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Biomedical subjects

A C Novick

Publications and source records attributed to A C Novick.

At least 109 records · Page 6Linked to original sources
PubMed1997

Renal microcirculatory effects of lovastatin in a rat model of reduced renal mass.

OBJECTIVES: Patients with reduced renal mass are at increased risk of developing renal failure. A remnant kidney model has been used to study the hemodynamic and structural changes that occur. We recently reported that the lipid-lowering agent lovastatin preserves renal function in this model. The purpose of the present study was to determine the specific effects of lovastation on the renal microcirculation of rats with reduced renal mass. METHODS: We used the rat hydronephrotic kidney preparation with a 5/6 partial nephrectomy. This model allows direct visualization of preglomerular and postglomerular vessels using videomicroscopy. The diameters and vascular responses to acetylcholine and angiotensin II of the interlobular, afferent, and efferent vessels were determined in two groups of animals with renal mass reduction: 15 rats with no lovastatin treatment and 18 rats treated with oral lovastatin (15 mg/kg body weight/day) for 2 weeks. RESULTS: In the lovastatin-treated rats, the baseline efferent vessel diameter was smaller by 21% (P < 0.05), but the interlobular and afferent vessel baseline diameters were not different from those in the untreated rats. Serum creatinine levels were lower in the treated rats (1.5 +/- 0.1 versus 2.0 +/- 0.2 mg/dL, P < 0.05), but serum lipids were not different. In the lovastatin-treated rats, vascular reactivity to acetylcholine was enhanced in the afferent and decreased in the efferent vessels. CONCLUSIONS: In this renal ablation model, lovastatin preserved renal function as measured by serum creatinine without lowering plasma lipid levels. Lovastatin treatment resulted in smaller efferent vessel diameters. Lovastatin also increased the vasodilatory response to acetylcholine in the afferent vessels. Together, these preglomerular and postglomerular changes would increase the single-nephron glomerular filtration rate. The renal protective effect of lovastatin may be due to these vasoactive effects on the renal microcirculation.

Animals↗
PubMed1997

Long-term survival after surgical revascularization for atherosclerotic renal artery disease.

PURPOSE: We analyzed the long-term clinical outcome and survival after surgical revascularization for atherosclerotic renal artery stenosis. MATERIALS AND METHODS: The study group comprised 222 patients who underwent surgical revascularization for atherosclerotic renal artery stenosis between 1974 and 1987. The indications for performing surgical revascularization were treatment of hypertension in 60 patients, preservation of renal function in 12, and control of hypertension and preservation of renal function in 148. Postoperative blood pressure, renal function and survival data were analyzed during a mean followup of 7.4 years. RESULTS: There were 5 operative deaths (2.2%) and postoperative thrombosis or stenosis of the repaired renal artery occurred in 16 patients (7.3%). Long-term cure or improvement of renovascular hypertension was achieved in 72.4% of patients. Preoperative renal function correlated significantly with a favorable blood pressure response to surgical revascularization (p = 0.013). Long-term improvement or stabilization of renal function was achieved in 71.3% of patients. Preoperative renal function (p = 0.034) and bilateral atherosclerotic renal artery stenosis (p = 0.04) correlated significantly with a favorable renal function result after surgical revascularization. Actuarial 5 and 10-year survivals for the entire series from the time of surgical revascularization were 81 and 53%, respectively. The expected 5 and 10-year survivals for a comparable healthy population are 89 and 77%, respectively. Using a multivariate analysis, factors correlating with diminished long-term survival were age older than 60 years (p = 0.002), coronary artery disease (p = 0.031), and previous vascular operations (p = 0.001). CONCLUSIONS: These data support the long-term therapeutic efficacy of surgical revascularization in patients with atherosclerotic renal artery stenosis. The merits of newer forms of therapy, such as percutaneous transluminal angioplasty and endovascular stenting, must ultimately be weighed against these results.

