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Biomedical subjects

D J Bagli

Publications and source records attributed to D J Bagli.

7 recordsLinked to original sources

Acellular bladder matrix allografts in the regeneration of functional bladders: evaluation of large-segment (> 24 cm) substitution in a porcine model.

OBJECTIVES: To evaluate the use of a large-segment (> 24 cm2) bladder substitution with porcine bladder acellular matrix allograft (BAMA) in a large animal model. Materials and methods Bladders were harvested from pigs at the time of necropsy and subjected to detergent and enzymatic extractions to render them acellular. The BAMA produced had the surgical handling and suture-retaining properties of normal bladder tissue. Six pigs had BAMA segments implanted under general anaesthesia, through a low midline abdominal incision and after partial cystectomy. The defect was repaired with a BAMA patch (mean size 43.88 cm2, range 12-72), with no urinary diversion. Two animals each were then killed at 9, 16 and 30 days and the bladders explanted. The native bladder and BAMA patch were analysed morphometrically to evaluate cellular re-population and matrix re-organization. RESULTS: All animals survived surgery; there were no urinary leaks and no stones detected in any of the bladders. At 9 days there was a diffuse infiltration with acute inflammatory cells, but no areas of necrosis. There were isolated areas of smooth muscle cell (SMC) infiltration of the BAMA. At 16 days the luminal surface was lined with a single layer of urothelium, there was stromal infiltration with disorganized SMC and angiogenesis, with mature vessels in the BAMA patch. At 30 days the urothelium was multilayered with organizing groups of SMCs and angiogenesis. The highest cell density was at the periphery of the repopulated BAMA patch, decreasing towards the centre. CONCLUSIONS: The implantation of large patches of BAMA is technically feasible and may prove to be a viable surgical alternative to bladder augmentation with intestinal segments. The advantages of BAMA include the potential for complete and functional regeneration of a bladder substitute. This model provides a tool with which to obtain a better understanding of the cellular and molecular aspects of matrix re-population.

Animals↗

Torsion of an indirect hernia sac: an unusual cause of acute scrotal swelling in children.

OBJECTIVES: An indirect inguinal hernia is a common cause of inguinoscrotal swelling in young boys. We describe 3 cases of an extremely unusual entity that has a similar clinical presentation to more commonly diagnosed intrascrotal processes. METHODS: Two patients presented with acute hemiscrotal enlargement and pain, and a third patient presented with scrotal enlargement only. All patients underwent a scrotal ultrasound evaluation and subsequent inguinoscrotal exploration. RESULTS: All patients had a multiseptated peritesticular fluid-filled mass on ultrasound evaluation. Subsequent inguinoscrotal exploration revealed a torsion of the indirect hernia sac in each case. A high ligation and excision of the sac was curative. CONCLUSIONS: Torsion of a hernia sac is an extremely rare entity, and current sonographic imaging fails to clearly diagnose this unusual phenomenon. Because pediatric urologists are commonly called to evaluate a child with an acutely swollen scrotum, awareness of this diagnosis is important.

Acute Disease↗

Demucosalized augmentation gastrocystoplasty with bladder autoaugmentation in pediatric patients.

PURPOSE: Potential metabolic complications in urinary reconstruction with bowel or stomach are due to the presence of the gastrointestinal mucosal layer. The advantage or disadvantage of each tissue has been debated. We report a procedure in which the mucosa of a gastric pedicle flap is removed and the remaining muscularis flap is transferred to an autoaugmented bladder. MATERIALS AND METHODS: Seven female and 4 male patients underwent the procedure at our institutions from October 1992 to November 1994. A retrospective chart review was performed to compare preoperative to postoperative urodynamic findings, continence status and complications. RESULTS: Mean followup was 23 months (range 8 to 33). Preoperative urodynamics showed an average bladder capacity of 109 cc (range 45 to 200) and compliance of 3 ml./cm. water (range 1 to 6). Urinary continence was achieved in 10 patients on clean intermittent catherization every 3 to 4 hours and 1 was wet due to low urethral resistance. All patients underwent postoperative urodynamics. Bladder capacity increased to 236 cc (range 150 to 300) with an average compliance of 9 ml./cm. water (range 5 to 14). No metabolic complications were noted. CONCLUSIONS: The gastric muscularis appears to be preserved along with the native urothelium to provide a compliant tissue that can be an alternative to bowel and stomach for bladder augmentation. Because the procedure involves demucosalizing the gastric patch as well as performing bladder autoaugmentation, operative time is increased compared to normal gastrocystoplasty or enterocystoplasty. However, the lack of metabolic complications and mucus-free urine are important considerations and substantial advantages.

