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PubMed1980

The protective effect of methyl prednisolone on the machine-preserved kidney.

Fifty cadaveric transplants were reviewed to determine whether graft failure was related to the method of preservation. Twenty-eight transplants were preserved by a combination of cold storage and perfusion with cryoprecipitated plasma. Twenty-two transplants were preserved by continuous perfusion with Plasmanate. The perfusate of 14 plasma-perfused kidneys contained 1.0 g of methyl prednisolone, whereas the Plasmanate contained only 100 mg hydrocortisone. Fourteen plasma-perfused kidneys functioned immediately (Group I), and 14 showed delayed function. Seventeen of 22 Plasmanate kidneys (Group III) functioned immediately. Of the Group I kidneys, 13 of 14 functioned for three to eight months, and eight (57%) are still functioning after two years vs. only three of 14 (21%) in Group II. Eleven of the 14 long-term surviving grafts were pretreated with methyl prednisolone. Only nine of the Plasmanate kidneys (39%) lasted more than three months; five (22%) survived more than 12 months. None of the Plasmanate-perfused kidneys that failed to function immediately lasted three months. It is concluded that immediate restoration of renal function after transplantation is a favorable sign for long-term graft survival. The addition of methyl prednisolone to the perfusate may enhance the survival of kidney allografts.

Graft Survival↗
PubMed1989

Segmental duct-obstructed pancreas grafts versus pancreaticoduodenal grafts with enteric diversion.

Between January 1985 and September 1987, we performed a prospective comparative study between segmental-pancreas transplantation with duct obstruction by neoprene (n = 17) and pancreaticoduodenal transplantation with enteric diversion to a Roux-en-Y intestinal loop (n = 14). All recipients had insulin-dependent diabetes. The immunosuppressive protocol consisted of low doses of the steroids cyclosporin A and azathioprine. Mean follow-up was 16.5 mo for the enteric-diversion group and 13.5 mo for duct-obstructed groups. Two-year patient and pancreas- and kidney-graft actuarial survival rates were 92.9, 75.5, and 74.2%, respectively, in the former group and 92.3, 58.4, and 63.7%, respectively, in the latter group (NS). Five whole-organ grafts were lost (3 vascular thromboses, 1 pancreatitis, 1 rejection), and four segmental grafts were lost (2 vascular thromboses, 1 bleeding, 1 patient's death with functional graft). More surgical complications occurred in the recipients of whole-organ grafts and were often related to the intestinal anastomosis. A satisfactory blood glucose control was observed at 3 mo and 1 yr in both groups. Provocative tests showed higher and prompter insulin secretion in patients with whole-organ grafts. In patients with segmental grafts, the response was lower and delayed with a general tendency to impaired glucose tolerance. A marked hyperinsulinemia after meals was observed in whole-organ graft recipients. Slight nocturnal hyperinsulinemia was observed in both groups. At 1 yr, glycosylated hemoglobin was normal in both groups. The absence of a significant difference between the two groups, in terms of survival and graft function, and the lower surgical complication rate seen with segmental grafts have made us return to neoprene-injected segmental grafts.

Circadian Rhythm↗
PubMedDate not supplied

Secondary microvascular tongue reconstruction: functional results.

Between 1978 and 1991, 56 microvascular composite flaps were used for oromandibular reconstructions: 15 for primary total and subtotal tongue reconstruction and five for secondary major tongue reconstruction. The delayed reconstructions were performed to improve the oral and pharyngeal phases of swallowing. Using a floor of the mouth composite bone grafting technique to reposition the tongue and obliterate the oral dead space intraoral food transport was improved (three of five patients), but aspiration persisted (three of four patients). When compared with 10 patients evaluated for primary total and subtotal tongue reconstruction the primary reconstruction group showed superior swallowing (eight dynamic oral transport, no aspiration) and speech results. The poor results of secondary reconstruction are attributed to scarring and irreversible damage to remaining functional muscles involved in protecting the laryngeal aditus.

Aged↗
PubMed2004

Antiviral immunity and T-regulatory cell function are retained after selective alloreactive T-cell depletion in both the HLA-identical and HLA-mismatched settings.

