Post-renal transplant monitoring: the value of biological assays.
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Biomedical subjects
Publications and source records attributed to M A Ghoneim.
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The feasibility of orthotopic substitution of the bladder after cystectomy for cancer has been realized. One must be careful about two potential drawbacks that may appear. Cases must be selected carefully and followed up to ensure that the adoption of such a procedure does not increase the risk of local recurrences. In the long term, if overcontinence proves to be a problem among a significant proportion of such cases, the logic of and the need for orthotopic substitution are lost. One then has to reconsider that intermittent catheterization of a continent cutaneous stoma provides a better alternative.
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PURPOSE: We present a new method of urinary diversion to the rectum. MATERIALS AND METHODS: Between 1992 and 1995 a new surgical procedure was used in 32 women, 20 men and 12 children 3 to 60 years old (mean age plus or minus standard deviation 35.4 +/- 2.2). The main indication for diversion was invasive bladder carcinoma. Surgery entailed creation of an S-shaped double folded rectosigmoid reservoir with implantation of the ureters via an extramural serous lined antireflux technique. RESULTS: One patient died of a massive pulmonary embolism postoperatively. Followup ranged from 6 to 36 months (mean 19.2 +/- 7.0). During the observation period 6 patients died of local recurrence and/or distant metastasis within 8 months. Of the patients 57 are currently evaluable. All patients are continent during the day with an emptying frequency of 2 to 4 times. Nocturnal enuresis was observed in 4 children who responded favorably to imipramine hydrochloride therapy. Upper urinary tract function was maintained or improved in 95% of the patients. No clinical evidence of acidosis was observed, since all patients were kept on prophylactic oral alkalization. CONCLUSIONS: The procedure can circumvent some of the inherent disadvantages of ureterosigmoidostomy and is a good alternative to orthotopic bladder substitution when the urethra cannot be used.
PURPOSE: We performed a critical analysis of the different prognostic factors affecting survival among patients with carcinoma of the bladder for whom cystectomy was indicated. The different patient and tumor characteristics were correlated to survival data by a univariate as well as multivariate analysis. MATERIALS AND METHODS: Between 1969 and 1990, 764 men and 262 women, average age plus or minus standard deviation 43 +/- 8 years, with invasive carcinoma of the bladder were eligible for 1-stage radical cystectomy and urinary diversion. Patients were followed regularly and examined signs for and location of treatment failure. Followup ranged from 0 to 24.2 years, with a median plus or minus standard deviation of 4.05 +/- 4.16 years. RESULTS: Postoperative mortality was 4%. Most of the patients presented with advanced stage (greater than P3) disease. Squamous tumors accounted for 59% of cases, transitional carcinoma 22% and adenocarcinoma 11%. Bilharzial eggs were seen in 85% of the specimens. Regional lymph nodes were involved in 18.3% of the cases. The 5-year survival rate was 48%. The survival estimate was correlated to patient and tumor characteristics by univariate and multivariate analyses. Only tumor stage and grade, and lymph node status had a significant impact on survival. CONCLUSIONS: Contemporary cystectomy with continent diversion for muscle invasive disease provides minimal morbidity, offers good locoregional disease control and results in acceptable quality of life. The presence of positive regional lymph nodes is not a contraindication to this therapy.
Since 1986 we have used the orthotopic substitution technique on some 280 male patients suffering from bladder carcinoma and 38 females. There is minimal morbidity and mortality, though patients are generally younger than those seen in Europe and the USA. Postoperative daytime continence is experienced by about 94% of patients and night-time continence by around 78%. Since some complications were encountered using the hemi-Kock's pouch, we devised an orthotopic bladder substitute from 40 cm of ileum, using no staples and without creating a nipple. The ileum is arranged in a W formation, the ante-mesenteric border is incised and the serosa of the two lateral limbs joined together. Two troughs are created on either side of the neo-bladder and each ureter is laid into its respective trough. The mucosa on either side is sutured in front of the ureter creating a tunnel. Some 87 male patients have undergone this revised procedure, and female patients, when the urethra can be utilised.
