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Biomedical subjects

Elizabeth A Stone

Publications and source records attributed to Elizabeth A Stone.

8 recordsLinked to original sources

Clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in cats with ureteral calculi: 163 cases (1984-2002).

OBJECTIVE: To determine clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in cats with ureteral calculi. DESIGN: Retrospective study. ANIMALS: 163 client-owned cats. PROCEDURE: Medical records were reviewed, and information on signalment, history, clinical signs, and results of clinicopathologic testing and diagnostic imaging was obtained. RESULTS: The number of cats in which ureterolithiasis was diagnosed each year increased progressively during the study period. Clinical signs tended to be non-specific and included inappetence, vomiting, lethargy, and weight loss. A combination of survey radiography and abdominal ultrasonography revealed ureteral calculi in 66 of 73 (90%) cats in which the diagnosis was confirmed at surgery or necropsy. Ultrasonography revealed that ureteral calculi were causing ureteral obstruction in 143 of 155 (92%) cats. One hundred thirty-four of 162 (83%) cats had azotemia, 84 of 156 (54%) had hyperphosphatemia, and 22 of 152 (14%) had hypercalcemia. Urinary tract infection was documented in 10 of 119 (8%). Fifty-eight of 76 (76%) cats with unilateral ureterolithiasis had azotemia and 33 (43%) had hyperphosphatemia, indicating impairment of renal function in the contralateral kidney or prerenal azotemia. Ultrasonographic imaging of the contralateral kidney in cats with unilateral ureteral calculi suggested that preexisting renal parenchymal disease was common in cats with ureterolithiasis. Ninety-one of 93 (98%) ureteral calculi contained calcium oxalate. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that abdominal imaging should be performed in all cats with chronic nonspecific signs or with acute or chronic renal failure to rule out ureterolithiasis. Preexisting renal disease may be common in cats with ureteral calculi.

Animals↗

Management and outcome of cats with ureteral calculi: 153 cases (1984-2002).

OBJECTIVE: To determine outcome of medical and surgical treatment in cats with ureteral calculi. DESIGN: Retrospective study. ANIMALS: 153 cats. PROCEDURE: Medical records were reviewed. Owners and referring veterinarians were contacted for follow-up information. RESULTS: All cats were initially treated medically before a decision was made to perform surgery. Medical treatment included parenteral administration of fluids and diuretics to promote urine production and passage of the ureteral calculus and supportive treatment for renal failure. Ureteral calculi in the proximal portion of the ureter were typically removed by ureterotomy, whereas ureteral calculi in the distal portion of the ureter were more likely to be removed by partial ureterectomy and ureteroneocystostomy. Ureterotomy could be performed without placement of a nephrostomy tube for postoperative urine diversion. Postoperative complication rate and perioperative mortality rate were 31% and 18%, respectively. The most common postoperative complications were urine leakage and persistent ureteral obstruction after surgery. Chronic renal failure was common at the time of diagnosis and continued after treatment, with serum creatinine concentration remaining greater than the upper reference limit in approximately half the cats. Twelve-month survival rates after medical and surgical treatment were 66% and 91%, respectively, with a number of cats dying of causes related to urinary tract disorders, including ureteral calculus recurrence and worsening of chronic renal failure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that medical and surgical management of ureteral calculi in cats are associated with high morbidity and mortality rates. Treatment can stabilize renal function, although many surviving cats will continue to have impaired renal function.

Animals↗

Combinatorial discovery of new asymmetric cis platinum anticancer complexes is made possible with solid-phase synthetic methods.

To efficiently access asymmetric cis platinum (II) complexes for biological evaluation, a new solid-phase synthesis was designed. This synthesis was used for the preparation of a small library of platinum compounds. Several compounds from this library revealed promising activity during a cytotoxicity screen. Two active compounds were, therefore, synthesised on a larger scale and tested more extensively against a larger panel of cell-lines, confirming their high potential as antitumour compounds. The work presented illustrates how a combination of a new methodology and established techniques can speed up the search for platinum complexes with improved cytotoxic profiles compared to cisplatin.

Cisplatin↗

Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection.

