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Biomedical subjects

Dean G Assimos

Publications and source records attributed to Dean G Assimos.

At least 19 recordsLinked to original sources

Xanthine urolithiasis.

Xanthine calculi are uncommonly encountered stones. When they occur, they typically do so in association with inborn metabolic disorders such as hereditary xanthinuria or Lesch-Nyhan syndrome. They may also occur in association with states of profound hyperuricemia such as myeloproliferative disease after treatment with allopurinol. If the underlying disorder is not addressed, a high risk of stone recurrence exists. Therefore, to raise clinical awareness, we reviewed and report our experience in the treatment of patients with these stones, discussing the underlying pathophysiology and approach to treatment.

Adolescent↗

New generation tissue sealants and hemostatic agents: innovative urologic applications.

Control of blood loss during urologic surgery is paramount to the success of patient recovery. Hemostatic agents and tissue sealants are used routinely to prevent excess blood loss and in reconstruction during surgical repair. Some of the available products include thrombin sealant, fibrin glue, bovine serum/albumin/glutaraldehyde, and gelatin matrix. Each of these agents differs in mechanism, cost, and application. Complications can include allergic reactions or thromboembolism and the risk of contracting bovine spongiform encephalitis or hepatitis. Many new hemostatic agents are being developed and approved. The benefits and risks of use of these agents versus conventional treatment need to be considered on a case-by-case basis by the surgeon.

Journal Article↗

Pitfalls in the management of patients with primary hyperoxaluria: a urologist's perspective.

The primary hyperoxalurias are rare, inherited diseases which commonly manifest early in life as urolithiasis. As these patients often present to the urologic surgeon, it is imperative that urologists understand the typical presentation, diagnosis, and management of urolithiasis associated with primary hyperoxaluria. In this review, the pertinent epidemiology and pathogenesis as they relate to the diagnosis and natural history of the disease are discussed. The literature on therapeutic options for primary hyperoxaluric patients with calculi is examined, and treatment strategies are suggested.

Humans↗

Ureterocalicostomy: a contemporary experience.

OBJECTIVES: To report our contemporary experience with ureterocalicostomy to determine whether the indications or results have changed in modern practice. Ureterocalicostomy is a well-established treatment for patients with complicated ureteropelvic junction (UPJ) obstruction and other forms of proximal ureteral obstruction. Although both retrograde and antegrade endourologic interventions have become accepted forms of management, the success rates do not approach those of open or even laparoscopic interventions, potentially leading to a greater number of patients with treatment failure and the need for more complicated reconstruction. METHODS: Between July 1991 and February 2004, 11 patients (4 women and 7 men), aged 19 to 68 years (mean 38), underwent open surgical ureterocalicostomy. The indications for surgery were primary UPJ obstruction in 4, failed cutting balloon incision for UPJ obstruction in 3, proximal ureteral stricture after ureteroscopic stone removal in 2, and obliterated UPJ after percutaneous nephrolithotomy and failed antegrade endopyelotomy in 1 patient each. RESULTS: Hospitalization ranged from 4 to 7 days (mean 5.1). No patient experienced a significant perioperative complication. With follow-up ranging from 5 to 32 months (mean 10.1), relief of obstruction was evident in all patients as documented by intravenous urography or nuclear renography. Furthermore, differential function on the involved side improved from a mean of 54.6% preoperatively to 60.1% postoperatively (P <0.05). CONCLUSIONS: The spectrum of indications for ureterocalicostomy has changed, although excellent results can still be achieved. Although laparoscopic approaches are currently being evaluated, most patients currently undergoing this reconstructive procedure still require open operative intervention.

Adult↗

Ureteroscopic management of renal calculi in anomalous kidneys.