Adolescent↗

Culture of a prostatic cell line in basement membrane gels results in an enhancement of malignant properties and constitutive alterations in gene expression.

Interaction of a transformed rat prostate epithelial cell (NbMC-2) with basement membrane gels (Matrigel) has been evaluated using a long-term matrix culture system. NbMC-2 cells, and single-cell clonal derivatives, formed spheroidal multicellular structures (aggregates) on Matrigel surfaces and were weakly invasive or noninvasive during a 1 week period. During subsequent 2-4 week periods, invasive cells originating from the aggregates and exhibiting a fusiform morphology became evident and increased in number in the matrix cultures. This biphasic pattern of behavior did not occur on laminin, type I or type IV collagen, or fibronectin substrates, but it did occur on Matrigel in serum-free medium. Characterization of sublines enriched in fusiform cells indicated that they maintained their distinct morphology with continuous culture. Further, they exhibited significantly greater invasive potential, saturation density, and random motility (chemokinesis) than the parent cell line. Steady-state levels of fibronectin mRNA were highly elevated in the fusiform variants, demonstrating a constitutive alteration in patterns of gene expression coinciding with the altered morphology. These results indicate that clonal NbMC-2 cells differentiate at a reproducible frequency into a more aggressive cell type in response to culture in the basement membrane-like matrix. The altered phenotypic properties appear to be stable since they can be inherited by daughter cells and because they are evident in the absence of matrix. These observations suggest a cell-specific mechanism for promotion of malignant growth by matrix-mediated induction of novel cell properties.

Animals↗

c-Ha-ras-I oncogene-induced differentiation and natural killer cell resistance in a human colorectal carcinoma cell line.

Natural killer (NK) activity is primarily a peripheral blood function of a lymphocyte population capable of spontaneous lysis of many transformed and metastatic targets. However, NK-susceptible targets tend to be relatively poorly differentiated. We have previously shown that poorly differentiated human colorectal carcinoma are lysed by NK cells. Well-differentiated and chemically differentiated colorectal carcinomas are insensitive to NK lysis. The present study demonstrates that transfection of the c-Ha-ras-I oncogene into a poorly differentiated colorectal carcinoma cell line also renders it NK resistant. This resistance is accompanied by a more differentiated colorectal carcinoma phenotype. Two ras-transfected lines (Clone-A-5 and Clone-A-4) showed a 30-66% decrease in susceptibility to NK lysis as compared to the parental line in standard cytotoxicity assays. The resistance of these transfectants was strictly dependent on expression of the activated p21, the H-ras protein product. Studies to assess the integrity of the initial binding step in NK lysis showed a significant decrease in the ability of these transfectants to form conjugates with fresh NK cells. It is likely that transfection with c-Ha-ras-I has selectively modulated critical NK target recognition structures.

Blotting, Western↗

Laminin expression in colorectal carcinomas varying in degree of differentiation.

We are studying the ability of colorectal carcinomas, which vary in degree of differentiation, to assemble a basement membrane and the relationship between differences in this ability and perturbations in laminin expression. For these studies, we are using human colorectal carcinoma cells grown both in vitro and in nude mice as well as tumors obtained at surgery. Immunoperoxidase staining of human tumors indicates that laminin is present in a defined basement membrane in moderately to well-differentiated tumors. This staining pattern is absent in poorly differentiated tumors. In these tumors, staining is discontinuous and sometimes observed intracellularly. The laminin synthesized by in vitro cells was immunoprecipitated and analyzed by acrylamide electrophoresis. Neither poorly nor well-differentiated carcinoma cells exhibit marked differences in the rate of synthesis of laminin. Differences are present in the rate at which newly synthesized laminin is secreted. These differences may result from alterations in posttranslational processing. Such alterations may contribute, along with other factors, to the inability of poorly differentiated tumors to make a basement membrane.

Animals↗

Neurogenic bladder.

Management of neurogenic bladder in children is challenging for the practising clinician. This involves consideration of multiple and diverse factors which must be balanced in an ever changing environment. Also the dynamics of a child's growth must always be considered because it contributes to the ongoing instability of the neurologic lesion. Prevention and proactive approaches have become the mainstay of the therapy. It is not appropriate to wait for problems to occur before treating these children, because changes that take place may not be reversible, even if they are detected early. The clinician should be aware of the various clinical presentations of neurogenic bladder dysfunction in children and familiarize themselves with the modes of treatment available. Long term follow-up is mandatory. Finally, the value of streamlining these children into society at an early age must always be considered.

Child↗