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Biomedical subjects

G P Alexandre

Publications and source records attributed to G P Alexandre.

At least 19 recordsLinked to original sources
PubMed1998

Creation of the "thymoheart" allograft: implantation of autologous thymus into the heart prior to procurement.

BACKGROUND: A state of tolerance may be more easily achieved if fully vascularized and functional donor thymus is transferred to the recipient at the time of whole organ transplantation. METHODS: A composite "thymoheart" allograft was created by implanting autologous thymus into a donor heart 60-90 days before organ procurement. Successful intracardiac engraftment of autologous thymus was documented by histology and by flow cytometric analysis. RESULTS: Histology of the thymic autografts at explantation revealed viable thymus with preservation of normal thymic architecture. Cells retrieved from thymic autografts 60 days after implantation exhibited the same MHC class I and class II staining profiles by flow cytometry as cells taken from the residual native thymus. CONCLUSION: We have created a novel composite organ that confers vascularized and functional donor thymus to heart allograft recipients at the time of transplantation without affecting cardiac function.

Animals↗
PubMed1998

[The current status of organ transplantation: the role of xenotransplantation?].

In the last few years, transplantation was an area of intense research activity. However, there is a worldwide shortage of donor organs for clinical transplantations. Currently, interest in xenotransplantation research is growing not only because of the increased demand for organs but also because of advances in molecular biology techniques that make possible the genetic or immunological manipulations of the animal donor rather than the human recipient. The better definitions of the mechanisms responsible for xenograft rejection should facilitate appropriate therapeutic strategies for long xenograft survival.

Animals↗
PubMed1992

Kidney transplantation in patients with Wilms' tumor.

We report our experience of renal transplantation in three patients treated for Wilms' tumor (with lung metastasis in two of them), and review 26 previously reported cases in order to define the current indications of transplantation in this setting. Our patients, aged 5-12 years, were transplanted 13-95 months after completion of Wilms' tumor treatment. All three are alive and tumor-free, two with a functioning graft 20 and 97 months after transplantation. Two findings emerge from the review of the literature. First, posttransplant mortality is influenced by the delay between completion of tumor treatment and transplantation. Mortality reaches 79% when that delay is less than one year but falls to 27% when that delay exceeds one year. Second, the prognostic value of pretransplant metastasis depends on its location. All four patients with pretransplant abdominal metastasis died with active metastatic disease. By contrast, of three patients treated before transplantation for metastasis confined to the lung, two are alive and tumor free. We conclude that renal transplantation should be offered to patients successfully treated for Wilms' tumor for at least one year, even if the disease has been complicated by pulmonary metastasis. Several long-term survivors attest that the disease can be cured even under maintenance immunosuppression.

Child, Preschool↗
PubMed1992

[Aseptic necrosis of the femoral head following renal transplantation: assessment of a 25-year experience].

From June 1963 to December 1988 aseptic necrosis of the femoral head has been treated surgically in 84 renal transplant recipients (150 surgical procedures). The long-term results of drilling of the neck and head of the femur (16), cup arthroplasty (32), cemented cup (1) and hemiarthroplasty (8) were unsatisfactory, as 23 of these 57 hips underwent a secondary procedure. Total hip arthroplasty progressively became the standard procedure for treatment of hip disease in transplanted patients. Since 1971, 63 renal transplant recipients underwent 92 cemented total hip replacement (THR) as a primary (73), secondary (16) or third (3) surgical procedure for severely symptomatic femoral head necrosis. Hospital stay averaged 22 days, and follow-up averaged 53 months. Two deaths related to the surgical procedure occurred in the first 4 years of our experience (one major local sepsis, one pulmonary infection). Other postoperative complications were urinary tract infection (12), pulmonary infection 1, transient sciatic nerve irritation (3), wound hematoma (6), reversible deterioration of renal function (3) and rejection of the graft (2). Thromboembolic complications did not occur. All operated hips showed a marked symptomatic improvement. Loosening of one or both components was definite in one, probable in two and possible in three of the 33 hips followed up more than 5 years. Other late complications included dislocation (6), painful class III heterotopic ossification (4), recurrence of previous sepsis (1) and late hematogenous sepsis. Late hip revision was required in 5 cases (recurrent dislocation, 1, ossification, 2, sepsis, 2). Two renal complications (one graft infarction and one reversible acute tubular necrosis) occurred after these revisions. The functional results of THR compare favourably with the results of other surgical procedures used in our early experience. We conclude that THR has become the treatment of choice for symptomatic established osteonecrosis of the femoral head in renal transplant patients. A relatively high rate of early and late complications is nevertheless to be expected.

