Clinical presentation of CADASIL in an Italian patient with a rare Gly528Cys exon 10 Notch3 gene mutation

CADASIL is an autosomal dominant arteriopathy characterised by diffuse white matter lesions and small subcortical infarcts on neuroimaging and a variable combination of recurrent cerebral ischaemic episodes, cognitive deficits, migraine with aura and psychiatric symptoms. It is caused by mutations in the NOTCH3 gene encoding a NOTCH3 receptor protein. Here, we describe the genetical, clinical, neuropsychological and neuroimaging findings in an Italian CADASIL patient with a rare mutation in exon 10 leading to a Gly528Cys substitution

Defects in ProTaper S1 instruments after clinical use: Fractographic examination

Aim: To investigate the mode of failure of a brand of nickel-titanium instruments separated during clinical use, by detailed examination of the fracture surface. Methodology: A total of 122 ProTaper S1 instruments were discarded from an endodontic clinic at a stomatological school in China over a period of 17 months; 28 had fractured. These fractured instruments were ultrasonically cleaned, autoclaved and then examined under a scanning electron microscope. From the lateral view the fracture was classified into 'torsional' or 'flexural'. The specimens were then re-mounted and the presence of characteristics of shear failure and fatigue striations was recorded under high-power view of the fracture surface. The difference in the mean lengths of fractured segment between the shear and fatigue groups was compared using Student's t-test. Results: Twenty-seven separated instruments were available for analysis. Under low-power magnification, only two fell into the category of 'torsional' failure when examined laterally; the others appeared to be 'flexural'. Close examination of the fracture surface revealed the presence of fatigue striations in 18 specimens. Nine instruments (including the two putative 'torsional' failures above) fell into the shear fracture group, in which fatigue striations were absent or characteristics of shear failure of the material were found. The mean length of fractured segments resulting from fatigue failure (4.3 ± 1.9 mm) was significantly greater than that for shear failure (2.5 ± 0.8 mm) (P < 0.001, two-sample t-test). Conclusions: Examination of the fracture surface at high magnification is essential to reveal features that may indicate the possible origin of cracks and the mode of material failure. Macroscopic or lateral examination of separated instruments would fail to reveal the true mechanism of failure. Fatigue seems to be an important reason for the separation of rotary instruments during clinical use. © 2005 International Endodontic Journal.link_to_subscribed_fulltex

Intraoperative Evaluation of Soft Tissue Sarcoma Surgical Margins with Indocyanine Green Fluorescence Imaging

Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0–2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon’s clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28–83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful

Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. Objectives: To determine the impact of occupational exposures on COPD morbidity. Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden