Cardiovascular Pathology. 004. Pathomorphological and CT-angiographical characteristics of coronary atherosclerotic plaques in cases of sudden cardiac death

Objective. The goal of this study was to present the pathological and radiological patterns of "vulnerable" atherosclerotic plaques in cases of sudden cardiac death. Method. This retrospective study was performed on forensic cases for which the cause of death was attributed to coronary artery disease. A complete autopsy was performed in all cases, along with either post-mortem CT-angiography, toxicological analyses and/or biochemistry. Results. 89 cases were selected (mean age 55±11.6 years; 75 men and 14 women). In 96.6% of cases a CT-angiography was performed. Acute coronary lesions were found in 60 cases (mean age 53±11.1 years), which included plaque erosion in 26 cases (mean age 47±8.3 years) and ruptures or intraplaque hemorrhage in 33 cases (mean age 58±10.4 years). Erosions were most frequently found in the left ascending artery (61.5 %), while only 36% of ruptures were observed in this artery. Chronic coronary pathology was described in 30 cases (mean age 58±10.4 years). CT-angiographies performed prior to the autopsy enabled an initial evaluation of coronary artery perfusion. Conclusion. In the face of decreasing clinical autopsy rates, postmortem studies on forensic autopsies, including modern radiological examinations, allow for a more thorough understanding of the clinical picture of disease which can result in sudden cardiac death.

Successful ageing and development: the contribution of generativity in older age

This paper examines the contributions that generativity in older age may make to the concept of successful ageing. To this end, two perspectives on successful ageing are described: successful ageing as a set of clinical criteria, and successful ageing as the application of adaptive processes aimed at achieving efficient functioning. After showing the limitations of the first perspective, particularly from a developmental point of view, the paper argues that the adaptive version of successful ageing helps to put ageing into a developmental frame, but needs to be complemented by identifying specific content and goals that guide these adaptive processes and establish new feasible gains for older people. Generativity in older age could play that role and provides a conceptual framework that enriches the concept of successful ageing, both by emphasising the social context in which people age and by highlighting a personal growth component.

Salvage treatment for venous aneurysm complicating vascular access arteriovenous fistula: use of an exoprosthesis to reinforce the vein after aneurysmorrhaphy.

OBJECTIVES: We report a new salvage technique for treating venous aneurysms (VAs) complicating vascular access arteriovenous fistula (AVF) using externally reinforced venous aneurysmorrhaphy. DESIGN: A retrospective study over a 20-month period from a single centre. PATIENTS: Patients presenting to the vascular surgery department, Bordeaux University Hospital for revision of a vascular access AVF were included. METHODS: Reinforced venous aneurysmorrhaphy consisted in removal of redundant vessel wall followed by reinforcement using an external prosthetic graft. Patency, diameter and flow were assessed by duplex ultrasound at 1, 6 and 12 months after salvage. RESULTS: Thirty-eight eligible patients were identified. Five were excluded because VA was associated with central vein stenosis; the remaining 33 underwent salvage. Indications were rapidly expanding or painful VA in seven cases; VA with frequent bleeding or damaged overlying skin in eight; VA in close relation to a stenosis in two; and VA associated with high-flow rate in 16. Cannulation was attempted after 30 days. Mean follow-up time was 12 S.D. 5 months (range: 4-22). Two repaired AVFs failed. Primary 1-year patency was 93%. No aneurysm or infection occurred. Reduction of high flow was successful in 12 of 16 patients. The remaining four required re-operation. CONCLUSIONS: Reinforced venous aneurysmorrhaphy is effective in controlling venous dilation and achieving patency. Reduction of high-flow rates was not always achieved. Further study is needed to evaluate long-term efficacy of this treatment.

Paper 5: Surveillance of multiple congenital anomalies: implementation of a computer algorithm in European registers for classification of cases.

