Prevalence of peripheral arterial disease in high-risk patients using ankle-brachial index in general practice: a cross-sectional study.

AIMS: The deleterious nature of peripheral arterial disease (PAD) is compounded by a status of underdiagnosed and undertreated disease. We evaluated the prevalence and predictive factors of PAD in high-risk patients using the ankle-brachial index (ABI). METHODS: The ABI was measured by general practitioners in France (May 2005-February 2006) in 5679 adults aged 55 years or older and considered at high risk. The primary outcome was prevalence of PAD (ABI strictly below 0.90). RESULTS: In all, 21.3% patients had signs or symptoms suggestive of PAD, 42.1% had previous history of atherothrombotic disease and 36.6% had two or more cardiovascular risk factors. Prevalence of PAD was 27.8% overall, ranging from 10.4% in patients with cardiovascular risk factors only to approximately 38% in each other subgroup. Prevalence differed depending on the localization of atherothrombotic events: it was 57.1-75.0% in patients with past history of symptomatic PAD; 24.6-31.1% in those who had experienced cerebrovascular and/or coronary events. Regarding the classical cardiovascular risk factors, PAD was more frequent when smoking and hypercholesterolemia history were reported. PAD prevalence was also higher in patients with history of abdominal aortic aneurysm, renal hypertension or atherothrombotic event. Intermittent claudication, lack of one pulse in the lower limbs, smoking, diabetes and renovascular hypertension were the main factors predictive of low ABI. CONCLUSIONS: Given the elevated prevalence of PAD in high-risk patients and easiness of diagnosis using ABI in primary care, undoubtedly better awareness would help preserve individual cardiovascular health and achieve public health goals.

Peripheral arterial disease and isolated systolic hypertension: the ATTEST study.

Hypertension is a risk factor for cardiovascular (CV) diseases, either coronary artery disease (CAD), peripheral artery disease (PAD) or cerebrovascular disease (CVD). The relationships between those different localizations of CV disease and the haemodynamic features of hypertension have been poorly evaluated in the past. In the ATTEST study, a geographically representative panel of 3020 general practitioners recruited 8316 consecutive patients with CV diseases (PAD, CAD or CVD, alone or in association). Blood pressure, which was not an inclusion criterion, was then measured and related to the different forms of CV diseases. Blood pressure classification involved 20% normotensive subjects, 24% subjects with controlled hypertension, 42% subjects with isolated systolic hypertension and 14% subjects with systolic-diastolic hypertension, all hypertensives with or without antihypertensive therapy. From multiple regression analysis, it appeared that subjects with systolic hypertension were characterized by the presence of PAD, with little or no presence of CAD and/or CVD. Subjects with systolic-diastolic hypertension were characterized by the presence of CAD and/or CVD, but without PAD. Although the former was only influenced by age, dyslipidaemia and diabetes mellitus influenced the latter. This study confirms the high prevalence of hypertension (80%) in a large population of patients with CV diseases selected in primary care. Analysis of different features of hypertension revealed that isolated systolic hypertension was the most prevalent form of hypertension in this treated population. Finally, one of the predominant goals of secondary prevention in subjects with PAD should be the treatment of isolated systolic hypertension.

[Influence of percutaneous coronary intervention in non ST-elevation acute coronary syndromes on prescription of secondary prevention medications. Data from the S-Témoin Registry]. / Prevention secondaire après syndrome coronaire aigu sans sus-décalage de ST en fonction de l'utilisation de l'angioplastie coronaire: l'étude S-Témoin.

