[The PRKAG2 cardiac syndrome with familial hypertrophic cardiomyopathy: an inherited burden. A case report. Review of the literature]. / La cardiomyopathie hypertrophique familiale dans le contexte de la mutation PRKAG2 : un lourd héritage. A propos d'un cas. Revue de la littérature.

We report the case of a young man without prior medical history who presented with a left ventricular heart failure because of a new onset atrial fibrillation. The evolution is characterized by a sinus rythm dysfunction, a complete atrioventricular block, a non-sustained ventricular tachycardia (which required a dual-chamber defibrillator implantation) and an ischemic testicular necrosis treated by orchidectomy. After ruling out differential diagnosis we evoked an hypertrophic cardiomyopathy. Medical family anamnesis revealed an hereditary component, and we concluded to a PRKAG2 cardiac syndrome presenting as a familial hypertrophic cardiomyopathy. Two years later, he presented with a type B aortic dissection. We review the literature and differentials diagnosis.

Le cas que nous présentons est celui d'un jeune patient sans antécédent médical qui présente une décompensation cardiaque gauche sur fibrillation auriculaire de novo. L'évolution est caractérisée par une dysfonction sinusale, un bloc atrioventriculaire syncopal, de la tachycardie ventriculaire non soutenue avec nécessité d'implanter un défibrillateur double chambre et par une nécrose testiculaire d'origine ischémique indiquant une orchidectomie. Plusieurs diagnostics différentiels sont évoqués. Les investigations plus poussées mettent en évidence une cardiomyopathie hypertrophique jusqu'alors asymptomatique. L'anamnèse familiale révèle une composante héréditaire qui nous amènera à évoquer le diagnostic de cardiomyopathie hypertrophique familiale liée à la mutation PRKAG2. Deux ans plus tard, il se présente avec une dissection aortique de type B. La littérature concernant cette pathologie et les diagnostics différentiels sont revus à cette occasion.

Analysis of mammographic diagnostic errors in breast clinic.

Mammography is the gold standard for detection of early breast cancer and it is still the only diagnostic tool which shows reduction of the mortality from that. Despite that, there is a high chance of false negatives that can lead to diagnostic errors resulting in delays of treatment and worsening of prognosis. The aim of this study is to analyze the rate of false negative in mammography and assess the source of diagnostic errors. Two radiologists have retrospectively evaluated 500 mammograms performed between January 2008 and December 2011 in Breast Imaging Clinic. 250 patients (Group A) had been operated for breast cancer and 250 patients (Group B) were healthy woman submitted to mammography according to the guideline for early detection of breast cancer. In Group A, 138 patients (55.2 %) were true missed cancer, 61 had minimal sign (24.4 %) and 53 were false negative (FN) (20.4 %). The source of errors amongst the FN were in 42 % of cases due to perception, in 15 % to interpretation, in 10 % to subtle/unusual lesion characteristics, in 9 % error for satisfaction of search, in 7 % to inherent limitations of mammography, in 4 % to poor technique and 13 % for inadequate clinical management. The diagnostic errors in breast clinic services are not negligible. The largest number of FN results from perception errors, misinterpretation and inadequate clinical management. These can be related to factors such as inattention, fatigue or lack of experience. To reduce it, it is necessary to have a dedicated multidisciplinary staff and adequate equipment and workloads.

Varietal and pre-fermentative volatiles during ripening of Vitis vinifera cv Nebbiolo berries from three growing areas.

Flavour analysis of grape is a key step in quality evaluation. The Stir Bar Sorptive Extraction technique (SBSE, 'Twister'®) was used to assess varietal and pre-fermentative volatile accumulation in 'Nebbiolo' berries, from véraison to harvest. Grapes were collected in three vineyards, representing different 'crus' in the cultivation areas of Barolo, Barbaresco and Roero (North-West Italy). Volatile constituents of grapes were identified and quantified by GC-MS. We demonstrate the influence exerted by the growing location on volatile concentration and profile, as well as on the timing of volatile accumulation. The accumulation of certain classes of compounds, considered favourable for defining berry quality, followed common patterns, and was negatively correlated to that of compounds with herbaceous and grassy notes, such as the C6 compounds. PCA analysis shows that the concentrations of varietal and pre-fermentative volatiles were more effective in separating growing areas than dates of harvest. Grapes from the Barbaresco area, showing higher values of the concentration ratio between favourable and unfavourable compounds throughout ripening, could be statistically separated from grapes from the other areas.

[Granulicatella adiacens: an underestimated cause of endocarditis]. / Granulicatella adiacens: une cause sous-estimée d'endocardite.