Adolescent↗
PubMed1991

Outcome of thirty patients with Alport's syndrome after renal transplantation.

Graft antiglomerular basement membrane nephritis in patients with Alport's syndrome (AS) is a unique complication related to the glomerular basement membrane (GBM) abnormality characteristic of the disease. Its prevalence and clinical significance however remain unknown. We used strict criteria of AS to select 30 patients (26 men, 4 women), aged 17 to 44 years (m: 27) in whom 35 grafts (30 first, 5 second) had been performed at our center between 1968 and 1988. Patient and graft survival were, respectively, 96 and 75% at 5 years, 77 and 42% at 10 years. Graft survival and function, as well as the incidence of rejection episodes in the AS group were not different from those of a control group without AS, matched for age, sex, graft origin, and immunosuppressive regimen. Fifteen grafts were examined by immunofluorescence at least 3 months after TP: linear IgG deposits along GBM were present in 5 cases in the absence of signs of crescentic glomerulonephritis. Circulating anti-GBM antibodies detected in one of these cases 8 months post-TP had disappeared 24 months later. The presence of linear IgG did not seem to influence graft survival and function. We conclude: (1) the overall outcome of TP in AS patients does not differ from a control group without AS; (2) appearance of linear glomerular IgG is frequent but is not necessarily associated with a poor graft outcome; (3) the course of de novo graft anti-GBM disease may be benign; and (4) the aggressivity of the disease could be determined by the degree of immunosuppression and/or by the specificity of the anti-GBM antibodies.

Adult↗
PubMed1990

Unrelated living donor kidney transplantation.

Since 1966, we have performed 41 renal transplants from unrelated living donors (ULD), 39 of which were "emotionally related". All donor-recipient pairs included in the present series were AB0-compatible. Recipients included 37 with primary and 4 with secondary transplants; 2 of the latter were diabetics. We compared these results to those of 41 recipients of cadaver donor kidneys matched for age, sex, immunosuppressive regimen, rank, and year of transplant, focusing our attention on the subgroups of patients under cyclosporin A (CyA) therapy (n = 24). We found that ULD transplantation was as successful as cadaver transplantation with good HLA matching: at 3 years, graft survival rates were 81% in ULD versus 86% in the control group under CyA. Moreover, grafts from ULD functioned more rapidly (no post-transplant dialysis and 70% of the patients with serum creatinine below 2 mg/dl within 3 days post-transplant). Graft tolerance was equivalent in both groups (50% of the patients experienced no rejection). We conclude that despite poor HLA matching, ULD transplantation with CyA as the basic immunosuppressive agent offers good results: benefiting from the quality of living donor kidney grafts, it helps to alleviate the persistent shortage of cadaver donors.

Adult↗
PubMed1990

Atrial natriuretic factor: a protective role after acute renal ischemia? Is there room for it in kidney transplantation?

Because of the deleterious effects of acute tubular necrosis (ATN) after kidney transplantation, the search for new and effective means of protecting the kidneys from ischemic or nephrotoxic injuries continues. The beneficial effects of hyperhydration with mannitol or furosemide infusions in renal allograft recipients have now been well documented. The recent discovery by De Bold and coworkers that hypervolemia (by atrial distension) induces the release of atrial natriuretic factor (ANF) suggests an important physiopathological, and perhaps therapeutic, role for this natriuretic peptide in kidney transplantation. In addition to providing an overview of the current knowledge about ANF and its effects on both intact and ischemically injured kidneys, the physiological role of ANF in various situations, similar to those found in kidney transplantation, is analyzed. The effects of ANF on arachidonic acid metabolites and on the nephrotoxic side effects of cyclosporin are also reported. If the results of the preliminary experimental studies appear to be effective, further prospective clinical trails must be carried out to confirm them.

