
PubMedDate not supplied

Noradrenergic pharmacotherapy, intracerebral infusion and adrenal transplantation promote functional recovery after cortical damage.

The research described in this review briefly summarizes evidence that short term pharmacological enhancement of noradrenergic (NA) synaptic activity, combined with symptom relevant experience (SRE), promotes functional recovery of some symptoms of cortical damage in rat, cat and human beings even when treatment is initiated from days to weeks after injury. A summary is provided of the numerous drugs tested in rodent cortical injury models which have been proven useful for predicting beneficial or harmful effects on behavioral outcome in human stroke. The pattern of drug effects indicates a central role for NA in functional recovery. Additionally, studies of the effects of direct intraventricular infusion of monoamine neurotransmitters are reviewed and further support the hypothesized role of NA in recovery from some symptoms of cortical injury. The site of NA/SRE interaction to promote recovery from hemiplegia apparently involves the cerebellar hemisphere contralateral to the cortical injury. Microinfusions of NA into the contra- but not ipsilateral cerebellar hemisphere dramatically enhance recovery. Furthermore, like its systemic action, microinfusion of the alpha 1-NA receptor antagonist, phenoxybenzamine, reinstates hemiplegia. A "permanent" symptom of motor cortex injury in the cat is the complete loss of tactile placing contralateral to the injury which does not spontaneously recover for as long as seven years after ablation. This postural reflex is temporarily restored for 8-12 hours following amphetamine administration. However, this permanently lost reflex can be enduringly restored by transplanting catecholamine secreting adrenal tissue into the wound cavity. The experiment is reviewed in detail and involves chromaffin cell autografts into the frontal cortex ablation wound cavity producing a restoration of tactile placing for the 7-10 month duration of the study. This enduring restoration of tactile placing is considered a result of the release of catecholamines into the CNS from the grafted chromaffin cells found, by histochemical methods, surviving 7-10 months after transplant. Lastly, we attribute these delayed treatment effects to an attenuation of a diaschisis, or remote functional depression, in morphologically intact areas anatomically connected to the area of injury. The widespread reduction of glycolytic and oxidative metabolism, produced by focal cortical injury, is normalized by the same treatment which alleviates symptoms and is worsened by drugs which exacerbate deficits. These data support the hypothesis that providing SRE during a period of enhanced NA synaptic activity produces an enduring functional recovery after cortical injury by attenuating remote functional depression. This treatment for enhancing recovery is especially attractive since it is effective even when begun weeks after cortical damage.

Adrenal Glands↗
PubMed1990

Recombinant GM-CSF in patients with poor graft function after bone marrow transplantation.

Poor graft function after bone marrow transplantation is an infrequent complication that is fatal for most patients secondary to severe infections or to bleeding. Even a second marrow infusion is usually not successful in restoring hematopoiesis. We treated nine patients with recombinant Escherichia coli derived human granulocyte-macrophage colony-stimulating factor (GM-CSF) for delayed engraftment or graft failure after autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). Six patients were given a dose of 10 micrograms/kg/d over 30 min; three patients received lower doses of 3-5 micrograms/kg/d. Seven patients lived longer than 3 days after commencing GM-CSF and could be evaluated for their response. Six of them had a marked rise in neutrophil counts; there was no effect on platelet and reticulocyte counts. Two patients died within the first 3 days after starting GM-CSF, although both seemed to have some response to GM-CSF (increasing blood neutrophils in one, and increasing macrophages in the bone marrow on autopsy in the other). Side effects most likely attributable to GM-CSF administration were mild and included diarrhea and abdominal pain, low grade fever and mild rash. Severity of graft-vs-host disease (GVHD) was not enhanced in the recipients of allogeneic marrow. We conclude that recombinant GM-CSF can be safely given to patients with poor graft function after marrow transplantation. In some patients, this may lead to a subsequently sustained neutrophil recovery.

Adolescent↗
PubMed2003

Laparoscopic (vs open) live donor nephrectomy: a UNOS database analysis of early graft function and survival.

