The prevalence of and factors related to calcium pyrophosphate dihydrate crystal deposition in the knee joint

SummaryObjectivesThe purpose of this study was to reveal the accurate prevalence and related factors to the presence of calcium pyrophosphate dihydrate (CPPD) crystal deposition in cadaveric knee joints.DesignControlled laboratory study.MethodsSix hundred and eight knees from 304 cadavers (332 male knees and 276 female knees, formalin fixed, Japanese anatomical specimens) were included in this study. The average age of the cadavers was 78.3 ± 10.7 years. Knees were macroscopically evaluated for the existence of CPPD, and the depth of cartilage degeneration of the femoro-tibial joint following the Outerbridge's classification. CPPD crystal was confirmed under Fourier transform infrared spectroscopy (FTIR) analysis using light microscopy. Statistical analysis was performed to reveal the correlation between the occurrence of CPPD deposition in the knee joint and gender, age, and the depth of cartilage degeneration of the femoro-tibial joint.ResultsThe prevalence of grossly visible CPPD crystal was 13% (79 knees). In all of these knees, CPPD crystal was confirmed under FTIR analysis. Statistical analysis showed significant correlation between the occurrence of CPPD deposition and gender (P < 0.001), and depth of cartilage degeneration in the femoro-tibial joint (P < 0.001). In the cartilage degeneration positive knees (Over grade 3 in Outerbridge's classification), average age of CPPD deposition knee was significantly higher than CPPD negative knees.ConclusionsIn this study, the prevalence of CPPD deposition disease was evaluated in a relatively large sample size of cadaveric knees. The prevalence of CPPD deposition disease was 13%, and was significantly correlated with the subject's age, gender, and severity of cartilage degeneration in the femoro-tibial joint

Isolation of stable non cyclic 1,2-disulfoxides: revisiting the thermolysis of S-aryl sulfinimines

The thermolysis of S-aryl sulfinimines is shown to generate 1,2-disulfoxides and disulfides via initial Cope elimination, dimerisation of the produced sulfenic acid to a thiosulfinate, and subsequent disproportionation of the thiosulfinate

The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET

INTRODUCTION: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. RESULTS: Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. CONCLUSIONS: Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols

Comparison of glucose tolerance in renal transplant recipients and hemodialysis patients

BACKGROUND: Impaired glucose tolerance is a risk factor for atherosclerosis in hemodialysis patients and renal transplant recipients. METHODS: To check the relationship of impaired glucose tolerance with the other atherosclerotic risk factors, fasting blood sugar and the standard two hour glucose tolerance test, serum tryglyceride, serum cholesterol, cyclosporine through level (in renal tranpslant recipients) and hemoglobin A1C were measured in 55 stable renal transplant recipients, 55 hemodialysis patients and 55 healthy controls with similar demographic characteristics. Patients with diabetes mellitus and propranolol consumers were excluded. The mean age and female to male ratio were 39 +/- 7 years and 23/22, respectively. RESULTS: Four of the renal transplant recipients and twelve of the hemodialysis patients had impaired glucose tolerance. Significant linear correlation was observed with body mass index and IGT only in hemodialysis patients (r = 0.4, p = 0.05). Glucose tolerance also had a significant correlation with triglyceride levels (217.2 +/- 55 mg/dl in hemodialysis patients vs. 214.3 +/- 13 mg/dl in renal transplant recipients and 100.2 +/- 18 mg/dl in control groups, p = 0.001). The glucose tolerance had significant relationship with higher serum cholesterol levels only in the renal transplant recipients (269.7 +/- 54 in renal transplant recipients vs. 199.2 +/- 36.6 mg/dl in hemodialysis and 190.5 +/- 34 mg/dl in control groups, p = 0.0001). In the renal transplant recipients, a linear correlation was observed with glucose tolerance and both the serum cyclosporine level (r = 0.9, p = 0.001) and the hemoglobin A1C concentration (6.2 +/- 0.9 g/dl). The later correlation was also observed in the hemodialysis patients (6.4 +/- 0.7 g/dl; r = 67, p = 0.001). CONCLUSIONS: We conclude that although fasting blood sugar is normal in non-diabetic renal transplant and hemodialysis patients, impaired glucose tolerance could be associated with the other atherosclerotic risk factors

Evaluation of 18F-2-deoxy-2-fluoro-glucose positron emission tomography for gastric cancer screening in asymptomatic individuals undergoing endoscopy