We report the case of an old man who was affected by an endocarditis related to Granulicatella adiacens, an uncommon bacteria, difficult to isolate and responsible for an important morbidity and mortality. Thus, it is mandatory to seek for endocarditis when this germ is demonstrated in order to start quickly an effective antibiotic treatment. Inversely, in the presence of unexplained endocarditis, further bacteriological investigations are needed to seek for this life nutrition deficient bacteria.

Breast cancer and primary systemic therapy. Results of the Consensus Meeting on the recommendations for pathological examination and histological report of breast cancer specimens in the Marche Region.

Primary systemic therapy (PST) adds some practical problems to the pathologic examination of neoplastic breast tissue obtained from patients before and after chemotherapy. Pathologists, oncologists, breast surgeons, radiotherapists and radiologists in the Marche Region held a Consensus Meeting in Ancona on May 13, 2010, in which 15 statements dealing with neoadjuvant chemotherapy were approved by all participants. The first two statements are related to the pre-PST phase and concern the technical procedures and the histological report of the core biopsy. The other statements deal with similar issues of the post-PST surgical specimen.

Exhaled nitric oxide as a marker of asthma control in smoking patients.

Exhaled nitric oxide fraction (F(eNO)), which is a reliable marker of eosinophilic airway inflammation, is partially suppressed by tobacco smoking. Consequently, its potential as a biomarker in asthma management has never been evaluated in smoking patients. In the present study, the authors tested the validity of F(eNO) to predict asthma control in this population. F(eNO) and the Asthma Control Questionnaire (ACQ) were recorded at least once in 411 nonsmoking (345 with at least two visits) and 59 smoking (51 with at least two visits) asthma patients. Despite similar mean ACQ scores (1.5 versus 1.7), F(eNO) was reduced in smoking asthmatics (18.1 ppb versus 33.7 ppb). A decrease in F(eNO) of <20% precludes asthma control improvement in nonsmoking (negative predictive value (NPV) 78%) and in smoking patients (NPV 72%). An increase in F(eNO) <30% is unlikely to be associated with deterioration in asthma control in both groups of patients (NPV = 86% and 84% in nonsmoking and smoking patients, respectively). It is concluded that, even in smokers, sequential changes in F(eNO) have a relationship with asthma control. The present study is the first to indicate that cigarette smoking does not obviate the clinical value of measuring F(eNO) in asthma among smokers.

Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients.

Controlled studies have shown that monitoring of the exhaled nitric oxide fraction (F(eNO)) improves asthma management. However, the studies seldom consider the full range of patients seen in clinical practise. In the present study, the ability of F(eNO) to reflect asthma control over time is investigated in a regular clinical setting, and meaningful F(eNO) cut-off points and changes are identified. Answers to the Asthma Control Questionnaire and F(eNO) were recorded at least once in 341 unselected asthma patients. The whole population and subgroups were considered, i.e. both inhaled corticosteroid (ICS)-naïve and low or high-to-medium (500 mug beclomethasone dipropionate equivalents.day(-1)) ICS-dose groups. An F(eNO) decrease <40% or increase <30% precludes asthma control optimisation or deterioration, respectively (negative predictive value 79 and 82%, respectively). In the present study's low-dose group, a decrease >40% indicated asthma control optimisation (positive predictive value (PPV) 83%). In ICS-naïve patients, F(eNO) >35 ppb predicted asthma control improvement in response to ICS (PPV 68%). In most cases, forced expiratory volume in one second assessments were not useful. In conclusion, in a given patient, exhaled nitric oxide fraction was found to be significantly related to asthma control over time. The overall ability of exhaled nitric oxide fraction to reflect asthma control was reduced in patients using high doses of inhaled corticosteroids. Forced expiratory volume in one second had little additional value in assessing asthma control.

Paradoxical worsening of tuberculosis in a heart-lung transplant recipient.

UNLABELLED: We report on a heart-lung transplant recipient who presented with pulmonary tuberculosis (TB) 2.5 months after transplantation and then developed a paradoxical reaction after 4 months of adequate anti-TB treatment. She eventually recovered with anti-TB and high-dose steroid treatments. METHODS: Using sequential bronchoalveolar lavages, we assessed the inflammatory response in the lung and investigated the alveolar immune response against a Mycobacterium tuberculosis antigen. RESULTS: The paradoxical reaction was characterized by a massive infiltration of the alveolar space by M. tuberculosis antigen-specific CD4(+) T cells and by the presence of a CD4(-)CD8(-) T lymphocyte subpopulation bearing phenotypic markers (CD16(+)/56(+)) classically associated with NK cells. CONCLUSION: This case report illustrates that even solid organ transplant recipients receiving intense triple-drug immune suppression may be able to develop a paradoxical reaction during TB treatment. Transplant physicians should be aware of this phenomenon in order to differentiate it from treatment failure.