The impact of laparoscopic (lap) live donor nephrectomy on early graft function and survival remains controversial. We compared 2734 kidney transplants (tx) from lap donors and 2576 tx from open donors reported to the U.S. United Network for Organ Sharing from 11/1999 to 12/2000. Early function quality (>40 mL urine and/or serum creatinine [creat] decline >25% during the first 24 h post-tx) and delayed function incidence were similar for both groups. Significantly more lap (vs. open) txs, however, had discharge creats greater than 1.4 mg/dL (49.2% vs. 44.9%, p = 0.002) and 2.0 mg/dL (21.8% vs. 19.5%, p = 0.04). But all later creats, early and late rejection, as well as graft survival at 1 year (94.4%, lap tx vs. 94.1%, open tx) were similar for lap and open recipients. Our data suggests that lap nephrectomy is associated with slower early graft function. Rejection rates and short-term graft survival, however, were similar for lap and open graft recipients. Further prospective studies with longer follow up are necessary to assess the potential impact of the laparoscopic procurement mode on early graft function and long-term outcome.

Adult↗
PubMed1990

Suppressive effects of morphine pellet implants on in vivo parameters of immune function.

Chronic morphine treatment elicits a variety of immunosuppressive effects in mice. Most of the work describing this immuno-suppressive activity of the opioid is based on in vitro assessments of the performance of certain components of the immune system in morphine-treated animals. Relatively little has been done by way of tracking the effects of chronic morphine treatment on immunologic parameters in the intact animal. Therefore, this study used several classic in vivo determinations of immune function in mice treated chronically with morphine. Morphine pellet (75 mg) implantation led to a significant inhibition (91%) of paw swelling in a picryl chloride-induced delayed type hypersensitivity response. Uptake of iododeoxyuridine in an in vivo lymphocyte proliferation assay and splenomegaly in a graft vs. host reaction were also significantly suppressed by morphine pellet implantation (34 and 52%, respectively). Coimplantation of a naltrexone pellet (10 mg) completely reversed the suppressive responses to morphine in each assay. Naltrexone alone had no significant effect in any of the assays. The suppressive effects of morphine were less pronounced in adrenalectomized mice in the graft vs. host assay (51% vs. 9% reduction in morphine-pelleted shams relative to morphine-pelleted adrenalectomized mice). These findings indicate the pathophysiologic significance of the previously reported suppression of in vitro correlates of immune function in morphine-pelleted mice. The results further demonstrate that the immunosuppressive effects observed after morphine pellet implantation are naltrexone reversible and suggest that activation of the adrenal is one potential mechanism for this effect.

Animals↗
PubMed1997

Syndactyly repair performed simultaneously with circumcision: use of foreskin as a skin-graft donor site.

A boy who had simple syndactyly involving the third web space of the left hand presented for elective syndactyly repair. Circumcision had been delayed because of neonatal medical problems. Elective syndactyly repair and circumcision were performed in one operation at age 9 months. Penile foreskin was used as a full-thickness skin graft for the syndactyly repair. The foreskin provided a functional syndactyly repair with good aesthetic characteristics. This obviated the need for two separate operations and for an additional skin graft donor site. To our knowledge, this is the first reported case in which foreskin was used for the repair of syndactyly. In boys with syndactyly, the authors advocate that parents be informed of this reconstructive option. Should the parents consider it to be suitable, then elective circumcision should be delayed until the time of syndactyly repair so that foreskin may be used for the syndactyly repair.

Circumcision, Male↗
PubMed1990

Generalized toxicity of L-leucyl-leucine-methyl ester for lymphocyte functions.

This study investigated the hypothesis that sensitivity to L-leucyl-leucine-methyl ester (Leu-leu-O-Me) can be used to identify a role for cytotoxic lymphocytes in alloreactivity. Treatment of donor lymphocytes with Leu-leu-O-Me profoundly inhibited their ability to induce three separate models of murine graft-versus-host reaction (GVHR). This was observed for all aspects of GVHR examined, including weight loss, splenomegaly and activation of natural killer (NK) cells. These effects were not influenced by whether specific cytotoxic T lymphocytes (CTL) were involved in individual models of GVHR. Leu-leu-O-Me not only eliminated NK and CTL activity in vitro, but had identical effects on the proliferation of T and B lymphocytes in response to a variety of mitogenic stimuli. Finally, Leu-leu-O-Me prevented immune lymphocytes from mediating both class I and class II major histocompatibility complex (MHC)-restricted delayed-type hypersensitivity (DTH) responses in vivo. It is concluded that Leu-leu-O-Me has non-specific toxicity for most lymphocyte function and that it cannot be used as a specific means of predicting the functional roles of CTL.

Animals↗