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1.

Background

Patients with Fabry disease (FD) develop progressive left ventricular hypertrophy (LVH). In screening studies in patients with LVH, the prevalence of FD ranges from 0 to 12%. This variability is attributable to different factors like diverging inclusion and exclusion criteria, the evaluation of selected populations and suboptimal screening methods.In this study, we aimed to determine the prevalence of FD in an unselected population of everyday clinical practice presenting LVH, defined as a maximal end-diastolic septal or posterior wall thickness ≥ 13 mm, without exclusion of patients with arterial hypertension or valvular pathology, and using optimal screening methods.

Methods

In adult males, a two-tier approach was used; α-Galactosidase A (aGAL A) activity was measured using a dried bloodspot test (DBS) and diagnosis was confirmed by mutation analysis of the GLA gene. In females, mutation analysis was the primary screening tool.

Results

362 men and 178 women were screened. Six patients were diagnosed with a genetic sequence alteration of the GLA gene. One man had a novel mutation, GLA p.Ala5Glu (c.44C > A), presenting as classical FD. Another man and three women had the previously described GLA p.Ala143Thr (c.427G > A) mutation, which generally presents as an attenuated phenotype. One woman had a novel sequence alteration c.639 + 6A > C, which appeared to be a polymorphism. All true Fabry patients had arterial hypertension (AHT), and one had hypertrophic obstructive cardiomyopathy (HOCM).

Conclusions

In a group of unselected patients with LVH, we found a prevalence of Fabry disease of 0.9%. AHT or type of hypertrophy should not be an exclusion criterion for screening for FD.  相似文献   

2.

Introduction and objectives

Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM.

Methods

We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied.

Results

The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, –17.52 to –6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, –14.49 to –1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables.

Conclusions

Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations.Full English text available from: www.revespcardiol.org/en  相似文献   

3.

Introduction

We report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal.

Methods

A direct invitation to participate was sent to cardiology departments. Baseline and outcome data were collected.

Results

A total of 29 centers participated and 1042 patients were recruited. Four centers recruited 49% of the patients, of whom 59% were male, and mean age at diagnosis was 53±16 years. Hypertrophic cardiomyopathy (HCM) was identified as familial in 33%. The major reason for diagnosis was symptoms (53%). HCM was obstructive in 35% of cases and genetic testing was performed in 51%. Invasive septal reduction therapy was offered to 8% (23% of obstructive patients). Most patients (84%) had an estimated five-year risk of sudden death of <6%. Thirteen percent received an implantable cardioverter-defibrillator. After a median follow-up of 3.3 years (interquartile range [P25-P75] 1.3-6.5 years), 31% were asymptomatic. All-cause mortality was 1.19%/year and cardiovascular mortality 0.65%/year. The incidence of heart failure-related death was 0.25%/year, of sudden cardiac death 0.22%/year and of stroke-related death 0.04%/year. Heart failure-related death plus heart transplantation occurred in 0.27%/year and sudden cardiac death plus equivalents occurred in 0.53%/year.

Conclusions

Contemporary HCM in Portugal is characterized by relatively advanced age at diagnosis, and a high proportion of invasive treatment of obstructive forms. Long-term mortality is low; heart failure is the most common cause of death followed by sudden cardiac death. However, the burden of morbidity remains considerable, emphasizing the need for disease-specific treatments that impact the natural history of the disease.  相似文献   

4.

Background

Fabry disease is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these 2 diseases diverge, with Fabry disease–specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy.

Methods

We studied a prospectively assembled consecutive cohort of 585 patients (71% male) from 2 hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α-galactosidase A activity levels and all females were tested for mutations in the GLA gene.

Results

In 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified 2 unrelated patients (0.34%), both with the GLA mutation encoding P.N215S, the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a man aged 53 years and a woman aged 69 years, and demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy. After family screening, a total of 27 new Fabry disease patients aged 2-81 years were identified in the 2 families, including 12 individuals who are now receiving enzyme replacement therapy.

Conclusions

These observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease–affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy.  相似文献   

5.

