Equine dental and skeletal fluorosis induced by well water consumption.

Two horses that consumed well water with high fluoride content exhibited clinical signs of chronic dental and skeletal fluoride toxicosis and were later euthanized and autopsied. Both horses had degenerative disease of multiple joints and multiple dental defects. Elevated fluoride concentrations were found in bone and tooth samples of both horses, well water, and feed. Microscopically, abnormalities were noted in bone and tooth samples, and consisted mostly of foci of cement necrosis and hypercementosis. Horses exhibiting bilateral, highly symmetrical dental and/or skeletal lesions, with chronic lameness, should be evaluated for the possible presence of fluoride toxicosis.

Image-Guided Transarterial Chemoembolization With Drug-Eluting Beads Loaded with Doxorubicin (DEBDOX) for Unresectable Hepatic Metastases from Melanoma: Technique and Outcomes.

PURPOSE: Hepatic metastasis from melanoma represents a therapeutic dilemma, with limited effective options for the 85% of cases deemed unresectable. Systemic agents confer toxicity and, along with traditional local hepatic arterial-directed therapies such as transarterial chemoembolization, have not led to a significant increase in survival. The aim of this study was to investigate the safety and dose-limiting toxicity of DEBDOX for the treatment of unresectable hepatic metastases from melanoma. METHODS: A multicenter (University of Louisville, Thomas Jefferson University, MD Anderson Cancer Center), prospective, non-controlled treatment trial (NCT01010984) of hepatic-directed therapy with DEBDOX for the treatment of melanoma liver metastasis was reviewed. Primary endpoints were response rates by modified response evaluation criteria in solid tumors, hepatic progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty patients received a total of 61 DEBDOX treatments from January 2010 to March 2013. The median hepatic tumor burden was 40% (range 20-55), 18 patients (90%) had bilobar disease, and 13 patients (65%) had concomitant extrahepatic disease. At median assessment of 2.5 months, 11 patients (55%) exhibited a tumor response and 16 (80%) exhibited disease control. Median follow-up was 5 months (range 1.1-34.3 months). Median hepatic PFS was 3 months (95% CI 1.4, 3.4), and OS was 5 months (95% CI 3.3, 10.5). CONCLUSIONS: Directed arterial therapy with DEBDOX is effective in managing unresectable liver-dominant metastasis from melanoma and should be considered a therapeutic option in the multidisciplinary treatment of this disease. Concurrent systemic therapy is merited given the high rate of extrahepatic progression. CLINICAL TRIAL: NCT01010984.

Assessment of chemotherapy response in colorectal liver metastases in patients undergoing hepatic resection and the correlation to pathologic residual viable tumor.

BACKGROUND: The Response Evaluation Criteria in Solid Tumors (RECIST), which evaluates maximum tumor diameter only, is commonly used to determine response to chemotherapy in patients with colorectal liver metastases. Limitations of RECIST include its inability to assess the changes in tumor enhancement. The aim of this study was to assess the correlation of these criteria as well as the modified RECIST (mRECIST) with pathologic tumor response. A novel semi-automated volumetric assessment of tumor size was also investigated. STUDY DESIGN: A review of a 1,948-patient prospective hepatic database to assess response and pathologic criteria was performed. Patients undergoing preoperative chemotherapy before hepatic resection for colorectal liver metastases were reviewed. Radiographic responses according to RECIST and mRECIST were determined. The percentage of viable tumor cells compared with the total tumor area was determined from the pathologic specimens. RESULTS: We identified 38 patients with adequate imaging who had undergone anatomic hepatic resection and full pathologic evaluation. The percentages of residual viable tumor in the resected specimens were significantly different across RECIST categories (p = 0.045), but not mRECIST (p = 0.305). For mRECIST, there were improved and significant linear trends for residual viable tumor, necrosis, and necrosis + fibrosis when compared with RECIST (p = 0.056). Neither RECIST nor mRECIST responses were predictive of residual viable tumor burden in regression analyses. A novel semi-automated volumetric assessment of tumor size correlated well with pathologic tumor size. CONCLUSIONS: Neither RECIST nor mRECIST were predictive of residual viable burden, although the linear trend for mRECIST and residual necrosis + fibrosis compared favorably with RECIST. Continued evaluation for tumor enhancement and standardization of tumor size remain a critical unmet need in patients with solid organ disease.

Widespread hyoscine hydrobromide toxicity due to contract manufacturer malpractice : the travacalm episode.