Actuarial Analysis↗
PubMed1997

Clinical practice guidelines: renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the most common renal malignancy and is increasing at an annual rate of approximately 2% worldwide. Metastatic RCC is among the more chemotherapy-refractory malignancies, with a 5-year survival rate less than 2%. A variety of therapies are currently under investigation for the treatment of metastatic RCC, particularly involving immunotherapeutic agents such as interferon alfa. OBJECTIVES: To review and compare historical and current data that define practice guidelines in the treatment of RCC. DISCUSSION: Of the various treatment modalities available for RCC, only surgery with complete removal of tumor burden can be considered as potentially curative, since the tumor is resistant to chemotherapy, hormonal therapy, and radiation therapy. However, biologic response modifiers (BRMs)-particularly immunotherapeutic agents such as interferon alfa-have been extensively studied and appear to produce objective tumor regression in selected patients with advanced disease. CONCLUSIONS: In patients with metastatic RCC, performance status is the most important predictor of outcome, and should therefore be utilized for therapeutic decision making. Immunotherapy with BRMs such as recombinant interferon alfa and recombinant interleukin-2 has been associated with meaningful antitumor responses in selected patients. Combination therapy with recombinant interferon alfa, recombinant interleukin-2, and 5-fluorouracil may offer considerable promise, and the subcutaneous administration of recombinant interferon alfa and recombinant interleukin-2 may improve the tolerability and convenience of these cancer treatments by reducing side effects and permitting outpatient administration. As treatment expectations for metastatic RCC are limited, experimental approaches are warranted.

Carcinoma, Renal Cell↗
PubMed1997

The use of kidneys from living donors with renal vascular disease: expanding the donor pool.

PURPOSE: The disparity between the number of patients awaiting organ transplantation and the number of available donor organs continues to increase. We report the outcomes of transplantation using kidneys from living donors who had unilateral renovascular disease. MATERIALS AND METHODS: We identified 5 living donors who had unilateral renovascular disease, including saccular renal artery aneurysms, an arteriovenous malformation, localized atherosclerosis and fibromuscular renal artery stenosis. Each donor was normotensive and asymptomatic, and had otherwise normal renal function. RESULTS: In each case the abnormal kidney was removed, the lesion was repaired ex vivo and the kidney was successfully transplanted without complication in the donor or recipient. Each recipient had a serum creatinine of less than 2 mg./dl. and each donor remained normotensive with stable renal function at up to 3 years of followup. CONCLUSIONS: Kidneys from living donors with renovascular disease can be transplanted safely provided that careful selection, informed consent and a normal remaining kidney are ensured.

Adult↗
PubMed1997

The current level of involvement of urological trainees and faculty in clinical kidney transplantation in the United States and Canada.

PURPOSE: We attempted to quantitate the level of participation of urology residents and faculty in clinical renal transplantation in the United States and Canada at the present time. MATERIALS AND METHODS: All 123 urology residency program directors in the United States and all 13 in Canada were mailed a questionnaire requesting information about the participation of their residents and faculty in clinical renal transplantation at their institutions. All program directors (100%) returned the surveys. RESULTS: In the United States 94% of residencies are affiliated with renal transplant programs and 81% provide a transplant rotation. In Canada each program provides a transplant experience. In the United States 22% and in Canada 85% of academic renal transplant programs are directed or codirected by urology. In the United States approximately 80% and in Canada more than 90% of residents are exposed to transplant surgery, although the majority have pre-urology or junior resident rotations. Approximately 50% of residents in each country receive training in immunosuppression. In the United States 25% of programs have urology faculty perform transplant surgery and administer immunosuppression, compared to more than 90 and only 15%, respectively, in Canada. CONCLUSIONS: Urological participation in clinical renal transplantation at academic medical centers remains strong with approximately 25% of programs directed or codirected by urology departments in the United States--a figure that has not changed appreciably during the last 10 years. In the future the continued presence of urology in transplantation requires a commitment from urology program directors to support exposure for residents as well as promoting the training and development of young transplant surgeons within our own specialty.

Canada↗
PubMed1997

Patterns of tumor recurrence and guidelines for followup after nephron sparing surgery for sporadic renal cell carcinoma.

PURPOSE: We delineated patterns of tumor recurrence and developed guidelines for followup after nephron sparing surgery for sporadic renal cell carcinoma. MATERIALS AND METHODS: Before December 1994, 327 patients underwent nephron sparing surgery for sporadic localized renal cell carcinoma at our clinic. Mean postoperative followup was 55.6 months. The course and outcome for patients with postoperative recurrent renal cell carcinoma were reviewed in detail. RESULTS: Renal cell carcinoma recurred after nephron sparing surgery in 38 patients (11.6%), including 13 (4.0%) who had local tumor recurrence with (7) or without (6) metastatic disease and 25 (7.6%) who had metastatic disease without local tumor recurrence. Recurrent renal cell carcinoma was detected by associated symptoms in 25 patients and by a followup chest x-ray or abdominal computerized tomography (CT) in 13. The respective incidences of postoperative local tumor recurrence and metastatic disease according to initial pathological tumor stage were 0 and 4.4% for stage T1, 2.0 and 5.3% for stage T2, 8.2 and 11.5% for stage T3a, and 10.6 and 14.9% for stage T3b disease. The peak postoperative intervals until local tumor recurrence were 6 to 24 months (7 of 10 patients with stage T3 renal cell carcinoma) and longer than 48 months (all 3 with stage T2 disease). Patients with isolated local tumor recurrence had better survival compared to those with local tumor recurrence and metastatic disease or metastases only. CONCLUSIONS: Followup for recurrent malignancy after nephron sparing surgery for renal cell carcinoma can be tailored according to the initial pathological tumor stage. All patients should be evaluated yearly with a medical history, physical examination and select laboratory studies. Patients with stage T1 renal cell carcinoma require no additional monitoring, while those with stage T2 disease should also undergo a yearly chest x-ray and abdominal CT every 2 years. The same recommendations are offered for patients with stage T3 renal cell carcinoma except that abdominal CT should be done every 6 months for the first 2 years postoperatively.

