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In order to prolong the cold ischaemia time and to improve the quality of donor kidneys, we have designed and developed a renal perfusion machine allowing the control of perfusion parameters (temperature, pressure, flow rate, resistance) during the various phases of a kidney perfusion and storage protocol at -4 degrees C.Twenty four rat kidneys were removed and the effects of perfusion and storage at -4 degrees C were studied using a perfusion/storage machine allowing the controlled addition of 2,3 butanediol in University of Wisconsin (UW solution). The kidneys were stored for 96 hours at -4 degrees C and were studied in terms of perfusion parameters (pressure, resistance) and according to their histological appearance.The machine allows controlled perfusion of a cryoprotective agent and preservation of kidneys at -4 degrees C for 96 hours.In animals, it is possible to store kidneys at a temperature of -4 degrees C for 96 hours by using a vecor solution (UW solution) and a cryoprotective agent (2,3 butanediol). The perfusion and storage of organs under these conditions must be performed by a computer-assisted machine, allowing monitoring and control of the various steps of perfusion/storage.

In a series of 1500 patients transplanted between 1976 and 1992, 12 patients presented urinary calculi. The symptoms presented included obstructive anuria in 3 patients and abdominal pain in 1 patient. There were 8 asymptomatic patients. The risk factors were mainly hyperparathyroidism and non-absorbable sutures. The occurrence of renal graft calculi is now ten times less frequent than in the 1980s. In all, 5 of the patients were treated using incisional surgery, 5 with ESWL and 4 using ureteroscopy; a double J stent was inserted for the 3 cases of obstructive anuria. Nine patients are currently calculus-free and 2 have relapsed. One asymptomatic patient was not treated. The renal function of these 12 patient was not modified and no hypertension was noted after treatment. Calculi are generally asymptomatic when they are diagnosed by ultrasonography and in our experience they can be treated using ESWL or by ureteroscopy. In our opinion all patients can be treated successfully but with a high rate of relapse if the causal factors are not treated.

The objective of this retrospective study was to determine whether the difference between the donor's weight (wd) and the recipient's dry weight (wr) could influence the function of renal transplants.Between 1987 and 1994, 185 patients with a mean age of 43.3 years +/- 12 were transplanted with a locally harvested cadaver kidney, corresponding to 120 men (42.2 years +/- 1.4) and 65 women (45 years +/- 12.8). The weight variation between donors and recipients (wd - wr) was 0.06 for men and 0.22 for women. The serum creatinine of recipients at 1 year was 147 mumol +/- 41.7. We used analysis of variance for univariate statistical analysis and multiple linear regression for multivariate analysis.On univariate analysis, the serum creatinine at 1 and 2 years was significantly higher (p0.02 and p0.035 respectively) when the donor's weight was 10% lower than the recipient's weight. Multivariate analysis, taking into account the donor's age and sex and the recipient's serum creatinine, confirmed the influence of the donor-recipient weight difference on serum creatinine at 2 years (p0.03), but also the role of the donor's age at 1 and 2 years (p0.0001 and p0.0004, respectively).In our study, the donor-recipient weight difference was a factor influencing the recipient's serum creatinine at 2 years. The donor's age also influences the recipient's serum creatinine, 1 and 2 years after renal transplantation.

The neurophysiology of erection remains poorly elucidated, particularly at the spinal cord level. We studied variation of intracavernous pressure (ICP) in rats. Tactile stimulation of the prepuce in conscious rats induces the appearance of sequences of reflex erectile responses affecting the corpora cavernosa and/or corpus spongiosum and glans. During this test, implantation of a telemetric pressure transducer allowed us to record ICP increases occurring simultaneously to erectile responses. These increases were characterized by brief suprasystolic peaks preceded by an infrasystolic plateau. Each type of reflex erectile response was accompanied by a characteristic profile of ICP increase. Participation of the corpora cavernosa was demonstrated, particularly during erections of the glans. In anaesthetised rats, electrical stimulation of the dorsal nerve of the penis induces an increase of intracavernous pressure which tends to reach blood pressure values. This erectile response of the corpora cavernosa is abolished by proximal section of the dorsal nerve of the penis, markedly decreased by section of the homolateral pelvic nerve, and abolished after bilateral section of the two pelvic nerves. Striated muscle paralysis does not abolish the erectile response. These data help to define the neurophysiology of the reflex erection. In particular, they provide a clearer explanation of the spinal integration of reflex erection.

