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Biomedical subjects

D G Assimos

Publications and source records attributed to D G Assimos.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular basis of inherited renal lithiasis.

Idiopathic calcium oxalate stone formation results from an interaction between genetic and environmental factors. Clearly identifiable risk factors for the disease that have a significant genetic influence are the excretions of calcium, oxalate and citrate. Candidate genes that may be responsible for these effects have been proposed. With the large-scale sequencing of the human genome and the identification of genetic polymorphisms, it is only a matter of time before these genes and the sequence differences within them that are associated with susceptibility to the disease are conclusively identified.

Journal Article↗
PubMed1998

Glyoxylate synthesis, and its modulation and influence on oxalate synthesis.

PURPOSE: We define the major pathways of hepatic oxalate synthesis in humans, examine the association with other metabolic pathways and identify ways that oxalate synthesis may be modified. In addition, we suggest what is required for further progress in this area. MATERIALS AND METHODS: We consolidated relevant data primarily from recently published literature, considered new pharmacological approaches to decrease oxalate synthesis, and formulated an overview of the regulation and modification of oxalate synthesis pathways. RESULTS: Experiments with animals, including humans, animal cells and in vitro preparations of cellular components, support the existence of a major metabolic pathway linking the amino acids serine, glycine and alanine. Oxalate synthesis is a minor, secondary reaction of a cascade of reactions termed the glyoxylate pathway, which has a prominent role in gluconeogenesis and ureagenesis. The enzymatic steps and effectors which regulate glyoxylate and oxalate synthesis are not well characterized. Pharmacological approaches can reduce oxalate synthesis by diminishing the glyoxylate pool and possibly modifying enzymatic reactions leading to glyoxylate synthesis. CONCLUSIONS: The individual steps associated with glyoxylate and oxalate synthesis can be identified. The glyoxylate pathway has a significant functional role in intermediary liver metabolism but the way it is regulated is uncertain. Oxalate synthesis can be modified by drugs, indicating that primary and idiopathic hyperoxaluria may respond to pharmacological intervention.

Animals↗
PubMed1997

Genes in idiopathic calcium oxalate stone disease.

An examination of the urinary excretions of 101 normal subjects indicated that the major genetic influence on calcium excretion is a codominant pair of alleles giving rise to three phenotypes, low, intermediate and high (hypercalciuric) excretors. This inference was based on variance, Hardy-Weinberg and segregation analyses. Similar independent gene pairs also appear to influence oxalate and citrate excretion, A 3-locus Hardy-Weinberg table using estimates of gene frequencies derived from the study of normals suggests that only 3 or 4 leading genes are involved in oxalate stone disease. Strong candidate genes identified from molecular and physiological studies cannot be proposed at present, but it is assumed that they influence the transport of these ions in either the intestine, kidney or both organs. The identification of the genes involved should be facilitated by the reduction of dietary influences on urinary excretions through the use of formula diets.

Calcium Oxalate↗
PubMed1997

Ureteral Stones Clinical Guidelines Panel summary report on the management of ureteral calculi. The American Urological Association.

PURPOSE: The American Urological Association convened the Ureteral Stones Clinical Guidelines Panel to analyze the literature regarding available methods for treating ureteral calculi and to make practice policy recommendations based on the treatment outcomes data. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles related to ureteral calculi published from 1966 to January 1996. Outcomes data were extracted from articles accepted after panel review. The data were then meta-analyzed to produce outcome estimates for alternative treatments of ureteral calculi. RESULTS: The data indicate that up to 98% of stones less than 0.5 cm. in diameter, especially in the distal ureter, will pass spontaneously. Shock wave lithotripsy is recommended as first line treatment for most patients with stones 1 cm. or less in the proximal ureter. Shock wave lithotripsy and ureteroscopy are acceptable treatment choices for stones 1 cm. or less in the distal ureter. CONCLUSIONS: Most ureteral stones will pass spontaneously. Those that do not can be removed by either shock wave lithotripsy or ureteroscopy. Traditional blind basket extraction, without fluoroscopic control and guide wires, is not recommended. Open surgery is appropriate as a salvage procedure or in certain unusual circumstances.

Humans↗
PubMed1997

Update on interventional uroradiology.