Beneficial effects of atorvastatin on sd LDL and LDL phenotype B in statin-naive patients and patients previously treated with simvastatin or pravastatin.

BACKGROUND: The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. METHODS: Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy (n=33), or as replacement therapy (n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment. RESULTS: In addition to the expected LDL-C decrease (-34%; p<0.0001), a major reduction in sd LDL occurred after atorvastatin therapy (-38.2%; p<0.0001). Interestingly, sd LDL decreased as much in patients previously treated with other statins (-36%; p<0.002). A close correlation (r=0.89, p<0.001) was found between reduction of sd LDL and that of LDL-C, in patients with phenotype B. Although high-density lipoprotein-cholesterol (HDL-C) was not affected by atorvastatin treatment, plasma triglycerides decreased by 27.4% (p<0.0001). Only a weak correlation (r=0.35, p<0.01) was found between the reduction of plasma triglycerides and the decrease of sd LDL after atorvastatin treatment. CONCLUSION: These results show that the reduction of LDL-C by atorvastatin largely reflects a lowering of sd LDL. Our data also suggest that triglyceride lowering plays only a partial role in sd LDL reduction.

Early invasive strategy in elderly patients with non-ST elevation acute coronary syndrome: comparison with younger patients regarding 30 day and long term outcome.

OBJECTIVES: To evaluate an early invasive strategy in elderly patients with non-ST elevation acute coronary syndrome (ACS). METHODS: All consecutive patients admitted with a diagnosis of non-ST elevation ACS from June 2002 to February 2004 were enrolled in this registry. Clinical outcome was assessed at 30 days and in long term follow up. RESULTS: An early invasive strategy was followed for 439 patients, of whom 159 (36%) were elderly and had a higher clinical risk profile and greater extent of coronary artery disease (CAD) than the younger patients. Coronary revascularisation was conducted in 133 (83%) elderly patients and 239 (85%) younger patients (not significant). At a mean (SD) follow up time of 10.7 (5.2) months overall mortality, cardiac death, and death plus myocardial infarction were significantly higher among elderly patients than among younger patients (9.4% v 2.1%, p < 0.001; 6.8% v 1.8%, p < 0.01; 11.3% v 5%, p = 0.02, respectively). The significant difference in cardiac death between the two groups was related more to elderly patients being treated by coronary artery bypass grafting (19.3% v 4.9%, p = 0.05) than by percutaneous coronary intervention (PCI) (2.9% v 1.1%, p = 0.3). Cox regression analysis showed age, serum creatinine > 115 micromol/l, no previous history of CAD, left ventricular ejection fraction > 45%, and the absence of diabetes to be independent predictors of the occurrence of major adverse cardiac events. CONCLUSIONS: In unselected elderly patients presenting with non-ST elevation ACS an early invasive strategy is feasible and leads to coronary revascularisation in the majority of cases, resulting in encouraging immediate and long term clinical results, particularly among PCI treated patients.

[Cardiac magnetic resonance. Myth and reality]. / IRM cardiaque. Mythes et réalités.

The authors report their own experience and a review of the current literature in the field of cardiac MR (CMR). Latest technical improvements now allow obtaining both anatomical and functional imaging of the beating heart and great vessels in most pathological conditions. Established CMR indications such as cardiac tumors, pericardial diseases, operated congenital heart diseases, valvular diseases, arythmogenic right ventricular dysplasia, specific cardiomyopathies and great vessels of the thorax are reviewed and updated. Current applications in post myocardial infarction such as perfusion and viability imaging sequences are described. Moreover, CMR applications in syndrome X and myocarditis are evoked. Medical contra-indications and technical limitations of CMR are also discussed. Finally, the authors insist on the interest of a real partnership between radiologists and cardiologists for these procedures.

Localized renal cell carcinoma of an unusually large size: case report.

Renal cell carcinoma has a variable clinical course. Size is a prognostic factor correlated with venous invasion, lymph node or distant metastases. These are more often encountered when the size exceeds 10 cm. For 20 years, incidental renal tumours have represented the majority of diagnosed cases, as a result of more common use of imaging techniques. We report a case of renal cell carcinoma of an unusually large size, without metastatic or locally advanced disease. Histology revealed a pT2 clear cell renal cell carcinoma of 31 x 31 x 10 cm, which was totally resected. It is the first case reported of localized conventional renal cell carcinoma reaching such a size.

