SESSION TYPE: Cancer Cases IPRESENTED ON: Monday, October 22, 2012 at 01:45 PM - 03:00 PM

INTRODUCTION:

Prostate is a rare site for Extra Pulmonary Small Cell Carcinoma (EPSCC). We report the first case of Tumor Lysis Syndrome (TLS) that developed in Prostatic EPSCC. This case was complicated by methemoglobinemia and severe hemolytic anemia after rasburicase (recombinant urate oxidase) use.

CASE PRESENTATION:

A 56-year-old African American with a metastatic small cell cancer of the prostate developed TLS within 2 day of initiation of chemotherapy. 15 days prior to admission, he had a biopsy of a 1.7 cm hypodense nodule in the left lobe of the prostate that demonstrated poorly-differentiated small cell cancer (immunostain negative for PSA and TTF-1, positive for chromogranin, synaptophysin and CD56). His Serum PSA was 6.1. Extensive metastases to pelvic lymph nodes, liver (despite advanced alcoholic liver cirrhosis), lumber spine and lungs were noted, all with significant uptake on PET CT. Despite intravenous hydration and steroids, his serum creatinine, phosphate and uric acid increased from normal to 4.0, 7.4 and 16 respectively. On day 5, he received a dose of rasburicase. After rasburicase, his uric acid and phosphorus started to decline. However he became tachycardiac, tachypneic and hypoxemic (oxygen saturation in mid-80s on room air). He was noted to have methemoglobinemia (5.9%) for which he was given a dose of methylene blue and was transferred to intensive care unit. His hemoglobin dropped from 13 to 6.6 gm/dl with peripheral smear demonstrating numerous bite cells. Bilirubin increased to 21, LDH peaked at 3234 (baseline 160), haptoglobin <30, absolute reticulocyte count and reticulocyte index peaked at 206 and 82.4, respectively. He received 11 units via red cell exchange transfusion. Patient condition was stabilized and he was transferred to floor with Hemoglobin of 13 g/dl, total bilirubin of 4.4, methemoglobin of 0.6 and creatinine of 4.0.

DISCUSSION:

TLS has not been reported in EPSCC of Prostate. This case highlights several important issues in prevention and treatment of TLS. Although our patient had normal baseline Creatinine, LDH and Uric Acid levels, he was at intermediate to high risk for developing TLS due to bulky tumor mass, extensive metastasis, urinary outflow-tract obstruction, high proliferative rate of malignant cells, chemo-sensitive malignancy and acidic urine. At risk patients should receive allopurinol or rasburicase prior to chemotherapy. Rasburicase treatment can induce hemolytic anemia in G6PD deficient cases but its routine measurement is not currently recommended. Methylene blue is not helpful in G6PD deficient cases and should not be used.

CONCLUSIONS:

: Tumor Lysis Syndrome should be anticipated and treated with cautions in high risk patients.1) Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med 2011; 364:1844-18542) Bauters T, Mondelaers V, Robays H, et al. Methemoglobinemia and hemolytic anemia after rasburicase administration in a child with leukemia. Int J Clin Pharm 2011; 33:58-6DISCLOSURE: The following authors have nothing to disclose: Sikander Zulqarnain, Terrence Bradley, Spiro DemitisNo Product/Research Disclosure InformationSUNY Downstate Medical Center, Brooklyn, NY.

SESSION TYPE: CAD/Coronary Syndromes PostersPRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PM

PURPOSE:

Elevated homocysteine levles are associated with impaired nitric oxide-mediated relaxation of the arterial vessel and increased smooth muscle cell proliferation. Production of uric acid by the catalytic oxidation of xanthine produces endothelium damaging superoxide radicals. These actions are injurious to the vascular endothelium and promote atherosclerosis. Homocysteinemia and hyperuricemia are both independently associated with increased cardiovascular disease. This study looks at their combined elevation in a hypertensive population.

METHODS:

We reviewed the charts of consecutive hypertensive patients seen in the office over a 2 month period. We found 210 hypertensive patients who had uric acid, homocysteine, folate and vitamin B12 levels measured. Uric acid was high if it was 7 mg/dl or more while homocysteine was high if it was 15 Umol/L or more. Folate levels were considered normal between 5.4-24.0 ng/ml and vitamin B12 levels normal between 211-911 pg/ml. Blood testing was done by a commercial laboratory.