BACKGROUND: The interaction between the use of percutaneous coronary intervention (PCI) for non-ST-elevation acute coronary syndromes and the use of secondary prevention medications was analysed in the French S-Témoin Registry. METHODS: The population consisted of 2433 patients seen by their cardiologists at an outpatient clinic 2-12 months after non ST-elevation ACS; the survey was carried out from September 2004 to April 2005. RESULTS: Overall, patients undergoing PCI (75% of the population) had higher levels of prescription of recommended secondary prevention medications. Multivariate logistic regression analysis showed that the use and type of coronary intervention (drug eluting versus bare metal stents) was an independent correlate of the use of dual antiplatelet therapy. In addition, time from the acute episode was also a strong correlate of dual antiplatelet therapy. Statins were also more often used in patients with PCI. CONCLUSION: Patients not treated with PCI are less likely to receive appropriate secondary prevention medications after non ST-elevation acute coronary syndromes. Specific efforts should be directed towards these patients, in particular as regards the prescription of dual antiplatelet therapy.

Detection and management of associated atherothrombotic locations in patients with a recent atherothrombotic ischemic stroke: results of the DETECT survey.

BACKGROUND: Cerebral infarction (CI), myocardial infarction, peripheral artery disease (PAD) and aortic atheroma are the main clinical manifestations of atherothrombosis. Long-term prevention after CI of atherothrombotic origin may require preventive measures at other sites, such as specific drug therapies, surgery, or angioplasty. Therefore the detection of other locations is potentially important. OBJECTIVES: The primary objective was to describe the other locations of atherothrombosis in patients hospitalized for a recent cerebral infarct of atherothrombotic origin. Secondary objectives were to describe their vascular risk factor profiles, and their management before and after the cerebral event. METHOD: This prospective, observational, multicenter survey was conducted in France between September 2003 and July 2004, mainly in neurological departments and stroke units. RESULTS: 753 patients were included (74% men; mean age 69.3 years). Previous coronary events had occurred in 119 (16%). Previous stroke or transient ischemic attacks had occurred in 233 (31%). PAD was already known in 109 (15%). A search for other atherothrombotic locations was positive in 216 patients (29%). The minimum prevalence for any associated atherothrombotic location (either present before or identified during hospitalization) was 47.5% for any location, 33.7% for coronary artery disease, 16.6% for aortic atheroma, and 22.7% for PAD. CONCLUSION: Fifty percent of the patients with recent atherothrombotic CI have other locations of atherothrombosis. For this reason, a systematic search for these other locations is recommended because of the possible therapeutic consequences. However, the question of the most appropriate period for this search after the cerebral event remains unsettled.

[Management of the cardiology patient with polyvascular disease: PRISMA study]. / Prise en charge du patient polyvasculaire en cardiologie de ville. Résultats de l'étude PRISMA.

INTRODUCTION: Myocardial infarction (MI), peripheral vascular disease and ischaemic cerebral vascular accident (CVA) are three manifestations of the same disease, atherothrombosis, and they share the same pathophysiology and prognosis. OBJECTIVE: The aim of this work was to describe the clinical characteristics and the medical management of polyvascular patients in cardiology. METHOD: Cardiologists from all over the country participated in a consultation register for 3 weeks. The clinical characteristics and medical management for the first 3 patients on the register for each cardiologist were studied in a national multicentre study and then compared according to whether the atherothrombotic disease was isolated or polyvascular. RESULTS: In total, 100,429 patients were examined during the period of the register and 2,780 were included in the study. Polyvascular patients represented 7% of the register and 22% of the vascular patients. These patients with multiple manifestations were frequently diabetics. A lipid profile was available less often in the cardiac patients when they had another disorder (72.4%) than in the case of an isolated disorder (78.9%). Whatever the initial disorder, dyslipidaemia was less often controlled in the case of polyvascular disease (63% of LDL-C > or = 1.3g/l in polyvascular cardiac patients vs 52% in cardiac patients with isolated disease). In cardiac patients, the presence of peripheral vascular disease was associated with less prescription of beta blockers (OR=0.4 [0.3-0.6]), the presence of CVA was associated with less prescription of statins (OR=0.7 [0.5-0.9]). Eight out of 10 polyvascular patients received anti-platelet aggregation treatment. The presence of multiple atherothrombotic manifestations was associated with greater prescription of ACEI, except in cardiac patients. CONCLUSION: These results improve our understanding of the specific management of polyvascular patients, for whom secondary prevention is paramount due to the higher risk of recurrence. They should prompt the reinforcement of measures which have been shown to be effective, such as managing major risk factors, and in particular the dislipidaemias.

