Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature

A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.     

Dural infolding during C1-2 myelography

Inward buckling of the dura at C1-2 may occasionally occur with hyperextension of the neck and can result in a difficult or unsuccessful puncture when the posterior lateral C1-2 approach is used for cervical myelography. In this circumstance, placement of the head in a neutral or slightly flexed position may widen the posterior subarachnoid space and facilitate the needle puncture.     

Determination of 238u/235u, 236u/238u and uranium concentration in urine using sf-icp-ms and mc-icp-ms: an interlaboratory comparison

Accidental exposure to depleted or enriched uranium may occur in a variety of circumstances. There is a need to quantify such exposure, with the possibility that the testing may post-date exposure by months or years. Therefore, it is important to develop a very sensitive test to measure precisely the isotopic composition of uranium in urine at low levels of concentration. The results of an interlaboratory comparison using sector field (SF)-inductively coupled plasma-mass spectrometry (ICP-MS) and multiple collector (MC)-ICP-MS for the measurement of uranium concentration and U/U and U/U isotopic ratios of human urine samples are presented. Three urine samples were verified to contain uranium at 1-5 ng L and shown to have natural uranium isotopic composition. Portions of these urine batches were doped with depleted uranium (DU) containing small quantities of U, and the solutions were split into 100 mL and 400 mL aliquots that were subsequently measured blind by three laboratories. All methods investigated were able to measure accurately U/U with precisions of approximately 0.5% to approximately 4%, but only selected MC-ICP-MS methods were capable of consistently analyzing U/U to reasonable precision at the approximately 20 fg L level of U abundance. Isotope dilution using a U tracer demonstrates the ability to measure concentrations to better than +/-4% with the MC-ICP-MS method, though sample heterogeneity in urine samples was shown to be problematic in some cases. MC-ICP-MS outperformed SF-ICP-MS methods, as was expected. The MC-ICP-MS methodology described is capable of measuring to approximately 1% precision the U/U of any sample of human urine over the entire range of uranium abundance down to <1 ng L, and detecting very small amounts of DU contained therein.     

c-myc and chromosome 8 centromere studies of ovarian cancer by interphase FISH.

Forty tumor specimens from patients with ovarian cancer were studied for amplification of the c-myc oncogene relative to chromosome 8 centromere number using dual-color FISH. Interphase cytogenetic analysis showed amplification of the c-myc oncogene in 40% (16/40) of tumors using the standard oncogene:centromere ratio method of analysis. Eleven of these showed moderate amplification of c-myc, and 5 samples showed high amplification. Eight of the sixteen (50%) amplified tumors were polysomic centromere 8 as were 14 of the 24 (58%) non-amplified tumors. In previously reported work with these samples, the oncogene HER-2/neu, the chromosome 17 centromere, and the tumor suppressor gene p53 had been studied. When using the standard oncogene:centromere ratio criteria, 5 samples had amplification of both the c-myc and the HER-2/neu oncogenes, 5 samples had HER-2/neu amplification but not c-myc, 11 samples had c-myc amplification but not HER-2/neu, and 19 samples had neither oncogene amplified. The p53 gene was found to be deleted in 22.5% (9/40) of samples. The loss of the p53 gene did not appear to have any clinical correlation. The presence of an extra centromere 8 also did not appear to have any clinical correlation. The Kaplan-Meier survival curve for those patients who have c-myc amplification, while not statistically significant, appears to show a trend toward poorer survival. The survival curve for patients whose tumors have HER-2/neu amplification shows no clinical significance. It is of great interest, however, that the Kaplan-Meier plot of survival for patients whose tumors have amplification of both c-myc and HER-2/neu shows a significant difference (P = 0.047). The median survival times of the doubly amplified patient group and the non-doubly amplified groups were 12 and 43 months, respectively. This is the first study of the oncogene c-myc using FISH. The results suggest that the amplification of c-myc may indicate a poorer patient survival and that the amplification of both c-myc and HER-2/neu in combination may be a better prognostic indicator of poor patient survival.     

Epstein-Barr virus-associated B cell lymphoproliferative disorder following mismatched related T cell-depleted bone marrow transplantation.