RESULTS:

Of the 210 patients, 30 had elevated homocysteine and 44 had elevated uric acid levels. Of the 30 with elevateed homocysteine levels 13 (43%) had elevated uric acide levels while of the 180 with normal homocysteine levels, 31 (17%) had elevated uric acid levels. Of the 44 with elevated uric acid levles, 13 (30%) had elevated homocystein levels while of the 166 with no hyperuricemia, 31 (19%) had elevated homocysteine levels. Folic acid and vitamin D levels were normal in both groups.

CONCLUSIONS:

Our study finds that hyperhomocysteinemia and hyperuricemia frequently coexist in hypertensive patients. This combination may be highly atherogenic. It is not clear if the therapeutic reduction of these levels result in better cardiovascular outcomes. However, till further studies are available, treatment with allopurinol and or supplemental vitamin B6, vitamin B12 or folic acid may be considered in this high risk subgroup.

CLINICAL IMPLICATIONS:

Hyperuricemia and homocysteinemia frequently coexist in hypertensives. This subgroup may be at a higher risk of atherogenesis.DISCLOSURE: The following authors have nothing to disclose: Shashi AgarwalNo Product/Research Disclosure InformationAgarwal Health Center, East Orange, NJ.

SESSION TYPE: Airway Student/Resident Case Report PostersPRESENTED ON: Tuesday, October 23, 2012 at 01:30 PM - 02:30 PM

INTRODUCTION:

Joint disease affecting adults with Cystic Fibrosis (CF) may present as episodic arthritis and/or hypertrophic pulmonary osteoarthropathy (HPOA). Gout is rarely reported in adults with CF. We report an adult CF patient who presented to us with Podagra.

CASE PRESENTATION:

A thirty year old white man with CF presented with severe pain in left big toe and redness for one week. He denied trauma to left foot. There was no history of fever, infectious complications. Family history was insignificant for gout. He was prescribed Indomethacin by for seven days without relief. His exam showed red and swollen left first metatarsophalyngeal joint with excruciating pain on movement. His foot x rays showed mild hallux valgus with bunion formation without evidence of erosive periostitis. His serum uric acid level came elevated at ten mg/dl. He was diagnosed with classical podagra and started on Indomethacin followed by allopurinol with complete relief of his symptoms.

DISCUSSION:

Arthropathy occurs in up to 12% of patients with CF and appears to be caused by immunologic processes. Acute episodes may affect all joints, are usually asymmetric, present with swollen, hot, red, and tender joints, often cause incapacitating pain, typically last seven to ten days, and usually are not erosive. Serologic analysis to exclude other causes of arthritis should be considered such as Gout which is rare. Joint fluid analysis is usually nonspecific and may be non inflammatory. Non-steroidals and steroidals anti-inflammatory medications are used in management of CF arthritis. HPOA is characterized by chronic, proliferative long-bone periostitis, causing symmetrical bone pain and painful oligosynovitis in the large joints.Unlike arthritis, HPOA exacerbations tend to accompany pulmonary infectious exacerbations. Ourpatient had classic findings of Podagra, elevated serum urate and response to appropriate therapy. It is a hypothesis that pancreatic enzyme supplements which contain high levels of purine may be responsible for hyperuricemia in adult CF patients.

CONCLUSIONS:

Surviellance of serum urate is not routinely performed but consideration should be given to adding this to investigations. Review of pancreatic enzyme intake in those with confirmed gout or extreme hyperuricemia can be considered.1) Gout and hyperuricaemia in adults with cystic fibrosis. Horsley A, Helm J, Brennan A, Bright-Thomas R, Webb K, Jones A.Manchester Adult Cystic Fibrosis Centre, Wythenshawe Hospital, Manchester, UK. J R Soc Med. 2011 Jul;104 Suppl 1:S36-9.2) Cystic Fibrosis Adult Care. Consensus Conference Report. ( Chest 2004; 125: 1S-39S)3) Schidlow DV, Goldsmith DP, Palmer J, et al. Arthritis in cystic Fibrosis. Arch Dis of child 1984; 59:377-379DISCLOSURE: The following authors have nothing to disclose: Sumaira Malik, Nauman ChaudaryNo Product/Research Disclosure InformationUMC, Brandon, MS.

