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Biomedical subjects

A C Novick

Publications and source records attributed to A C Novick.

At least 19 recordsLinked to original sources

Studies on the afferent and efferent renal nerves following autotransplantation of the canine kidney.

The presence of both afferent and efferent renal nerves following renal transplantation was investigated in a canine autotransplant model. The efferent postganglionic sympathetic renal nerves were studied using the glyoxylic acid histofluorescence technique to identify renal tissue adrenergic amines (Grade 0-4). The afferent sensory renal nerves were studied by the systemic blood pressure response to renal arterial injection of capsaicin. In 8 control dogs with native innervated kidneys (Group I), intrarenal injection of capsaicin significantly increased the systemic blood pressure from baseline by 32.4 +/- 6.3 mm. Hg (p less than 0.01). This response was equivalent to the blood pressure increase following injection of capsaicin into the mesenteric artery which was 37.3 +/- 9.8 mm. Hg. The renal tissue histofluorescence grade in this group was 4. Six dogs were studied two to three weeks after autotransplantation of a solitary kidney (Group II). Intrarenal injection of capsaicin did not increase the systemic blood pressure in these animals. Three dogs in this group had no evidence of renal tissue adrenergic amines by histofluorescence (Grade 0); the remaining two animals had renal tissue histofluorescence grades of 1 and 2. Eight dogs were studied 12 to 35 months after autotransplantation of a solitary kidney (Group III). Intrarenal injection of capsaicin in these animals significantly increased the systemic blood pressure from baseline by 10 +/- 1.4 mm. Hg (p less than 0.001). The renal tissue histofluorescence grade in this group ranged from 1 to 3. These data support the presence of both afferent and efferent renal nerves in the kidney at greater than or equal to one year post-transplant.

Animals

Clean intermittent catheterization and urinary diversion in the management of renal transplant recipients with lower urinary tract dysfunction.

Renal transplant recipients with lower urinary tract dysfunction may be managed by urinary diversion or clean intermittent catheterization. To evaluate the comparative problems associated with each mode of therapy we studied 13 patients managed by clean intermittent catheterization (group 1, 6 patients) or urinary diversion (group 2, 7 patients). All 6 and 2 of 7 recipients in groups 1 and 2, respectively, had a neuropathic bladder. Mean followup was 3.7 +/- 1.5 (group 1) and 5.7 +/- 4.9 (group 2) years. Three allografts were lost in group 2 due to rejection (2) and death (1). Two patients each in groups 1 and 2 had febrile urinary tract infections requiring hospitalization and intravenous antibiotics. Complications related to urinary diversion developed in 4 patients in group 2. The serum creatinine at 1 and 3 years, number of hospital days per patient, total number of rejection episodes and number of patients employed in a full-time job following transplantation were similar in both groups. In summary, clean intermittent catheterization appears to have more morbidity in immunosuppressed transplant versus nontransplant patients but it may be preferable in renal transplant recipients due to the overall simplicity, positive psychological effect and comparable morbidity to other forms of management.

Adult

Functional equivalence of end and loop ileal conduit stomas.

A total of 458 patients underwent ileal conduit urinary diversion between 1970 and 1984. An end stoma was constructed in 44% of the patients and a Turnbull loop stoma in 56%. The median interval between appliance changes for all patients was 5 days. Patients with an end stoma had a longer median interval between appliance changes than those with a loop stoma. A total of 51 patients had 66 complications. Operations for stomal revisions were required in 5.5% of the patients. There was no difference in interval until initial complication between the end and loop stoma groups, although the end stoma was more prone to ischemic complications than the loop stoma. We conclude that the ileal conduit stoma constructed in an end or loop fashion yielded clinically equivalent long-term function.

Adolescent

Transplant renal artery stenosis in a canine model: evaluation of hemodynamic changes, renal function, and captopril renography.

The utility of captopril renography in the diagnosis of renal artery stenosis was examined in a canine model of renal autotransplantation with and without renal artery clipping. Autotransplantation of the left kidney to the right iliac fossa with contralateral nephrectomy was done in female mongrel dogs. One group served as controls (n = 6). A second group underwent constriction of the external diameter of the renal artery at the time of the operation to produce renal artery stenosis (n = 7). At two weeks postoperatively, glomerular filtration rate was significantly lower in the renal artery stenosis group (26.2 +/- 3.4 ml./min. vs. 38.2 +/- 3.2 ml./min., p less than 0.05), and deteriorated further after captopril administration (17.9 +/- 2.7 ml./min. vs. 26.2 +/- 3.4 ml./min., p less than 0.05). Despite the presence of hemodynamically significant renal artery stenosis, mean arterial pressure was not different between the two groups (134 +/- 4 mm. Hg vs. 132 +/- 6 mm. Hg, control vs. renal artery stenosis, p = NS). Captopril renography did not enable detection of renal artery stenosis in this autotransplant model.