OBJECTIVES: To review our experience with ureteroscopy in treating patients with renal calculi in anomalous kidneys and to evaluate the efficacy of this approach. METHODS: Eight patients with renal calculi in anomalous kidneys who were managed by ureteroscopic procedures were identified. Demographic information, preoperative stone burden, operative information (ureteroscope size, lithotrite used, instruments used, duration of surgery, complications, stenting), follow-up imaging, and complications were obtained from the medical record. This information was analyzed to determine the most frequently used instruments and stone-free rates. RESULTS: Our cohort consisted of 4 patients with horseshoe kidneys (HSK) and 4 patients with pelvic kidneys (PK) (6 male, 2 female, mean age, 50.6 years). The average preoperative stone burden of the 11 treated calculi was 1.4 cm, with 5 stones located in the renal pelvis, 2 in the upper pole, and 4 in lower pole calyces. A 7.5F flexible ureteroscope, holmium laser lithotripsy, and nitinol baskets and graspers were used in all patients. Six patients had complete clearance of the stone on postoperative imaging (75% HSK, 75% PK), with 88% of patients asymptomatic after their procedure. No patients required additional surgical intervention. CONCLUSIONS: Flexible ureteroscopy with holmium laser lithotripsy and the use of nitinol baskets and graspers provides a reasonable alternative to shock wave lithotripsy in the management of patients harboring renal calculi in anomalous kidneys. In addition, ureteroscopy can be considered a primary option for managing select patients with symptomatic stones in PKs before a percutaneous surgical approach.

Adult↗

Genetic and dietary factors in urinary citrate excretion.

BACKGROUND AND PURPOSE: Hypocitraturia, an important risk factor for calcium oxalate nephrolithiasis, is the result of numerous factors. We studied citrate excretion by patients with and without stones consuming normal and controlled formula diets. SUBJECTS AND METHODS: Subjects with and without a history of calcium oxalate stones (N = 101 per group) provided two or three 24-hour urine specimens during consumption of self-selected diets. Data also were collected on subsets of subjects consuming formula (Ensure) diets. Citrate was determined using the citrate lyase method of Petrarulo and associates, and values for multiple specimens were averaged. The data were adjusted for creatinine excretion and examined on a per-day basis. RESULTS: The mean citrate excretion of the non-stone formers was slightly but not significantly higher than that of the stone formers (442 +/- 217 versus 378 +/- 153 mg/g of creatinine). All statistical analyses revealed highly significant differences between, but not within, individuals, a result compatible with a genetic influence. In the normal population, 5% of subjects had a citrate excretion <200 mg/g of creatinine, whereas this result was seen in 34% of the stone-forming subjects. When the subjects consumed a formula diet, women in both groups had much higher citrate excretion than when on a self-selected diet, but little difference was seen in the men. The patterns of citrate recovery suggest low, intermediate, and high excretors. In the normal population, 15% of subjects excreted <340 mg/g of creatinine, whereas this was true of 43% of the stone-forming subjects. Analysis of six families suggested three excretor phenotypes, with a codominant pattern of inheritance. CONCLUSION: These findings imply a genetic influence on citrate excretion, as has already been demonstrated for calcium excretion. Further studies of genetic influences on calcium oxalate stone formation are warranted.

Adult↗

Dietary oxalate loads and renal oxalate handling.

PURPOSE: Dietary oxalate makes a significant contribution to urinary oxalate excretion and, thus, may have a role in calcium oxalate kidney stone formation. Studies have indicated that the ingestion of oxalate rich foods results in transient increases in plasma oxalate concentrations and urinary oxalate excretion. We examined changes in plasma and urinary oxalate following oral crystalline oxalate loading under controlled dietary conditions to further define the renal handling of oxalate by normal adults. MATERIALS AND METHODS: Six normal adult subjects consumed controlled diets of known oxalate content for 1 week before ingesting loads of 0, 2, 4 and 8 mmol of oxalate. Urinary and plasma changes were measured to assess renal oxalate handling. Urinary excretion of proximal tubule derived enzymes and isoprostanes was monitored to assess for renal injury and oxidative stress. RESULTS: Time and dose dependent changes in plasma oxalate, urinary oxalate and in the clearance ratio of oxalate-to-creatinine were observed. A significant correlation (r=0.43, p <0.001) between the oxalate-to-creatinine clearance ratio and plasma oxalate levels was identified. No changes in urinary markers of oxidative stress or renal injury were observed following the 8 mmol oxalate load. CONCLUSIONS: Oxalate is rapidly absorbed and cleared by the kidney by filtration and secretion following an oral oxalate load. Renal oxalate secretion has a significant role in the renal handling of an oral oxalate load. There is no evidence of acute renal injury or oxidative stress with oral oxalate loads in these experimental conditions.

Adult↗

Adjunctive therapy to promote stone passage.