Nonselective T-cell depletion reduces the incidence of severe graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, but the cost is delayed and disordered antigen-specific immune reconstitution and increased infection. We use a method of selective depletion of alloreactive T cells expressing the activation marker CD69 after coculture with stimulator cells in a modified or standard mixed lymphocyte reaction. The technique has been shown to reduce alloreactivity while retaining third-party responses in vitro and, in a mismatched murine model, led to donor T-cell engraftment with a virtual absence of graft-versus-host disease and increased survival. We show in a human HLA-mismatched and unrelated HLA-identical setting that this technique retains >80% of specific cellular antiviral activity by cytomegalovirus-tetramer analysis and cytomegalovirus/Epstein-Barr virus peptide-stimulated interferon-gamma ELISpot assay. Furthermore, CD4(+) CD25(+) T-regulatory cells are not removed by this method of selective allodepletion and retain their function in suppressing allogeneic proliferative responses. Preservation of antiviral cytotoxic T lymphocytes in selectively allodepleted stem cell grafts would lead to improved antiviral immunity after transplantation. The retention of immunosuppressive CD4(+) CD25(+) T-regulatory cells could lead to more ordered immune reconstitution and further suppress alloreactive responses after transplantation.

Animals↗
PubMed2004

Human islet graft function in NOD-SCID mice predicts clinical response in islet transplant recipients.

The purpose of this study was to evaluate the utility of nondiabetic immune-deficient NOD-SCID mouse model in assessing the functional capacity of isolated human islets. We transplanted 2000 islet equivalents obtained from six preparations used for human islet transplantation in three patients under the kidney capsule of groups of 10 mice. Human (Hu) C-peptide and insulin levels were determined following intraperitoneal (i.p.) glucose challenge at days 0, 7, 14, 21, 30, 60, 90, and 120. The Hu C-peptide level >1.5 ng/mL was the threshold for islet function in this model. The first patient did not achieve insulin independence and had minimal (0.5 ng/mL) fasting C-peptide levels that mirrored the low C-peptide levels observed in the mice. After the first infusion, the insulin requirements were reduced by 50% in the second patient. She became insulin free 10 days after her second infusion with a C-peptide level of 3.0 ng/mL, which corresponded to the peak C-peptide level (3.9 ng/mL) observed in the mice. By 150 days' posttransplant, the decline in C-peptide level paralleled the decline observed in mice. Within 2 weeks after the first transplant, insulin dose was reduced by 75% in the third patient, which corresponded to the robust C-peptide production in mice (7.3 ng/mL). Both patient and mice had a delay in islet function following the second infusion. She remained with a C-peptide level of 1.8 ng/mL and insulin free until suffering a rejection episode 3 months later. We observed that human islet graft function in NOD-SCID mice correlated with clinical response in islet transplant recipients.

Animals↗
PubMed2006

Opening wedge high tibial osteotomy: an operative technique and rehabilitation program to decrease complications and promote early union and function.

BACKGROUND: High tibial osteotomy has been associated with significant complications, including delayed union or nonunion, loss of correction, arthrofibrosis, and patella infera. HYPOTHESES: A technique for opening wedge osteotomy that incorporates an autogenous iliac crest bone graft will prevent delayed union or nonunion, allow early rehabilitation and weightbearing, and prevent knee arthrofibrosis and patella infera. Secondly, the authors' methods for calculating the desired correction of valgus alignment prevent undesired alterations in tibial slope. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 55 consecutive patients who underwent high tibial osteotomy were observed at a mean of 20 months postoperatively. Preoperative and postoperative measurements of radiographs were conducted by independent examiners for bony union, tibial slope, and patellar height. The osteotomy opening size ranged from 5 to 17.5 mm; 35 knees (64%) had openings < or =10 mm, and 20 knees (36%) had openings >11 mm. RESULTS: The osteotomy united in all patients. Three patients had a delay in union, which resolved by 6 to 8 months postoperatively. A loss of fixation occurred in 1 patient, who admitted to full weightbearing immediately after surgery; the osteotomy required revision. The iliac crest graft site healed without complications, and there were no infections, loss of knee motion, nerve or arterial injuries, alterations in tibial slope, or cases of patellar infera postoperatively. Full weightbearing was achieved at a mean of 8 weeks (range, 4-11 weeks) postoperatively. CONCLUSIONS: The operative technique including use of an autologous iliac crest bone graft in addition to a progressive rehabilitation program successfully prevented nonunion, change in tibial slope, and knee arthrofibrosis in this study.

Adult↗
PubMedDate not supplied

Spinal tuberculosis with neurological deficits.