Introduction

Prompt identification of higher-risk patients presenting with ST-segment elevation myocardial infarction (STEMI) is crucial to pursue a more aggressive approach.

Objective

We aimed to assess whether the modified shock index (MSI), the ratio of heart rate to mean arterial pressure, could predict six-month mortality among patients admitted with STEMI.

Methods

A retrospective observational cohort study was performed in a single center including 1158 patients diagnosed with STEMI, without cardiogenic shock on admission, between July 2009 and December 2014. They were divided into two groups: group 1 – patients with MSI <0.93 (72%); group 2 – patients with MSI≥0.93 (28%). The primary endpoint was six-month all-cause mortality.

Results

MSI≥0.93 identified patients who were more likely to have signs of heart failure (p=0.002), anemia (p<0.001), renal insufficiency (p=0.014) and left ventricular systolic dysfunction (p=0.045). They more often required inotropic support (p<0.001), intra-aortic balloon pump (p<0.001) and mechanical ventilation (p<0.001). Regarding in-hospital adverse events, they had a higher prevalence of malignant arrhythmias (p=0.01) and mechanical complications (p=0.027). MSI≥0.93 was an independent predictor of overall six-month mortality (adjusted HR 2.00, 95% CI 1.20-3.34, p=0.008).

Conclusion

MSI was shown to be a valuable bedside tool which can rapidly identify high-risk STEMI patients at presentation.  相似文献   

6.

Background

In recent years, the prevalence of asthma has risen in developed countries, and its extent related to a change in our indigenous microbiota. Helicobacter pylori disappearance across the population represents a fundamental change in our human microbiota and has preceded the rise in asthma prevalence.

Objective

To assess the relationship between childhood asthma and Helicobacter pylori infection.

Methods

Quantitative determination of Helicobacter pylori IgG among 90 asthmatic children and 90 – age and gender – matched non-atopic, non-asthmatic healthy children was performed using ELISA in serum of all participants.

Results

Helicobacter pylori IgG seropositivity was found in 25.6% of asthmatics compared to 44.4% of controls. Asthmatics showed lower median Helicobacter pylori IgG titre compared to healthy controls. We also detected a significant inverse relationship between Helicobacter pylori IgG titre and asthma severity.

Conclusion

Helicobacter pylori seropositivity protects against childhood asthma and inversely correlates to its clinical and functional severity.  相似文献   

7.

Introduction and objectives

The number of older patients with congestive heart failure has dramatically increased. Because of stagnating cardiac transplantation, there is a need for an alternative therapy, which would solve the problem of insufficient donor organ supply. Left ventricular assist devices (LVADs) have recently become more commonly used as destination therapy (DT). Assuming that older patients show a higher risk-profile for LVAD surgery, it is expected that the increasing use of less invasive surgery (LIS) LVAD implantation will improve postoperative outcomes. Thus, this study aimed to assess the outcomes of LIS-LVAD implantation in DT patients.

Methods

We performed a prospective analysis of 2-year outcomes in 46 consecutive end-stage heart failure patients older than 60 years, who underwent LVAD implantation (HVAD, HeartWare) for DT in our institution between 2011 and 2013. The patients were divided into 2 groups according to the surgical implantation technique: LIS (n = 20) vs conventional (n = 26).

Results

There was no statistically significant difference in 2-year survival rates between the 2 groups, but the LIS group showed a tendency to improved patient outcome in 85.0% vs 69.2% (P = .302). Moreover, the incidence of postoperative bleeding was minor in LIS patients (0% in the LIS group vs 26.9% in the conventional surgery group, P < .05), who also showed lower rates of postoperative extended inotropic support (15.0% in the LIS group vs 46.2% in the conventional surgery group, P < .05).

Conclusions

Our data indicate that DT patients with LIS-LVAD implantation showed a lower incidence of postoperative bleeding, a reduced need for inotropic support, and a tendency to lower mortality compared with patients treated with the conventional surgical technique.Full English text available from: www.revespcardiol.org/en  相似文献   

8.

