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Biomedical subjects

M A Koyle

Publications and source records attributed to M A Koyle.

At least 55 records · Page 3Linked to original sources

Management of ureteropelvic junction obstruction in neonate.

Fetal hydronephrosis demonstrated by maternal ultrasonography should lead to early investigation during the neonatal period. Postnatal confirmation of the diagnosis of ureteropelvic junction obstruction usually can be established by combining the radiologic modalities of ultrasound, diuretic isotope renal scan, and voiding cystourethrography. Rarely should intravenous urography, antegrade pyelography, or cystoscopy and retrograde pyelography be necessary. Findings of high-grade obstruction and/or significantly diminished function on the affected side(s) should prompt early neonatal reconstruction. Pyeloplasty was performed within the first month of life in 17 infants (20 kidneys) diagnosed as having significant ureteropelvic junction obstruction. Early reconstruction in the neonatal period can be performed successfully with minimal complications and a relatively brief period of hospitalization. This may ultimately achieve maximal preservation of renal function.

Female↗

A technique for ureteral stump ablation.

A total of 5 children underwent successful electrofulguration of a distal ectopic ureteral stump with reflux. Electrofulguration was performed endoscopically in 4 girls and in 1 boy the stump was ablated during an open operation. The procedure, which is simple and safe, obviates the potential nidus for recurrent infection.

Choristoma↗

Cadaveric renal transplantation: surgical results and expectations in the cyclosporine era.

During a 36-month period 100 patients received 104 cadaveric renal transplants with cyclosporine-based immunosuppression. Of the patients 26 required 31 additional operations. Of the 19 secondary operations performed 1 month after transplantation 18 were emergency in nature, whereas beyond this period the majority of the procedures were elective. Both deaths in this series were related to the operation. Only 1 graft loss was directly attributed to a secondary operation. The patient undergoing cadaveric renal transplantation is at significant risk (25 per cent) of requiring at least 1 additional operation. However, despite this high probability of reoperation, graft loss and patient death after such procedures should be rare.

Adult↗

Immunopathologic features of de novo membranous nephropathy in renal allografts.

De novo membranous nephropathy (MN) is now one of the most common forms of posttransplant glomerular disease, second only to allograft glomerulopathy. We investigated several immunopathologic and physicochemical properties of the immune complex (IC) or IC components displayed in the sera of patients with de novo MN. The parameters studied included detection of small (9S) preformed IC by monoclonal rheumatoid factor, determination of IC isoelectric point by chromatofocusing, detection of cationic IgG spectrotypes (pI 8.0-9.2), and demonstration of brush border or tubular epithelial/interstitial antibodies in the sera by indirect immunofluorescence. Of 7 de novo MN sera, 5 demonstrated the presence of each of these four immunopathologic features, whereas normal transplant patients, transplant recipients with recurrent focal sclerosis (FSGN), and those with chronic rejection did not display such features. Sera of patients with untreated idiopathic MN revealed immunochemical properties of IC that were similar to those seen in circulating IC of de novo MN. These studies suggest that a strongly nephritogenic internal milieu exists in transplant recipients with de novo MN. Our data indicate that unique immunochemical properties of IC or their components may predispose to subepithelial immune deposit formation and should provide new insights into the pathogenesis of idiopathic human MN.

Adult↗

Reversibility of cyclosporine-induced hypoandrogenism in rats.

In an attempt to determine whether the inhibition of the hypothalamic-pituitary-testicular axis induced by oral cyclosporine (CsA) is reversible, intact adult male rats were treated with 30 mg/kg oral CsA daily for 4 weeks, and then vehicle (orange juice) for the next 4 weeks. A second group of animals (control) was fed orange juice throughout the entire 8 weeks of the experiment. Serum testosterone (T) was decreased significantly (P less than 0.01) after 4 weeks of CsA treatment when compared with controls. After cessation of oral CsA for the next 4 weeks, there was no difference in serum T between the control and CsA-treated groups. Serum LH, intratesticular T, ventral prostate (VP) and seminal vesicle (SV) weights paralleled the serum T levels at 4 and 8 weeks--i.e., all values were decreased in the 4-week CsA-treated group when compared with controls, and these returned to normal at 8 weeks. Intratesticular 17 alpha-hydroxylase and 17,20-desmolase activities were significantly lower after 4 weeks of CsA treatment; following cessation of the CsA, these enzymatic values returned to normal within 4 weeks. These data demonstrate that at the duration of treatment and the dose studied, the CsA-induced inhibition of the hypothalamic-pituitary-testicular axis of the intact adult rat is completely reversible.