BACKGROUND: Surveillance of multiple congenital anomalies is considered to be more sensitive for the detection of new teratogens than surveillance of all or isolated congenital anomalies. Current literature proposes the manual review of all cases for classification into isolated or multiple congenital anomalies. METHODS: Multiple anomalies were defined as two or more major congenital anomalies, excluding sequences and syndromes. A computer algorithm for classification of major congenital anomaly cases in the EUROCAT database according to International Classification of Diseases (ICD)v10 codes was programmed, further developed, and implemented for 1 year's data (2004) from 25 registries. The group of cases classified with potential multiple congenital anomalies were manually reviewed by three geneticists to reach a final agreement of classification as "multiple congenital anomaly" cases. RESULTS: A total of 17,733 cases with major congenital anomalies were reported giving an overall prevalence of major congenital anomalies at 2.17%. The computer algorithm classified 10.5% of all cases as "potentially multiple congenital anomalies". After manual review of these cases, 7% were agreed to have true multiple congenital anomalies. Furthermore, the algorithm classified 15% of all cases as having chromosomal anomalies, 2% as monogenic syndromes, and 76% as isolated congenital anomalies. The proportion of multiple anomalies varies by congenital anomaly subgroup with up to 35% of cases with bilateral renal agenesis. CONCLUSIONS: The implementation of the EUROCAT computer algorithm is a feasible, efficient, and transparent way to improve classification of congenital anomalies for surveillance and research.

Pycnodysostosis. A report of 3 clinical cases

Pycnodysostosis is a rare clinical entity, first described in 1962 by Maroteaux and Lamy. It is a genetic disorder, usually diagnosed at an early age. However, the diagnosis is sometimes late, made as a result of bone fracture, given the severe bone fragility resulting from increased bone density. Oral and maxillofacial manifestations of this disease are very clear. The head is usually large, the nose beaked, the mandibular angle obtuse, and both maxilla and mandible hypoplastic. Dental abnormalities and impaction are observed, as well as alterations in eruption and frequent dental crowding. The differential diagnosis is established with osteopetrosis, cleidocranial dysplasia and idiopathic acro-osteolysis. This article reviews the clinical and radiographic characteristics of pycnodysostosis based on three clinical cases of patients with this disease.

Airway stenting with the LT-Mold? for severe glotto-subglottic stenosis or intractable aspiration: experience in 65 cases.

The purpose of this study was to assess the safety and efficacy of stenting in upper airway reconstructions for benign laryngotracheal stenosis (LTS) with a newly designed prosthesis, the LT-Mold?. The LT-Mold and its proper use during open surgery and endoscopy are described, and the experience gathered from a prospectively collected database on 65 patients treated for complex LTS or severe aspiration is reported. This series is compared to the results of other stenting methods. All patients were available for evaluation. In all but one case, the prosthesis was removed at the end of the study. The new prosthesis did not induce any stent-related trauma to the supraglottis, glottis and subglottis. Before adding a distal round-shaped silicone cap to the LT-Mold, granulation tissue was usually seen at the stent-mucosal interface at the tracheostoma level. In 14 cases, there has been a spontaneous extrusion of the prosthesis through the mouth; this problem was solved by fixing the prosthesis through the reinforced portion of the prosthesis at the cap level and by adding one fixation stitch in the supraglottis. We have to document the loss of the silicone cap in three cases. This problem was resolved by designing a new prototype with an integrated cap, glued with a slow hardening silicone glue. Fifty-four (83 %) of 65 patients were decannulated after a mean duration of stenting of 3 months (range 1-12 months). The mean follow-up after decannulation was 23 months (range 1 month to 10 years). The experience gathered with the LT-Mold shows that long-term stenting for complex LTS is safely achieved when the prosthesis is used with its distal integrated silicone cap. The softness and smoothness of the prosthesis with a round-shaped configuration of both extremities help avoid ulceration and granulation tissue formation in the reconstructed airway. Adequate fixation is mandatory to avoid extrusion.