Animals

Long-term followup after nephron sparing surgery for renal cell carcinoma in von Hippel-Lindau disease.

We reviewed the long-term outcome of nephron sparing surgery in 9 patients with localized bilateral renal cell carcinoma and von Hippel-Lindau disease. One patient died of metastatic renal cell carcinoma 43 months postoperatively. One patient has not had recurrent tumor and was alive at 74 months postoperatively. The remaining 7 patients (mean followup 88 months) had local recurrence of tumor in the operated kidney and a secondary renal operation was done in 6 of them. Overall, 6 patients are free of tumor but only 3 of them retain functioning native renal parenchyma. We conclude that the results of nephron sparing surgery in patients with renal cell carcinoma and von Hippel-Lindau disease are less satisfactory than in patients with sporadic renal cell carcinoma.

Adult

The role of renal-sparing surgery for renal cell carcinoma.

Nephron-sparing surgery provides effective therapy for patients with localized RCC in whom preservation of renal function is a relevant clinical consideration. The technical success rate with this approach is excellent, and long-term patient survival free of cancer is comparable with that obtained after radical nephrectomy, particularly for stage I RCC. The major disadvantage of conservative surgery is the approximately 10% risk of postoperative local tumor recurrence. The risk of local recurrence after radical nephrectomy has not been determined but is presumably less. The indications for nephron-sparing surgery in patients with unilateral RCC and a completely normal opposite kidney are not established, and radical nephrectomy should still be considered the treatment of choice in this setting.

Carcinoma, Renal Cell

Long-term follow-up after partial removal of a solitary kidney.

BACKGROUND: The removal of more than one kidney in animals leads to proteinuria and progressive renal failure due to focal segmental glomerulosclerosis. This injury may be the result of chronic glomerular hyperfiltration. The purpose of this study was to determine the effect of a reduction in renal mass of more than 50 percent on residual renal function and morphology in humans. METHODS: We evaluated long-term renal function in 14 patients with a solitary kidney who had undergone partial nephrectomy for renal-cell or transitional-cell carcinoma. In 12, the first kidney had been removed 2 months to 21 years previously for the same type of cancer; in 2, the other kidney was congenitally atrophic. Before surgery, no patient had clinical or histopathological evidence of primary renal disease. All 14 patients underwent partial nephrectomy to remove a localized tumor, with 25 to 75 percent of the solitary kidney being excised. They were evaluated 5 to 17 years after surgery (mean, 7.7). RESULTS: Twelve patients had stable postoperative renal function, and end-stage renal failure developed in two. There were no changes in blood pressure in any patient during follow-up. Nine patients had proteinuria, which was mild (0.15 to 0.8 g of urinary protein per day) in five. The extent of proteinuria was inversely correlated with the amount of remaining renal tissue (P = 0.0065) and directly correlated with the duration of follow-up (P = 0.0005). Four patients with moderate-to-severe proteinuria had renal biopsies, which revealed focal segmental glomerulosclerosis in three patients and global glomerulosclerosis in one. CONCLUSIONS: Long-term renal function remains stable in most patients with a reduction in renal mass of more than 50 percent. These patients are, however, at increased risk for proteinuria, glomerulopathy, and progressive renal failure.

Adult

Improved renal transplant preservation using a modified intracellular flush solution (PB-2). Characterization of mechanisms by renal clearance, high performance liquid chromatography, phosphorus-31 magnetic resonance spectroscopy, and electron microscopy studies.