18F-2-deoxy-2-fluoro-glucose Positron Emission Tomography (FDG-PET) has been recently proposed as a promising cancer-screening test. However, the validity of FDG-PET in cancer screening has not been evaluated. We investigated the sensitivity of FDG-PET compared with upper gastric endoscopy in gastric cancer screening for asymptomatic individuals. A total of 2861 consecutive subjects (1600 men and 1261 women) who were asymptomatic and who underwent both FDG-PET and upper gastrointestinal endoscopy between 1 February 2004 and 31 January 2005 were included in this study. Both endoscopists and a radiologist were unaware of the results of the other diagnostic tests. The FDG-PET images were examined using criteria determined by the pattern of FDG accumulation. Sensitivity and specificity of FDG-PET were calculated compared with endoscopic diagnosis as the gold standard. Among 2861 subjects enrolled in the study, there were 20 subjects with gastric cancer, of whom 18 were T1 in depth of cancer invasion. Positive FDG-PET results were obtained only in 2 of the 20 cancer subjects. The calculated sensitivity and specificity for overall gastric cancers were 10.0% (95% confidence interval (CI): 1.2–31.7%) and 99.2% (95% CI: 98.8–99.5%), respectively. 18F-2-deoxy-2-fluoro-glucose Positron Emission Tomography was poorly sensitive for detection of gastric cancer in the early stages

Modulating Activity of Vancomycin and Daptomycin on the Expression of Autolysis Cell-Wall Turnover and Membrane Charge Genes in hVISA and VISA Strains

Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can influence the development of resistance to daptomycin. Although the phenotypic and molecular changes of hVISA/VISA have been the focus of different papers, the molecular mechanisms responsible for these different phenotypes and for the vancomycin and daptomycin cross-resistance are not clearly understood. The aim of our study was to investigate, by real time RT-PCR, the relative quantitative expression of genes involved in autolysis (atl-lytM), cell-wall turnover (sceD), membrane charges (mprF-dltA) and regulatory mechanisms (agr-locus-graRS-walKR), in hVISA and VISA cultured with or without vancomycin and daptomycin, in order to better understand the molecular basis of vancomycin-reduced susceptibility and the modulating activity of vancomycin and daptomycin on the expression of genes implicated in their reduced susceptibility mechanisms. Our results show that hVISA and VISA present common features that distinguish them from Vancomycin-Susceptible Staphylococcus aureus (VSSA), responsible for the intermediate glycopeptide resistance i.e. an increased cell-wall turnover, an increased positive cell-wall charge responsible for a repulsion mechanism towards vancomycin and daptomycin, and reduced agr-functionality. Indeed, VISA emerges from hVISA when VISA acquires a reduced autolysis caused by a down-regulation of autolysin genes, atl/lytM, and a reduction of the net negative cell-envelope charge via dltA over-expression. Vancomycin and daptomycin, acting in a similar manner in hVISA and VISA, can influence their cross-resistance mechanisms promoting VISA behavior in hVISA and enhancing the cell-wall pathways responsible for the intermediate vancomycin resistance in VISA. Daptomycin can also induce a charge repulsion mechanism both in hVISA and VISA increasing the activity of the mprF

Loss of Octarepeats in Two Processed Prion Pseudogenes in the Red Squirrel, Sciurus vulgaris

The N-terminal region of the mammalian prion protein (PrP) contains an ‘octapeptide’ repeat which is involved in copper binding. This eight- or nine-residue peptide is repeated four to seven times, depending on the species, and polymorphisms in repeat number do occur. Alleles with three repeats are very rare in humans and goats, and deduced PrP sequences with two repeats have only been reported in two lemur species and in the red squirrel, Sciurus vulgaris. We here describe that the red squirrel two-repeat PrP sequence actually represents a retroposed pseudogene, and that an additional and older processed pseudogene with three repeats also occurs in this species as well as in ground squirrels. We argue that repeat numbers may tend to contract rather than expand in prion retropseudogenes, and that functional prion genes with two repeats may not be viable

Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

Objective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tumor lesion before and during therapy. Results: At baseline, mean BF and MRgluvaried among different tumor lesions, but mean Vdwas comparable in all lesions. After one course of chemotherapy, mean MRgludecreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. Vddecreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRgluresponse could be very heterogeneous, even within similar types of metastases. BF and MRgluincreased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up. Conclusion: BF and MRgluchanges separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRgluparameters can be remarkably heterogeneous in patients with multiple lesions