The majority of individuals with nephrolithiasis have small ureteral stones that pass spontaneously. However, patients may experience severe pain during this process, which significantly alters their quality of life and may limit their vocational responsibilities. Therefore, measures to facilitate stone passage are uniformly embraced. We discuss methods to enhance spontaneous stone passage as well as the elimination of fragments generated with extracorporeal shock-wave lithotripsy.

Journal Article↗

Glycolate and glyoxylate metabolism in HepG2 cells.

Oxalate synthesis in human hepatocytes is not well defined despite the clinical significance of its overproduction in diseases such as the primary hyperoxalurias. To further define these steps, the metabolism to oxalate of the oxalate precursors glycolate and glyoxylate and the possible pathways involved were examined in HepG2 cells. These cells were found to contain oxalate, glyoxylate, and glycolate as intracellular metabolites and to excrete oxalate and glycolate into the medium. Glycolate was taken up more effectively by cells than glyoxylate, but glyoxylate was more efficiently converted to oxalate. Oxalate was formed from exogenous glycolate only when cells were exposed to high concentrations. Peroxisomes in HepG2 cells, in contrast to those in human hepatocytes, were not involved in glycolate metabolism. Incubations with purified lactate dehydrogenase suggested that this enzyme was responsible for the metabolism of glycolate to oxalate in HepG2 cells. The formation of 14C-labeled glycine from 14C-labeled glycolate was observed only when cell membranes were permeabilized with Triton X-100. These results imply that peroxisome permeability to glycolate is restricted in these cells. Mitochondria, which produce glyoxylate from hydroxyproline metabolism, contained both alanine:glyoxylate aminotransferase (AGT)2 and glyoxylate reductase activities, which can convert glyoxylate to glycine and glycolate, respectively. Expression of AGT2 mRNA in HepG2 cells was confirmed by RT-PCR. These results indicate that HepG2 cells will be useful in clarifying the nonperoxisomal metabolism associated with oxalate synthesis in human hepatocytes.

Alcohol Oxidoreductases↗

The impact of dietary oxalate on kidney stone formation.

The role of dietary oxalate in calcium oxalate kidney stone formation remains unclear. However, due to the risk for stone disease that is associated with a low calcium intake, dietary oxalate is believed to be an important contributing factor. In this review, we have examined the available evidence related to the ingestion of dietary oxalate, its intestinal absorption, and its handling by the kidney. The only difference identified to date between normal individuals and those who form stones is in the intestinal absorption of oxalate. Differences in dietary oxalate intake and in renal oxalate excretion are two other parameters that are likely to receive close scrutiny in the near future, because the research tools required for these investigations are now available. Such research, together with more extensive examinations of intestinal oxalate absorption, should help clarify the role of dietary oxalate in stone formation.

Animals↗

Utility of frozen section analysis of resection margins during partial nephrectomy.

OBJECTIVES: To evaluate the utility of routine intraoperative frozen-section histologic analysis during partial nephrectomy to ensure negative surgical margins. Partial nephrectomy has gained acceptance for surgical treatment of small renal cancers. Many surgeons send specimens for intraoperative frozen section histologic analysis to ensure negative margins. METHODS: We reviewed the records of 78 patients who underwent partial nephrectomy for presumed malignancy. Patient demographics, intraoperative findings, and pathologic and clinical outcomes were analyzed. RESULTS: Seventy-nine partial nephrectomies were performed in 78 patients. Frozen sections were obtained intraoperatively in 76 cases. In 1 case (1.3%), a single margin was interpreted as positive for carcinoma, prompting deeper resection. The final histopathologic finding was interpreted as angiomyolipoma rather than carcinoma. The final pathologic examination revealed renal cell carcinoma in 52 (66%) of 79 cases. The mean oncologic follow-up was 16.2 months. One local recurrence was noted (1.9%). It arose in the resection bed 19 months after removal of a 4.5-cm tumor (pathologic Stage T3a). Both intraoperative frozen section margins and final pathologic margins were negative in this case. One patient developed pulmonary metastases and represented the only metastatic recurrence, as well as the only cancer-related death in our cohort (1.9%). CONCLUSIONS: Our data suggest that when partial nephrectomy is performed with attention to excising a perimeter of grossly normal-appearing parenchyma, sending specimens for intraoperative frozen section analyses may provide an unnecessary expense without providing meaningful, reliable information. Additional studies, including larger cohorts and extended follow-up, are needed to support these results.

Adenoma, Oxyphilic↗