A number of new intracellular renal flush solutions have been found to be more efficacious than Collins-2 (C-2) solution in extending organ viability during simple cold storage. However, the mechanism of action of these solutions remains poorly understood. To delineate better underlying intracellular mechanisms, we studied a modified, simple, hypothermic, intracellular (340 mOsm/kg) flush solution (PB-2). The development of PB-2 solution is based on the ability of some of its individual components to minimize ischemic adenine nucleotide (AN) catabolism and endothelial post "reperfusion injury." Preliminary results in 10 canine autorenal transplants show a significant (P less than 0.02) improvement in renal recovery and viability (recipient posttransplant inulin clearance and survival) after 50 h of cold storage compared with 10 canine kidneys similarly preserved using conventional C-2 flush solution. High performance liquid chromotography (HPLC) studies show a significant (P less than 0.01) loss of AN using C-2, while PB-2 was associated with regeneration of AN within 45 min of reperfusion. Magnetic resonance spectroscopy using phosphorus 31 (31P-MRS) showed more high energy phosphorus metabolites (phosphomonoester and nicotinamide-adenine-dinucleotide phosphate: P less than 0.001) at 50 h cold storage using PB-2 compared with C-2. Electron micrographs (EM) revealed normal microcapillary morphology for the PB-2 group; however, moderate vascular red and white blood cell clumping was observed in the C-2 group. Characterization of the basic preservation mechanisms by HPLC, 31P-MRS, and EM studies indicates that PB-2 solution enhances renal preservation by diminution of both reperfusion injury and the loss of intracellular high energy metabolites that are necessary for viability.

Animals

Role of percutaneous nephrostomy in patients with upper urinary tract transitional cell carcinoma.

Percutaneous nephrostomy has become a well-established procedure for a wide variety of urologic disorders. However, its role in the management of patients with upper urinary tract transitional cell carcinoma has not been defined. We utilized percutaneous nephrostomy in 23 renal units for the evaluation or treatment of 21 patients in whom standard techniques were inconclusive or inadequate. The percutaneous nephrostomy provided adequate relief of obstruction in the face of significant azotemia or infection. Diagnostic abilities were improved through the use of antegrade pyelography, selective cytologic examination, and, at times, by providing direct access for endoscopic visualization and biopsy. In select cases, the percutaneous access provided a route for definitive or adjunctive treatment of the lesion. Complications were few and seeding of the tract or local tumor spread has not occurred at follow-up ranging from one to one hundred twenty-one (mean 27.8) months.

Adult

Pericarditis following renal transplantation.

We analyzed data on renal allograft recipients over a 27-year period in order to investigate the frequency, etiology, and outcome of pericarditis developing during the first two months following renal transplantation. Of the 1497 patients receiving renal transplants between 1963 and 1990, 34 patients developed 36 episodes of pericarditis and/or pericardial effusions, for an overall incidence of 2.4%. Pericarditis was attributed to uremia in 14 episodes, cytomegalovirus infection in three, both uremia and CMV infection in four, nonspecific bacterial infection in three, and tuberculosis and minoxidil therapy in one episode each. No etiologic diagnosis could be established in 10 episodes. No statistically significant differences were found between pericarditis and case-matched control patients considering demographic features, the number of immediately functioning grafts, the duration of posttransplant acute renal failure, the number of supportive dialysis days, pre- and postoperative CMV status of the patients, and pretransplant BUN and serum creatinine levels. There were more uremic-related complications (pulmonary edema, gastrointestinal bleeding, central nervous system symptoms) in the pericarditis group. Five allografts in the pericarditis group never functioned, versus only one in the control group. Three patients with pericarditis developed pericardial tamponade. Early diagnosis, close follow-up, and in the case of cardiac tamponade early invasive treatment, should improve the prognosis of this potentially life-threatening complication.

Adolescent

Comparison of OKT3 with ALG for prophylaxis for patients with acute renal failure after cadaveric renal transplantation.

A randomized, prospective comparison of OKT3 vs. ALG (University of Minnesota) was performed in patients who had acute renal failure after a cadaver renal transplantation. Criteria for admission to the study were oliguria or increasing serum creatinine in the first 12 hr after renal transplantation. ALG or OKT3 was administered after randomization beginning 12-36 hours posttransplantation. There were no significant differences in age, sex, original disease, ischemia time, or HLA matching between groups. Graft survivals at 1 and 6 months were 84% and 84%, respectively for the ALG group. One- and 6-month graft survival for the OKT3 group was 88% and 84%, respectively. These differences were not statistically significant. The number of rejection episodes and the number of patients with rejection episodes were greater, and the time to first rejection was shorter in the OKT3 group compared with the ALG group, although none of these differences reached statistical significance. There were significantly less side effects in the ALG group compared with the OKT3 group (P less than .05). The greatest reductions in side effects were in fever and hypotension. Patients were monitored with flow cytometry analysis measuring the number of CD2 (T11) and CD3 (T3) cells to adjust the dose of both OKT3 and ALG. Starting doses were 10 mg/kg/day of ALG and 5 mg/day of OKT3. There were no significant differences in the incidence of infections (viral or bacterial) between the two groups. There were no rejection episodes during the prophylactic therapy with either ALG or OKT3. In summary, both ALG and OKT3 provided effective prophylaxis for patients with acute renal failure after renal transplantation. OKT3 was associated with a statistically significant increase in incidence of symptomatic side effects.