Androgens↗

Effects of cyclosporine on the hypothalamic-pituitary-gonadal axis in the male rat: mechanism of action.

In the intact adult male rat, cyclosporine (CsA) induces a significant decrease in serum testosterone (T), serum LH, and intratesticular T. To elucidate the mechanism of action of this CsA-induced hypogonadotropic hypogonadism, castrated male rats were treated with oral CsA (30 mg/kg.day) or vehicle alone, and serum LH was measured after 1, 2, and 4 weeks of treatment. Surprisingly, serum LH was higher in these CsA-treated castrated rats at 1, 2, and 4 weeks than in castrated controls. To provide insight into the cause of this increase in serum LH, a T implant (8 mm) was inserted (at week 5 of treatment) in both CsA-treated and control castrated animals, and serum LH was measured 1 week after insertion of the T implant. Serum LH levels decreased to control values after insertion of the T implant. Subsequently, two other groups of rats received 8-mm T implant at the time of castration and were then treated up to 4 weeks with either CsA or vehicle alone. Serum LH showed a significant decrease in these CsA- plus T-treated animals compared to the vehicle- plus T-treated animals. A GnRH stimulation test performed after 2 weeks of CsA/vehicle treatment showed a significant increase in serum LH in all the rats 30 min after GnRH administration (1, 10, 30, and 100 ng/100 g BW, ip), indicating a normal pituitary response. The increase in LH after exogenous GnRH treatment was more significant in CsA-treated intact rats than in the controls. There was no difference in creatinine clearance between intact and castrate T-treated rats regardless of whether they received CsA. These studies indicate that the hypogonadotropic hypogonadism induced by CsA in intact male rats is mediated through the hypothalamic-pituitary axis, primarily at its hypothalamus end, does not seem to be due to the nephrotoxicity of CsA, and is modulated by T and/or its metabolites.

Animals↗

Infection patterns in cyclosporine-treated cadaveric renal transplant patients.

Immunosuppression with Cs regimens has not significantly altered infection patterns relative to earlier modalities. However, reports of increased infection, especially with CMV/PCC, are not borne out in our experience both in numbers and timing of infections. Patients on low-dose Cs immunosuppression do continue to acquire infectious complications but, in general, rarely will lose their grafts or lives.

Cyclosporins↗

Spontaneous perinephric hemorrhage from extrarenal angiomyolipoma.

We believe this is the first reported case of spontaneous perinephric hemorrhage arising from an extrarenal angiomyolipoma. To date there have been no cases reported of extrarenal angiomyolipoma associated with tuberous sclerosis. All extrarenal angiomyolipomas have been benign and treated with simple excision.

Female↗

The bladder mucosal graft for urethral reconstruction.

Single stage repairs of a variety of congenital and acquired urethral anomalies were performed in 16 male patients with free grafts of bladder mucosa. Of the patients 10 previously had undergone unsuccessful attempts at urethral reconstruction, including 9 boys with hypospadias. Grafts ranged between 2 and 8.5 cm. long. A fistula occurred postoperatively in 1 patient and it responded to prolonged suprapubic drainage. Meatal stenosis necessitated a further operation in 1 patient. The bladder mucosal graft technique should be considered for urethral reconstruction when prior attempts at repair have failed or when the disorder is primary, and local penile or preputial skin is deficient.

Adolescent↗

The current role of pre-transplant blood transfusions and tissue typing in cadaveric renal transplantation.

In a retrospective analysis of 74 consecutive cadaveric renal transplants performed at our center during a 38-month period we assessed the influence of random blood transfusions and tissue matching on graft and patient survival. All patients received cyclosporine and low dose prednisone with or without azathioprine as immunosuppressive therapy. Actual patient survival was 100 per cent at 1 year and actuarial 1-year graft survival was 82 per cent. Random blood transfusions and histocompatibility matching at the HLA-DR locus did not influence graft survival. Matching at 2 or more HLA-A and B loci was associated with a significant detrimental influence (p less than 0.05) on graft survival. We conclude that the use of cyclosporine-based immunosuppression overcomes much of the adverse effect of poor tissue matching and may obviate the need for random blood transfusions in cadaveric renal transplantation during the first year of engraftment.