[Peripheral arterial disease: what management practices for general practitioners?]. / L'artériopathie des membres inférieurs en médecine générale. Quelle prise en charge?

OBJECTIVE: The purpose of this study was to analyze the results of the ATTEST study in order to evaluate general medicine management practices for peripheral arterial disease (PAD). Our analysis was based on the guidelines for good practice which recommend measurement of the systolic pressure index (SPI), search for other localizations of atherothrombosis, treatment of risk factors including smoking, walking exercises, and long-term prescription of anti-platelets. METHODS: ATTEST is a cross-sectional multicentric observational epidemiologic study conducted in metropolitan France. The study has recruited 8.475 analyzable patients with symptomatic PAD alone (3811 patients) or associated with other atherothrombotic localizations (2416 patients) or other cardiovascular diseases (2248 patients). These patients were followed by 3020 physicians. The current analysis thus included 6227 patients (81.2% men, 18.8% women, mean age 67.2 years), including 78.8% who had reached the stage of intermittent claudication. Risk factors included current or past smoking (61%), hypercholesterolemia (66.3%), hypertension (63.1%) and diabetes mellitus (26%). RESULTS: Arterial duplex Doppler exams of the lower limbs were performed in 91.2% of the patients but measurement of the SPI for diagnostic purposes had been performed in only 17%. The majority (85.8%) of the patients with proven coronary artery disease or cervico-encephalic involvement had had an ECG and 69.3% had had a duplex Doppler of the supra-aortic trunks. Smoking continued in 39% of the patients and an aid to cease smoking had been prescribed for only 7% of the patients who were non-smokers for less than one year. Nearly two-thirds of the patients analyzed had received advice concerning physical activities. Finally, anti-platelets had been prescribed for 92.2% of the patients. CONCLUSIONS: The general practitioner plays a crucial role in the diagnosis and treatment of PAD. Although measurement of the SPI is recommended as an early diagnostic tool and for evaluation of severity, it had been performed in less than one-third of the patients. Search for another localization of atherothrombosis had been performed in more than half of the patients. The physicians generally delivered advice on physical exercise and prescribed anti-platelets. The fight against smoking was however largely insufficient. The results of this study warrant further optimization of the collaboration between general practitioners and vascular disease specialists.

The Frye hearing in Florida: an attempt to exclude scientific evidence.

State Supreme Courts require a minimum threshold of reliability and acceptance in the scientific community for all medical and similar evidence to be admitted at trial. In Florida and some other states, the courts adhere to what is known as the Frye standard, whereas in most states and in Federal Courts, it is the so-called Daubert standard. The jurisdiction of the present case is Hillsborough County (Tampa), Florida. Forensic pathologists seldom, if ever, are requested to participate in such hearings, unlike their toxicological and basic science colleagues who are more involved in research methodology and technical procedures. The burden is on the proponent of the evidence to prove the general acceptance of both the underlying scientific principle of the test and procedures used to apply that principle to the facts of the case at hand. The trial judge has the sole discretion to determine this question and general acceptance must be established by a preponderance of the evidence. The authors describe in detail a hearing in a case in which they were all involved. One author (WQS) had researched and documented the original scientific methodology in the literature. The situation involved a car and tractor trailer crash with the two occupants of the car dying of multiple trauma, whereas the truck driver was not injured. Autopsy of the auto driver revealed multiple injuries with exsanguination, and only vitreous humor and liver tissue, but not blood, were tested for ethyl alcohol. The estate of the driver of the automobile brought suit against the owner of the trucking company for wrongful death. The plaintiff requested a Frye hearing to question the reliability of testing other body specimens to translate to probable blood alcohol level. The testimony, submitted documents, and eventual decision by the judge are discussed.