Le fixateur externe dans les lésions traumatiques graves du bassin: résultats à propos de 20 cas consécutifs [External fixator in severe traumatic injuries of the pelvis: results apropos of 20 consecutive cases]

From August 91 to December 94, 20 external fixators were used for severely injured patients (avg. ISS 25.2). The fractures were essentially open book with or without lateral compression and vertical lesions. The indication for fixation was treatment of shock and stabilization in 8 cases, stabilization alone in 9 cases, and in 3 cases as complementary fixation after internal fixation of posterior lesions. The fixation of the pelvis was effective on the amount of blood loss. One acetabulum fracture required surgery, two patients had internal fixation for loss of reduction and two others for late pubic and posterior pain. The clinical results are good; they are more related to the severity of the initial lesion than to the mode of fixation or the quality of the reduction. No superficial sepsis or osteitis was observed in relation to the pins.

Syndrome of birt-hogg-dubé, a histopathological pitfall with similarities to tuberous sclerosis: a report of three cases.

: Birt-Hogg-Dubé Syndrome (BHD) is a rare condition, transmitted as an autosomal-dominant trait. The etiology is due to a mutation in the BHD gene, which encodes folliculin (FLCN), located on chromosome 17p. The skin changes observed are benign skin tumors consisting of hamartomas of the hair follicle with dermal changes. Patients with BHD have an increased risk of spontaneous pneumothorax due to rupture of lung cysts and an increased risk of kidney tumors. We report 3 new cases of BHD and discuss their clinical features, histopathological findings, and molecular diagnostics. We highlight the importance of genetic analysis to confirm the diagnosis because of the clinical pitfalls involved in establishing a diagnosis. Finally, we discuss the histopathological features in BHD and tuberous sclerosis complex and focus on their overlapping criterias. A correct diagnosis is essential as it can be life saving for patients.

Acute respiratory syndrome after inhalation of waterproofing sprays: a posteriori exposure-response assessment in 102 cases

Waterproofing agents are widely used to protect leather and textiles in both domestic and occupational activities. An outbreak of acute respiratory syndrome following exposure to waterproofing sprays occurred during the winter 2002-2003 in Switzerland. About 180 cases were reported by the Swiss Toxicological Information Centre between October 2002 and March 2003, whereas fewer than 10 cases per year had been recorded previously. The reported cases involved three brands of sprays containing a common waterproofing mixture, that had undergone a formulation change in the months preceding the outbreak. A retrospective analysis was undertaken in collaboration with the Swiss Toxicological Information Centre and the Swiss Registries for Interstitial and Orphan Lung Diseases to clarify the circumstances and possible causes of the observed health effects. Individual exposure data were generated with questionnaires and experimental emission measurements. The collected data was used to conduct numeric simulation for 102 cases of exposure. A classical two-zone model was used to assess the aerosol dispersion in the near- and far-field during spraying. The resulting assessed dose and exposure levels obtained were spread on large scales, of several orders of magnitude. No dose-response relationship was found between exposure indicators and health effects indicators (perceived severity and clinical indicators). Weak relationships were found between unspecific inflammatory response indicators (leukocytes, C-reactive protein) and the maximal exposure concentration. The results obtained disclose a high interindividual response variability and suggest that some indirect mechanism(s) predominates in the respiratory disease occurrence. Furthermore, no threshold could be found to define a safe level of exposure. These findings suggest that the improvement of environmental exposure conditions during spraying alone does not constitute a sufficient measure to prevent future outbreaks of waterproofing spray toxicity. More efficient preventive measures are needed prior to the marketing and distribution of new waterproofing agents.

Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections.