95% of renal transplantations performed in France use cadaver donor kidneys. Two donor nephrectomy techniques are proposed: a beating heart technique and an arrested heart technique. In the very great majority of cases (80%), donor nephrectomy can be performed during multi-organ removal, performed according to bioethical regulations: unrelated, anonymity between donor and recipient, security, traceability and evaluation. The urologist has a role to play at each step of organ donation, in which he is the main protagonist. The first steps are performed in close collaboration with the intensive care unit which established the diagnosis of brain death of the potential donor. The following steps, guided by the French transplant establishment, are the urologist's responsibility: He is responsible for abdominal exploration looking for a tumour or any other abnormality. A strictly aseptic technique is essential to prevent contamination of the organ. He is responsible for removing kidneys in such a way as to ensure the shortest possible warm ischaemia time, the best storage solution, and the best preservation of their anatomical structure. He must be familiar with the outcome of transplants in order to adapt his technique to the results of transplants.

Twenty five double kidney-pancreas transplantations were performed according to the total pancreas transplantation technique with drainage of exocrine secretions into the bladder via a vesicoduodenostomy. 72% of kidney-pancreas grafts were functional at one year and 59% were functional at four years. The authors observed a slightly higher rejection rate (0.56 versus 0.34) and a higher incidence of urinary tract infection (60% versus 35%) following double pancreas and renal transplantation than after isolated renal transplantation. Complications were rare: two venous thromboses and two cases of urethritis requiring of rediversion of the duodenum into the intestine. These good results, comparable to those reported in the international registry, reflect the value of the pancreatic and renal transplantation technique using a total pancreas drained into the bladder. It would probably be preferable to transplant patients earlier, when chronic renal failure secondary to insulin-dependent diabetes induces end-stage renal failure and the need for haemodialysis.

Multiple cystic clear cell renal tumors and in situ renal clear cell carcinoma occurred in a woman with von Hippel-Lindau disease. Kidney lesions in von Hippel-Lindau disease are one of the main features including renal cysts and renal cell carcinoma. In situ renal clear cell carcinoma has not yet been reported.

After years of pioneering research and clinical applications, renal transplantation has now moved into the era of routine practice-the first line treatment for renal failure in more than 1500 new patients each year in France. Despite this success, transplantation is not a cure, it simply replaces one disease by another-immunodepression. As a result, over the next 20 years, 60% of the recipients will undoubtedly develop cancer. In addition, the life span of a transplanted kidney is shorter than that of the recipient. Consequently most of them will require a second graft 8 to 10 years after the first. Together with the development of new innovating immunology agents such as FK 506 and mycophenolate, for example, these current facts raise the challenging question of the future for renal transplantation. Will adequation between donors and recipients be achieved? Should we develop single organ transplantation units within our current nephrology-urology structures or create multiorgan units devoted solely to transplantation? And finally, will (or perhaps when will) progress in immunology completely control the problem of organ rejection? One technical point is also of interest. Being (with orthopaedic surgery) one of the rare indications where open surgery can be expected to continue over the next 20 years, renal transplantation units will play an essential role in training future surgeons.