Acute Kidney Injury

The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys.

Several reports in animals, and sporadic case reports in humans, have suggested that kidneys with decreased nephron mass may be more susceptible to the development of focal-segmental glomerosclerosis. This prompted a reexamination of our previously reported group of pediatric donor-adult recipient renal transplant combinations. Data were analyzed from 31 adult recipients who had received renal transplants from cadaver pediatric donors (less than 6 years) with graft function for greater than 6 months and no evidence of chronic rejection. These were compared with a control group transplanted during the same period with adult donor kidneys. Immunosuppression consisted of azathioprine/prednisone or quadruple therapy in 16 and 15 patients respectively. End-stage renal disease (ESRD) was secondary to chronic glomerulonephritis (n = 9), diabetes mellitus (n = 6), polycystic kidney disease (n = 5), and miscellaneous causes (n = 11). Twenty patients had radiographic documentation of renal hypertrophy posttransplant. All patients had serial 24-hr urinalysis for protein and creatinine after transplantation during periods of stable renal function. Ten patients had renal biopsies performed at a mean time from transplant to biopsy of 10.4 +/- 1.6 months. Seven recipients had biopsies that revealed glomerulosclerosis at 13 +/- 6 months posttransplant. Protein excretion and serum creatinine in these patients were significantly higher than in control patients (1.6 +/- 0.37 vs. 0.49 +/- 0.15 g/24 hr and 1.96 +/- 0.11 vs. 1.64 +/- 0.09 mg%; P less than 0.03 and P less than 0.01, respectively). Only 3 of 25 control adult donor recipients developed proteinuria greater than 0.8 g/24 hr within 2 years of transplantation vs. 15/31 pediatric donor recipients. No correlations with the etiology of ESRD, age (greater than or less than 40 years), weight, sex, diabetes, hypertension, or the number of acute rejection episodes could be found. Our data suggest that adult recipients of pediatric donor renal transplants may be at greater risk for the development of glomerulosclerosis than those recipients receiving adult donor kidneys.

Adult

The outcome of renal transplantation in children without prolonged pre-transplant dialysis.

Controversy in the literature exists over whether or not it is beneficial to maintain a patient on dialysis for a prolonged time before transplantation. Because no data exist comparing children who have had prolonged dialysis before transplantation to those who have none, we reviewed the charts of all children transplanted at the Children's Hospital of the Cleveland Clinic Foundation. Of those, we selected three groups for analysis: group one (n = 12) consisted of patients who had had less than or equal to 10 weeks of dialysis before transplantation (6.8 +/- -2.2 weeks, +/- = SD); group two (n = 21) were patients who had had more than 10 weeks of dialysis (142 + +/- -148 weeks). Both groups had two years of follow-up data. Group three (n = 13) consisted of patients who had had less than two years of follow-up (18.7 +/-/-7 months) but no dialysis before transplantation. There were no differences in mode of dialysis between groups one and two nor in the type of transplant (living-related donor vs. cadaveric). Significantly, the patients in group three received more cyclosporine A and less anti-lymphocyte globulin than the other two groups (p less than 0.05). Patients in group two received more transfusions (11.9 +/- 14.3) than patients in group one (4.0 +/- 2.7) and group three (3.5 +/- 7.3). There were no differences in number of patients who experienced at least one rejection episode among the three groups. Although the mean serum creatinine concentration at two years of follow-up was higher in group two (3.6 +/- -3.9 mg/dl), this was not significantly different from group one (1.7 +/- -0.7 mg/dl) or group three (1.9 +/- -0.5, n = 7). Sixty-three percent of patients in group one, 60% of patients in group two and 91% in group three had functioning allografts at two years follow-up. Although there may be other considerations, our data do not indicate any increase in rejection or decrease in graft survival in children who do not receive prolonged dialysis.

Adolescent

Resection of inferior vena cava tumor thrombi from renal cell carcinoma.

