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Biomedical subjects

A C Novick

Publications and source records attributed to A C Novick.

At least 127 records · Page 7Linked to original sources
PubMed1996

Renal hemodynamic effects of lovastatin in a renal ablation model.

OBJECTIVES: Patients with renal mass reduction of more than 50% are at increased risk for progressive renal failure. Lipid-lowering agents have been shown to preserve renal function in various models of chronic renal failure. This study was performed to evaluate the hemodynamic effects of lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, in the remnant kidney model. METHODS: Two groups of animals were studied. Group 1 (n = 9) served as controls and group 2 (n = 14) received lovastatin, 15 mg/kg/day orally, for 2 weeks after renal ablation. Glomerular filtration rate (GFR, inulin clearance), renal blood flow (RBF, ultrasonic flow probe), and 24-hour protein excretion were measured in anesthetized rats. RESULTS: Two weeks after renal ablation, GFR was 0.28 +/- 0.09 mL/min/gkw (gram kidney weight) in group 1, whereas in group 2, lovastatin preserved GFR at 0.58 +/- 0.3 mL/min/gkw (P < 0.05). RBF in group 1 was 1.2 +/- 0.2 mL/min/gkw and increased to 2.1 +/- 0.4 mL/min/gkw in group 2 (P < 0.05), representing a 43% increase. Protein excretion decreased significantly to 13 +/- 1.7 mg/24 hr in group 2. The lovastatin-treated group had a lower serum cholesterol (59 +/- 3 mg/dL versus 71 +/- 2 mg/dL, P < 0.05), but serum triglyceride levels were not different between the two groups. CONCLUSIONS: Lovastatin preserves renal function in a renal ablation model after 2 weeks of treatment. It specifically increased total RBF. Therefore, in addition to its known cholesterol lowering effect, lovastatin also has the direct renal hemodynamic effect of increasing RBF and maintaining GFR.

Animals↗
PubMed1996

Long-term followup after surgical treatment for renal cell carcinoma extending into the right atrium.

PURPOSE: Renal cell carcinoma extends into the inferior vena cava in 4 to 10% of patients and it is believed that the cephalad extent of inferior vena caval involvement is inversely correlated with survival. We evaluated this issue further. MATERIALS AND METHODS: From June 1984 to August 1993, 18 patients underwent surgical treatment for localized renal cell carcinoma and an inferior vena caval thrombus extending into the right atrium. One patient had a contralateral adrenal metastasis at operation. All patients underwent complete tumor excision with radical nephrectomy and inferior vena caval thrombectomy using adjunctive cardiopulmonary bypass and deep hypothermic circulatory arrest. Pathological study indicated no renal capsular penetration of renal cell carcinoma in 10 patients and perinephric fat involvement in 8. RESULTS: The overall and cancer-specific 5-year survival rates were 56.6% and 60.2%, respectively. Eight patients (45%) were free of malignancy at a mean of 71.6 months. One patient was alive with metastatic disease 15 months postoperatively. There was 1 operative death, while 8 patients died of metastatic renal cell carcinoma at a mean of 18.8 months postoperatively. Mean postoperative survival was significantly improved in patients with no renal capsular penetration by tumor compared to those with perinephric fat involvement (58.1 versus 19.7 months, p = 0.035). CONCLUSIONS: Long-term survival after surgical treatment is possible in patients with localized renal cell carcinoma extending into the right atrium. In patients with localized renal cell carcinoma and an inferior vena caval tumor thrombus the cephalad extent of inferior vena caval involvement does not appear to be prognostically important.

Adult↗
PubMed1996

The influence of cytokines on the adhesion of renal cancer cells to endothelium.

