The role of adjuvant treatment for early-stage uterine clear cell carcinomas.

BACKGROUND: Uterine clear cell carcinoma is a rare and aggressive subtype of endometrial carcinoma. Prospective clinical trials have not been feasible for this rare tumor, and data regarding the optimal adjuvant treatment regimen for early-stage uterine clear cell carcinomas is limited. Our study's objective was to determine if adjuvant chemotherapy or radiation therapy improves patients' outcomes in stage I and II uterine clear cell carcinoma. METHODS: Patients with stage I and II uterine clear cell carcinoma were identified at a single institution. All cases were reviewed by a gynecologic pathologist. Both pure and mixed non-serous uterine clear cell carcinomas were included. Primary outcomes were recurrence free survival and overall survival. RESULTS: A total of 71 patients were identified including 39 (55%) pure and 32 (45%) mixed clear cell carcinoma. Most patients were FIGO stage IA (77.5%). Most patients (n = 58, 82%) received adjuvant therapy, including 43 (61%) receiving chemotherapy, 50 (70%) receiving radiation therapy, and 35 (49%) receiving both. Recurrence free survival was not significantly different among patients receiving no or <6 cycles of chemotherapy versus patients receiving 6 cycles of chemotherapy (p = 0.39). However, median OS was significantly different among patients receiving no or <6 cycles of chemotherapy versus 6 cycles of chemotherapy (p = 0.004). On univariable analysis, 6 cycles of chemotherapy was significantly associated with improved OS (HR 0.1, 95% CI 0.01-0.07). Presence of LVSI, mutated p53, number of pelvic and para-aortic lymph nodes assessed, adjuvant chemotherapy (any number of cycles), and >2 medical co-morbidities were not significant predictors of OS on univariable analysis. On multivariable analysis, 6 cycles of adjuvant chemotherapy remained a significant predictor of improved OS (HR 0.1, 95% CI 0.01-0.8). CONCLUSIONS: In this study, administration of 6 cycles of chemotherapy appears to significantly improve OS. This finding suggests consideration of 6 cycles of adjuvant chemotherapy in patients with early-stage uterine clear cell carcinoma, however clinical trials are needed to confirm these findings.

Cost-effectiveness analysis of tumor molecular classification in high-risk early-stage endometrial cancer.

PURPOSE: Tumor molecular analyses in endometrial cancer (EC) includes 4 distinct subtypes: (1) POLE-mutated, (2) mismatch repair protein (MMR) deficient, (3) p53 mutant, and (4) no specific molecular profile. Recently, a sub-analysis of PORTEC-3 demonstrated notable differences in treatment response between molecular classification (MC) groups. Cost of testing is one barrier to widespread adoption of MC. Therefore, we sought to determine the cost-effectiveness of MC in patients with stage I and II high-risk EC. METHODS: A Markov decision model was developed to compare tumor molecular classification (TMC) vs. no testing (NT). A healthcare payor's perspective and 5-year time horizon were used. Base case data were abstracted from PORTEC-3 and the molecular sub-analysis. Cost and utility data were derived from public databases, peer-reviewed literature, and expert input. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Sensitivity analyses were performed to test model robustness. RESULTS: When compared to NT, TMC was cost effective with an ICER of $25,578 per QALY gained; incremental cost was $1780 and incremental effectiveness was 0.070 QALYs. In one-way sensitivity analyses, results were most sensitive to the cost of POLE testing, but TMC remained cost-effective over all parameter ranges. CONCLUSIONS: TMC in early-stage high-risk EC is cost-effective, and the model results were robust over a range of parameters. Given that MC can be used to guide adjuvant treatment decisions, these findings support adoption of TMC into routine practice.

Inhibition of d-Ala incorporation into wall teichoic acid in Staphylococcus aureus by desleucyl-oritavancin.

The mode of action for desleucyl-oritavancin was investigated by adding an antibiotic to Staphylococcus aureus during its growth in a defined medium containing l,d-[1-15N]Ala and l-[1-13C]Lys, or d-[1-15N]Ala. 13C{15N} and 15N{13C} rotational-echo double resonance NMR determined that desleucyl-oritavancin inhibited the incorporation of d-[1-15N]Ala into wall teichoic acid.

Evaluation of dentin abrasion during professional tooth cleaning in an in vitro model.

