Intrarater and interrater reliability of a hand-held dynamometric technique to quantify palmar thumb abduction strength in individuals with and without carpal tunnel syndrome

Study Design

Clinical measurement.

Fungicidal activity of cecropin A.

Cecropin A (CA) fungicidal properties were explored. Nongerminated and germinated Aspergillus spp. and Fusarium spp. conidia were treated with CA. CA achieved complete lethality at < or = 25 microM (99 micrograms/ml) for germinating, but not nongerminating, conidia of Aspergillus spp. CA achieved total lethality for nongerminated and germinating conidia of Fusarium spp at 1.5 microM (6 micrograms/ml). MIC and minimal lethal concentration assays in buffered RPMI medium gave similar results.     

A study of confidential unit exclusion

The effectiveness of the confidential unit exclusion (CUE) procedure recommended by the Food and Drug Administration has been questioned by the blood banking community. The purpose of this study was to determine whether donors were informing the blood center correctly regarding the disposition (transfuse or do not transfuse) of their donated blood. A letter explaining the confidential study and requesting permission to send the participant a questionnaire noting his or her self-exclusion choice was mailed to 230 donors who had chosen transfuse and 276 donors who had chosen do not transfuse. After consent was obtained, participants were sent a second packet and asked to indicate whether they had chosen correctly and, if not, to identify reasons for that incorrect choice. A seven-word terminology quiz made up of words from the CUE form was also enclosed. All participants who had chosen transfuse indicated that this was the correct choice. Approximately 50 percent of those who had chosen do not transfuse indicated that this was an incorrect choice; the most common reason was that "I was not paying attention." The most frequently misunderstood term was "confidential." Donors who chose do not transfuse had a significantly higher rate of error on the terminology quiz (p less than 0.01) than did those who chose transfuse.     

Effects of cyclopentyladenosine on isoproterenol response in adult and senescent cardiac tissue from Fischer 344 rats

To characterize age-related changes in beta-adrenergic responsiveness and to test the hypothesis that an increase in the effects of adenosine contribute to impaired beta-adrenergic responsiveness, Fischer 344 rat right atria (RA), left atria (LA), and left ventricular trabeculae carnae were exposed to the beta-receptor agonist isoproterenol (ISO), followed by four doses of the selective adenosine A(1) receptor agonist cyclopentyladenosine (CPA). Spontaneous contractile rates of adult RA were inhibited more than senescent RA by CPA. Contractility (+dF/dt) of adult LA was reduced more than senescent LA by CPA. Left trabeculae carnae tissue responded weakly to CPA, but senescent tissue was less responsive than adult tissue. Senescent atrial A(1) receptor density was 56% greater than in adult tissue, whereas the density in senescent ventricles was 39% lower than in adult tissue. No significant difference in antagonist affinities (K(d)) of A(1) receptor was observed between adult and senescent atria. In addition, agonist competition curves indicated a significant increase in senescent atrial and a decrease in senescent ventricular tissue in the affinity of agonist for high-affinity A(1) receptors with no difference in dissociation constant (K(i)). No significant age-related differences in atrial or ventricular tissues occurred in either the antagonist affinity (K(d)) or density (B(max)) of the beta-adrenergic receptors. CPA was found to inhibit ISO-stimulated adenylate cyclase activity more in senescent than in adult atrial and ventricular membrane preparations. We conclude that age-related differences in functional response to ISO and CPA, A(1) receptor density, and ISO-stimulated adenylate cyclase activity differ in atrial and ventricular myocardium.     

Effects of pioglitazone and metformin fixed-dose combination therapy on cardiovascular risk markers of inflammation and lipid profile compared with pioglitazone and metformin monotherapy in patients with type 2 diabetes

. Type 2 diabetes mellitus (T2DM) treatment should not increase cardiovascular (CV) risk and at best could provide benefit beyond lowering glucose. Pioglitazone has demonstrated a favorable CV profile relative to other oral antidiabetic drugs (OADs) in outcome and observational studies. This randomized, double-blind, parallel-group controlled study examined circulating biomarkers of CV risk in T2DM patients receiving a fixed-dose combination (FDC) of pioglitazone/metformin compared with the respective monotherapies. Patients with stable glycosylated hemoglobin (HbA(1c) ) for 3 months taking no OADs were treated with pioglitazone 15mg/metformin 850mg FDC twice daily (bid), pioglitazone 15mg bid, or metformin 850mg bid for 24 weeks. FDC and pioglitazone increased high-density lipoprotein cholesterol by 14.20% and 9.88%, respectively, vs an increase of 6.09% with metformin (P<.05, metformin vs FDC). Triglycerides decreased with all three treatments -5.95%, -5.54% and -1.78%, respectively; P=not significant). FDC and pioglitazone significantly decreased small low-density lipoprotein and increased large low-density lipoprotein particle concentrations. Reductions in high-sensitivity C-reactive protein were greater in the FDC and pioglitazone groups. Increases in adiponectin were significant in the FDC and pioglitazone groups (P<.0001 vs metformin). Overall, adverse events were not higher with the FDC. Thus, treatment with the FDC resulted in improved levels of CV biomarkers, which were better than or equal to monotherapy.     