IntroductionHigh-dose methotrexate, defined as dose ≥1 g/m(2), is commonly used in chemotherapy protocols. Certain drugs such as acyclovir, allopurinol, proton pump inhibitors and some antibiotics have been associated with delayed renal clearance of methotrexate and may predispose patients to toxicities. Currently, no specific recommendations exist on adjusting the high-dose methotrexate regimen in the presence of potential interacting drugs. This study aims to determine whether presence of interacting drugs is associated with delayed methotrexate clearance.

METHODS:

/st>This was a case-control study of adult oncology patients who received their first cycle of high-dose methotrexate. Cases were defined as patients who experienced delayed methotrexate clearance, as indicated by serum methotrexate level ≥ 0.1 umol/L at 72 h. The primary endpoint was the frequency of presence of interacting drugs between cases and controls. These were compared using Fisher's exact test. Where possible, adjustment for significant baseline differences that can affect methotrexate clearance was made using logistic regression. The secondary endpoint was frequency of methotrexate-related clinical toxicities between groups and included myelosuppression, nephrotoxicity, hepatotoxicity and mucositis.

RESULTS:

/st>From January 2004 to March 2011, 73 patients met study criteria, of which 23 were defined as cases. Significant baseline differences were methotrexate dose received (9116 mg ± 4339 versus 6054 mg ± 2874, p=0.012) and renal impairment (5 versus 0, p = 0.002). The presence of interacting drugs was not associated with delayed methotrexate clearance (OR 0.91, 95% CI 0.24-3.38, p > 0.999). After adjusting for methotrexate dose, drugs observed more frequently (allopurinol, proton pump inhibitors and sulfamethoxazole/trimethoprim) were not associated with delayed methotrexate clearance (p = 0.95, 0.59 and 0.20, respectively). Cases experienced more severe anemia (grade 2.52 versus 1.68, p = 0.007) and higher rates of mucositis (65.2% versus 20.0%, p < 0.001).

CONCLUSION:

/st>This study showed no significant association between presence of interacting drugs and delayed methotrexate clearance. Patients who experienced delayed methotrexate clearance had higher incidence of severe anemia and mucositis.

The leaves of Myrica rubra sieb. et zucc. have been used in oriental traditional medicine for the treatment of burns, skin diseases, and as an antidiarrheal in China, Japan, and Korea. Activity guided isolation of the leaves of M. rubra has led to the isolation of five flavonoid: myricetin (1), myricitrin (2), myricetin 3-O-(2″-O-galloyl)-α-L-rhamnopyranoside (3), myricetin 3-O-(2″-O-galloyl)-β-D-galactopyranoside (4), and quercetin 3-O-(2″-O-galloyl)-β-D-galactopyranoside (5). All isolates were evaluated for their antioxidant potency against the superoxide anion (O2 (-)), and compounds 3-5 showed potent scavenging activities with 50 % inhibition concentration (IC50) values compared to the positive control, allopurinol. Compounds 1-5 were evaluated as inhibitors of various macrophage functions involved in the inflammatory process. These five compounds significantly and dose dependently inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO), pro-inflammatory cytokines, and the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Our results suggest that galloyl flavonol glycosides (3-5) isolated from M. rubra might be beneficial for the treatment of inflammation-related diseases.

A retrospective study was performed using 53 client owned dogs with leishmaniasis to determine whether the degree of proteinuria, evaluated by the urine protein/creatinine ratio (UP/C), changes following treatment with meglumine antimoniate and allopurinol. Medical records of dogs with leishmaniasis in clinical stage C (according to the Canine Leishmaniasis Working Group staging system) and either proteinuric or borderline proteinuric (according to the International Renal Interest Society [IRIS] staging system) were reviewed. All dogs were treated with meglumine antimoniate and allopurinol for 4-8 wk. After treatment, UP/C, total protein, and total globulin significantly decreased and albumin and the albumin/globulin ratio (A/G) increased. After treatment, 7 of the 53 dogs (13.4%) became nonproteinuric following either a proteinuric or borderline proteinuric stage. Moreover, 12 of the 53 proteinuric dogs (22.6%) changed their stage to borderline proteinuric. The antileishmaniasis treatment with meglumine antimoniate in combination with allopurinol in dogs significantly reduced the degree of proteinuria in a short period of time. The results of the current study may be useful to the veterinary practitioner in the clinical management of canine leishmaniasis (CanL) in dogs with proteinuric chronic kidney disease.

IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. About 25-30% of IgAN patients will progress to end-stage kidney disease in 20-25 years. Early-onset symptoms that are highly suggestive of progressive IgAN include massive proteinuria, hypertension, renal damage, glomerular sclerosis, crescent formation, and tubulointerstitial fibrosis. Progressive IgAN may progress to renal failure in a short time. Optimized supportive therapy is the fundamental treatment for progressive IgAN patients, and includes renin-angiotensin system blockers, blood pressure control, antiplatelet and anticoagulant drugs, statins, and allopurinol. In progressive IgAN patients whose clinical and pathological manifestations are more severe, active therapy may be considered including glucocorticoid therapy, cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, and other immunosuppressants. However, there are currently controversies on the definition and treatment of progressive IgAN.

Hypothyroidism may predispose to the development of canine leishmaniosis or it may appear during the course of the latter due to infiltration and destruction of the thyroid gland by infected macrophages. The main purpose of this study was to evaluate thyroid function through measurement of serum total thyroxin (tT4), free thyroxin (fT4), and canine thyroid stimulating hormone (cTSH) concentrations in 36 dogs with leishmaniosis, before and after 2 and 4 weeks of treatment with allopurinol with or without meglumine antimonate. Before treatment 27/36 (75%) dogs had serum tT4 concentrations below the lower limit of the reference interval but only 2 of them had concurrently serum fT4 concentrations below the lower limit of the reference interval and none had increased serum cTSH concentrations. During treatment there were no significant changes in serum tT4 or fT4 concentrations, whereas a significant increase in serum cTSH was observed. Two dogs had decreased serum tT4 and fT4 but normal cTSH concentrations before treatment and two other dogs had decreased serum tT4 and increased cTSH, but normal fT4 concentrations during the treatment period. Although hypothyroidism could not be definitively excluded in these dogs it is considered unlikely based on their overall hormonal profile, clinical presentation, and response to treatment. Therefore, hypothyroidism does not appear to be an important predisposing disease or a frequent complication of canine leishmaniosis.

AIM:

Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents.

MATERIALS AND METHODS:

Post-hoc analysis of 312 diabetic and 1,957 non-diabetic gout patients (baseline serum urate levels [sUA] ≥8.0 mg/dL) enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout, and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA <6.0mg/dL. Safety was monitored throughout the trial.

RESULTS:

Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (BMI >30 kg/m(2) ) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p <0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhea and URIs as the most common AEs.

CONCLUSIONS:

Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dL more often than febuxostat 40 mg or allopurinol at commonly prescribed doses.

OBJECTIVE:

Studies in human volunteers have shown that vitamin C reduces serum urate (SU). The aim of this study was to determine effects of vitamin C on SU in patients with gout.

METHODS:

Patients with gout and SU >0.36mmol/L were recruited. 20 patients already receiving allopurinol were randomised to an increase in allopurinol dose or commenced on vitamin C 500mg/d. 20 patients not receiving allopurinol were randomised to start allopurinol or vitamin C 500mg/d. Plasma ascorbate, creatinine, and SU were measured at day 0 and week 8.

RESULTS:

There was no significant difference in baseline SU or eGFR between those who received vitamin C and those who did not (SU 0.50±0.11mmol/l vs. 0.50±0.09mmol/l p=0.89; eGFR 65.5±15.7ml/min/1.73m(2) vs. 67.9±20.7 ml/min/1.73m(2) p=0.67). 30% in the vitamin C group and 25% in the no vitamin C group were receiving diuretics (p=0.72). In the patients receiving vitamin C there was a significant increase between week 0 and 8 in plasma ascorbate. The reduction in SU was significantly less in those patients receiving vitamin C compared to those who started or increased the dose of allopurinol (0.014mmol/l vs. 0.118mmol/l p<0.001).

CONCLUSION:

Modest dose vitamin C (500mg/d) for 8 weeks had no clinically significant urate lowering effect in patients with gout despite increasing plasma ascorbate. These results differ from findings in hyperuricaemic healthy controls. The uricosuric effect of modest dose vitamin C appears less in patients with gout both as monotherapy and in combination with allopurinol. © 2013 American College of Rheumatology.