OBJECTIVES: Professional tooth cleaning (PTC) may lead to loss of exposed dentin. The aim of the present study was to determine the absolute loss of dentin during PTC using various product combinations with an in vitro model. MATERIAL AND METHODS: Dentin specimens (72) were randomly assigned to nine groups. In four groups each, prophy brushes and prophy cups were used in combination with four different abrasives (calcium pyrophosphate, pumice, Hawe cleanic, Nupro coarse). In the ninth group, a rubber cup with embedded fluoride and abrasives was used (pasteless prophy cup). The treatment time was 37 s. Surface loss was determined by profilometry. RESULTS: The surface loss in the nine groups was as following: (1) brush/calcium pyrophosphate: 6.18 microm (a); (2) brush/pumice: 5.51 microm; (3) brush/Nupro coarse: 10.10 microm (b); (4) brush/Hawe cleanic: 1.88 (a, b); (5) prophy cup/calcium pyrophosphate 2.07 (c); (6) prophy cup/pumice: 6.07 microm; (7) prophy cup/Nupro coarse: 5.93 microm (c); (8) prophy cup/Hawe cleanic: 4.93 microm (c); (9) pasteless prophy cup: 11.86 microm (c). Groups with the same letter in parentheses are statistically significant different at p<0.05. In a pooled analysis, no statistically significant difference between brushes and prophy cups was found. CONCLUSION: In the present study, the surface loss of about eight PTC procedures was simulated. Hence, the dentin loss ranged between 0.24 and 1.48 microm per PTC. Therefore, PTC does not seem to be a main factor in dentin loss.

World Trade, disease and Florida's animal populations. The changing dynamics.

One of Florida's three leading economic industries is agriculture. Agriculture feeds and enhances the lives of millions of people in Florida, the United States, and the entire world. Agriculture in Florida results in more than $6 billion in farm cash receipts, employment for more than 60,000 people a month, more than $18 billion in farm-related economic activity and stretches from the farm gate to the state's supermarkets with an impact of nearly $45 billion. The domestic and wild animal populations of Florida, our unique relationship to the Caribbean, Atlantic Ocean, Gulf of Mexico, Central and South America, as well as tourism, diverse human population growth and immigration, all add to the complexity of an environment capable of establishing many animals, animal pests and diseases not native to the United States. Never before have the dynamics of disease control involved as much challenge and diversity. Is the balance at risk, or is the risk over-balanced? Can science, economics and politics blend to maintain this balance? How will the balance affect world trade, disease control and the animal populations of Florida?

Fluoxetine in drug-dependent delinquents with major depression: an open trial.

Although fluoxetine might be more effective than placebo for treating adolescent depression without major comorbidity, little is known about the response of depressive symptoms to antidepressants in adolescents with comorbid conduct disorder (CD) and substance use disorders (SUD). Male adolescents, who remained or became depressed after > or = 1 month of abstinence from abused substances during residential treatment for SUD, were treated in an open trial for > or = 7 weeks with a fixed dose of 20 mg of fluoxetine. The eight adolescents (ages 14-18 years) with CD, SUD, and major depression were not in drug withdrawal or receiving other pharmacotherapy. A > or = 50% improvement was observed in mean scores on Ten Point Depression Scale rated by clinician (p < 0.01) and patients (p < 0.01), Carroll Self-Ratings for depression (p < 0.02), and Severity of Illness scores on the Clinical Global Impression (p < 0.01). Of the eight adolescents, seven showed marked improvement and wished to continue fluoxetine after the trial. Side effects were mild and transient. No subject required dosage reduction or discontinuation of medication because of side effects. Fluoxetine appeared useful in treating substance-dependent delinquents whose major depressions persisted or emerged after 4 weeks of abstinence. These preliminary findings justify a controlled trial in such youths.

Acute cholecystitis or metastatic renal cell carcinoma? a diagnostic dilemma.

Renal cell carcinoma is known to metastasize to many different organ systems. Lung and bone are clearly the most common sites of metastasis, but the symptoms at presentation may simulate those of other diseases of the organ system involved. The patient with metastatic renal cell carcinoma described here had symptoms of acute cholecystitis.

Twenty-year experience with the Mentor bladder pacemaker.