Epstein-Barr virus (EBV) is closely associated with the progressive and often fatal lymphoproliferative disorders (LPD) in post bone marrow transplantation (BMT) and immunocompromised hosts. The incidence increases significantly when alternative donors or manipulation of marrow graft are used. A total of 318 consecutive BMT from partially mismatched related family donors (PMRD) were performed between February 1993 and June 1998. Known risk factors for the development of EBV-LPD were analyzed which included HLA mismatches, T cell depletion, antithymocyte globulin (ATG), and graft-versus-host disease (GVHD). Eighteen patients (5.7%) developed EBV-LPD at a median of 137 days post BMT (range 48-617). The estimated probability of developing EBV-LPD was 0.13 (95% CI 0.07-0.19) at 5 years. The incidence of grade II to IV GVHD was 19.2%, which translated into an increased trend of EBV-LPD. No correlation with other risk factors was observed. Treatment consisted of supportive antiviral agents, tapering of immunosuppressive regimens, donor leukocyte infusions and radiation. Three patients are alive and disease-free at a median follow-up of 69 months (range 36-71). We observed a lower than expected incidence of EBV-LPD despite existing multiple high-risk factors. We believe prevention and early control of GVHD may contribute to this finding.     

Chemically induced oxidative stress disrupts the E-cadherin/catenin cell adhesion complex.

The impact of xenobiotics on intercellular adhesion, a fundamental biological process regulating most, if not all, cellular pathways, has been sparsely investigated. Cell-cell adhesion is regulated in the epithelium primarily by the E-cadherin/catenin complex. To characterize the impact of oxidative stress on the E-cadherin/catenin complex, precision-cut mouse liver slices were challenged with two model compounds for the generation of oxidative stress, diamide (DA; 25-250 microM) or t-butylhydroperoxide (tBHP; 5-50 microM), for 6 h. At the concentrations used, neither compound elicited cytotoxicity, as assessed by intracellular K+ content and leakage of lactate dehydrogenase into the culture media. However, a 25% reduction in non-protein sulfhydryl levels, an indication of oxidative perturbation, was seen in liver slices treated with DA or tBHP. Total protein expression of E-cadherin, beta-, or alpha-catenin was not affected by challenge with DA or tBHP. A decrease of beta-catenin in the SDS-soluble fraction of slices, an indicator of the formation of the adhesion complex, was observed. Additionally, a decrease in beta-catenin interactions with E-cadherin and alpha-catenin, as assessed by immunoprecipitation and Western blot analysis, was seen. Disruption of the E-cadherin/catenin complex by tBHP, but not DA, correlated with enhanced tyrosine phosphorylation of beta-catenin. These results suggest that noncytotoxic oxidative stress disrupts the E-cadherin/catenin cell adhesion complex in precision-cut mouse liver slices.     

A retrospective review of the course of patients with pancreatitis discharged on jejunal feedings.

INTRODUCTION: Although parenteral nutrition (PN) has been the standard nutrition therapy in patients with pancreatitis requiring nutrition support, it is associated with a higher rate of catheter-related sepsis and gut atrophy. Research suggests enteral nutrition (EN) is possible in patients with pancreatitis without exacerbating symptoms when infused jejunally. The purpose of this study was to review the course of patients with resolving pancreatitis discharged to home on EN. METHODS: The medical records of 33 patients with a percutaneous endoscopic gastrostomy tube with jejunal extension (PEG-J) or nasojejunal tube (NJ) who received home EN were reviewed. The data collected included duration of EN, formula used, goal and maximum tolerated flow rates, anthropometric measures, and gastrointestinal complications. RESULTS: Ninety-seven percent of patients received a standard polymeric formula providing an average of 1845 +/- 421 kcal/d. Forty-two percent of patients took pancreatic enzyme supplements. Complications occurring in patients included nausea and vomiting (42%), feeding rate intolerance (18%), diarrhea (12%), and PEG site infection (27%). Seventy-seven percent of patients achieved nutritional goals. CONCLUSION: Standard polymeric EN seems to be safe and efficacious in the home setting for patients with resolving pancreatitis.