Seventeen patients with N+ urothelial bladder tumours were treated by a combination of deep endoscopic resection and concomitant radiochemotherapy (5FU cisplatin). 15 patients completed their course of treatment. 52.9% of these 17 patients are in complete remission at 6 months, 35.2% are in complete remission at 1 year, 30% of patients in complete remission developed distant metastases, 52.9% developed local progression and 40% developed distant metastases. This protocol of deep resection combined with radiochemotherapy can therefore be effective in the local control of the tumour and can allow preservation of the bladder in the case of complete remission. However, it is insufficient to prevent the development of distant metastases. It is therefore preferable to intensify this treatment by performing complete endoscopic resection, by increasing the radiotherapy dose rate and by intensifying the chemotherapy protocol.

Apoptosis has been investigated in NB4, a t(15;17) human promyelocytic leukemia cell line susceptible to maturation by all-trans or 9-cis retinoic acid, and in NB4-R1, a subclone resistant to differentiation. Maturation resistant NB4-R1 cells exhibited an onset of cell death after RA-treatment (72 h), whereas maturation responsive NB4 cells showed no such apoptosis, cell death being considerably delayed after cell maturation. Only a few NB4-R1 cells underwent apoptosis in response to low doses of RA (below 0.1 microM), the surviving cells became refractory to higher doses of RA. While these cells became 'resistant' to apoptosis they became competent for maturation. Typically, these RA-'primed' cells responded to cAMP by maturation, then apoptosis followed rapidly. This model furnishes situations where cells are either resistant or susceptible to apoptosis, depending on whether they can or cannot undergo maturation. The potential role of the Bcl-2 protein in the regulation of apoptosis was analyzed. In NB4 and NB4-R1 cell lines, a high expression of the Bcl-2 protein was detected by immunocytology and Western blotting. NB4 cells treated with either all-trans or 9-cis retinoic acid (1 microM) were induced to differentiate and the level of Bcl-2 protein decreased to undetectable levels during terminal maturation when only a few apoptotic cells were detected. In NB4-R1 cells, while treatment with retinoids does not induce maturation, as much as 64% of cells became apoptotic, and immunocytological labelling of NB4-R1 showed a strong cytoplasmic labelling of Bcl-2. Although the expression of Bcl-2 remained high, cells were not protected from apoptosis. To assess whether Bcl-2 expression could be modulated as a consequence of differentiation, NB4-R1 cells previously 'primed' for maturation were triggered with cAMP. Downregulation of Bcl-2 protein occurred concomitant with maturation, followed by apoptosis. Clearly, NB4 and NB4-R1 cells show reciprocal behavior with regards to proliferation, maturation, Bcl-2 regulation and apoptosis in response to RA. Our results suggest, first, that the Bcl-2 downregulation in NB4 cells belongs to the maturation program rather than to apoptosis, and second, that neither a high Bcl-2 expression in NB4 cells is sufficient to protect cells from 9-cis RA induced apoptosis, nor is its full downregulation sufficient to produce apoptosis. Finally, this work suggests that apoptosis and maturation programs include events which cannot occur simultaneously.

Two non-randomized groups of 100 kidney transplants each were compared in relation to the flush-out solution used. The two groups were similar with the exceptions of the number of multiple artery kidneys and the proportion of kidneys procured in our center. The rate of vascular complications such as arterial venous thrombosis and renal artery stenosis was higher in the Eurocollins (19) group than in the UW group (4) p0.01, even if the multiple artery kidneys are excluded. These results need to be confirmed by a randomized study but it is clear that the use of the UW solution leads to a better arterial flow with fewer vascular complications.

The authors present their experience of surgery for persistent hyperparathyroidism in renal transplant recipients, based on a series of 944 patients transplanted between 1983 and 1992. 56 patients underwent subtotal parathyroidectomy for persistent secondary hyperparathyroidism. Control of serum calcium was excellent in 83% of patients: 2 patients retained a well controlled hypocalcaemia, 2 are still hypercalcaemic and 3 others have developed recurrent hyperparathyroidism. The postoperative course was marked by one death not related to parathyroidectomy and one recurrent laryngeal nerve palsy. Subtotal parathyroidectomy combined with removal of the thyrothymic tissue is an effective operation to control phosphorus and calcium metabolism in patients with persistent hyperparathyroidism after renal transplantation.