OBJECTIVE: To identify disease causing mutation in three generations of a Swiss family with pattern dystrophy and high intrafamilial variability of phenotype. To assess the effect of intravitreal ranibizumab injections in the treatment of subfoveal choroidal neovascularization associated with pattern dystrophy in one patient. METHODS: Affected family members were ascertained for phenotypic and genotypic characterization. Ophthalmic evaluations included fundus photography, autofluorescence imaging, optical coherence tomography, and International Society for Clinical Electrophysiology of Vision standard full-field electroretinography. When possible family members had genetic testing. The proband presented with choroidal neovascularization and had intravitreal injections as needed according to visual acuity and optical coherence tomography. RESULTS: Proband had a multifocal type pattern dystrophy, and his choroidal neovascularization regressed after four intravitreal injections. The vision improved from 0.8 to 1.0, and optical coherence tomography showed complete anatomical restoration. A butterfly-shaped pattern was observed in her cousin, whereas a fundus pulverulentus pattern was seen in a second cousin. Aunt had a multifocal atrophic appearance, simulating geographic atrophy in age-related macular degeneration. The Y141C mutation was identified in the peripherin/RDS gene and segregated with disease in the family. CONCLUSION: This is the first report of marked intrafamilial variation of pattern dystrophy because of peripherin/RDS Y141C mutation. Intravitreal ranibizumab injections might be a valuable treatment for associated subfoveal choroidal neovascularization.

Changes in biomarkers of liver disease during successful combination antiretroviral therapy in HIV-HCV-coinfected individuals.

BACKGROUND: We investigated changes in biomarkers of liver disease in HIV-HCV-coinfected individuals during successful combination antiretroviral therapy (cART) compared to changes in biomarker levels during untreated HIV infection and to HIV-monoinfected individuals. METHODS: Non-invasive biomarkers of liver disease (hyaluronic acid [HYA], aspartate aminotransferase-to-platelet ratio index [APRI], Fibrosis-4 [FIB-4] index and cytokeratin-18 [CK-18]) were correlated with liver histology in 49 HIV-HCV-coinfected patients. Changes in biomarkers over time were then assessed longitudinally in HIV-HCV-coinfected patients during successful cART (n=58), during untreated HIV-infection (n=59), and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4 years on cART. All analyses were conducted before starting HCV treatment. RESULTS: Non-invasive biomarkers of liver disease correlated significantly with the histological METAVIR stage (P<0.002 for all comparisons). The mean ±sd area under the receiver operating characteristic (AUROC) curve values for advanced fibrosis (≥F3 METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86 ±0.05, 0.84 ±0.08, 0.80 ±0.09 and 0.81 ±0.07, respectively. HYA, APRI and CK-18 levels were higher in HIV-HCV-coinfected compared to HIV-monoinfected patients (P<0.01). In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%, respectively; P=0.1), mainly due to the reversion of HIV-induced thrombocytopaenia, whereas HYA and CK-18 levels remained unchanged. During long-term cART, there were only small changes (<5%) in median biomarker levels. Median biomarker levels changed <3% during untreated HIV-infection. Overall, 3 patients died from end-stage liver disease, and 10 from other causes. CONCLUSIONS: Biomarkers of liver disease highly correlated with fibrosis in HIV-HCV-coinfected individuals and did not change significantly during successful cART. These findings suggest a slower than expected liver disease progression in many HIV-HCV-coinfected individuals, at least during successful cART.

The Effects of Crushed Particles in Asphalt Mixtures, HR-311 and MLR-88-16, Part 1, 1990

One of the most serious impediments to the continued successful use of hot mix asphalt (HMA) pavements is rutting. The Iowa Department of Transportation has required 85% crushed particles and 75 blow Marshall mix design in an effort to prevent rutting on interstate roadways. The objective of this research and report is to develop relation~hips between the percent of crushed particles and resistance to rutting in pavement through the use of various laboratory test procedures. HMA mixtures were made with 0, 30, 60, 85 and 100% crushed gravel, crushed limestone and crushed quartzite combined with uncrushed sand and gravel. These aggregate combinations were used with 4, 5 and 6% asphalt cement (ac). Laboratory testing included Marshall stability, resilient modulus, indirect tensile and creep. A creep resistance factor (CRF) was developed to provide a single numeric value for creep test results. The CRF values relate well to the amount of crushed particles and the perceived resistance to rutting. The indirect tensile test is highly dependent on the ac with a small effect from the percent of crushed particles. The Marshall stability from 75 blow compaction relates well to the percent of crushed particles. The resilient modulus in some cases is highly affected by grade of ac.