Twenty years after placement of a Mentor bladder pacemaker, a 38-year-old woman with spina bifida cystica still has controlled detrusor contraction and complete bladder emptying. The varied treatment modalities for this difficult group of patients has included electronic bladder stimulation. Although no longer commonly used, electronic bladder stimulation has shown long-term efficiency in this patient.

Interspecies differences in systemic drug availability following subcutaneous pulsatile administration in cattle, sheep, dogs, and rats.

Rats, dogs, sheep, and cattle were implanted subcutaneously with stainless-steel tissue cages. Bolus injections of cefoxitin and ivermectin were administered to the interiors of the tissue cages 11, 32, and 60 days after implantation to simulate pulsatile drug release from an implanted device. Plasma drug levels were determined for 6 h for cefoxitin and up to 8 days for ivermectin. Tissue cages were retrieved 3 and 6 months after implantation for macroscopic and microscopic examination. In dogs and rats, plasma levels of both drugs following administrations to the tissue cages were significantly lower than those following subcutaneous injection, suggesting that the tissue growth around and in the cages posed a barrier to systemic drug availability in those species. In cattle and sheep, the tissue cages and associated tissue did not inhibit systemic availability of either drug as compared with routine subcutaneous administration.

Management of chronic cancer pain using a computerized ambulatory patient-controlled analgesia pump.

Chronic pain associated with neoplastic disease can be difficult to treat. The development of a computerized ambulatory, patient-controlled analgesia (PCA) pump may provide the patient and clinician with an alternate approach in management of chronic cancer pain. The pump delivers a constant infusion of analgesic and allows for additional on-command doses for breakthrough pain. Patients with chronic cancer pain poorly controlled with conventional narcotic regimens were eligible for this trial. Four patients were included in this trial. Upon admission, each patient was started on a morphine infusion via a peripheral site and titrated to an effective dose. Once the optimal dose was achieved, the patients were converted to the ambulatory pump. The pump was programmed to deliver identical morphine infusions and any PCA doses. Infusion access was provided by a long-term central venous catheter or subcutaneous infusion set. Final maintenance infusions ranged from 0.8 to 60 mg morphine per hour. Three patients required PCA doses. Patients and family members were trained on catheter care and operation of the infusion pump. At home, patients reported acceptable pain relief while engaging in many activities of daily living. Complications included constipation, possible drug tolerance, and accidental catheter removal. Overall, patient acceptance of the pump was good with improved pain control, minimal adverse reactions, and ease of use at home.

1,1-Dichloroethylene hepatotoxicity: proposed mechanism of action and distribution and binding of 14C radioactivity following inhalation exposure in rats.

1,1-Dichloroethylene is reported to produce renal tumors in male mice. It is an hepatotoxin in fasted rats after inhalation. We found that trichloropropane epoxide, an inhibitor of epoxide hydrase, enhances hepatic injury as measured by serum sorbitol dehydrogenase elevation. A significant elevation of hepatic citric acid concentration was seen in fasted but not fed rats. We hypothesized that mitochondrial injury was associated with inhibition of the tricarboxylic acid cycle and postulated that monochloroacetic acid was a toxic metabolite of 1,1-DCE. Fluoroacetic acid and chloroacetic acid were similar in their ability to inhibit oxygen uptake when pyruvic and malic acids were substrates in isolated mitochondria supplemented with adenosine diphosphate. In experiments where 1,1-DCE metabolism was estimated, no difference between the rate of uptake in a 2-hr period was detected between fed and fasted animals. Urinary output of radioactivity at 26 hr for fed and fasted rats was similar. Water-soluble (i.e. TCA-soluble) 1,1-DCE metabolites were found in tissues of fasted rats in excess of that seen in fed rats. The kidney had the largest concentration of total metabolites. Tissue-bound, or TCA-insoluble, radioactivity was associated with the mitrochondrial and microsomal fraction of fasted rats in excess of that seen in fed rats. The disappearance of TCA-insoluble radioactivity from the mitochondrial and microsomal fractions was comparable in rate between fed and fasted rats respectively. These results suggest that 1,1-DCE is metabolized quite rapidly in the organism to TCA-soluble components which are excreted by the kidneys. Metabolites of 1,1-DCE may enter the metabolic pool, since a reasonably short turnover of (14)C-labeled, bound material was observed. The metabolite of 1,1-DCE appears to inhibit the mitochondria so that citric acid accumulates. This may occur by a process of lethal synthesis.