Central granular cell odontogenic tumor: a histopathologic and immunohistochemical study

The central granular cell odontogenic tumor (CGCOT) is a rare lesion that usually affects the posterior region of the mandible of young adults. We present a case of CGCOT involving the mandible of a 20-year-old white woman, emphasizing the immunohistochemical characteristics using a large panel of antibodies. The lesion was removed surgically, and after 4 years of follow-up, there are no evidences of recurrences. The odontogenic epithelium (OE) showed positivity for cytokeratins (CKs) AE1/AE3, 34βE12, CK5, CK7, CK8, CK14, CK19, E-cadherin, β-catenin, CD138, and p63. The granular cells were positive for vimentin, CD68, lysozyme, muscle-specific actin, α-smooth muscle actin, calponin, neuron-specific enolase (NSE), CD138, and bcl-2. Dendritic-like cells surrounding the OE displayed positivity for vimentin, CD1a, S100, CD68, and bcl-2, but it was negative for factor XIIIa, supporting a Langerhans cell phenotype. Ki-67 labeling index was 1.8%, whereas p53 was negative. These data confirm the benign nature of CGCOT, the association of OE with Langerhans cells, and a variable phenotype of the granular cells.     

Dicer1 functions as a haploinsufficient tumor suppressor

While the global down-regulation of microRNAs (miRNAs) is a common feature of human tumors, its genetic basis is largely undefined. To explore this question, we analyzed the consequences of conditional Dicer1 mutation (Dicer1 “floxed” or Dicer1^fl) on several mouse models of cancer. Here we show Dicer1 functions as a haploinsufficient tumor suppressor gene. Deletion of a single copy of Dicer1 in tumors from Dicer1^fl/+ animals led to reduced survival compared with controls. These tumors exhibited impaired miRNA processing but failed to lose the wild-type Dicer1 allele. Moreover, tumors from Dicer1^fl/fl animals always maintained one functional Dicer1 allele. Consistent with selection against full loss of Dicer1 expression, enforced Dicer1 deletion caused inhibition of tumorigenesis. Analysis of human cancer genome copy number data reveals frequent deletion of DICER1. Importantly, however, the gene has not been reported to undergo homozygous deletion, suggesting that DICER1 is haploinsufficient in human cancer. These findings suggest Dicer1 may be an important haploinsufficient tumor suppressor gene and, furthermore, that other factors controlling miRNA biogenesis may also function in this manner.     

Suppression of Rev3, the catalytic subunit of Pol{zeta}, sensitizes drug-resistant lung tumors to chemotherapy

Platinum-based chemotherapeutic drugs are front-line therapies for the treatment of non-small cell lung cancer. However, intrinsic drug resistance limits the clinical efficacy of these agents. Recent evidence suggests that loss of the translesion polymerase, Polζ, can sensitize tumor cell lines to cisplatin, although the relevance of these findings to the treatment of chemoresistant tumors in vivo has remained unclear. Here, we describe a tumor transplantation approach that enables the rapid introduction of defined genetic lesions into a preclinical model of lung adenocarcinoma. Using this approach, we examined the effect of impaired translesion DNA synthesis on cisplatin response in aggressive late-stage lung cancers. In the presence of reduced levels of Rev3, an essential component of Polζ, tumors exhibited pronounced sensitivity to cisplatin, leading to a significant extension in overall survival of treated recipient mice. Additionally, treated Rev3-deficient cells exhibited reduced cisplatin-induced mutation, a process that has been implicated in the induction of secondary malignancies following chemotherapy. Taken together, our data illustrate the potential of Rev3 inhibition as an adjuvant therapy for the treatment of chemoresistant malignancies, and highlight the utility of rapid transplantation methodologies for evaluating mechanisms of chemotherapeutic resistance in preclinical settings.     

Tissue-specific p19Arf regulation dictates the response to oncogenic K-ras

The ability of oncogenes to engage tumor suppressor pathways represents a key regulatory mechanism that can limit the outgrowth of incipient tumor cells. For example, in a number of settings oncogenic Ras strongly activates the Ink4a/Arf locus, resulting in cell cycle arrest or senescence. The capacity of different cell types to execute tumor suppressor programs following expression of endogenous K-ras^G12D in vivo has not been examined. Using compound mutant mice containing the Arf^GFP reporter and the spontaneously activating K-ras^LA2 allele, we have uncovered dramatic tissue specificity of K-ras^G12D-dependent p19^Arf up-regulation. Lung tumors, which can arise in the presence of functional p19^Arf, rarely display p19^Arf induction. In contrast, sarcomas always show robust activation, which correlates with genetic evidence, suggesting that loss of the p19^Arf-p53 pathway is a requisite event for sarcomagenesis. Using constitutive and inducible RNAi systems in vivo, we highlight cell type-specific chromatin regulation of Ink4a/Arf as a critical determinant of cellular responses to oncogenic K-ras. Polycomb-group complexes repress the locus in lung tumors, whereas the SWI/SNF family member Snf5 acts as an important mediator of p19^Arf induction in sarcomas. This variation in tumor suppressor induction might explain the inherent differences between tissues in their sensitivity to Ras-mediated transformation.