Mucocele-like tumour of the breast.

Mucocele-like (ML) lesions of the breast are rare tumours and were reported as benign lesions that histologically resembled colloid carcinoma of the breast when first described about sixteen years ago. Only subsequent reports identified ML lesions associated with ductal hyperplasia or carcinoma. The Authors report an additional case of ML tumour of the breast and review the available medical literature. A young asymptomatic woman, without family history of breast cancer, presented with a palpable breast mass. As the radiological aspect was not typical of a simple cyst, the patient underwent a fine needle aspiration biopsy which showed a doubtful pathological pattern compatible with fibroadenoma. The patient underwent surgery and the gross examination of the surgically removed mass revealed multiple aggregated cysts containing mucinous material. Microscopic examination showed a ML tumour of the breast, with aspects of cribriform ductal hyperplasia.

Reverse fasciosubcutaneous flap versus distally pedicled sural island flap: two elective methods for distal-third leg reconstruction.

In case of soft-tissue injury to the distal third of the leg, a safe and effective repair technique should be adopted. The use of complex procedures such as free flaps and cross-leg flaps is not always advisable. The authors present two methods that have proved to be both reliable and effective in obtaining long-lasting satisfactory results: the reverse fasciosubcutaneous sural flap and the reverse fasciocutaneous island sural flap. Since 1992 the authors have operated on 25 patients affected by traumatic tissue loss of the distal third of the leg and the calcaneal region. They used the fasciosubcutaneous flap in 14 patients and the sural flap in 11. Both of these flaps are technically simple, safe, and effective, and cause minimal injury to the donor site. The sural flaps are more useful for moderate-size wounds, especially in the calcaneal region, whereas the fasciosubcutaneous flap is better for repairing larger lesions of the leg and the ankle.

Early effect of ultrarush venom immunotherapy on the IgG antibody response.

BACKGROUND: We have previously shown in several allergy models that allergic and tolerance status with respect to allergens is associated with a somewhat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunotherapy (VIT), which induces clinical tolerance after only a few hours of treatment. METHODS: Antibody titers and specificity were evaluated through solid-phase ELISA using streptavidin-biotin technology in 12 patients allergic to wasp venom before and during the ultrarush procedure (at 12 h, 24 h, and 15 days). The results were compared with those from another group of 20 patients treated with venom injections for at least 2 years. RESULTS: No significant change was observed in IgG titers during the early phase of VIT. The capacity of individual sera to prevent the antigen binding of pooled IgG from allergic patients changed rapidly, with mean percentage inhibitions falling from 80+/-15%, before starting VIT, to 26+/-14%, 35+/-15%, and 34+/-5% after 12 h, 24 h, and 15 days of treatment, respectively (P<0.001 by one-way ANOVA). The capacity of individual sera to prevent the antigen binding of pooled IgG from patients receiving prolonged VIT changed, with mean percent inhibitions increasing from 47+/-8%, before starting VIT, to 76+/-7%, 83+/-6%, and 87+/-6% after 12 h, 24 h, and 15 days of treatment, respectively (P<0.001 by one-way ANOVA). CONCLUSIONS: During the initial phase of ultrarush VIT, a change in IgG specificity, i.e., a change in the set of epitopes dominantly recognized by IgG on wasp-venom antigens, occurred concomitantly with early clinical tolerance and was already detectable a few hours after the onset of treatment. Although it may be an epiphenomenon, this change represents the earliest humoral modification described so far during this procedure. The mechanism is unknown, but it appears to be a selective depletion of the highest avidity antibody fraction by the venom injected in large doses at this stage of therapy. Finally, our data now show the previously documented association between a particular IgG specificity and the clinical status (allergy vs tolerance) to be true also with ultrarush VIT, a model in which the clinical ability to display allergic symptoms is rapidly reversed.

Absence of nitrate tolerance after long-term treatment with ramipril: an endothelium-dependent mechanism.