Animals↗
PubMed1990

Outcome of patients with tuberous sclerosis after renal transplantation.

The fate of tuberous sclerosis (TS) patients after renal transplantation (RT) for end-stage renal failure remains to be defined. We report three patients with a posttransplantation follow-up averaging 54 months and review 6 previously published cases. Three women, aged 27-46 years, received a cadaver kidney 26-67 months after starting dialysis. None had mental retardation, 2 had suffered from seizures during infancy and 2 had intracranial calcification; neurological involvement was equally mild in the 6 reported patients. Currently, 16-84 months after RT, our 3 patients are fully rehabilitated with a well-functioning graft (serum creatinine 1.2-1.7 mg/dl). Results of RT are also satisfactory in the 4 other reported cases for whom a follow-up is available, except for 1 death unrelated to the initial disease. Neurologic disorders did not progress. Renal cell carcinoma was discovered in one removed kidney, and cells suggestive of malignant transformation in another case. No metastases were discovered up to 4 years later. No neoplastic transformation was observed up to 7 years after RT in the 3 patients who retained their native kidneys. TS patients with end-stage renal failure are good candidates for RT. The probably small risk of neoplastic transformation of native kidneys warrants a close monitoring by CT scan of the few patients who have not undergone bilateral nephrectomy.

Adult↗
PubMed1990

Atrial natriuretic factor, arachidonic acid metabolites and acute renal ischemia: experimental protocol in the rat.

The effects of an atrial natriuretic factor (ANF) infusion upon the production of the arachidonic acid metabolites (thromboxane B2, TxB2; 6-keto-prostaglandin F1 alpha, 6-keto-PGF1 alpha, PGI2, or prostaglandins E2, PGE2) were investigated after acute renal ischemia in the rat. This experimental protocol included a right nephrectomy and a 45-min left renal artery occlusion. Fifteen minutes after declamping, blood samples were collected from the left renal venous effluent for the assay of plasmatic prostanoid concentrations. Three experimental groups were studied: group I (n = 9) sham, no ischemia-group II (n = 9) control group, 45 min of left renal ischemia, followed by a 15-min revascularization, and group III (n = 10) ANF group, a similar ischemic protocol to that in group II was used but, after declamping, synthetic Atriopeptin III was infused (0.5 micrograms/kg/min) during the 15-min of vascular reflow. Fifteen minutes after declamping, TxB2 secretion significantly increased after ischemia in the control and ANF groups: TxB2: 210 +/- 22.4 pg/ml (control group) and 234.8 +/- 25.1 pg/ml (ANF group) versus 135.8 +/- 17.8 pg/ml (sham group) (p less than 0.05 and 0.01, respectively). On the other hand, the 6-keto-PGF1 alpha plasma levels were significantly higher after ischemia in the ANF group (221 +/- 34 pg/ml) in comparison with the sham (124 +/- 24.1 pg/ml) or with the control group (116.7 +/- 12.5 pg/ml). The calculated TxB2/6-keto-PGF1 alpha ratio was therefore higher in the control group, 1.93 +/- 0.27, than in physiological conditions (sham group), 1.2 +/- 0.17.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

[Results of renal transplantation in children with obstructive uropathy due to malformations].

180 renal transplants have been performed at our center in children less than 15 years old. Even if the distribution is equivalent (50/50%) between kidneys from living and cadaver donors, graft actuarial survival rate is 20% better at 5 years in the first group. 42 grafts have been implanted for end-stage renal failure due to chronic pyelonephritis (CNP). Among them, 17 were due to obstructive L.U.T. uropathies (posterior urethral valves): even if the results are identical in that subgroup compared to CPN group, there is an increased morbidity risk as 2 ureterovesical stenosis and 1 secondary vesico-ureteral reflux were observed (3/17 versus 4/163 in the remnant population).

