Progressive knowledge loss: a longitudinal case study.

The evolution of the progressive loss of semantic knowledge of a patient, VZ, with lesions mainly affecting the infero-medial temporal lobes, was followed for two years. At the beginning of the study VZ's performance was mainly characterized by a category-specific deficit for living things and a modality-specific deficit for perceptual attribute knowledge. As time went on, VZ's disorder affected all categories by changing the relationship between category and attribute knowledge. Data show that dissociations may change in the course of progressive cognitive breakdown, depending on both degeneration stage and task demands. VZ's performance is discussed in the light of the most influential theoretical accounts. Methodological suggestions regarding longitudinal studies of degenerative patients are also put forward.     

Cholesterol-sensing receptors, liver X receptor alpha and beta, have novel and distinct roles in osteoclast differentiation and activation.

The liver X receptor (alpha,beta) is responsible for regulating cholesterol homeostasis in cells. However, our studies using the LXRalpha-/-, LXRbeta-/-, and LXRalpha-/-beta-/- mice show that both LXRalpha and beta are also important for bone turnover, mainly by regulating osteoclast differentiation/activity. Introduction: The liver X receptors (alpha,beta) are primarily responsible for regulating cholesterol homeostasis within cells and the whole body. However, as recent studies show that the role for this receptor is expanding, we studied whether the LXRs could be implicated in bone homeostasis and development. MATERIALS AND METHODS: pQCT was performed on both male and female LXRalpha-/-, LXRbeta-/-, LXRalpha-/-beta-/-, and WT mice at 4 months and 1 year of age. Four-month-old female mice were additionally analyzed with reference to qPCR, immunohistochemistry, histomorphometry, transmission electron microscopy, and serum bone turnover markers. RESULTS: At the mRNA level, LXRbeta was more highly expressed than LXRalpha in both whole long bones and differentiating osteoblast-like MC3T3-E1 and osteoclast-like RAW 264.7 cells. Four-month-old female LXRalpha-/- mice had a significant increase in BMD because of an increase in all cortical parameters. No difference was seen regarding trabecular BMD. Quantitative histomorphometry showed that these mice had significantly more endosteal osteoclasts in the cortical bone; however, these cells appeared less active than normal cells as suggested by a significant reduction in serum levels of cross-linked carboxyterminal telopeptides of type I collagen (CTX) and a reduction in bone TRACP activity. Conversely, the female LXRbeta-/- mice exhibited no change in BMD, presumably because a significant decline in the number of the trabecular osteoclasts was compensated for by an increase in the expression of the osteoclast markers cathepsin K and TRACP. These mice also had a significant decrease in serum CTX, suggesting decreased bone resorption; however, in addition presented with an increase in the expression of osteoblast associated genes, bone formation markers, and serum leptin levels. CONCLUSIONS: Our findings show that both LXRs influence cellular function within the bone, with LXRalpha having an impact on osteoclast activity, primarily in cortical bone, whereas LXRbeta modulates trabecular bone turnover.     

Serum creatinine assay: results of a multicentric study with 16 analytical systems]

During a multicenter evaluation, 16 methods for creatinine measurement have been tested according to the guidelines of the Société fran?aise de biologie clinique (SFBC) protocol. Kinetic Jaffé methods, widely used in France, performed on different analytical systems (Astra Beckman, IL 508, RA 1000 Technicon, Hitachi 704, 705, 717 Boehringer, Fara Roche, Progress Kone, Kem-O-Mat Coulter, Perspective France Monitor) have been compared to a continuous flow method with aqueous standards, to enzymatic methods using creatinine amidohydrolase with a colorimetric measurement (Boehringer and Ektachem Kodak) and to an HPLC method. Reproducibility, estimated with four different control sera, proved to be unsatisfactory in some cases as compared to current criteria for imprecision (less than +/- 10 mumol/l for intralaboratory and less than +/- 20 mumol/l for interlaboratory imprecision). The same selected patients sera covering the whole range of physiopathological concentrations have been analyzed with each method, and compared with the continuous flow results. Differences are more dependent on the sample than on the calibrators. The influences of haemolysis, bilirubin, acetoacetate, albumin, lipids, glucose, and some cephalosporins have been evaluated with spiked human sera. Haemolysed, turbid and jaundiced patient samples have been analyzed as well. The results vary according to the analytical procedure. This study took place in the implementation of a selected method for routine purpose with special regards to interferences and an acceptable imprecision. The method must satisfy the physicians' demands in the renal function exploration, especially in kidney-transplant patients.     