The procedure was designed to overcome some problems seen with uterosigmoidostomy (with a submucosal tunnel), namely obstructions at the anastomotic site, nocturnal enuresis, metabolic acidosis and tumorogenesis. A colo-rectal valve isolates the rectal bladder to prevent regurgitation of urine, an anti-reflux technique is used for ureteric implantation and the rectum is patched with ileum to improve urodynamics and provide better compliance and continence, particularly at night. A second intussusception valve creates zero reflux and extremely low strictures, while also solving problems with dilated ureters. The double-folded rectosigmoid pouch has several advantages: it is a relatively simple procedure requiring no staples, it produces an anti-reflux mechanism suitable for normal or dilated ureters and provides a high-capacity reservoir. It does, however, create metabolic acidosis, and there is the possibility of future carcinogenesis, which may be prevented if NSAIDs are given.
SPAI, originally isolated as a sodium/potassium-ATPase inhibitor and now considered to be a proteinase inhibitor of unknown specificity based on its similarity to elafin (an elastase inhibitor), is a new type of plasma protein that has a transglutaminase substrate domain, which serves as an anchoring sequence to be covalently cross-linked at target sites. To determine the source of SPAI, we carried out in situ hybridization and immunohistochemistry using an antisense cRNA probe and an antiserum against recombinant SPAI, respectively. Since previous RNase protection analysis had indicated that SPAI mRNA is almost exclusively expressed in the porcine small intestine, we used its frozen sections for the staining. The lower crypt was decorated with both the cRNA probe and antiserum, indicating that SPAI is synthesized and secreted by the enteroendocrine cells located near the crypt base. The native form of SPAI was also characterized by Western blotting. This result together with the previous biochemical and molecular biological characterizations may set the stage for identifying the physiological roles of the conceptually very interesting protein SPAI.
The criteria for evaluation of urinary diversion procedures in children must be strict since their life expectancy is long. Our experience with the modified rectal bladder in children with considerable follow-up periods is reported herein. All patients were continent by day and night. Urography studies revealed a normal upper tract in all cases. Three early complications were encountered among patients who had a submucous tunnel reimplantation. Reflux to the proximal colon or the kidneys was not demonstrated. The metabolic status and growth-rate patterns of these patients were within normal limits without alkaline therapy. All urine samples aspirated from the renal pelves were sterile. We conclude that a modified rectal bladder with a second ileal intussusception valve is the operation of choice whenever urinary diversion in children is indicated.
A new antirefluxing ureteroileal anastomosis is described in which the implanted ureter is placed between the ileal segment and psoas muscle. The procedure was studied in eight experimental dogs, which were observed for 20 weeks. Radiologic and bacteriologic examinations, necropsy assessment and histopathologic results provided evidence that this ileo-psoas tunnel technique allows a unidirectional, non-obstructed flow of urine. The technique could be applied when ileal replacement of the ureter is necessary or in association with continent bladder replacement.
OBJECTIVE: To review published reports of surgically treated adrenal myelolipomas and report experience with a further eight cases. PATIENTS AND METHODS: Eight patients (three men and five women, mean age 50.7 years) with adrenal myelolipoma were treated surgically because of the tumour size, symptomatology and/or associated renal pathology. Associated medical problems included hypertension in three patients and diabetes mellitus in one but none of the tumours was endocrinologically active. RESULTS: Five patients were diagnosed definitively by abdominal ultrasonography, computed tomography and angiography while the other three were incidentally diagnosed during surgical intervention for ipsilateral renal cell carcinoma in one patient, hydronephrotic kidney in another and multiple renal stones in the third. On pathological examination, the masses removed were surrounded by a thin fibrous capsule and compressed cortical tissue. A cut section was bright yellow with foci of red-brown discoloration. Microscopically, the tumour consisted mainly of mature adipose tissue with scattered islands of haemopoietic cells. There was no operative mortality and no gross morbidity. CONCLUSION: The management of adrenal myelolipoma should be appropriate to each individual case. Operative intervention should be reserved for symptomatic patients or those with large 'silent' tumours that may produce life-threatening shock secondary to spontaneous haemorrhage. Small asymptomatic tumours with definite radiological findings can be followed expectantly.