Sex- and sequence-specific patterns of methylation of mammalian DNA are established during gametogenesis and are believed to be important for genomic imprinting and developmental gene regulation. DNA methylation in mammalian cells is performed predominantly by the enzyme DNA (cytosine-5)-methyltransferase (DNA MTase). For a better understanding of how DNA methylation events are regulated during spermatogenesis, a developmental study comparing the expression of DNA MTase mRNA, protein, and enzyme activity was performed. Northern and Western blotting and enzyme activity assays were carried out on testes and purified populations of cells from the testes of mice aged 6-70 days. The 5.2-kb DNA MTase transcript was most abundant in testes of mice aged 6-10 days (2-3-fold the 70-day values); it had decreased in abundance by 40% by Day 20 and reached steady adult levels by 63 days. On Western blot analysis, developmental changes in the relative abundance of DNA MTase protein paralleled the changes seen in mRNA concentrations. DNA MTase enzyme activity in the testis was highest at 6 days of age (10-fold the 70-day values); it had decreased by more than 65% by 20 days and reached steady adult levels at 35 days. Analysis of purified germ cells from the adult testis revealed high levels of expression of both DNA MTase mRNA and protein in haploid round spermatids. In conclusion, DNA MTase is clearly developmentally regulated during spermatogenesis at the level of mRNA, protein, and enzyme activity. These results argue for an important role for this DNA-methylating enzyme during spermatogenesis.

119 patients with prostatic or vesical tumours without metastases were studied by lymphography-aspiration cytology to detect lymph node metastases. 12% of aspiration cytologies were uninterpretable, corresponding to N-patients. 12% of the 105 interpretable cases were positive. Some of the patients with negative biopsies were treated nonsurgically. 28 bladder tumours were treated intravesically. 11 prostatic cancers were treated by radiotherapy and 63 patients underwent surgical resection. These 63 patients had an interpretable aspiration cytology and surgical control. Aspiration cytology was falsely negative in 7 cases: 4 microscopic metastases and 3 macroscopic metastases. The sensitivity of aspiration cytology after lymphography is 66% and its specificity is 100%. The positive predictive value is 100% and the negative predictive value is 92.3%. These 7 false-negative results included 3 macroscopic metastases already identified on CT scan and 4 micrometastases in which surgical resection was legitimate.

Ureteral stenosis in kidney transplantation is a relatively frequent complication which requires surgical treatment to preserve renal function. In 1981 Goldstein reviewed 4307 kidney transplantations and estimated the incidence of obstruction at 2.6 %. Kinnaert reported an incidence of ureteral obstruction after kidney transplantation which varied between 2 and 7.5 % (7, 11).

Urothelial adhesion of Escherichia coli is one of the principal factors of colonisation and infection of the upper urinary tract. We compared 3 measurements of bacterial adhesion: 1) Mannose-Resistant Haemagglutination (MRHA), é) Adhesion to urothelial cells, 3) Latex particle agglutination, to test 85 strains of Escherichia coli in 42 cases of acute pyelonephritis and 43 cases of acute cystitis. These tests were positive in 73.8% to 85.7% of the acute pyelonephritis population and in 4% to 2.3% of the acute cystitis population (statistically significant difference). This study confirms the major role of strains carrying type PAP adhesion in the pathogenesis of acute pyelonephritis.

The authors report their experience of 200 consecutive emergency admissions for iliopelvic uteric stones. 82 patients (41%) eliminated their stones with medical treatment. 118 patients (59%) required ureteroscopic treatment either by immediate basket extraction (n = 58) or by contact fragmentation (pulsed laser = 57, ultrasound = 1, electrohydraulic catheter = 2). 6 failures were observed and one case of distant ureteric stenosis was successfully treated by balloon dilatation. This therapeutic approach cured 187 (93.5%) of the patients of their stones within an average of 8 days (82 "spontaneous", 105 "endourological") with a mean hospital stay of 2.3 days and 2.7 days, respectively. Ureteroscopy had a success rate of 95% and appears to be the most effective treatment, but the medical option remains the basic treatment for stones of the lower ureter.