Gender differences in informal caring

Men have hitherto largely been invisible in research on informal care. This paper examines gender differences in informal caring, focusing on gender differences according to the relationship between the carer and care-recipient and the location of caring. The paper uses secondary analysis of the 1990–91 General Household Survey, which identified over 2700 adults as informal carers. Four per cent of men and women provide care for someone living in the same household. More women than men, 13% compared with 10%, provide care for someone living in another household. Men carers are less involved in care provision than women, providing fewer hours of care each week, and are less likely to be the main carer. However, gender differences are most marked among married carers, apart from those caring for their spouse, and least among unmarried carers. Married men can often rely on their wives to perform caring roles rather than performing them personally. Women carers are more likely to provide personal care than men carers, but the gender difference is least among those caring for their spouse or for disabled children. Cross-sex personal care is performed within the marital relationship and by parents caring for disabled children, but seldom by adult children caring for their parents or in more distant caring relationships. Evidence of cross-sex taboos in giving personal care is largely restricted to care provided in another household. Since the majority of elderly people in need of care are women, such cultural taboos may reinforce the pressure on mid-life women to care for mothers and mothers-in-law.     

Postoperative ST-segment elevation: was vasospasm caused by anaphylaxis or by its treatment with epinephrine?

BACKGROUND: Anaphylaxis must be recognized and treated promptly to avoid significant morbidity and mortality. In this clinical setting, electrocardiographic changes can be multifactorial. OBJECTIVE: To discuss vasospasm as a cause of myocardial ischemia and its possible triggering by anaphylaxis itself or by the administration of epinephrine. METHODS: We describe a patient with multiple previous allergies who received intravenous epinephrine to treat suspected anaphylaxis. She immediately developed crushing chest pain with ST-segment elevations in the inferior leads. Throughout the discussion, we address differential diagnoses, physiologic features, and treatment. RESULTS: Her symptoms and electrocardiographic changes were consistent with vasospasm, which resolved after treatment with sublingual nitroglycerin. However, the reaction was sufficient to cause an elevation in the troponin T level and, therefore, myocardial damage on the cellular level. CONCLUSIONS: Cardiovascular complications, including electrocardiographic changes, may be induced by anaphylactic mediators or by medications used for its treatment.     

Stapled Hemorrhoidopexy: A Prospective Study From Pathology to Clinical Outcome

Stapled hemorrhoidopexy is widely accepted to treat hemorrhoids, but serious complications have been reported. In this prospective audit, we correlated clinical outcome with pathological findings. From January 2003 to April 2007, 94 patients underwent hemorrhoidopexy. Macroscopic appearance of the specimen (shape, size, and depth) was recorded. Microscopically, the presence of columnar, transitional, and squamous epithelium, the involvement of circular/longitudinal smooth muscle, and features of mucosal prolapse were assessed. Clinical outcome was evaluated by a validated questionnaire. Postoperative pain, secretion, and bleeding durations were 12.7 +/− 10.6, 5.6 +/− 9.6, and 6.3 +/− 8.4 days. Patient’s return to work averaged 16.7 +/− 10.7 days. Fissure, skin tags, and anal strictures were observed in 23.4%. Seven patients experienced pain for a significantly longer period of time. All specimens contained columnar mucosa, but 29.8% contained columnar and transitional epithelium and 12.8% contained columnar, anal transitional, and stratified squamous epithelium. Smooth muscle was observed in 62.7%. Pain was significantly increased if transitional epithelium was present in the specimen. No correlation or differences were observed if smooth muscle was present, although postoperative bleeding was more frequent. Hemorrhoidopexy is safe and effective. The specimen should always be sent for pathology examination. Only columnar epithelium should be present and, although the presence of smooth muscle does not influence the outcome in terms of functional results, its presence may play a role in postoperative bleeding. Presented as poster at the Digestive Disease Week, May 2007, Washington, USA     

Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.

(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors.     

Pseudoachalasia: not only esophago-gastric cancer

Pseudoachalasia is a rare clinical entity which has clinical, radiographic and manometric features often indistinguishable from achalasia. A small primary adenocarcinoma arising at the gastroesophageal junction or a tumor of the distal esophagus are the most frequent causes. Rarely, processes other than esophagogastric cancers may lead to the development of pseudoachalasia. We present three cases of pseudoachalasia in which the primary cause of the disease was not an esophagogastric cancer. The causes were a pancreatic carcinoma, a breast cancer and an histiocytosis X. Aspects of these three patients' diagnostic and therapeutic course are discussed in detail.