Introduction and objectives

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by polymorphic or bidirectional ventricular arrhythmias (VA) triggered by physical or emotional stress in young people with a structurally normal heart. Beta-blockers are the cornerstone of treatment, while flecainide has recently been incorporated into the therapeutic arsenal. The aim of this study was to report our experience with this drug.

Methods

The cohort included 174 genotype-positive CPVT-patients from 7 families. We collected data from patients who were receiving flecainide and analyzed the indications, adverse effects and dosage, clinical events, VA and arrhythmic window during exercise testing, and implantable cardioverter-defibrillator (ICD) shocks during follow-up.

Results

Eighteen patients (10.4%) received flecainide; 17 patients in combination with beta-blockers, and 1 patient as monotherapy due to beta-blocker intolerance. None of the patients presented side effects. In 13 patients (72.2%) the indication was the persistence of exercise-induced VA and in 5 patients (27.7%) persistent ICD-shocks, despite on beta-blockers. After flecainide initiation, the exercise-induced VA quantitative score was reduced by more than 50% in 66.7% of the members of family 1 (32.76 ± 84.06 vs 74.38 ± 153.86; P = .018). The arrhythmic window was reduced (5.8 ± 11.9 bpm vs 19.69 ± 21.27 bpm; P = .007), and 4 of 5 patients with appropriate ICD shocks experienced no further shocks in the follow-up.

Conclusions

In CPVT-patients flecainide reduces clinical events, exercise-induced VA, the arrhythmic window, and ICD shocks, with good tolerance.Full English text available from:www.revespcardiol.org/en  相似文献   

9.

Introduction

Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil.

Methods

A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul – Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment.

Results

A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p?=?0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p?=?0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p?=?0.047).

Conclusion

The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.  相似文献   

10.

Background

Probiotics have beneficial effect on obesity related disorders in animal models. Despite a large number of animal data, randomized placebo-controlled trials (RCT) concluded that probiotics have a moderate effect on glycemic control-related parameters. However, effect of probiotics on insulin resistance are inconsistent.

Aim

In a double-blind single center RCT, effect of alive multistrain probiotic vs. placebo on insulin resistance in type 2 diabetes patient were assessed.

Methods

A total of 53 patients met the criteria for inclusion. They were randomly assigned to receive multiprobiotic “Symbiter” (concentrated biomass of 14 probiotic bacteria genera Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium) or placebo for 8-weeks administered as a sachet formulation. The primary main outcome was the change HOMA-IR (homeostasis model assessment-estimated insulin resistance) which calculated using Matthews et al.’s equation. Secondary outcomes were the changes in glycemic control-related parameters, anthropomorphic variables and cytokines.

Results

Supplementation with alive multiprobiotic for 8 weeks was associated with significant reduction of HOMA-IR from 6.85?±?0.76 to 5.13?±?0.49 (p?=?0.047), but remained static in the placebo group. With respect to our secondary outcomes, HbA1c insignificant decreased by 0.09% (p?=?0.383) and 0.24% (p?=?0.068) respectively in placebo and probiotics groups. However, in probiotic responders (n?=?22, patient with decrease in HOMA-IR) after supplementation a significant reduction in HbA1c by 0.39% (p?=?0.022) as compared to non-responders was observed. In addition, from markers of chronic systemic inflammatory state only TNF-α and IL-1β changes significantly after treatment with probiotics.

Conclusion

Probiotic therapies modestly improved insulin resistance in patients with type 2 diabetes.  相似文献   

11.

Introduction

Fabry disease (FD) is a hereditary disorder caused by a deficiency of α-galactosidase A enzyme activity. The transmission of the disorder is linked to the X chromosome.

Objectives

The objectives of the study were: 1. To quantify the presence of podocytes in paediatric patients with FD and compare them with the value of the measured podocyturia in healthy controls. 2. To determine whether a greater podocyturia is related to the onset of pathological albuminuria in patients with FD. 3. To determine the risk factors associated with pathological albuminuria.

Methods

We performed an analytical, observational study of Fabry and control subjects, which were separated into 2 groups in accordance with the absence of the disease (control group) or the presence of the disease (Fabry group).