Renal cell carcinoma is an unusual cancer with the propensity to invade not only the renal vein but to propagate into the inferior vena cava (IVC) as a tumor thrombus. Experience has recently confirmed that MRI will be valuable in evaluating the extent of the tumor thrombus. The surgical techniques used to remove the thrombus are dependent on the extent of the cancer. For lesions involving the infrahepatic IVC, only proximal and distal control of the IVC are necessary. For a thrombus involving the intrahepatic IVC, isolation of the suprahepatic IVC, hepatic circulation, and infrahepatic IVC or cardiopulmonary bypass can be used. For the large thrombus in the supradiaphragmatic IVC or atrium, cardiopulmonary bypass either with or without deep hypothermic circulatory arrest is appropriate. In a review of 48 cases with renal cell carcinoma with IVC tumor thrombi, the tumor thrombus was removed intact in 58 per cent and in multiple fragments ("piece-meal") in 42 per cent of the patients. Cardiac bypass has been used in 26 cases with 22 undergoing deep hypothermic circulatory arrest. The postoperative mortality of 48 cases between 1965 and 1987 was 4 per cent. Removal of the most complicated and extensive renal cell carcinoma tumor thrombi is now technically feasible. In patients with large tumor thrombi, however, the ultimate outlook remains poor in the absence of effective systemic adjuvant therapy.

Carcinoma, Renal Cell

Management of renovascular disease. A surgical perspective.

The role of surgical revascularization in the management of patients with renal artery disease has changed in recent years. This has occurred due to the advent of percutaneous transluminal angioplasty as an effective method of treatment for certain patients, improved results of surgical revascularization in older patients with atherosclerosis, an enhanced appreciation of advanced atherosclerotic renal artery disease as a correctable cause of renal failure, and the development of more effective surgical techniques for patients with severe aortic atherosclerosis and branch renal artery disease. Surgical revascularization is currently the treatment of choice for patients with branch renal artery disease, ostial atherosclerotic renal artery disease, a renal artery aneurysm, and patients in whom renal percutaneous transluminal angioplasty has been unsuccessful. Excellent clinical results continue to be achieved with surgical revascularization in properly selected patients.

Angioplasty, Balloon

Management of renal cell carcinoma with vena caval thrombi via cardiopulmonary bypass and deep hypothermic circulatory arrest.

Cardiopulmonary bypass with deep hypothermic circulatory arrest allows safe and effective removal of renal tumors with extensive thrombi involving the vena cava under controlled circumstances without permanent side effects. The technique averts extensive dissection of the inferior vena cava and occlusion of major vessels while providing up to 60 minutes of safe operating time in a bloodless field and complete visibility of the interior of the vena cava. Adjunctive procedures for tumor excision or cardiac revascularization can be performed at the same time without increased operative risk.

Carcinoma, Renal Cell

Renal cell carcinoma with inferior vena cava tumor thrombi.

Renal cell carcinoma is a unique neoplasm because of its common propensity to propagate into the renal vein and inferior vena cava (IVC) as tumor thrombus. Historically, the surgical difficulties encountered in removal of these cancers limited the ability of a single institution to obtain experience with large numbers of instances. Between January 1956 and July 1987, 68 patients with renal cell carcinoma extending into the IVC or right atrium underwent radical nephrectomy with vena cava thrombus extraction at the Cleveland Clinic. Twenty-five patients had partial resection of the IVC with reconstruction. Fifteen patients had partial resection and reconstruction of the IVC; however, because of narrowing of the infrarenal IVC, persisting bland thrombus in the proximal IVC or iliac veins or concern regarding postoperative pulmonary emboli, the infrarenal IVC was either ligated or clipped. Seven patients underwent cavectomy with division of the IVC. A right atriotomy was performed upon 14 patients and cardiopulmonary bypass was used in 20 patients, with 17 also having deep hypothermic circulatory arrest. The tumor thrombus was removed intact in 64 per cent of the patients and in multiple small fragments ("piecemeal") in 36 per cent of the patients. The mortality rate was 7 per cent. Survival was examined relative to extent of vena caval thrombus. Patients with extension into the atrium had a significantly worse prognosis than those with other levels of vena caval involvement. Other factors, such as lymph node status, perinephric fat involvement, resection of IVC and intact or "piecemeal" extraction, did not influence the survival rate. Patients with pre-existing metastases preoperatively had an extremely poor survival rate. The techniques now available for surgical resection of all levels of tumor thrombus of the IVC make resection feasible in most patients. In our opinion, the addition of deep hypothermic circulatory arrest has been a significant advance.

Carcinoma, Renal Cell