Background
Objective methods for distinguishing melanoma in situ (MIS) from photodamaged skin (PS) are needed to guide treatment in patients with melanocytic proliferations. Melanocyte density (MD) ...could serve as an objective histopathological criterion in difficult cases. Calculating MD via manual cell counts (MCC) with immunohistochemical (IHC)‐stained slides has been previously published. However, the clinical application of this method is questionable, as quantification of MD via MCC on difficult cases is time consuming, especially in high volume practices.
Methods
ImageJ is an image processing software that uses scanned slide images to determine cell count. In this study, we compared MCC to ImageJ calculated MD in microphthalmia transcription factor‐IHC stained MIS biopsies and control PS acquired from the same patients.
Results
We found a statistically significant difference in MD between PS and MIS as measured by both MCC and ImageJ software (P < 0.01). Additionally, no statistically significant difference was found when comparing MD measurements recorded by ImageJ vs those determined by the MCC method.
Conclusion
MD as determined by ImageJ strongly correlates with the MD calculated by MCC. We propose the use of ImageJ as a time‐efficient, objective, and reproducible tool to assess MD.
Organ Procurement and Transplant Network (OPTN) policy currently requires the testing of all potential organ donors for human T‐cell lymphotrophic virus (HTLV)‐1/2. Most Organ Procurement ...Organizations (OPO) use the Abbott HTLV‐I/HTLV‐II Enzyme Immunoassay (EIA). This assay will no longer be manufactured after December 31, 2009; the only commercially available FDA‐licensed assay will be the Abbott PRISM HTLV‐I/II assay which poses many challenges to OPO use for organ donor screening. As a result, screening donors for HTLV‐1/2 in a timely manner pretransplant after December 31, 2009 will be challenging. The true incidence of HTLV‐1 in United States (U.S.) organ donors is not well described but appears to be low (∼0.03–0.5%). HTLV‐1 is associated with malignancy and neurological disease; HTLV‐2 has not been convincingly associated with disease in humans. Donors that are HTLV‐1/2 seropositive are infrequently used despite most results being either false positive or resulting from HTLV‐2 infection. There is urgent need to encourage the development of assays, instruments and platforms optimized for organ donors that can be used to screen for transmissible disease in donors; these must have appropriate sensitivity and specificity to identify all infections while minimizing organ loss through false positive testing.
HTLV‐1/2 screening in the solid organ donor population is increasingly challenging: donors that are HTLV1/2 positive are infrequently used despite most results being either false positive or due to HTLV‐2, which has not been associated with disease. See editorial by Humar on page 199.
Sodium/proton antiporters or exchangers (NHE) are integral membrane proteins present in most, if not all, living organisms. In mammals, these transporters chiefly catalyze the electroneutral exchange ...of Na(+) and H(+) down their respective concentration gradients and are crucial for numerous physiological processes, ranging from the fine control of intracellular pH and cell volume to systemic electrolyte, acid-base and fluid volume homeostasis. NHE activity also facilitates the progression of other cellular events such as adhesion, migration, and proliferation. Thus far, eight distinct NHE genes (NHE1/SLC9A1-NHE8/SLC9A8) and several pseudogenes have been identified in the human genome. The functional genes encode proteins of varying primary sequence identity (25-70%), but share a common predicted secondary structure comprising 12 conserved membrane-spanning segments at the amino-terminus and a more divergent, cytoplasmically-oriented, carboxy-terminus. They show considerable heterogeneity in their patterns of tissue/cell expression and membrane localization. Functional studies have revealed further differences in their kinetic properties, sensitivity to pharmacological antagonists, and regulation by diverse hormonal and mechanical stimuli. Altered NHE activity has been linked to the pathogenesis of several diseases, including essential hypertension, congenital secretory diarrhea, diabetes, and tissue damage caused by ischemia/reperfusion. Further characterization of their functional properties should lead to a better understanding of their unique contributions to human health and disease.
Background: Ethics consultation is used regularly by some doctors, whereas others are reluctant to use these services. Aim: To determine factors that may influence doctors to request or not request ...ethics consultation. Methods: A survey questionnaire was distributed to doctors on staff at the University Community Hospital in Tampa, Florida, USA. The responses to the questions on the survey were arranged in a Likert Scale, from strongly disagree, somewhat disagree, neither agree nor disagree, somewhat agree to strongly agree. Data were analysed with the Wilcoxon test for group comparisons, the χ2 test to compare proportions and a logistic regression analysis. Results: Of the 186 surveys distributed, 121 were returned, giving a 65% response rate. Demographic data were similar between the groups saying yes (I do/would use ethics consultation when indicated) and no (I do not/would not use ethics consultation when indicated). No statistically significant differences were observed between the user and non-user groups in terms of opinions about ethics consultants having extensive training in ethics or participating in ethics educational opportunities. On the issue “Ethics committee members or consultants cannot grasp the full picture from the outside”, the non-users were neutral, whereas the users somewhat disagreed (p = 0.012). Even more significant was the difference between surgeons and non-surgeons, where, by logistic regression analysis, surgeons who believed that ethics consultants could not grasp the full picture from the outside were highly likely to not use (p = 0.0004). Non-users of ethics consultations thought that it was their responsibility to resolve issues with the patient or family (72.2% agree, p<0.05). Users of ethics consultation believed in shared decision making or the importance of alternate points of view (90.8% agree, p<0.05). Implications: Ethics consultations are used by doctors who believe in shared decision making. Doctors who did not use ethics consultation tended to think that it was their responsibility to resolve issues with patients and families and that they were already proficient in ethics.
A cDNA encoding a new isoform of the rat Na/H exchanger (NHE) family has been identified by cross-hybridization with an NHE-1
cDNA probe. The 3.9-kilobase stomach cDNA encodes a protein of 813 amino ...acids with an M(r) of 91,296. The amino acid sequence
of the protein, termed NHE-2, is 42% identical to NHE-1, 36% identical to NHE-3, and 57% identical to NHE-4. Na/H exchanger-deficient
Chinese hamster ovary cells that were transfected with an expression construct containing the complete coding sequence of
this cDNA exhibit amiloride-sensitive, H+-dependent 22Na+ influx, demonstrating that the protein it encodes is a functional
Na/H exchanger. Northern hybridization analyses show that the corresponding mRNA is expressed predominantly in small intestine,
colon, and stomach, with much lower levels present in skeletal muscle, kidney, brain, testis, uterus, heart, and lung. This
suggests that NHE-2 plays an important role in gastrointestinal physiology and functions in many other organ systems as well.
Despite successful remission induction in 60-80% of patients with newly diagnosed acute myeloid leukemia, there remain a significant number of patients who exhibit primary refractory disease. Here we ...examine the data for predicting likelihood of having refractory disease, available therapeutic options, and how to decide the appropriate treatment option for a patient.
Recently identified recurrent molecular mutations and early response to chemotherapy as determined by kinetics of peripheral blast clearance or nadir bone marrow biopsy assist in determining the likelihood of primary refractory disease. Newer cytotoxic agents, used as salvage chemotherapy, or in novel conditioning regimens for hematopoietic stem cell transplant may represent improvement over prior regimens. FMS-like tyrosine kinase 3 gene inhibitors and other targeted therapies currently in clinical trials show promise for select patients. Hypomethylating agents provide benefit to patients who are not candidates for other therapies.
Recent advances in understanding the pathogenesis of acute myeloid leukemia have not yet translated to a significantly improved outlook for patients with refractory disease. While there are several therapeutic options, outcomes remain poor and further studies are needed to identify and validate novel approaches.
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