To determine whether nitrate tolerance is attenuated on aortas isolated from rats treated in the long term with an angiotensin-converting enzyme (ACE) inhibitor, five groups of rats were studied in parallel. Group 1 received ramipril, 1 mg/ kg/day, p.o., for 6 weeks; group 2 received ramipril at the same dose for 4 weeks, and the last 2 weeks, a cotreatment with ramipril plus HOE 140 (a bradykinin B2 antagonist, 500 microg/ kg/day, s.c. injections); group 3 received losartan, 2 mg/kg/day, p.o., for 6 weeks; group 4 received losartan at the same dose, and the last 2 weeks, a cotreatment with losartan plus HOE 140; and group 5 served as control. Rings of thoracic aorta from these groups were studied in organ baths. After nitroglycerin preincubation (10 microM for 30 min) in vitro, the dose-response curves to nitroglycerin were significantly shifted to the right in the control group but not in group 1. This protective effect was partially present in group 3; it was completely abolished in groups 2 and 4. In groups 1 and 3, it also was abolished after nitric oxide synthase (cNOS) inhibition (L-NMMA incubation) or removal of the endothelium. Superoxide anion accumulation (assessed by lucigenin chemiluminescence) was increased by nitroglycerin incubation in the control group but not in groups 1 and 3. After in vivo exposure to nitroglycerin (50 mg/kg subcutaneously twice daily for 4 days), this protection against nitrate tolerance also was observed in groups 1 and 3. Thus long-term ACE inhibition prevents nitrate tolerance by an endothelium-dependent mechanism involving mainly an enhanced NO availability via B2-kinin receptor. This effect on the cNOS pathway seems to attenuate the superoxide anion accumulation induced by nitroglycerin exposure (probably via a downregulation of oxidative enzyme).

[Case of cardiac amyloidosis associated with IgG-K multiple myeloma in the framework of restrictive myocardiopathy]. / Caso di amiloidosi cardiaca, in mieloma multiplo IgG-K secernente, con quadro di miocardiopatia restrittiva.

Primary amyloidosis, due to amassing of fragments of light chains of IgG, often causes cardiac involvement. We describe a 65-year-old woman with multiple myeloma efficaciously treated with chemotherapy. Amyloidosis had been supported by myelic biopsy. The patient came to our observation because of right heart failure, hypotension and syncope: she was treated with a dopamine i.v. and was in cachectic status. She had a moderate pericardial effusion. ECG showed reduction of QRS amplitude, I degree atrioventricular block, posterior fascicular and right bundle branch block. Right cardiac catheterization showed a restrictive situation. After 1 week exitus occurred by asystole. In this case, there were other involvements by amyloidosis, besides the cardia one: that of autonomic nervous system and, probably, surrenal.

Modified antigenic reactivity of anti-phospholipase A2 IgG antibodies in patients allergic to bee venom: conversion with immunotherapy and relation to subclass expression.

BACKGROUND: We have previously reported that, in addition to modifying IgG levels and subclass distributions, wasp venom immunotherapy (VIT) rapidly changes IgG antibody specificity. OBJECTIVES: We investigated whether such a change can be documented in the IgG response to the major bee venom allergen, phospholipase A2 (PLA2), from patients allergic to bees treated with VIT; whether it is coupled to the shift in IgG subclass distribution (IgG4 predominance) usually observed during VIT; and whether it restores the specificity displayed by IgG antibodies from nonallergic individuals. METHODS: Antibody specificity was evaluated in 17 patients allergic to bee venom in competitive ELISAs by using streptavidin biotin technology. Patients were tested before and during specific immunotherapy (at 15 days and 6 months) and compared with another group of 17 patients treated with venom injections for at least 2 years (VIT patients) and 30 healthy individuals. RESULTS: The capacity of individual sera to prevent PLA2 binding of pooled IgG from allergic patients changed rapidly with mean percentage inhibitions falling from 84% +/- 14% before starting VIT to 27% +/- 13% and 28% +/- 7% after 15 days and 6 months of treatment, respectively (p < 0.001 by one-way analysis of variance [ANOVA]). IgG titers were only slightly increased. The capacity of individual sera to prevent the binding of pooled IgG from patients receiving VIT changed rapidly with mean percentage inhibition increasing from 60% +/- 12% before starting VIT to 85% +/- 6% and 82% +/- 6% after 15 days and 6 months of treatment, respectively (p < 0.001 by one-way ANOVA). Similar results were found regardless of whether pooled IgG1 or pooled IgG4 were used. CONCLUSION: VIT results in a rapid change in the antigenic reactivity of anti-PLA2 IgG antibody of human allergic sera, restoring, although not completely, the specificity peculiar to lgG from healthy individuals. This suggests that allergic status and immunoprotection correlate with the preferential expression of distinct IgG specificities, which appear equally distributed over the IgG1 and IgG4 antibody subclasses. It is, however, not known whether the shift in IgG specificity is one of the operative mechanisms of VIT.