PURPOSE: The development of tumor metastasis requires direct adhesive interactions between tumor cells and vascular endothelium. We examined the adherence of renal cell carcinoma (RCC) lines to endothelium after stimulation with different cytokines that induce expression of the vascular adhesion molecules endothelial leukocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used to determine the adhesion of the RCC lines CCF-RC1, 2 and 7 to endothelium. Expression of cell adhesion molecules (CAM) on HUVEC and RCC lines was measured with immunoflowcytometry. RESULTS: Stimulation of HUVEC with rIl-1 beta, rTNF-alpha, or PMA resulted in a time-dependent 1.4- to 2.9-fold increase of RCC adhesion to HUVEC. Significant increased tumor cell binding was observed after 4 hours and paralleled the time-dependent induction of ELAM-1 and VCAM-1. Immunocytometry demonstrated the presence of the ligands sialyl Lewis X and VLA-4 on RCC, and blocking studies with monoclonal antibodies directed against tumor cell-endothelial interactions mediated by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X demonstrated marked inhibition of tumor cell adherence to cytokine-stimulated HUVEC. CONCLUSIONS: This study demonstrates that cytokine-induced increases in RCC adherence to HUVEC are mediated in part by VCAM-1/VLA-4 and ELAM-1/sialyl Lewis X interactions and suggest that these molecules may play an important role in the ability of RCC to metastasize.

Carcinoma, Renal Cell↗
PubMed1996

Lovastatin has direct renal hemodynamic effects in a rodent model.

PURPOSE: Lovastatin, an HMG-CoA reductase inhibitor, has been shown to preserve renal function in models of chronic renal failure. We determined the effect of lovastatin on renal function and hemodynamics in normal nonpathologic kidneys in a rodent model. MATERIALS AND METHODS: Renal function was measured in anesthetized (Inactin) control rats (n = 13) and lovastatin-treated rats (15 mg./kg./day, 3 weeks, orally, n = 17). Renal blood flow was measured with an ultrasonic flowprobe, and glomerular filtration rate was measured by inulin clearance. The effect of lovastatin on pre- and postglomerular vessel diameters was also observed in a hydronephrotic kidney preparation by videomicroscopy. RESULTS: Lovastatin significantly increased (p < 0.05) renal blood flow and glomerular filtration rate by 17% (3.4 +/- 0.2 ml./min./gram kidney weight (gKW) versus 2.9 +/- 0.2 ml./min./gKW) and 49% (0.67 +/- 0.04 ml./min./gKW versus 0.45 +/- 0.06 ml./min./gKW). The increase in renal blood flow was mediated by preglomerular vasodilation (expressed as percent increase from baseline diameter, n = 20), 25% in the interlobular artery and 20% in the afferent arteriole (p < 0.05). CONCLUSIONS: In addition to its known lipid-lowering properties, lovastatin has a direct renal hemodynamic effect, increasing renal blood flow and glomerular filtration rate in normal nonpathologic kidneys. Lovastatin's selective preglomerular vasodilation may account for the observed increase in renal blood flow and glomerular filtration rate. Accordingly, this additional hemodynamic effect may be useful in preserving renal function in models of chronic renal failure.

Animals↗
PubMed1996

Nephron sparing surgery in patients with metastatic renal cell carcinoma.

PURPOSE: We evaluated the role of nephron sparing surgery in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: A total of 15 patients with metastatic renal cell carcinoma underwent nephron sparing surgery and treatment of metastases, including 4 who received adjunctive biological response modifier therapy. The 9 patients in group 1, who previously underwent contralateral nephrectomy for renal cell carcinoma and complete resection of all metastases, presented for treatment of localized renal cell carcinoma in the remaining kidney with no other evidence of disease. The 6 patients in group 2 presented with localized renal cell carcinoma requiring nephron sparing surgery and concomitant distant metastases. Mean postoperative followup was 30.4 months. RESULTS: Of 9 patients in group 1, 6 (66.7%) were disease-free at a mean of 31.3 months after nephron sparing surgery and 102.2 months after detection of metastatic disease, while 3 (33.3%) died at a mean of 53.3 and 73.0 months, respectively. Among the 6 patients in group 2, 4 (66.7%) were disease-free at a mean followup of 16.8 months and 2 (33.3%) died at a mean of 20.5 months postoperatively. Of the 4 patients who received adjunctive biological response modifier therapy 3 were disease-free at a mean of 12.7 months and 1 died 7 months after treatment. Satisfactory overall renal function was preserved in 14 of 15 patients after nephron sparing surgery. CONCLUSIONS: We conclude that nephron sparing surgery can provide effective treatment for select patients with renal cell carcinoma and previously or recently treated metastatic disease.