Two hundred patients suffering from tuberculosis (TB) of the spine with neurological complications were the subjects of this review. They were graded according to the Frankel system into--A: complete neurological deficit; B: sparing of some sensation; C: sparing of sensation but no useful motor function; D: sparing of sensation and useful motor function; and E: no deficits. Investigations carried out included detailed neurological assessment, radiography, contrast myelography and, in the later stages of the study, spinal computerized tomography (CT) scan. The authors believe that contrast myelography provides the best indication of spinal compression in TB spine. Treatment was by surgical decompression followed by chemotherapy. The surgical approach for thoracic spine disease was by the anterior transthoracic route. Cervical lesions were also approached by the anterior route, lateral to the carotid vessels. Unexpected findings during operation included lymphoma, plasmacytoma, non-tuberculous granulation tissue, salmonella osteomyelitis and tumour metastasis. Ten patients died during the postoperative period, all of whom had extensive systemic TB. When indicated, antituberculous drugs were administered postoperatively for two years and immobilization was done in a plaster cast for 3 months. Only 30 patients showed partial recovery. Improvement was found to be related to the grade of deficit; thoracic lesions with severe neurological deficits showed the least improvement while lumbar disease had the best outcome. The study recommended a combination of surgery and chemotherapy for all cases of TB spine with neurological deficits after a short delay during which respiratory function should be improved. The surgery should aim at decompression of the cord by removal of pus, granulation tissue and sequestra, with internal splintage with bone grafts to reduce the hospital stay. Conservative treatment is unwise because it is not always possible to distinguish between TB and neoplastic lesions.

Female↗
PubMed2006

Stable graft function after reduction of calcineurin inhibitor dosage in paediatric kidney transplant patients.

BACKGROUND: Chronic calcineurin inhibitor (CNI) toxicity contributes to the development and progression of chronic allograft nephropathy (CAN), which is still the major cause of transplant dysfunction and graft loss. Reduction in dosage of CNI may delay the development of CAN, leading to longer graft survival. METHODS: Therefore, 19 paediatric kidney transplant patients under immunosuppressive therapy with CNI (12/19 ciclosporin A, CSA, 7/19 tacrolimus, Tac), mycophenolat mofetil and some patients on steroids were included in a prospective study. Over a period of 9 months CNI dosage was stepwise reduced from CSA trough levels of 100-150 ng/ml to 50-70 ng/ml and Tac trough levels of 5-8 ng/ml to 2-3 ng/ml, respectively. RESULTS: Glomerular filtration rate was stabilized in patients after CSA and Tac reduction. One borderline rejection occurred in a patient prior to reduction of Tac. In patients on CSA, one interstitial cellular rejection (BANFF IA) was noted. Reduction of CNI had no significant effects on blood pressure, lipid status and the infection frequency. CONCLUSIONS: In paediatric kidney transplant patients, reduction of CNI down to low trough levels stabilizes renal function. However, the risk of acute rejection episodes may be increased. Therefore, further studies based on protocol biopsies within a randomized trial are warranted.

Adolescent↗
PubMed2002

Short-term outcomes of Thymoglobulin induction in pediatric renal transplant recipients.

No data are currently available that describe the clinical outcomes associated with Thymoglobulin (rabbit polyclonal anti-thymocyte globulin) induction in pediatric renal transplant recipients. We report the outcomes of 17 pediatric renal transplant recipients (mean age 10.1+/-5.2 years) transplanted between 1 August 1999 and 31 July 2001. Eleven patients (65%) were Caucasian and 6 (35%) were African-American. Eleven (65%) recipients received cadaveric allografts. Two patients (12%) were second allograft recipients. One patient had primary allograft non-function secondary to vascular thrombosis. Two patients (12%) had delayed allograft function. Immunosuppression consisted of Thymoglobulin induction (mean number of doses 6+/-1.7) with tacrolimus (62%) or cyclosporine A (38%), mycophenolate mofetil, and prednisone. One year post transplant, patient and graft survival was 100% and 93%, respectively. No acute rejection episodes occurred during the first 6 months after transplantation in any of the recipients. Additionally, no rejection episode occurred among the 14 patients followed for 1 year after transplant. The incidences of asymptomatic cytomegalovirus (CMV) and Epstein-Barr virus (EBV) seroconversion at 1 year in seronegative recipients with a seropositive donor were 100% of 4 patients and 0% of 4 patients, respectively. No symptomatic CMV or EBV infections and no post-transplant lymphoproliferative disease have occurred in any patient. These short-term data suggest that Thymogobulin induction is safe and effective in combination with triple immunosuppressive therapy for preventing early rejection in pediatric renal transplant recipients.

Acute Disease↗
PubMed1999

Reconstruction of large defects in the scalp with fasciocutaneous flaps.