Aged↗
PubMed1996

Determinants of chronic renal allograft rejection in cyclosporine-treated recipients.

We analyzed the development of chronic rejection in 511 kidney-only renal transplants in 507 patients between July 1987 and November 1994. A database was established for recipients > or = 18 years old who received cyclosporine-based immunosuppression and demonstrated graft survival for a minimum of 12 months. The 347 recipients of cadaver transplants (67.9%) and 164 recipients of live donor transplants (32.1%) were followed for 12 to 102 months (mean 51 months). Chronic rejection was diagnosed in 124 transplants (24%), with a mean time to diagnosis of 23+/-18 months (range 3-92). Risk factors were identified in a multivariate analysis using the Cox model. The impact of the timing and severity of rejection episodes was analyzed in a univariate model. The presence of chronic rejection resulted in decreased (P=0.0001) 5-year graft survival for both cadaver graft (83.7% vs. 58.2%) and live donor graft (93.2% vs. 53.1%) recipients. Significant variables for the development of chronic rejection included an acute rejection episode (P=0.0001), a black recipient (P=0.0006), donor age > or = 50 years (P=0.006), and a serum creatinine level >2.0 mg/dl by 6 months after transplantation. Severity of rejection measured by peak serum creatinine or posttreatment return to baseline was not related to chronic rejection. However, acute rejection episodes lasting for more that 5 days (P=0.03) or occurring after 6 months (P=0.001) did influence time to chronic rejection. In addition, mismatching for donor-recipient race was a significant (P=0.008) risk factor for recipients of cadaver grafts. We conclude that acute rejection is the most significant risk factor for chronic rejection, and the long-term fate of grafts may be determined as early as the first 6 months. Racial matching of donor-recipient pairs may be useful to minimize chronic rejection risk. Future advances that diminish the incidence and severity of acute rejection may have the greatest impact on long-term survival.

Acute Disease↗
PubMed1996

Induction of chemokine gene expression during allogeneic skin graft rejection.

The factors mediating trafficking of alloantigen-primed T cells and mononuclear phagocytes to the site of an allograft during the graft rejection process remain largely undefined. Based upon their demonstrated chemoattractant properties, chemokines may play a role in directing inflammatory cells to graft sites and initiate rejection. To begin to investigate the role of chemokines in graft rejection, we used Northern blot analysis to examine the temporal expression of 6 chemokine genes in murine allogeneic skin grafts disparate at the entire MHC and minor antigens and grafts with a disparity at either single class I or class II MHC determinants. Two general patterns of chemokine gene expression in each of the allografts were observed. Intragraft expression of 1 group of chemokine genes, including macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, JE, and KC was observed at peak levels 3 days posttransplant in each of the 3 different allograft models. Expression of these genes in control isografts was at low levels, with the exception of JE, which was expressed at equivalent levels in all iso- and allografts for the first 4-5 days posttransplant, and KC, which was expressed at equivalent levels in C57BL/6 isografts and bm1 and bm12 allografts. A second group of chemokine genes, including RANTES (regulated upon activation normal T cell expressed and secreted) and IP-10 (interferon-gamma inducible protein), was expressed at low levels at early times after transplantation but at high levels 3-4 days before rejection of the allografts was complete. Isograft expression of RANTES and IP-10 was undetectable at the late time points. The results suggest that these 2 patterns of chemoattractant cytokine gene expression may be representative of the early inflammatory and the late T cell-mediated phases of the allograft rejection process, respectively.

Animals↗
PubMed1996

Hyperfiltration nephropathy as a cause of late graft loss in renal transplantation.