Aged↗
PubMed1996

Transplantation into the long-term defunctionalized bladder.

PURPOSE: We evaluated the outcome of transplantation into a long-term defunctionalized bladder. MATERIALS AND METHODS: Since 1985 we performed transplantation in 5 dialysis dependent patients after excision of the ileal conduit and native kidneys. The bladder was evaluated before transplantation with cystoscopy, voiding cystography, urodynamics and demonstration of continence. Bladder rehabilitation was accomplished by cycling through a suprapubic tube or urethral catheter, and no bladder augmentation was done. All patients received antibiotic prophylaxis for several years. RESULTS: Five male recipients underwent transplantation at ages 22, 29, 30, 31 and 55 years, and they had had a defunctionalized bladder for 15, 17, 23, 25 and 26 years. All patients were alive with a functioning allograft at 6, 84, 90, 112 and 120 months after transplantation. Current serum creatinine values are 1.2, 1.6, 1.8, 2.3 and 2.5 mg./dl. Median urodynamic values before and after transplantation were bladder capacity 60 and 300 cc, respectively, peak flow rate 5 and 18 cc per second, respectively, and post-void residual 20 and 15 cc, respectively. One patient required self-catheterization. CONCLUSIONS: Renal transplantation into a long-term defunctionalized bladder can be performed safely in carefully selected patients. Bladder function and continence should be confirmed before transplantation using a program of progressive bladder rehabilitation.

Adult↗
PubMed1996

Long-term results with single pediatric donor kidney transplants in adult recipients.

PURPOSE: We investigated whether transplantation of single pediatric donor kidneys into adults leads to an increased incidence of functional allograft impairment and complications, as previously reported. MATERIALS AND METHODS: To evaluate long-term functional outcome using single pediatric donor kidneys 60 adults (study group) who underwent transplantation between March 1973 and December 1988 using single pediatric donor kidneys 6 years old or younger (mean donor age plus or minus standard deviation 41.1 +/- 17.9 months) were compared to 58 matched adults (control group) who underwent transplantation with adult kidneys (mean donor age 29.7 +/- 10.8 years). The groups were identical for era of transplantation, recipient age, sex and followup (82 versus 83 months). RESULTS: There was no difference in patient survival between the study and control groups (p = 0.26). In the study group there were an increased requirement for early dialysis (45 versus 24%, p = 0.02), a higher incidence of proteinuria (greater than 0.8 gm./24 hours, 67 versus 48%, p = 0.04) and a higher incidence of rejection within the first 6 months (80 versus 64%, p = 0.05). There was also an increased incidence of graft failure from acute rejection in the study group. Early differences in serum creatinine levels in the 2 groups dissipated after 3 months. Renal allograft histopathology revealed no significant difference in the incidence of focal segmental glomerulosclerosis in the study versus control groups after transplantation (22.9 versus 13.3%, p = 0.70). However, focal segmental glomerulosclerosis manifested sooner after transplantation in study than control patients (mean 37 versus 82 months). After transplantation proteinuria developed in study patients with focal segmental glomerulosclerosis at a mean of 4.6 months compared to 31.8 months in controls with post-transplant focal segmental glomerulosclerosis. Graft survival in the study group was superior when cyclosporine was given rather than conventional noncyclosporine based immunosuppression. Five-year graft survival rates were 48 versus 44% for cyclosporine treated and 33 versus 44% for conventionally treated study versus control patients. CONCLUSIONS: These data suggest that with cyclosporine immunosuppression transplanting single pediatric kidneys into adults yields the same long-term functional graft outcome as adult donor kidneys.

Adult↗
PubMed1996

The Le Bag orthotopic urinary diversion.