Although recent reports have emphasised free microsurgical transfer for reconstruction of extensive defects in the scalp, in our experience a carefully planned scalp flap is a simpler and safer method than a free transfer. Twenty-one patients with defects as large as 10%-60% of the scalp surface area were reconstructed; the calvarium was resected in five cases and the dura mater in two. In 18 cases the flaps were based on a single pedicle: the superficial temporal artery. In three cases the blood supply of the flaps was based on three major homolateral arteries: the superficial temporal, the posterior auricular, and the occipital. The blood supply of all scalp flaps was based on the interconnected network of the aponeurotic plexus and the pedicles were included into flap in 18 cases. The principles of fasciocutaneous flaps were applied for all 21 scalp flaps. The reconstruction of the skull was delayed in all cases, and the dura was replaced by free autogenous periosteum. The donor area was covered with a skin graft in all cases. In all patients the aesthetic and functional results were considered excellent by them and by us. There were no postoperative complications.

Aged↗
PubMed1994

The role of nucleotides in adult nutrition.

Dietary nucleotides, found in normal diets, have been recently determined to be required for normal immune defenses. Rejection of cardiac transplants, graft-vs.-host disease, and delayed cutaneous hypersensitivity in animal models are all suppressed by a diet deficient in nucleotides. T lymphocytes seem to require dietary nucleotides for normal maturation and function. Host resistance to bacterial and fungal infections is decreased in mice on nucleotide free diets; addition of RNA or uracil prevents this vulnerability to infection. Dietary RNA is required to restore lost immune function after protein deprivation. Adequate calories and protein alone do not return immune function to normal. Dietary nucleotides can restore lost immune function even during protein starvation and weight loss. Because all parenteral and most enteral nutrient solutions are nucleotide free, clinical studies were undertaken comparing a new nucleotide containing diet (Impact) to a standard high protein enteral feeding. In two separate double blind clinical studies the patients fed the enteral diet containing nucleotides had improved immune function compared with patients receiving a nucleotide free diet. In addition, infectious complications and length of hospital stay were reduced in postoperative cancer patients fed Impact compared with a control group.

Adult↗
PubMed1977

Lip and laryngeal flaps for reconstruction of the floor of the mouth following glossectomy.

Following glossectomy, the reconstruction of the floor of the mouth is a major problem facing the head and neck surgeon. We have devised split-lip and laryngeal mucosal flaps for this. In selected patients, they have a significant advantage over distant skin flaps. The initial postoperative deformity, from the lip being drawn into the mouth, is corrected by a secondary operation with split-skin graft reconstruction of the vestibule. These lip and laryngeal flaps do not require a delay procedure prior to the cancer surgery, and the operating time is considerably reduced. The cosmetic and functional results have been satisfactory.

Glossectomy↗
PubMed2001

Early fracture of the sacrum or pelvis: an unusual complication after multilevel instrumented lumbosacral fusion.

STUDY DESIGN: A retrospective review of a series of cases with a complication of instrumented lumbosacral fusion. OBJECTIVES: To present a previously undescribed complication, early sacral or pelvic stress fracture, after instrumented lumbosacral fusion and to identify the risk factors associated with this complication. BACKGROUND: There are a number of well-described complications of instrumented lumbosacral fusion, including delayed stress fracture of the pelvis. Early sacral or pelvic stress fracture after instrumented lumbosacral fusion has not been previously reported, to the authors' knowledge. METHODS: The authors present three cases of early stress fracture occurring at 2-4 weeks after surgery in patients who underwent instrumented multilevel lumbosacral fusions for degenerative lumbosacral disease. RESULTS: Two patients had sacral fracture, which to the authors' knowledge, has not been previously reported. Risk factors included lumbosacral instrumentation and fusion, osteoporosis in elderly women, and iliac crest bone graft procurement. All patients were treated conservatively, with restricted ambulation and gradual return to activity. CONCLUSION: This complication can cause significant morbidity and a delay in the patient's return to function. A better understanding of the related biomechanical forces and preoperative risk factors may identify patients at risk and may aid in surgical planning and in expectations of postoperative recovery.

Aged↗
PubMed2002

Proliferative and cytokine responses in CTLA4-Ig-treated diabetic NOD mice transplanted with microencapsulated neonatal porcine ICCs.