Results

We studied 31 patients, 11 with FD and 20 controls, with a mean age of 11.6 years.The difference between the mean time elapsed from the diagnosis of FD to the measurement of podocyturia (40 months) and the onset of pathological albuminuria (34 months) was not significant (p = 0.09). Podocytes were identified by staining for the presence of synaptopodin and the mean quantitative differences between both podocyturias were statistically significant (p = 0.001). Albuminuria was physiological in 4 of the patients with FD and the relative risk to develop pathological albuminuria according to podocyturia was 1.1 in the control group and 3.9 in the Fabry group, with a coefficient of correlation between podocyturia and albuminuria in the Fabry group of 0.8354. Finally, the 2 risk factors associated with the development of pathological albuminuria were podocyturia (OR: 14) and being aged over 10 years (OR: 18). We found no significant risk with regard to glomerular filtrate renal (GFR) (OR: 0.5) or gender (OR: 1.3). The mean GFR remained within normal values.

Conclusion

The detection of podocyturia in paediatric patients with FD could be used as an early marker of renal damage, preceding and proportional to the occurrence of pathological albuminuria.  相似文献   

12.

Background

There are very few data available regarding risk factors associated with antibiotic resistant-Neisseria gonorrhoeae.

Methods

A study was conducted on 110 samples from 101 patients with gonococcal infection, in order to describe their characteristics and compare them with the antimicrobial susceptibility profile of their samples.

Results

An association was observed between resistant infections and heterosexual men, older age, concurrent sexually transmitted infection, and unsafe sexual behaviors.

Conclusion

There is a need for improved data on the risk factors associated with antibiotic resistant gonococcal infection in order to identify risk groups, and to propose public health strategies to control this infection.  相似文献   

13.

Introduction

Fabry disease is a lysosomal storage disorder linked to an alpha-galactosidase A deficiency that can lead to heart and kidney failure. There is little data about the prognosis of patients who undergo a combined heart and kidney transplantation.

Case reports

Two brothers who were diagnosed with Fabry disease after the age of 30 years underwent a combined heart and kidney transplantation at respectively 49 and 42 years of age because of a severe hypertrophic cardiomyopathy with end stage renal failure. They are alive respectively 4 and 9 years after the transplantation. No recurrence of the disease in the transplanted organs has been found.

Conclusion

Combined heart and kidney transplantation in Fabry disease is an efficient therapy for the cardiomyopathy and kidney failure. Its prognosis can be good when the patients are carefully selected. However, an early diagnosis is critical in order to avoid a procedure associated with a high perioperative mortality.  相似文献   

14.

Introduction

Our main objective was a revision of clinical, microbiological and epidemiological results of Clostridium difficile-associated infection in paediatric patients (2010-2015). We compared the diagnoses performed by detection of toxins in feces and those performed by real-time PCR.

Methods

This retrospective study included 82 paediatric patients. Detection of toxigenic C. difficile was performed sequentially, in diarrheal feces and under clinical request.

Results

A total of 39% of the patients were attended at Haematology-oncology Unit and >50% of them had previously received cephalosporins. Fever associated with diarrhea was more frequent in the group of toxin detection, whereas not receiving specific antibiotic treatment was more frequent in the group of positive PCR, without statistically significant differences.

Conclusions

We highlight the presence of C. difficile infection in children under 2 years old. A diagnostic testing in selected paediatric patients would be advisable when there is clinical suspicion of infection.  相似文献   

15.

Background

Ashwagandha (Withania somnifera Linn.) a rejuvenative herb has long been used as an immunomodulator in Indian subcontinent. As immunity plays an important role in pathogenesis and treatment of tuberculosis (TB), so role of W. somnifera as an adjuvant has been studied on selected parameter.