The growth-promoting potential of growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 micrograms/l in two stimulation tests (arginine, insulin), but above 12 (24-90) micrograms/l after intravenous GHRH, 1 microgram/kg. GHRH, 50 micrograms/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRH insufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 micrograms/l and from 10 to 85 mIU/l, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate rose from 0.24 to 0.48 mm/week after 6 weeks of treatment (p = 0.03) and then rapidly declined; the mean 6-month stadiometric height velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions.

An ectopic prostatic polyp situated in the bladder is a rare cause of terminal haematuria. The authors present an extensive review of the literature concerning this lesion which must be recognised not only by histologists, responsible for establishing the diagnosis, but also by urologists, who must be aware of its benign nature.

Vesicosphincteric disorders are frequent in patients with Parkinson's disease, due to a lesion of the locus niger of the extrapyramidal tract which no longer secretes sufficient dopamine to activate the nigrostriatal tract. The commonest symptoms are urgent micturition, dysuria or a combination of the two. 50% of patients with Parkinson's disease present with disturbances of micturition and these symptoms may be presenting complaint of the disease in 10% of cases. Cystomanometry reveals detrusor hyperactivity in more than 60% of cases and hypoactivity in less than 30% of case, while dyssynergia is less common. Delayed relaxation of the striated sphincter may sometimes be observed. Urological problems must therefore be distinguished from urological problems in these patients. A combined urological and urodynamic assessment is essential as the risk of incontinence following prostate surgery is 20%. Stress urinary incontinence in women may mask or be associated with urgency. These vesicosphincteric disorders must therefore be treated cautiously with a combination of medical treatment (dopatherapy increases detrusor control), retraining and occasionally surgery after a detailed urodynamic assessment.

Of special concern in the management of neurogenic tumours arising in the thorax is spinal-cord compression resulting from either intraspinal lesions or vertebral-body destruction and collapse. A review of 16 cases disclosed three dumbbell tumours, six intrathoracic tumours, one case of neurofibromatosis with multiple intraspinal neurogenic tumours, two malignant neurogenic tumours with vertebral-body destruction causing spinal-cord compression and four foraminal lesions with central intraspinal (extradural) extension. There were 3 men and 13 women, ranging in age at the time of operation from 37 to 79 years. Three patients, of the six with intrathoracic tumours, were asymptomatic; the remaining 13 had preoperative symptoms ranging in duration from 3 weeks to 12 months (average, 9 months). Back pain with intercostal neuralgia was present in eight patients and neurologic signs were present in six patients. A routine chest radiograph was abnormal in 10 patients, and x-rays of the thoracic spine were abnormal in 4 of the other 6 patients. The tumour was excised surgically in all patients. Complications developed postoperatively in two patients: one had Horner's syndrome, transient paraparesis and bleeding; the other had a small subarachnoid-cutaneous fistula. The authors conclude that dumbbell neurogenic tumours and those causing vertebral-body destruction and collapse demand a multidisciplinary one-stage surgical approach. If the lesion is malignant and resection is not complete, radiotherapy or chemotherapy is necessary.

Twenty patients with astrocytomas recurrent after surgery +/- radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.