PURPOSE: We reviewed our experience with Le Bag orthotopic urinary diversion in 38 cases. MATERIALS AND METHODS: Between April 1990 and January 1995, 38 men underwent radical cystectomy and Le Bag urinary diversion for treatment of bladder cancer. Approximately 20 cm. each of detubularized ileum and cecum were used to construct the pouch. A total of 22 pouches was fashioned with absorbable staples. In 21 cases freely refluxing Bricker ureterointestinal anastomoses were used. RESULTS: There was no significant difference in major complication rates in the hand sewn versus stapled anastomosis groups, and there were no complications specifically related to the use of staples. There were 3 episodes of febrile urinary tract infection: 2 in the Bricker group and 1 in the tunneled anastomosis group. There was no significant difference between the 2 groups with respect to ureteral obstruction. The daytime continence rate was 91%, and 80% of the patients are completely dry or have only mild incontinence at night. Most patients had mild hyperchloremic metabolic acidosis postoperatively as evidenced by a decrease in median serum bicarbonate level (28 versus 24 mmol./l.). This difference appears to be related to pouch length (r = 0.58, p = 0.0002). CONCLUSIONS: We conclude that the Le Bag technique is a technically feasible form of urinary diversion with functional results similar to other forms of orthotopic diversion. Use of absorbable staples simplifies pouch construction without increasing complications. This form of urinary diversion is associated with hyperchloremic metabolic acidosis, which is related to pouch length.

Anastomosis, Surgical↗
PubMed1996

Options for therapy of ischemic nephropathy: role of angioplasty and surgery.

The development of chronic renal failure from progressive atherosclerotic renal arterial occlusive disease, termed "ischemic nephropathy," is an important clinical problem in older patients with generalized atherosclerosis obliterans. Studies on the natural history of atherosclerotic renal artery disease have made it possible to identify those patients in whom this disease poses a significant threat to overall renal function. Several factors must be considered in evaluating the renal functional benefit of intervention to relieve arterial obstruction. These include the severity and extent of renal artery obstruction, the level of renal function, renal histopathologic information, and the general medical condition of the patient. Intervention to restore normal renal arterial blood flow is indicated in selected patients to prevent deterioration of renal function that may culminate in the need for dialytic replacement therapy. Percutaneous transluminal angioplasty is the treatment of choice for patients with non-ostial atherosclerotic lesions. Most reports in the literature indicate that surgical revascularization provides more effective long-term therapy for patients with ostial atherosclerotic lesions.

Angioplasty, Balloon↗
PubMed1995

Expression of cell adhesion molecules in an established and characterized new human renal cell cancer line, CCF-RC7.

In order to investigate the importance of cell adhesion molecules (CAMs) in renal cell carcinoma (RCC), a cell line, designated as CCF-RC7, was established from a human RCC of the clear cell type. CCF-RC7 was passaged over 50 times in vitro for 3 1/2 years. The cell line has an epithelial morphology and a doubling time of 30 h, forming colonies in soft agar with an average efficiency of 10.4% and producing clear cell tumors in athymic nude mice. CCF-RC7 cells have an aneuploid-hypotetraploid karyotype with a modal chromosome number of 82 and rearrangements in chromosomes 9, 12 and 14. Immunohistochemical and flow immunocytometric analyses revealed high expression of ICAM-1 (CD54), and Hermes antigen (CD44), which was significantly upregulated by cytokine and PMA treatment. VLA-4 was expressed on approximately 20% of tumor cells and could not be altered by cytokine or PMA stimulation. High expression of sialyl Lewis X was also demonstrated by immunohistological examination. This newly characterized cell line will serve as a useful model for the study of CAMs during hematogenous metastasis and host defense mechanisms in human RCC.

Adult↗
PubMed1995

Management of small unilateral renal cell carcinomas: radical versus nephron-sparing surgery.