Despite improved immunosuppression and early allograft survival, long-term survival of allografts remains unchanged. Late renal allograft loss has traditionally been considered to result from repeated or unresolved episodes of acute rejection that lead to chronic immune-mediated allograft rejection. However, late renal allograft loss is known to occur in the absence of prior episodes of acute rejection. It is therefore proposed that factors other than histocompatibility influence long-term allograft survival. Evidence for nonimmunologic factors contributing to late allograft loss is presented. The central hypothesis is that following renal allograft mass reduction (from any etiology), glomerular hyperperfusion and hyperfiltration develop and lead to progressive renal dysfunction, proteinuria, histopathologic allograft changes, and late allograft failure. Multiple nonimmunologic factors that could contribute to reduced renal mass and ultimately promote chronic allograft loss as a result of hyperfiltration nephropathy are presented along with possible therapeutic strategies for the prevention and treatment of glomerular hyperfiltration.

Glomerular Filtration Rate↗
PubMed1996

Long-term follow-up of kidneys transplanted from elderly cadaveric donors.

This report examines the long-term results obtained in 50 patients transplanted between 1977 and 1990 with kidneys from cadaveric donors aged 55-70 (median 59) years. The recipients comprised 27 men and 23 women aged 8-68 (median 42) years. In all, 20 patients (40%) had end-stage renal disease on the basis of glomerulonephritis, whereas 8 (16%) were diabetic. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine and prednisone in all patients in addition to cyclosporine in the 35 patients transplanted since 1985. Immediate graft function occurred in 18 patients (36%), and 36 patients (72%) were off dialysis at 1 year posttransplant. Altogether, 25 patients (50%) had functioning grafts at 5 years posttransplant, and at up to 13 years of follow-up (mean 5.8 years), 22 patients (44%) are off dialysis and their serum creatinine levels range from 0.8 to 3.8 mg/dl (mean 2.0 mg/dl). In all, 12 patients (24%) expired from 2 months to 15.5 years posttransplant (mean 4.3 years), and 5 of these patients died with functioning grafts. These 5 deceased recipients and the 22 who remain alive with functioning grafts had a mean antigen match of 2.27 with their donors. The other 23 patients whose grafts failed had a mean antigen match of 2.13 (P = 0.77). The 15 recipients who were transplanted prior to the cyclosporine era had lower 1- and 5-year allograft survival rates of 67% and 47%, respectively, as compared with their counterparts, who took cyclosporine-based immunosuppression (74% and 51%, P = 0.58 and 0.76, respectively). Likewise, the 32 recipients with delayed graft function had lower 1- and 5-year allograft survival rates of 66% and 47%, respectively, as compared with the group with immediate graft function (83% and 56%, P = 0.18 and 0.56, respectively). We conclude that acceptable long-term patient and graft survival may be achieved by transplanting these organs and that the degree of HLA matching does not affect their outcome significantly. Patients with immediate allograft function also tended to do better over the long term. Although cyclosporine-based immunosuppression was advantageous within 1 year of transplant, its beneficial effect was less marked 5 years out.

Adolescent↗
PubMed1996

Post-transplant renal artery stenosis: impact of therapy on long-term kidney function and blood pressure control.

PURPOSE: We assessed the long-term outcome of different treatment methods for transplant renal artery stenosis. MATERIALS AND METHODS: Outcome data for 23 patients with transplant renal artery stenosis treated during a 16-year period were reviewed and analyzed. RESULTS: There was a higher incidence of renal artery stenosis in cadaveric donor kidneys compared to living donor kidneys (2% versus 0.3%, p < 0.02), and in cadaveric kidneys from pediatric donors less than 5 years old compared to those from adults (13.2% versus 1.3%, p < 0.01). Six patients underwent primary medical treatment for renal artery stenosis, with a successful outcome in 4 (mean followup plus or minus standard error 57 +/- 22 months) and failure in 2. Of the patients 16 were treated with percutaneous transluminal angioplasty, including 12 who were cured or improved with respect to hypertension (followup 44.7 +/- 7.6 months). Five patients underwent surgical revascularization for renal artery stenosis with postoperative improvement of hypertension (followup 18.8 +/- 11.6 months). Overall, 21 of 23 patients (91%) were treated successfully for transplant renal artery stenosis with cure or improvement of associated hypertension. Posttreatment renal function was stable or improved in 18 patients, while renal function deteriorated due to parenchymal disease in 3. CONCLUSIONS: Most patients with transplant renal artery stenosis can be treated successfully. Percutaneous transluminal angioplasty is the initial interventive treatment of choice for high grade renal artery stenosis. Surgical revascularization is indicated if percutaneous transluminal angioplasty cannot be done or is unsuccessful.

Adult↗
PubMed1996

Intraoperative evaluation of renal cell carcinoma: a prospective study of the role of ultrasonography and histopathological frozen sections.