Effect of dimethicone (polysilane gel) on the stereoselective pharmacokinetics of ketoprofen.

OBJECTIVE: Since dimethicone may be employed to improve gastrointestinal tolerability of non steroidal anti-inflammatory drugs (NSAIDs), we studied its influence on the pharmacokinetics of ketoprofen in subjects receiving a single oral dose of racemic ketoprofen. PATIENTS AND METHODS: In a cross-over experimental design, 12 healthy fasting volunteers were given a single oral dose (100 mg) of racemic ketoprofen, administered with or without dimethicone. The kinetic parameters measured were area under the concentration (AUC), maximum peak plasma concentration (Cmax), time to reach peak concentration (tmax), elimination half-life (t1/2), mean residence time (MRT) and urinary excretion for R and S enantiomers. RESULTS: Dimethicone reduced the peak concentration of both R and S ketoprofen by about 10% (P<0.05) and also induced a slight but non-significant increase in the mean time to achieve peak concentration. However, this treatment had no significant effect on the bioavailability and the elimination of R and S enantiomers, as shown by AUC, t1/2 and MRT values. The absorption patterns were equivalent for both ketoprofen isomers, since plasma pharmacokinetic parameters were similar. Nevertheless, the urinary recovery was significantly lower for R ketoprofen than for its antipode. The administration of dimethicone did not alter this stereoselectivity. CONCLUSION: The administration of dimethicone to alleviate the epigastralgic effects related to NSAIDs does not affect the efficacy of the treatment. Dimethicone did not significantly alter the bioavailability of ketoprofen, chosen as an example of an NSAID, especially that of the pharmacologically active S enantiomer.

[Comparison between effects of morning and evening administration of effervescent calcium carbasalate (equivalent of 160 mg aspirin) on the gastroduodenal mucosa in healthy volunteers]. / Comparaison de l'effet de la prise matinale et vespérale du carbasalate calcique effervescent (equivalent a 160 mg d'aspirine) sur la muqueuse gastroduodénale chez le volontaire sain.

The aim of this randomised, cross-over trial was to compare the gastroduodenal tolerability and anti-aggregating effect of effervescent calcium carbasalate (ECC equivalent to 160 mg aspirin) given once daily either in the morning or in the evening. Twelve healthy volunteers received calcium carbasalate for 2 periods of 5 days (21 days of wash-out between the 2 periods). The principal criterion was the gastroduodenal tolerability assessed by the total number of lesions at upper gastro-intestinal endoscopy. The same treatment-blinded endoscopist performed all evaluations. Efficacy was evaluated by thromboxane B2 measurement and collagen-induced platelet aggregation tests. No difference was observed between morning and evening administration of ECC on gastroduodenal tolerability and platelet agregation. ECC was very well tolerated as assessed by upper gastrointestinal endoscopy and almost totally inhibited platelet aggregation.

The medical examiner. When to report and help with death certificates.

Medical examiners perform autopsies on victims of criminal violence and such deaths must be reported to the medical examiner. Because few medical personnel are cognizant of the full extent of the types of deaths which must be reported and of the substantial noncriminal aspects of medical examiner services, this description of the Florida Medical Examiner System emphasizes these areas and deaths due to late sequelae of violence. Proper death certification is one aspect of medical practice in which most physicians receive absolutely no training; therefore the essential elements are briefly outlined.

Sudden infant death with anomalous origin of the left coronary artery.