From its humble beginnings as a method of expediently decompressing the obstructed kidney, the field of interventional uroradiology has evolved in the hands of urologists and interventional radiologists to a means of addressing myriad problems in the urinary tract and has changed the day-to-day practice of urology. The foundation of interventional uroradiology is the creation of an appropriate entry into the urinary system. After a review of this basic procedure, extensions of the technique and new applications of emerging technology are reviewed.

Cystoscopy↗
PubMed1997

The effects of (L)-2-oxothiazolidine-4-carboxylate on urinary oxalate excretion.

PURPOSE: A phase I study was done to evaluate the safety and pharmacokinetics of (L)-2-oxothiazolidine-4-carboxylate (OTZ). An ancillary objective was to compare the effects of treatment with 2 levels of OTZ to placebo on urinary oxalate excretion in healthy male subjects. MATERIALS AND METHODS: Individuals underwent intravenous infusion of 70 (6) or 100 (6) mg/kg, body weight OTZ, or placebo for 2 hours at 4, 8-hour intervals. Urine was collected during the 12 hours before treatment, and at 0 to 4, 4 to 8, 8 to 24, 24 to 28, 28 to 32 and 32 to 48 hours after the initial infusion. Urine samples were assayed for creatinine, oxalate, citrate, sulfate, urate, phosphate and pH. RESULTS: Urinary oxalate excretion relative to creatinine decreased significantly in the 100 mg./kg. dose group by 4.1 mg./gm. during the first 24 hours and by 4.6 mg./gm. in 24 to 48 hours compared to baseline values (p < 0.05). Slight decreases of 0.9 and 1.1 mg./gm., respectively, in the 70 mg./kg. dose group, and 1.6 and 2.3 mg./gm., respectively, in the placebo group were observed. Oxalate excretion on day 2 in the 100 mg./kg. dose group was significantly less than that in the placebo group (p = 0.04). Urinary pH decreased and sulfate excretion increased with OTZ therapy. CONCLUSIONS: Treatment with 100 mg./kg. OTZ every 8 hours decreases urinary oxalate excretion in healthy men.

Adult↗
PubMed1997

Pathways of hepatic oxalate synthesis and their regulation.

Important features of hepatic oxalate synthesis remain uncertain despite its clinical significance. To clarify the terminal steps of the biosynthetic pathway and their modulation, we have examined oxalate and glyoxylate synthesis in vitro using isolated guinea pig peroxisomes and purified lactate dehydrogenase (LDH). Glycolate was rapidly oxidized to glyoxylate by isolated peroxisomes followed by a slower conversion of glyoxylate to oxalate. The glycolate oxidase (GO)-catalyzed conversion of glyoxylate to oxalate was strongly inhibited by physiological concentrations of glycolate and lactate. In contrast, the LDH-catalyzed conversion of glyoxylate to oxalate was only marginally affected by physiological concentrations of lactate and unaffected by physiological glycolate concentrations. This inhibition pattern suggests that LDH, not GO, catalyzes this conversion in vivo. Alanine inhibited oxalate synthesis by converting the bulk of the glyoxylate to glycine. On exposure to high alanine concentrations, however, inhibition was not complete and peroxisomes were able to convert sufficient glycolate to oxalate to account for daily endogenous oxalate production. NADH was a potent inhibitor of oxalate production by LDH by increasing glycolate formation from glyoxylate. Glycine was an ineffective source of glyoxylate, and an alkaline pH, a high-glycine concentration, and a prolonged incubation time were required to obtain a detectable synthesis. These results suggest that oxalate synthesis will be modulated by the metabolic state of the liver and resultant changes in NADH, lactate, and alanine levels.

Alanine↗
PubMed1996

Nephrolithiasis due to primary hyperparathyroidism and enteric hyperoxaluria: a case report.

Enteric hyperoxaluria and primary hyperparathyroidism have been associated with the development of nephrolithiasis. We report a case involving a patient who had hyperparathyroidism due to a parathyroid adenoma and enteric hyperoxaluria resulting from a small bowel bypass and who had severe stone-related complications. This combination of stone-generating factors has heretofore not been reported. The pathophysiology of these entities is discussed.

Adult↗
PubMed1996

Utility of chest radiography and cystoscopy in the evaluation of patients with localized prostate cancer.