Azathioprine↗

Recurrent Henoch-Schönlein purpura following renal transplantation.

A 20-year-old patient with Henoch-Schönlein purpura leading to end-stage renal failure received a living-related renal transplant. She was treated with conventional immunosuppressive therapy. Following a quiescent period of 18 months pretransplant, at 3 months after engraftment there was recurrence of purpuric lesions with subsequent abdominal pain and glomerulonephritis. Renal and skin biopsies confirmed the immunopathologic changes of Henoch-Schönlein purpura. This case represents the second report of an adult with multiorgan recurrence of Henoch-Schönlein purpura following transplantation.

Adolescent↗

Cyclosporine inhibits testosterone biosynthesis in the rat testis.

To determine whether the immunosuppressive agent cyclosporine (CsA) has an effect on testicular androgen function in the male rat, four groups of adult animals were treated daily for 28 days with either orange juice or three doses of CsA (7.5, 15, or 30 mg/kg X day). Twenty-four hours after the last dose of CsA, the animals were killed and the following parameters were measured: testis, seminal vesicle, and ventral prostate weights; serum levels of CsA, creatinine, testosterone (T), and LH; and intratesticular levels of pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, and T. There were no differences between the control (orange juice) and the three CsA-treated groups with respect to serum creatinines and testis, seminal vesicle, and ventral prostate weights. Serum T decreased significantly in the 15 and 30 mg/kg CsA-treated groups. The intratesticular T level decreased significantly only in the 15 and 30 mg/kg CsA-treated groups. In the 15 and 30 mg/kg CsA-treated groups, the intratesticular pregnenolone, progesterone, and 17 alpha-hydroxyprogesterone levels all showed a significant decline compared to controls. There was no significant change in the androstenedione levels in any of the CsA-treated groups. To determine whether the decrease in T production by the testis exposed to CsA is via inhibition of the hypothalamic-pituitary axis, serum LH was measured in all four groups. Serum LH decreased significantly only in the 15 and 30 mg/kg CsA-treated groups. These data suggest that oral CsA administration in doses greater than 15 mg/kg X day results in diminished intratesticular T production that appears to be mediated via inhibition of pituitary LH function.

17-alpha-Hydroxyprogesterone↗

Pyelovesicostomy as a form of urinary reconstruction in renal transplantation.

The development of ureteral obstruction or ureteral fistula formation in the renal transplant recipient usually requires surgical repair. This involves reconnecting the donor ureter to either the recipient ureter (ureteroureterostomy) or bladder (ureteroneocystostomy), or creating an anastomosis between the renal pelvis and recipient native ureter (pyeloureterostomy). Occasionally, the donor or recipient ureter is absent, necrotic or diseased so that a ureteroureterostomy, ureteroneocystostomy or pyeloureteral anastomosis cannot be performed. In 8 such cases we have performed a direct anastomosis between the donor renal pelvis and recipient bladder (pyelovesicostomy) with a followup of between 2 months and 11 years. In all 8 patients there has been no deterioration in renal function attributed to obstruction at the anastomotic site or to the free reflux between the bladder and renal pelvis. Because of the excellent short-term and long-term results of pyelovesicostomy, this procedure should be considered as an excellent alternative to pyeloureterostomy, ureteroureterostomy and ureteroneocystostomy in the reconstruction of the upper urinary tract of the renal transplant patient.

Adult↗

Association between abdominal wall defects and cryptorchidism.

To determine whether intra-abdominal pressure may have a role in the process of testicular descent in man, we reviewed retrospectively the records of all male infants who presented during a 10-year period with severe abdominal wall defects, such as gastroschisis (28), omphalocele (29) and umbilical hernia (53), and calculated the incidence of cryptorchidism in these patients. The incidence of cryptorchidism at birth and at 1 year after birth was 18 and 15 per cent, respectively, in patients with gastroschisis, 52 and 33 per cent, respectively, in those with omphalocele, and 6 and 6 per cent, respectively, in those with umbilical hernia. For all 3 disorders the incidence of cryptorchidism was higher than in documented historical controls. From these data we conclude that in male infants there is an association between these 3 abdominal wall defects and cryptorchidism. The demonstration that intra-abdominal pressure is lowered significantly by these abdominal wall defects would suggest a possible role for intra-abdominal pressure in the process of testicular descent in man.

Abdominal Muscles↗