BACKGROUND: Tenofovir disoproxil fumarate (DF) is the first nucleotide reverse transcriptase inhibitor approved for use in combination with other antiretroviral agents in the treatment of HIV-1 infection in the United States. Unlike the nucleoside reverse transcriptase inhibitors, which must undergo 3 intracellular phosphorylation steps for activation. nucleotide analogues such as tenofovir require only 2 such steps. This reduction in the phosphorylation requirement has the potential to produce more rapid and complete conversion of the drug to its pharmacologically active metabolite. OBJECTIVE: This article describes the pharmacologic properties and potential clinical usefulness of tenofovir DF. METHODS: Relevant information was identified through searches of MEDLINE (1996-April 2002), Iowa Drug Information Service (1996-April 2002), and International Pharmaceutical Abstracts (1970-April 2002), as well as from meeting abstracts of major HIV/AIDS conferences (1996-2002), using the search terms tenofovir tenofovir disoproxil fumarate, PMPA, bis(POC)PMPA, GS-4331-05, acyclic nucleoside phosphonate, and nucleotide reverse transcriptase inhibitor. Additional information was obtained from material submitted to the US Food and Drug Administration by the manufacturer of tenofovir DF in support of its New Drug Application. RESULTS: In vitro, tenofovir DF has exhibited anti-HIV activity in various HIV-infected cell lines and has produced a synergistic or additive effect against HIV when combined with other antiretroviral agents. In adult humans, tenofovir has a volume of distribution of 0.813 L/kg, is minimally bound to plasma protein (7.2%), has a plasma elimination half-life of 12.0 to 14.4 hours, and is mainly excreted unchanged in urine (70%-80%). Dose adjustment based on sex or body weight does not appear to be necessary, although dose reduction may be necessary in the elderly; there are currently no data on tenofovir DF in renal or hepatic insufficiency. The results of clinical trials suggest the efficacy of tenofovir DF in reducing plasma levels of HIV-1 RNA when used as an add-on to a stable antiretroviral regimen. The most commonly (>3%) reported adverse events in clinical trials have included nausea, diarrhea, asthenia, headache, vomiting, flatulence, abdominal pain, and anorexia. The most commonly (>2%) reported laboratory abnormalities (grade III or IV) included increases in creatine kinase, triglycerides, amylase, aspartate aminotransferase, and alanine aminotransferase, as well as hyperglycemia and glucosuria. Serious adverse events leading to discontinuation of tenofovir DF were infrequent (5%), occurring with an incidence similar to that with placebo (8%). The recommended dosage of tenofovir DF in adults is 300 mg/d PO; pharmacokinetic and efficacy studies in children are ongoing. CONCLUSION: Although additional studies are needed, tenofovir DF appears to be a promising agent for the treatment of HIV infection.

Adenine↗

Caspofungin: an echinocandin antifungal agent.

BACKGROUND: The mainstays of treatment for nosocomial fungal infections have been amphotericin B and azole derivatives. Caspofungin acetate is a new echinocandin antifungal agent with a mechanism of action that targets a structural component of the fungal cell wall. OBJECTIVE: This article describes the pharmacologic properties and potential clinical usefulness of caspofungin. METHODS: Relevant information was identified through searches of MEDLINE (1966-September 2001). Iowa Drug Information Service (1966-September 2001), and International Pharmaceutical Abstracts (1970-September 2001), as well as meeting abstracts of the Infectious Diseases Society of America and the Interscience Conference on Antimicrobial Agents and Chemotherapy (1996-2001), using the terms caspofungin, MK-0991, pneumocandin, echinocandin, candin, and beta-(1,3)-glucan inhibitor. RESULTS: In vitro, caspofungin exhibits antifungal activity against an array of clinically important yeasts and molds, including Candida and Aspergillus spp. The proposed susceptibility breakpoint for caspofungin against Candida spp, the most common cause of nosocomial fungal infections, is a minimum inhibitory concentration of < or =1 microg/mL. In humans, caspofungin has a volume of distribution of 9.67 L, is extensively bound to albumin (97%), has a plasma elimination half-life of 9 to 11 hours, and is metabolized to inactive metabolites in the liver. Dose adjustment based on age, sex, race, or renal function does not appear to be necessary, although patients with moderate hepatic insufficiency (Child-Pugh score 7-9) should receive a lower maintenance dose. The results of clinical trials, although somewhat preliminary, suggest that caspofungin is effective in the treatment of esophageal and oropharyngeal candidiasis and invasive aspergillosis. When combined with other antifungal agents, caspofungin produces a synergistic or additive effect against a variety of clinically important fungi. The most commonly reported adverse events with caspofungin have included fever, infusion-related reactions, headache, nausea, elevations in liver transaminase levels, and histamine-type reactions. The recommended dosage in adults is 70 mg IV on day 1 followed by 50 mg/d, with the duration of treatment depending on the severity of the patient's underlying condition and the clinical response. CONCLUSION: Although additional studies are needed, caspofungin appears to be a promising agent for the treatment of patients with difficult-to-treat or life-threatening fungal infections.

Aged↗