OBJECTIVE: To study the morphology and function of the upper urinary tract over the long-term in dogs with an enterocystoplasty and a refluxing or anti-refluxing uretero-intestinal anastomosis. MATERIALS AND METHODS: Subtotal cystectomy and "cup" ileocystoplasty were performed in 13 dogs. The right ureter was implanted into the cystoplasty with a refluxing technique in seven and with an anti-reflux procedure in six dogs. The left renal unit acted as an intact control in 11 dogs, while in two the intramural part of the left ureter was incised to produce reflux. Thus, of the 26 renal units, nine had a refluxing junction (anastomosis), six were anti-refluxing and 11 served as intact controls. Total and separate glomerular filtration rates (GFRs) were measured preoperatively and regularly thereafter, and cystometry, urography and ascending enterocystography were performed. At necropsy, urine was obtained for culture from the cystoplasty and renal pelves, and both kidneys were examined histologically. RESULTS: The cystometric pressure was low in 12 of the 13 dogs: urography showed no obstruction. The fall in separate GFR did not differ significantly among the groups (with and without reflux protection, and control units). Reflux was detected in three of nine renal units with refluxing anastomosis and in three of 11 control units. Bacteriuria was found in the cystoplasty in all dogs; the incidence in the upper urinary tract was seven of eight renal units with a refluxing anastomosis, one in five of those with an anti-refluxing anastomosis and three of nine control units. Pyelonephritis was found in none of the control kidneys, in six of nine kidneys with a refluxing and in two of six with an anti-refluxing anastomosis: it was less severe in the latter. CONCLUSION: Refluxing ureteric implantation in a low-pressure enterocystoplasty was commonly associated with bacteriuria in the upper urinary tract and with pyelonephritis. Thus, anti-reflux implantation was beneficial for renal preservation in this setting.
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The primary and gene structures and tissue distribution of porcine SPAI-2, a protein that belongs to the WAP protein superfamily and has a sodium-potassium ATPase inhibitory activity, were determined by molecular cloning and Northern analysis. A full-length cDNA clone was isolated from a porcine duodenum cDNA library. The cDNA insert encoded a polypeptide of 187 amino acids, which is composed of three domains: a hydrophobic presequence of 21 amino acids, a prosegment of 105 amino acids ending with Asp126, and the mature SPAI-2 sequence of 61 amino acids beginning with Pro127. The prosegment contained 16 repeats of a hexapeptide that is highly homologous to the repetitive sequence found in the transglutaminase domain of the human elafin, an elastase-specific inhibitor that also belongs to the WAP superfamily. The repetitive sequence was demonstrated to be a good substrate of transglutaminase using a recombinant preparation produced in Escherichia coli. A porcine genomic library was then screened for the SPAI gene. Characterization and sequencing of positive clones indicated that the gene is similar to the elafin gene, having 3 exons encoding the 5'-untranslated region and signal sequence, proSPAI, and 3'-untranslated region, respectively. Northern blot analysis revealed intestine-specific expression of SPAI mRNA; the message was especially abundant in the small intestine. ProSPAI was also found in the circulation. The similarity of proSPAI to elafin in the domain structure, the acid-labile nature of the cleavage site (Asp126-Pro127), and the fact that the major form of SPAI in the plasma is proSPAI strongly suggest that proSPAI is not the precursor but rather it is the native form of SPAI. Like elafin, therefore, SPAI appears to be a new type of biologically active substance with a transglutaminase substrate domain that acts as an anchoring sequence.