PURPOSE: Nephron sparing surgery is being performed increasingly for treatment of renal cell carcinoma, including in select patients with a normal contralateral kidney. The number of tumors in the involved kidney (single versus multiple) and presence or absence of perinephric fat involvement (pathological stage T1 to 2 versus T3A) are important prognostic factors. In a prospective study we evaluated the accuracy of intraoperative histopathological frozen section analysis of renal capsular biopsies for assessing local tumor stage, and the accuracy of intraoperative ultrasonography for assessing tumor focality. MATERIALS AND METHODS: Intraoperative frozen section biopsies and ultrasonography were compared with information obtained from preoperative computerized tomography (CT), intraoperative inspection of the kidney by the surgeon and permanent histopathological specimens. RESULTS: We evaluated 99 patients (102 kidneys) with localized sold renal masses undergoing either radical nephrectomy (48) or nephron sparing surgery (54). Final pathological analysis revealed 95 renal cell carcinomas (stage T3A in 24), 6 oncocytomas and 1 angiomyolipoma. Multiple tumors were detected in 18 of 102 kidneys overall. Frozen section analysis identified 87% of the stage T3A lesions with no false-positive results, compared to CT, which only identified 67%. Ultrasonography identified 14 of 18 multifocal tumors (78%) and was not more accurate than the combination of CT and intraoperative inspection. However, during nephron sparing surgery ultrasonography was useful to localize the intrarenal extent of tumors (17 cases). CONCLUSIONS: Our results clarify the role of intraoperative ultrasonography and frozen section analysis in patients undergoing nephron sparing surgery for renal cell carcinoma. Frozen section analysis may be useful in select patients with small peripheral tumors who are under consideration for elective nephron sparing surgery.

Carcinoma, Renal Cell↗
PubMed1996

Cadaveric kidney transplantation under prophylactic polyclonal antibody immunosuppression with anti-lymphoblast globulin versus anti-thymocyte globulin.

OBJECTIVES: This retrospective study was undertaken to evaluate and compare the clinical and immunologic outcomes following prophylactic induction treatment with Minnesota anti-lymphoblast globulin (MALG) and Upjohn anti-thymocyte globulin (ATGAM) in cadaver renal transplantation. METHODS: From 1990 to 1994, 63 patients with renal transplants from cadavers received MALG and 77 patients received ATGAM for induction treatment. Most pretransplant parameters were equivalent in both groups. There was no significant difference in the total dose and mean duration of MALG/ATGAM administration. The post-transplant outcome in these groups was compared. RESULTS: There was no difference between the MALG and ATGAM groups with respect to the overall number of rejection episodes, median days to rejection, or the number of steroid-resistant rejection episodes. However, MALG-treated patients experienced a greater number of rejections in the first 60 days postoperatively (P = 0.06). There was no difference in the nadir serum creatinine level in the first 20 postoperative days in the two groups; however, it took fewer days to reach the nadir in the ATGAM group (P = 0.03). The incidence of delayed graft function was higher in the MALG group than in the ATGAM group (38% versus 31%) but not statistically significant. Graft survival at 12 and 24 months was comparable in both groups. However, patient survival was superior at 12 and 24 months in ATGAM-treated transplant recipients (P = 0.03). The mean serum creatinine at 6, 12, and 24 months was similar in both the MALG and ATGAM groups. The mean fall and recovery of CD3, CD4, and CD8 T-lymphocyte subsets while on MALG/ATGAM were similar in both groups. The incidence of infectious complications was greater in the MALG group. CONCLUSIONS: MALG and ATGAM have comparable clinical immunosuppressive effects. Patients receiving ATGAM experienced fewer rejections in the first 2 months, fewer infections, and better survival.

Antilymphocyte Serum↗
PubMed1996

Renal pathology in patients with primary hyperaldosteronism secondary to an adrenal cortical adenoma.

OBJECTIVES: The cause of persistent hypertension following the removal of an aldosterone-producing adrenal adenoma is unknown. The purpose of this study was to determine whether this occurrence is due to existing renal histopathologic damage. METHODS: Thirty-two patients with primary hyperaldosteronism due to an aldosterone-secreting adrenal cortical adenoma underwent open renal biopsy at the time of unilateral adrenalectomy. Biopsy results were correlated with the duration and severity of hypertension before and after surgery. RESULTS: Nineteen patients were cured of their hypertension postoperatively, whereas 13 patients had persistent diastolic hypertension. Statistical analysis of these two groups revealed no difference when renal histopathologic variables, preoperative severity of hypertension, or preoperative duration of hypertension were compared. CONCLUSIONS: Persistent hypertension in these patients does not appear to be due to renal histopathologic changes; coexisting essential hypertension is a more likely cause.

Adolescent↗