Adolescent↗
PubMed1989

Organ procurement in children--surgical, anaesthetic and logistic aspects.

To cover the need in paediatric organ transplantation, every potential donor should be considered as a multi-organ donor. Successful transplantation may be performed with kidneys retrieved from very young infants, even anencephalic neonates if the en-bloc technique using both kidneys is used. Regarding the liver, paediatric donors can be accepted from one month of age while livers harvested from older children and even young adults can be transplanted into small children after ex-vivo reduction of the size of the graft. Multi-organ procurement from the same donor provides valuable organs if the anaesthetic management of the donor is appropriate. Active transplant programs needs international cooperation which is made possible by the organ exchange organizations.

Adolescent↗
PubMed1989

Treatment of renal graft artery stenosis. Comparison between surgical bypass and percutaneous transluminal angioplasty.

In order to compare saphenous bypass (SB) and percutaneous transluminal angioplasty (PTA) as treatment of renal graft artery stenosis (GAS), we have reviewed the results of both procedures in 33 patients treated consecutively by either SB (n = 16) or PTA (n = 17). All patients had become hypertensive within the first year after transplantation despite triple hypotensive drug therapy. SB was performed 17 (range 3-55) and PTA 19 (range 2-96) months after transplantation. SB failed in only 1 patient as a result of vascular thrombosis with graft loss. PTA was technically unsuccessful in 3 patients and was complicated by vascular branch thrombosis in 1 patient. Blood pressure decrease was similar in both groups: from 179/114 before SB to 147/90 (n = 15, P less than .001) at 6 months and 150/93 (n = 14, P less than .005) at 12 months after SB and from 177/110 before PTA to 149/93 (n = 13, P less than .01) at 6 months and 150/95 (n = 10, P less than .02) at 12 months. At 1 year, control of BP was improved in 85% of SB group patients and 74% of PTA group patients. Recurrent stenosis was documented in 3 PTA group patients: subsequently 1 had a successful SB and the 2 others a repeated PTA--successful in 1, unsuccessful in the other. We conclude that both methods are equally effective for BP control but that PTA entails a higher rate of initial failure and a significant rate of restenosis. However, because of technical ease and better tolerance, PTA emerges as the first-choice treatment of GAS, SB remaining indicated when PTA is not feasible or has failed.

Adult↗
PubMed1989

Prevention of acute cyclosporine nephrotoxicity by atrial natriuretic factor after ischemia in the rat.

The present experimental study investigates whether the atrial natriuretic factor (ANF) is able to prevent the nephrotoxic effects of cyclosporine infused after 30 min of warm renal ischemia in the rat. At 2 hr after the end of ischemia, the glomerular filtration rate was improved by an ANF infusion: 390 +/- 19 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in ANF and saline-infused rats, respectively (P less than 0.05). Intravenous CsA infusion at a dose of 2.5 mg/kg/day produced a more pronounced fall in GFR when compared with the control: 205.4 +/- 19.7 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in CsA and saline, respectively (P less than 0.05). In contrast, a synthetic rat atriopeptin III (0.5 microgram/kg/min) infusion after ischemia given together with CsA prevented its deleterious effects upon GFR: 316 +/- 22 microliters/min/100 g versus 205.4 +/- 19 microliters/min/100 g in ANF/CsA versus CsA alone (P less than 0.001). Moreover, the natriuretic ANF effects remained unaffected by high plasma CsA peak levels: indeed, other parameters of renal function--urinary flow, urinary sodium concentration and excretion rates, and urinary sodium reabsorption and fractional excretion rates, were significantly increased in ANF alone or CsA/ANF groups. These preliminary results suggest that ANF may be useful in renal transplantation or in the management of patients given large doses of CsA (liver or heart transplant) since, despite nephrotoxic CsA levels (greater than 1500 ng/ml), ANF provides an improved GFR and tubular function after ischemia.

Acute Kidney Injury↗