Twenty three renal tumours: 6 clear cell carcinomas, 3 granular cell carcinomas, 8 mixed cell carcinomas, 3 tubulopapillary tumours, 2 spindle cell carcinomas and 1 oncocytoma, were retrospectively submitted to a staining technique which reveals argyrophilic proteins related to Nucleolar Organizer Regions (NORs). The semiautomated quantification of the number and mean surface area of the argyrophilic granules was performed by means of a quantimeter. The results were compared to the nuclear grade, which constitutes the reference histological prognostic factor. A very good correlation was observed between NORs and nuclear grade. The mean number of argyrophilic granules per nucleus (n) and more particularly their surface area (s) were very significantly increased in high-grade carcinomas (n = 1.96), s = 3.72) in comparison with low-grade carcinomas (n = 1.50, s = 1.35). Quantification of NORs therefore allowed objective differentiation between a low nuclear grade and a high nuclear grade. The quantification method used emphasised the value of not only measuring the number but also the surface area of the argyrophilic granules.

Injury data in the paper medical record are often inaccurate or lack adequate specificity to evaluate trauma patient care. To improve the quality of recorded injury data, we are testing a graphical, anatomic-based interface for quick collection of detailed injury information directly from the trauma physician. Navigation and data collection throughout the interface are facilitated by anatomic illustrations, menus, lists, and "dialog boxes". Using a "point and click" method, the user selects a specific anatomic structure (i.e., the spleen) from drawings. Detailed injury information, specific to the selected structure, is then collected from the user in an "intelligent" modal dialog box. The software uses SNOMED III nomenclature to create and store ICD, AIS, and trauma registry codes for each injury. Users can review and print abbreviated and detailed injury information for each patient. This demonstration will walk viewers through the injury collection and review process for injuries to the abdomen. We plan to evaluate the interface for accuracy, speed, user satisfaction and resources expended by comparing it with current methods of data collection and injury coding at our level I trauma facility.

LO-Tact-1 is a rat anti-human monoclonal antibody which is directed to the 55-kDa alpha-chain of the interleukin 2 (IL2) receptor. We conducted a pilot trial in 15 first-time cadaveric renal transplant patients undergoing for immunosuppression a 14-day course of LO-Tact-1 (10 mg i.v. daily) together with cyclosporine, low dose steroids (0.5 mg/kg) and azathioprine. Results showed a good immunosuppressive effect, as measured by the similar incidence of acute rejection episodes (0.6 per patient) when compared with 20 patients treated during the same period with our standard quadruple prophylactic combination with higher initial doses of steroids (2 mg/kg) and antilymphocyte globulin (ALG) instead of LO-Tact-1 (0.4 per patient). At 2 years post-transplant, graft survival was 93%, and only 1 patient lost his kidney by rejection. No local or general adverse effect of antibody administration was encountered, and haematological changes remained of minor importance. Local bacterial infection was observed in 3 patients, but viral diseases (including cytomegalovirus, CMV) remained exceptional. In contrast, severe clinical CMV infections occurred in 3 patients (15%) treated by ALG. Nine of 15 patients developed rat-specific antibodies, but only 4 before the completion of LO-Tact-1 treatment, without any correlation with the further development of acute rejection. Patients who suffered rejection had lower LO-Tact-1 levels and higher soluble IL2 receptor levels during the period of infusion, suggesting the crucial importance of pharmacokinetic monitoring to adjust individual doses.

To reduce anti-HLA immunization, 15 patients waiting for a renal graft received the following treatment: 5 to 7 immunoadsorption sessions on protein A-Sepharose columns, immunosuppressive drugs (corticosteroids 1 mg/kg (bw/day+cyclophosphamide 2 mg/kg bw/day) and iv polyclonal immunoglobulins. Before this treatment, panel-reactive antibodies ranged from 65 to 100% and antibody titers varied from 1/8 to 1/128. In all patients, antibody, titers were decreased. However, antibody resynthesis was incompletely blocked by this protocol. Eight out of 12 grafted patients had a functional kidney transplant 3 months to 3 years post-grafting. There early kidney failures occurred in the subgroup of 5 patients who had had historical positive cross matches prior to treatment. This treatment did not seem to increase the frequency of infectious complications before or after grafting.