Method

A randomized, double-blind placebo-control study was conducted in two groups of 60 newly diagnosed sputum smear positive pulmonary TB patients on Directly Observed Treatment – short course (DOTS) regime. W. somnifera root extract or placebo capsules were given as add-on therapy for duration of 12 weeks. Effects on sputum conversion, Hemoglobin (Hb), body weight, Erythrocyte Sedimentation Rate (ESR), RBC counts, WBC counts, CD4 and CD8 counts, Serum Glutamic-Oxaloacetic Transaminase (SGOT), Serum Glutamic-Pyruvic Transaminase (SGPT), serum uric acid and HRQL (Health Related Quality of Life) Index scores were studied.

Results

At the end of 8 weeks, sputum conversion was seen in 86.6% patients in study group and 76.6% in placebo group. At the end of 12 weeks a highly significant increase was seen in both CD4 and CD8 counts in study group. A raised SGOT and SGPT levels (>35 IU/L) were observed in 16.6% and 33.3% patients in study group; 43.33% and 53.33% in the placebo group of patients. Elevated serum uric acid levels (>6 mg/dl) were observed in 20% and 33.33% in study and placebo group respectively. Average gain in HRQL score was better in patients of study group.

Conclusion

Use of W. somnifera as an adjuvant in conjunction with anti-TB drugs used as DOTS showed a favorable effect on symptoms and immunological parameters in patients with pulmonary TB.  相似文献   

16.
17.
18.

Introduction

Staphylococcus spp. – both S. aureus, including methicillin-resistant strains (MRSA) and coagulase negative staphylococci (CoNS) – are relevant agents of healthcare-associated infections. Therefore, the rapid recognition of MRSA and methicillin-resistant CoNS from blood stream infections is critically important for patient management. It is worth noting that inappropriate empiric therapy has been associated with higher in-hospital mortality.

Material and methods

In this study we evaluated a multiplex polymerase chain reaction (multiplex PCR) standardized to detect Staphylococcus spp., S. aureus, and mecA gene-encoded oxacillin resistance directly from blood culture bottles. A total of 371 blood cultures with Gram-positive microorganisms confirmed by Gram-stain were analyzed. Results from multiplex PCR were compared to phenotypic characterization of isolates.

Results

Staphylococcus aureus was detected in 85 (23.0%) blood cultures and CoNS in 286 (77.0%). There was 100% agreement between phenotypic and multiplex PCR identification. Forty-three (50.6%) of the 85 S. aureus carried the mecA gene and among the 286 CoNS, 225 (78.7%) were positive for the mecA gene.

Conclusions

The multiplex PCR assay developed here was found to be sensitive, specific, rapid, and showed good agreement with the phenotypic results besides being less expensive. This PCR method could be used in clinical laboratories for rapid identification and initiation of specific and effective treatment, reducing patient mortality and morbidity. Furthermore, this method may reduce misuse of antimicrobial classes that are more expensive and toxic, thus contributing to the selection of antibiotic-resistant Staphylococcus spp.  相似文献   

19.
20.

Introduction

Allergic diseases have become an increasingly common reality in the last years, extending beyond the family context.

Objective

Assessing the level of knowledge on asthma, food allergies and anaphylaxis of asthmatic children's parents/caregivers (PC), elementary school teachers (EST) and university students (US) in Uruguaiana, RS, Brazil.

Method

577 individuals (PC – N = 111; EST – N = 177; US – N = 299) took part in the study, answering the Newcastle Asthma Knowledge Questionnaire (validated for Portuguese) and another questionnaire on Food Allergy (FA) and anaphylaxis.

Results

Although PC have asthmatic children, their asthma knowledge level was average, slightly above that of EST and EU. The lack of knowledge on passive smoking, use of medications and their side effects should be highlighted. US have shown to be better informed about FA and anaphylaxis. However, even though a significant proportion of respondents know the most common symptoms of FA and anaphylaxis, few named subcutaneous adrenaline as the drug of choice for treating anaphylaxis. Although a significant number of respondents know about the possibility of anaphylactic reactions happening at school or in activities outside the school, we were surprised by the absence of conditions in schools to provide emergency care to such students.

Conclusion

Despite the high prevalence of allergic diseases in childhood, asthmatic children's parents/caregivers, elementary school teachers and university students have inadequate levels of knowledge to monitor these patients.  相似文献   

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