OBJECTIVES: There is controversy concerning the management of small unilateral renal cell carcinomas. The present study was undertaken to evaluate the relative efficacy of radical nephrectomy versus nephron-sparing surgery in such patients. METHODS: Patients with a single, small (less than 4 cm), localized, unilateral, sporadic renal cell carcinoma (RCC) were identified from an institutional registry. From 1975 to 1992, 88 patients fulfilling these criteria were treated with either radical nephrectomy (n = 42) or nephron-sparing surgery (n = 46). The mean postoperative follow-up interval is 48 +/- 29 months. RESULTS: The radical and nephron-sparing surgical groups were well matched for patient age, sex, renal function, diabetes, hypertension, tumor size, tumor location, and tumor stage. All patients in both groups had low pathologic stage RCC. There was no difference between the two groups in terms of the mean hospital stay, the requirement for blood transfusions, or the occurrence of surgical complications. There was no difference in the mean preoperative and postoperative serum creatinine levels for patients in the nephron-sparing surgery group. However, the mean postoperative serum creatinine levels were significantly higher than the mean preoperative levels for patients in the radical nephrectomy group (P < 0.001). A single patient in each group developed recurrent RCC postoperatively. The cancer-specific 5-year survival rate for patients in the radical and nephron-sparing surgical groups is 97% and 100%, respectively. CONCLUSIONS: Radical nephrectomy and nephron-sparing surgery each provide safe and effective curative treatment for patients with a single, small, unilateral localized RCC. The long-term renal functional advantage of nephron-sparing surgery in this setting is not established.

Aged↗
PubMed1995

Definitive tumor resection and percutaneous bacille Calmette-Guérin for management of renal pelvic transitional cell carcinoma in solitary kidneys.

OBJECTIVES: This study was done to evaluate the safety and initial efficacy of definitive tumor resection combined with percutaneous bacille Calmette-Guérin (BCG) for management of renal pelvic transitional cell carcinoma (TCC) in patients with solitary kidneys. METHODS: Eight patients with anatomically solitary kidneys, all of whom had a prior history of TCC elsewhere in the urinary tract, were treated with either partial nephrectomy (n = 2) or percutaneous resection (n = 6) combined with a 6-week course of topical BCG administered percutaneously. Seven (87.5%) of the 8 patients tolerated the complete BCG course without adverse effects. One patient required cessation of treatment for renal insufficiency, which resolved with discontinuation of therapy. Follow-up nephroscopy was performed 3 months after the initial tumor resection in 6 of the 8 patients, and all patients underwent regular follow-up surveillance at 3- to 6-month intervals thereafter with radiographic, cytologic, and, in some cases, ureteroscopic examinations. RESULTS: With follow-up ranging from 9 to 59 (mean, 22) months, local tumor recurrence has become evident in only 1 patient. Two other patients have developed distant metastatic disease, both of whom had invasive TCC elsewhere in the urinary tract prior to treatment of the upper tract tumor. CONCLUSIONS: Combining a 6-week course of percutaneously administered topical BCG with definitive tumor resection is generally well tolerated, and, ultimately, this protocol may result in a decreased incidence of local tumor recurrence in these high-risk patients.

Aged↗
PubMed1995

Long-term renal function in cyclosporine-treated renal allograft recipients.

OBJECTIVES: The purpose of this study was to analyze the factors affecting long-term renal function in cyclosporine-treated kidney transplants. METHODS: The study population comprised 167 patients with more than 5 years of graft function on cyclosporine therapy. Patients were subdivided into those with a serum creatinine level 2.0 mg/dL or less (group I, n = 123) versus those with a level more than 2.0 mg/dL (group II, n = 44) at 5 years post-transplant. Patient survival, graft survival, rejection episodes, renal function, cyclosporine dose and trough level, and proteinuria were compared in these two groups. RESULTS: There was no significant difference between groups I and II in terms of race, sex, donor source, donor age, primary renal disease, retransplants, transfusions, presensitization, histocompatibility locus antigen match, or initial nonfunction. At 6 months post-transplantation, the mean serum creatinine level in group II was significantly higher than group I (P = 0.00001), and this difference increased at subsequent follow-up intervals. The incidence of proteinuria was significantly higher in group II compared with group I (P < 0.001). Renal allograft survival beyond 5 years post-transplant was significantly better in group I compared with group II (P = 0.005). There was no significant difference in the mean cyclosporine dose or the mean cyclosporine trough level between groups I and II at any time following transplantation. The most important difference between groups I and II was the finding of significantly more early (P < 0.001) and late (P < 0.001) rejection episodes in group II. CONCLUSIONS: These data suggest that long-term renal function in cyclosporine-treated kidney transplant patients is primarily influenced by the occurrence of early and late rejection episodes rather than by the dosage or duration of cyclosporine therapy.

Adult↗