An outbreak of hyoscine hydrobromide toxicity was detected through the Australian pharmacovigilance system. The unexpectedly wide variation in hyoscine hydrobromide content between individual tablets within single packets created difficulties in initially explaining the clinical experiences. Strict time requirements for review of incoming adverse drug reaction reports and close involvement of the highly skilled national drug regulatory laboratory resulted in early identification of the cause of the outbreak and led in turn to the identification of malpractice by the contract manufacturer.

Incidence and predictors of major vascular complications after percutaneous coronary intervention in the glycoprotein IIb/IIIa platelet inhibitor era.

Since the introduction of platelet glycoprotein (GP) IIb/IIIa inhibitors, reports of vascular complications after percutaneous coronary intervention (PCI) have focused on bleeding and the need for surgical repair, whereas specific major vascular complications have been less consistently identified. Moreover, data from clinical trials may lack applicability to the general population. The purpose of this study was to determine the incidence of major vascular complications after PCI and to identify associated risk factors in patients routinely receiving GP IIb/IIIa inhibitors. During a 12-month period, 1,634 consecutive patients underwent PCI at a single institution. Clinical characteristics and procedural data were collected prospectively; data regarding vascular sheath removal were obtained retrospectively. Univariate and multivariable regression methods were used to identify independent predictors of major vascular complications. Major vascular complications occurred in 2.9% of patients. Multivariable analysis revealed advanced age (odds ratio [OR] 1.05, P = 0.0025) and female sex (OR 2.9, P = 0.0002) as clinical characteristics associated with major vascular complications, whereas hypertension had an inverse relationship (OR 0.46, P = 0.013). Procedural factors included use of the following: stents (OR 5.59, P < 0.0001), vascular sheaths >6F (OR 3.25, P = 0.016), and mechanical clamp (OR 2.71, P = 0.0012). The presence of a hematoma >4 cm(2) had a positive predictive value of 12% for major vascular complications. The incidence of major vascular complications in this large, single-center study from the GP IIb/IIIa inhibitor era is consistent with data from the pre-GP IIb/IIIa inhibitor era and recent randomized trials.

Ultrastructure and synaptic targets of tectothalamic terminals in the cat lateral posterior nucleus.

The recent appreciation of the fact that the pulvinar and lateral posterior (LP) nuclei receive two distinct types of cortical input has sparked renewed interest in this region of the thalamus. A key question is whether the primary or "driving" inputs to the pulvinar/LP complex originate in cortical or subcortical areas. To begin to address this issue, we examined the synaptic targets of tectothalamic terminals within the LP nucleus. Tectothalamic terminals were labeled using the anterograde transport of biotinylated dextran amine (BDA) or Phaselous leucoagglutinin placed in the superior colliculus or using immunocytochemical staining for substance P, a neurotransmitter found to be used by the tectothalamic pathway (Hutsler and Chalupa [ 1991] J. Comp. Neurol. 312:379-390). Our results suggest that most tectothalamic terminals are large and occupy a proximal position on the dendritic arbor of LP relay cells. In the medial LP, tectothalamic terminals labeled by the transport of neuronal tracers or substance P immunocytochemistry can form tubular clusters that surround the proximal dendrites of relay cells. In a rostral and lateral subdivision of the lateral LP nucleus (LPl-2), tectothalamic terminals form more typical glomerular arrangements. When compared with existing physiological data, these results suggest that a unique integration of tectal and cortical inputs may contribute to the response properties of LP neurons.

Trained and supervised physician assistants can safely perform diagnostic cardiac catheterization with coronary angiography.

Using a prospectively collected database of patients undergoing cardiac catheterization, we sought to compare the outcomes of procedures performed by supervised physician assistants (PAs) with those performed by supervised cardiology fellows-in-training. Outcome measures included procedural length, fluoroscopy use, volume of contrast media, and complications including myocardial infarction, stroke, arrhythmia requiring defibrillation or pacemaker placement, pulmonary edema requiring intubation, and vascular complications. Class 3 and 4 congestive heart failure was more common in patients who underwent procedures by fellows compared with those undergoing procedures by PAs (P = 0.001). PA cases tended to be slightly faster (P = 0.05) with less fluoroscopic time (P < 0.001). The incidence of major complications within 24 hr of the procedure was similar between the two groups (0.54% in PA cases and 0.58% in fellow cases). Under the supervision of experienced attending cardiologists, trained PAs can perform diagnostic cardiac catheterization, including coronary angiography, with complication rates similar to those of cardiology fellows-in-training.