Autopsy of a 3-month-old girl, an apparent case of sudden infant death syndrome, revealed anomalous origin of the left coronary artery from the right aortic sinus. Acute angulation of the left coronary artery along the aortic root, as well as a focal intramyocardial course within the ventricular septum, may have contributed to episodic luminal narrowing. Anomalous coronary origins of similar type have been associated with sudden death in children, teenagers, and young adults, but have not necessarily been associated with sudden death in older adults. Somewhat similar malformations have been reported in sudden infant death; two cases involved the left coronary artery and six involved the right.

Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype.

We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, papillary thyroid carcinoma (PTC), is a novel rearranged version of the ret tyrosine-kinase protooncogene. Thyroid neoplasms include a broad spectrum of malignant tumors, ranging from well-differentiated tumors to undifferentiated anaplastic carcinomas. To determine the frequency of ret oncogene activation, we analyzed 286 cases of human thyroid tumors of diverse histologic types. We found the presence of an activated form of the ret oncogene in 33 (19%) of 177 papillary carcinomas. By contrast, none of the other 109 thyroid tumors, which included 37 follicular, 15 anaplastic, and 18 medullary carcinomas, and 34 benign lesions, showed ret activation.

Primary cardiac angiosarcoma: a clinicopathologic study of six cases.

Autopsy or surgical specimens from six patients with primary cardiac angiosarcoma seen at the Mayo Clinic (all in men) between 1939 and 1988 were studied (patients' ages, 31 to 80 years; mean 50 years). The symptoms were nonspecific and included dyspnea and thoracoabdominal pain in six; anorexia in five; fatigue, hemoptysis, or orthopnea in four; nausea and vomiting, fever, or weight loss in three; and night sweats in two. Cardiomegaly was present in five, and a pericardial effusion or density, a mass adjacent to the heart, or nonspecific ST-T wave changes were present in three. All six neoplasms arose from the right atrium and exhibited epicardial or endocardial extension; three produced obstructive intracavitary right atrial masses. Pulmonary metastatic lesions were noted in five patients. The cardiac neoplasm was diagnosed by computed tomography or magnetic resonance imaging in the three most recent patients, and surgical resection was performed in two of them. Mean survival was 6 months after presentation. Causes of death were pulmonary hemorrhage in three, thoracic metastasis in two, and hemopericardium in one. The diagnosis of primary cardiac angiosarcoma was established at operation in two patients and at autopsy in four. Despite diagnosis by noninvasive imaging procedures and aggressive early surgical intervention, survival was less than 6 months. Thus optimal therapy is unclear.

Characterization of an inversion on the long arm of chromosome 10 juxtaposing D10S170 and RET and creating the oncogenic sequence RET/PTC.

RET/PTC is a transforming sequence created by the fusion of the tyrosine kinase domain of the RET protooncogene with the 5' end of the locus D10S170 designated by probe H4 and is frequently found activated in human papillary thyroid carcinomas. RET and D10S170 have been mapped to contiguous regions of the long arm of chromosome 10: q11.2 and q21, respectively. To identify the mechanism leading to the generation of the oncogenic sequence RET/PTC, a combined cytogenetic and molecular analysis of several cases of papillary thyroid carcinomas was done. In four cases the results indicated that these tumors had RET/PTC activation and a paracentric inversion of the long arm of chromosome 10, inv(10)(q11.2q21), with breakpoints coincident with the regions where RET and D10S170 are located. Therefore, a chromosome 10q inversion provides the structural basis for the D10S170-RET fusion that forms the hybrid transforming sequence RET/PTC.

[Effect of folic acid and folinic acid on zinc absorption]. / Effet de l'acide folique et de l'acide folinique sur l'absorption du zinc.

