Topical Diclofenac-Induced Hepatotoxicity.

The hepatotoxic potential of diclofenac, a commonly used non-steroidal anti-inflammatory agent, is well established in literature. However, cases of diclofenac-induced liver disease have occurred almost exclusively with the oral formulation of this medication. We report the case of an elderly man with Paget's disease and osteoarthritis who developed acute hepatotoxicity, as evidenced by laboratory diagnostics, four months after use of topical diclofenac 1% gel. Once diclofenac gel was discontinued, repeat blood work three weeks after discharge demonstrated return of liver function tests to baseline. Given the temporal relationship between the initiation and escalation of topical diclofenac and the changes in liver function tests, the likelihood of diclofenac-induced liver injury was deemed possible using a well-recognized causality assessment tool. Further research on topically administered non-steroidal anti-inflammatory agents is needed to identify monitoring intervals for early detection and avoidance of adverse effects in patients using topical diclofenac.

Acquired Hemophilia A and urothelial carcinoma.

Acquired Hemophilia A (AHA) is a rare entity, resulting from the production of autoantibodies against Factor VIII of the coagulation cascade. These autoantibodies may develop in response to autoimmune conditions, drugs, neoplastic diseases, and pregnancy. Diagnosis involves clinical presentation, mucocutaneous or intramuscular bleeding, and laboratory findings, such as prolonged activated partial thromboplastin time, decreased levels of Factor VIII, and the presence of Factor VIII autoantibodies. The etiology is diverse, with a variety of underlying culprits. Malignancy-associated AHA has been associated with approximately 15% of cases. Urothelial malignancy-mediated AHA is exceedingly rare, with only two previously published reports. The management of AHA includes stabilization and control of bleeding via the use of hemostatic agents, and elimination of the inhibitor with immunosuppressive therapy. Here, we report a case of AHA secondary to urothelial malignancy and review the pathobiology and pathogenesis of Hemophilia A and AHA.

Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation.

A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.

Functional magnetic resonance imaging study of word recognition in normal elders.

Four healthy, cognitively intact elders participated. Subjects underwent fMRI scanning while performing a word recognition task with an easy condition (low demand) and a difficult condition titrated to each subject's ability (titrated demand). Relative to low, titrated demand was associated with increased activation of the left medial frontal (cluster level P <.002), right superior temporal (P <.007) and right superior parietal cortices (P<.001). Increased activation of bilateral cortical areas by elders during the more challenging titrated demand compared with low demand may indicate recruitment of additional brain regions, enabling subjects to maintain performance despite increasing difficulty. Alternatively, the bilateral activation on this word recognition task may reflect compensatory use of right hemisphere networks.

Volumetric measurements in the detection of reduced ventricular volume in patients with normal-pressure hydrocephalus whose clinical condition improved after ventriculoperitoneal shunt placement.

OBJECT: The syndrome of normal-pressure hydrocephalus (NPH) refers to the clinical triad of gait disturbance, dementia, and urinary incontinence in association with idiopathic ventriculomegaly and normal intracranial pressure. Ventriculoperitoneal (VP) shunt placement often yields significant clinical improvements, sometimes without apparent reduction of ventricular size. The authors hypothesized that careful volumetric measurements would show a decrease in ventricular volume in these patients. METHODS: Twenty consecutive patients with NPH underwent placement of VP shunts equipped with programmable valves. In 11 patients pre- and postoperative neuroimaging was performed, which allowed volumetric analysis. Volumetric measurements of the lateral ventricles were calculated in triplicate by National Institutes of Health image-processing software to assess standard computerized tomography (CT) scans (eight patients) or magnetic resonance (MR) images (three patients) obtained before and after shunt placement. Ventricular volumes were also assessed by an independent neuroradiologist. Postoperative studies were performed at a time of clinical improvement, between 1 and 9 months postsurgery (mean 5 months). Preoperative and postoperative Unified Parkinson's Disease Rating Scale evaluations were performed in four patients. Significant clinical improvement occurred in all patients after shunt placement (mean follow-up period 17.5 months). Although 10 (91%) of 11 patients demonstrated a calculable decrease in volume in the lateral ventricles (mean decrease 39%), formal interpretation of neuroimages indicated a definite decrease in lateral ventricular volume in only three (27%) of 11 patients. CONCLUSIONS: Volumetric measurements obtained to compare preoperative and postoperative CT or MR studies obtained in patients with NPH in whom clinical improvement was seen after shunt placement surgery show a demonstrable decrease in ventricular size. Volumetric measurements may be helpful in clinical assessment postoperatively and in guiding programmable valve pressure settings.

ACR Appropriateness Criteria on low back pain.

Acute low back pain with or without radiculopathy is one of the most common health problems in the United States, with high annual costs of evaluation and treatment, not including lost productivity. Multiple reports show that uncomplicated acute low back pain or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Guidelines for recognition of patients with more complicated status can be used to identify those who require further evaluation for suspicion of more serious problems and contribute to appropriate imaging utilization.

Naturally occurring adenines within mRNA coding sequences affect ribosome binding and expression in Escherichia coli.

Translation initiation requires the precise positioning of a ribosome at the start codon. The major signals of bacterial mRNA that direct the ribosome to a translational start site are the Shine-Dalgarno (SD) sequence within the untranslated leader and the start codon. Evidence for the presence of many non-SD-led genes in prokaryotes provides a motive for studying additional interactions between ribosomes and mRNA that contribute to translation initiation. A high incidence of adenines has been reported downstream of the start codon for many Escherichia coli genes, and addition of downstream adenine-rich sequences increases expression from several genes in E. coli. Here we describe site-directed mutagenesis of the E. coli aroL, pncB, and cysJ coding sequences that was used to assess the contribution of naturally occurring adenines to in vivo expression and in vitro ribosome binding from mRNAs with different SD-containing untranslated leaders. Base substitutions that decreased the downstream adenines by one or two nucleotides decreased expression significantly from aroL-, pncB-, and cysJ-lacZ fusions; mutations that increased downstream adenines by one or two nucleotides increased expression significantly from aroL- and cysJ-lacZ fusions. Using primer extension inhibition (toeprint) and filter binding assays to measure ribosome binding, the changes in in vivo expression correlated closely with changes in in vitro ribosome binding strength. Our data are consistent with a model in which downstream adenines influence expression through their effects on the mRNA-ribosome association rate and the amount of ternary complex formed. This work provides evidence that adenine-rich sequence motifs might serve as a general enhancer of E. coli translation.

Pseudo-Meig's syndrome with multiple synchronous benign and malignant pelvic tumors.

BACKGROUND: Meig's and Pseudo-Meig's syndromes have been reported in association with several malignancies but the concomitant existence of multiple synchronous benign and malignant tumors in association with Pseudo-Meigs' syndrome has not been reported in the published literature. CASE: A 55-year old African American woman presented with mild asthma exercebation, right ovarian mass, hydrothorax and elevated CA-125 levels. Histological examination confirmed a right ovarian carcinoid tumor embedded within a mature cystic teratoma while the left ovary, fallopian tube and the uterus contained a poorly differentiated adenocarcinoma of the endometrium. CONCLUSION: This is the first case report of Pseudo-Meig's syndrome in association with ovarian carcinoid tumor and multiple synchronous benign and malignant pelvic tumors.