Our goal is to develop effective islet xenografts for treating human diabetes. We have studied microencapsulated neonatal porcine islet cell clusters (ICCs) transplanted intraperitoneally in spontaneously diabetic NOD mice, where they function to maintain normoglycemia in the autoimmune host. Nonencapsulated neonatal porcine ICCs functioned for 4.5 +/- 0.5 days before being rejected; encapsulation prolonged graft function to 17 +/- 2 days. CTLA4-Ig treatment did not enhance the survival of nonencapsulated ICCs. However, CTLA4-Ig treatment significantly extended the function of encapsulated ICCs to 73 +/- 5 days. Histological analyses demonstrated a profuse pericapsular cellular reaction associated with rejection of encapsulated islet xenografts in untreated mice, while this reaction was significantly reduced in CTLA4-Ig-treated mice. To study mechanisms of xenograft rejection in this model, we analyzed proliferative responses to neonatal porcine ICCs and cytokines present in the peritoneal cavities of transplanted mice. Spleen cells from both CTLA4-Ig-treated and untreated rejecting NODs exhibited vigorous proliferation in the absence of antigenic stimulation, suggesting prior activation in vivo, while splenocytes from CTLA4-Ig-treated NODs with functioning grafts had low proliferative levels, equal to controls. Islet-specific proliferation was not detected in islet-rejecting mice, perhaps due to their high background levels. With the exception of elevated IL-6 levels, empty capsules did not provoke a significant peritoneal cytokine response compared with sham surgery or untransplanted control mice. However, IL-5, IL-12, TGF-beta, and IL-1beta were significantly elevated in NODs receiving encapsulated neonatal porcine ICCs compared with untransplanted controls. There were no significant differences between peritoneal cytokine concentrations in CTLA4-Ig-treated mice with long-term functioning grafts compared to mice that rejected grafts at earlier time points. We conclude that the combination of donor islet microencapsulation and brief treatment of the recipient with co-stimulatory blockade delays sensitization of the host, possibly by altering mechanism(s) for recruitment and/or activation of host effector cells.

Abatacept↗
PubMed1993

Fractures of the femoral shaft adjacent to long stem femoral components of total hip arthroplasty: report of seven cases.

Seven femoral shaft fractures adjacent to the distal aspect of long stem revision femoral components of total hip arthroplasty were evaluated at a mean of 6 years (range: 2 to 12) after fracture. Nonoperative treatment with a spica cast was used in four patients. Complications were delayed union in two patients and malunion in two. Operative treatment included revision and bone grafting in one patient and open reduction and internal fixation in two. Plate fracture and delayed union occurred in one patient. Operative treatment resulted in no malunions and earlier recovery of function than with nonoperative management. Femoral shaft fractures adjacent to long stem total hip arthroplasties are difficult to manage; the complication rate is 71%.

Aged↗
PubMedDate not supplied

The role of popliteal artery embolectomy in the management of acute lower limb ischemia: our experience.

INTRODUCTION: The Authors report their experience in the management of acute lower limbs ischemia through distal popliteal artery approach. PATIENTS AND METHODS: Five popliteal embolectomy through a medial approach were performed; in one patient a posterior approach was carried out. Patients were included in two groups on the basis of ischemia duration: group A<6 hours (3 patients) and group B>6 hours (3 patients). Colour-duplex scan was performed in all the patients The arteriotomy was closed with interrupted 7/0 monofilament polypropylene sutures. RESULTS: There were no peri-operative deaths. The primary limb salvage rate was 83.3% (5 patients). In one case (16.7%) a major amputation was performed. In one case (16.7%) a drop foot occurred. CONCLUSIONS: The popliteal embolectomy is followed by excellent results and should be consider prior to thrombolysis or bypass graft revascularization. An appropriate use of duplex scan and a medial approach can lead to an high successful rates in terms of limb function and limb salvage also in cases with delayed ischemia.

Acute Disease↗
PubMed1987

Experimental evaluation of a new albumin-impregnated knitted dacron prosthesis.

The performance of a new albumin-impregnated, knitted vascular graft stored damp in saline was assessed by a comparative study in the canine aorta. Knitted grafts interposed into the descending thoracic aorta for 4 weeks included: albumin-coated and stored damp in saline (damp albuminated) (n = 6), albumin-coated and freeze-dried (dry albuminated) (n = 5), collagen-coated (n = 4), and uncoated (n = 4). The results of macroscopic and microscopic evaluation were subjected to one-way analysis of variance (Newman-Keuls). Damp albuminated grafts had significantly less transinterstitial blood loss than uncoated grafts (P less than 0.05). No significant differences in thrombogenicity, thrombus-free surface area, tissue ingrowth, or endothelial coverage existed between the damp albuminated and the uncoated grafts. However, significantly less thrombogenicity (P less than 0.05) and more endothelial cell coverage (P less than 0.05) were present in the damp albuminated grafts than in the collagen-coated grafts. No evidence for delayed graft hemorrhage or distal embolization was found in any group. The new damp albuminated graft is a minimally thrombogenic prosthesis combining low implantation porosity with relative ease of handling. It should function well as a low porosity graft for great vessel replacement.

Animals↗