We have investigated the effect of folic and folinic acids on intestinal zinc absorption in humans, using zinc tolerance tests. Zinc (30 mg) as the gluconate was given by mouth to 10 healthy subjects, alone (1), with 200 mg of folic acid (2) or with 200 mg of folinic acid (3). The zinc/folate molar ratio was 1:1. These three oral loading doses were given after overnight fasting to each of the 10 subjects, at weekly intervals. Serum zinc was measured at 0, 1, 2, 3, 6, 12 and 24 h. Zinc was also determined in urine collected for a 6-hour period following the ingestion of oral loading dose. The results do not indicated any inhibition of zinc absorption and urinary zinc excretion by folates. The areas under the curves varied from 48.2 +/- 20.0 mumol/6 h (1) to 57.0 +/- 10.3 mumol/6 h (3), peak zinc concentration from 28.8 +/- 7.3 mumol/l (1) to 32.1 +/- 4.1 mumol/l (3), half-life from 3.12 +/- 1.12 h (3) to 3.42 +/- 1.48 h (1), elimination rate constant from 0.22 +/- 0.08 (1) to 0.24 +/- 0.07 (3), mean urinary zinc excretion from 58.1 mumol/6 h (2) to 98.7 mumol/6 h (1) and mean zinc clearance from 1.15 l/h (3) to 3.26 l/h (1). All these indices were not statistically significantly different among the three different loading doses.

Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers.

Cytogenetic studies have shown frequent clonal abnormalities in papillary carcinoma (PTC) and follicular carcinoma (FTC). Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has not been reported in these neoplasms. These studies were undertaken to determine if consistent chromosomal abnormalities are associated with thyroid cancer, to determine likely regions for molecular genetic investigations, and to determine if there is allelic loss in thyroid tumors. Cytogenetic analysis of 26 PTC and 5 FTC showed clonal abnormalities in 9 and included -Y, +5, or inv(10)(q11.2q21.2) in PTC, and -Y or near haploidy in FTC. Using DNA probes specific for chromosomes 1, 3, 10, 16, and 17, we carried out restriction fragment length polymorphism analysis on 6 FTC, 3 follicular adenomas (FA), and 12 PTC. LOH of all informative loci on chromosome 3p was observed in all 6 FTC, but not in FA or PTC. No LOH was observed for loci mapped to chromosome 10 in PTC. Our results suggest: cytogenetic abnormalities of chromosome 10q are associated with PTC; cytogenetic and molecular abnormalities of chromosome 3 are associated with FTC; and a tumor suppressor gene may be present on the short arm of chromosome 3 important for the development or progression of FTC.

Cytogenetics of six follicular thyroid adenomas including a case report of an oxyphil variant with t(8;14)(q13;q24.1).

Cytogenetic analyses were performed on six follicular thyroid adenomas. Five had normal karyotypes and one, an oxyphil adenoma, had a t(8;14)(q13;q24.1). This patient also had a history of pleomorphic adenoma of the parotid gland. This clonal abnormality may suggest a primary genetic lesion in this patient who had two different benign neoplasms.

Abnormal chromosome in Prader-Willi syndrome.

A Prader-Willi Syndrome (PWS) patient was found to have an extra satellite chromosome, smaller than the normal Chromosome 22, in 60% of her metaphases. G- and C-bandings showed that the extra chromosome did not derive from a Chromosome 15 as has been reported in some PWS patients. Because of variation in chromosomal abnormalities in the PWS patients reported, it was concluded that the chromosomal abnormalities found in them may be a secondary phenomenon rather than the cause of PWS.

Abnormal chromosomes in histocytic lymphoma.

Five of six diffuse histocytic lymphoma patients had chromosomal abnormalities. Four had abnormal clones; three, a large acrocentric chromosome (LAC); and one, an abnormal large submetacentric chromosome (LSC). The LAC was a 14q+ and the LSC, a 4q+. Although no cytogenetic abnormality was found in a normal lymph node of a patient whose diseased lymph node had an LAC, abnormal chromosomes were seen in three patients with normal morphological bone marrow and in two peripheral blood specimens with a normal differential count. Since staging is important in aiding the clinician to select the type of treatment in this disease, it is recommended that cytogenetic studies in all biopsied tissues should be done as part of an overall diagnostic procedure in patients suspected of this disease.