OBJECTIVES: Candidates for radical prostatectomy have been frequently evaluated with chest radiography and occasionally with cystoscopy. The utility of these studies was assessed. METHODS: A retrospective review of 236 cases of radical prostatectomy performed over 5 years was conducted. Chest x-ray results were correlated with certain comorbidities believed to be risk factors for radiographic abnormalities, including hypertension, cardiac disease, pulmonary problems, and tobacco use. Cystoscopic findings were analyzed with regard to urologic history and urinalysis results. RESULTS: Chest radiography was normal in 208 (88.1%) and abnormal in 28 (11.9%) patients. All 28 patients with abnormalities had one or more of the aforementioned risk factors. Sixty-two individuals (26.3%) had no risk factors, and chest radiography was uniformly normal in this group. Cystoscopy was performed in 91 patients. State Ta transitional cell carcinoma of the bladder was detected in 6 of these patients (6.6%); these 6 patients all had either a history of this problem or hematuria. One individual had a mild bladder-neck contracture that did not warrant treatment. Endoscopic findings were normal in the remaining patients. CONCLUSIONS: Chest radiography is not routinely needed to evaluate radical prostatectomy candidates. It should only be performed in patients who have or are at risk for cardiopulmonary disease. Cystoscopy is not warranted in this setting unless there is clinical suspicion of other urologic pathology.

Adult↗
PubMed1996

Is radiographic evaluation of the chest necessary following flank surgery?

PURPOSE: We determined whether routine postoperative chest radiography is warranted after flank surgery to assess for pneumothorax. MATERIALS AND METHODS: A retrospective study of 253 adult flank operations performed during a 6-year period was conducted. RESULTS: Incidental pleurotomy occurred in 63 cases (24.9%). The performance of rib resection and the level of rib removed as well as female gender had a significant impact on this occurrence. Pleurotomy was treated by a simple evacuation technique and tube thoracostomy was not necessary. Only 2 patients (0.8%) had a postoperative pneumothorax without intraoperative recognition of pleurotomy, which resolved without intervention. CONCLUSIONS: Routine postoperative chest radiography to assess for pneumothorax following open flank surgery is not necessary.

Female↗
PubMed1995

Collagen injections for treatment of urinary incontinence secondary to intrinsic sphincter deficiency.

The injection of glutaraldehyde cross-linked collagen (Contigen) is a recently approved method for treating patients with urinary incontinence secondary to intrinsic sphincter deficiency (ISD). Forty-five patients with ISD, 33 males and 12 females, with a mean age of 60 years (range 5-87 years) have been treated with collagen at our institution since its Food and Drug Administration approval. The etiology of incontinence was radical retropubic prostatectomy (RP) in 22, neurogenic bladder (NB) in 11, and Type III female stress urinary incontinence (FISD) in 12 individuals. The whole group underwent an average of 1.76 treatment sessions (range 1-4), and a mean collagen injection volume of 12.26 cc (range 5-27.5 cc) was delivered per session. There were no postoperative complications. Six patients achieved total continence, 28 were still incontinent but improved, 9 experienced no change, while 2 developed worsening incontinence. Further analysis indicated that male patients with ISD as a result of RP may achieve some degree of improvement, but the chances for eradicating incontinence are minimal, whereas female patients with FISD and individuals with ISD secondary to NB significantly benefit from collagen injection therapy. Longer follow-up is needed to determine the durability of these encouraging results.

Adolescent↗
PubMed1995

Glucagon increases urinary oxalate excretion in the guinea pig.

Factors that influence hepatic oxalate synthesis are poorly defined. Hormones are important regulators of hepatic metabolism and could potentially be involved. The effects of hyperglucagonemia were examined in guinea pigs injected with either saline or pharmacological doses of glucagon for 4 days. Glucagon treatment increased mean urinary oxalate excretion by 77% in male and 34% in female animals. The levels of hepatic peroxisomal enzymes involved in oxalate synthesis declined with glucagon treatment, but experiments with isolated peroxisomes indicated that oxalate synthesis in vitro was unaffected. Glucagon decreased hepatic alanine levels by 66%, lactate by 69%, and pyruvate by 73%, but glycolate and glyoxylate levels were unaffected. This decrease in alanine would substantially lower the activity of alanine-to-glyoxylate aminotransferase activity in vivo and make more glyoxylate available for oxalate synthesis. The decrease in lactate and pyruvate concentrations would stimulate the enzymatic conversion of glyoxylate to oxalate and may account for the increase in oxalate synthesis without an increase in glyoxylate concentration. These results demonstrate that hepatic oxalate synthesis is influenced by metabolic changes and that alterations in hepatic alanine, lactate, and pyruvate concentrations may be important elements.

Animals↗