Infertility and hypergonadotropic hypogonadism as first evidence of hereditary apolipoprotein A-I amyloidosis

Purpose: We report that primary infertility and hypergonadotropic hypogonadism in young patients may be caused by testicular amyloidosis and it is associated with the presence of a mutation in the apoA-I gene, resulting in the replacement of proline for leucine at residue 75 of the protein. Materials and Methods: Ten patients presenting with infertility, gynecomastia, decreased libido, erectile dysfunction or a family history of amyloidosis underwent clinical evaluation, hormone assays, semen analysis, ultrasonographic investigation of the testicles, testicular biopsy and DNA sequencing of the apoA-I gene. Results: All patients showed azoospermia and 9 had increased testicular volume. Massive amyloid deposition was observed in all testicular biopsies and the apoA-I mutation of replacement of proline for leucine at residue 75 of the protein was noted. Five patients showed hypergonadotropic hypogonadism and 5 had normal testosterone values with high gonadotropin levels. Conclusions: Nonobstructive azoospermia and macro-orchidism with or without hypogonadism may be caused by hereditary apoA-I amyloidosis in young patients. Testicular amyloidosis can be the first manifestation of this systemic disease. Specific staining for amyloid deposits and genetic analysis of apoA-I mutations are recommended in young, infertile patients with macro-orchidism. Finally, surveillance in asymptomatic mutation carriers is suggested to evaluate the opportunity to implement sperm retrieval and start androgen replacement therapy when necessary

Anabolic steroids purchased on the Internet as a cause of prolonged hypogonadotropic hypogonadism

OBJECTIVE: To report a case of hypogonadotropic hypogonadism due to the chronic abuse of anabolic steroids purchased over the Internet. DESIGN: Case report. SETTING: Endocrinology unit of the University of Brescia. PATIENT(S): A 34-year-old man. INTERVENTION(S): A single dose (100 μg) of triptorelin (triptorelin test). MAIN OUTCOME MEASURE(S): Clinical symptoms, androgen normalization, levels of serum testosterone, follicle-stimulating hormone, and luteinizing hormone. RESULT(S): Within 1 month, the patient's serum testosterone was in the normal range, and he reported a return to normal energy and libido. CONCLUSION(S): The World Anti-Doping Code has proved to be a very powerful and effective tool in the harmonization of antidoping efforts worldwide, but it is insufficient to combat this illegal phenomenon. To tackle the serious side effects caused by doping we believe that it is necessary to increase monitoring and adopt severe sanctions, particularly with regard to Internet sites

Renal apolipoprotein A-I amyloidosis: a rare and usually ignored cause of hereditary tubulointerstitial nephritis

12openopenGregorini G; Izzi C; Obici L; Tardanico R; Röcken C; Viola BF; Capistrano M; Donadei S; Biasi L; Scalvini T; Merlini G; Scolari F.Gregorini, G; Izzi, C; Obici, L; Tardanico, R; Röcken, C; Viola, Bf; Capistrano, M; Donadei, S; Biasi, L; Scalvini, T; Merlini, G; Scolari, Francesc

Teleconsultation service to improve healthcare in rural areas: acceptance, organizational impact and appropriateness

Background: Nowadays, new organisational strategies should be indentified to improve primary care and its link with secondary care in terms of efficacy and timeliness of interventions thus preventing unnecessary hospital accesses and costs saving for the health system. The purpose of this study is to assess the effects of the use of teleconsultation by general practitioners in rural areas. Methods: General practitioners were provided with a teleconsultation service from 2006 to 2008 to obtain a second opinion for cardiac, dermatological and diabetic problems. Access, acceptance, organisational impact, effectiveness and economics data were collected. Clinical and access data were systematically entered in a database while acceptance and organisational data were evaluated through ad hoc questionnaires. Results: There were 957 teleconsultation contacts which resulted in access to health care services for 812 symptomatic patients living in 30 rural communities. Through the teleconsultation service, 48 general practitioners improved the appropriateness of primary care and the integration with secondary care. In fact, the level of concordance between intentions and consultations for cardiac problems was equal to 9%, in 86% of the cases the service entailed a saving of resources and in 5% of the cases, it improved the timeliness. 95% of the GPs considered the overall quality positively. For a future routine use of this service, trust in specialists, duration and workload of teleconsultations and reimbursement should be taken into account. Conclusions: Managerial and policy implications emerged mainly related to the support to GPs in the provision of high quality primary care and decision-making processes in promoting similar services

Renin Angiotensin System Blockers and Risk of Mortality in Hypertensive Patients Hospitalized for COVID-19: An Italian Registry

Background: It is uncertain whether exposure to renin\u2013angiotensin system (RAS) modifiers affects the severity of the new coronavirus disease 2019 (COVID-19) because most of the available studies are retrospective. Methods: We tested the prognostic value of exposure to RAS modifiers (either angiotensin-converting enzyme inhibitors [ACE-Is] or angiotensin receptor blockers [ARBs]) in a prospective study of hypertensive patients with COVID-19. We analyzed data from 566 patients (mean age 75 years, 54% males, 162 ACE-Is users, and 147 ARBs users) hospitalized in five Italian hospitals. The study used systematic prospective data collection according to a pre-specified protocol. All-cause mortality during hospitalization was the primary outcome. Results: Sixty-six patients died during hospitalization. Exposure to RAS modifiers was associated with a significant reduction in the risk of in-hospital mortality when compared to other BP-lowering strategies (odds ratio [OR]: 0.54, 95% confidence interval [CI]: 0.32 to 0.90, p = 0.019). Exposure to ACE-Is was not significantly associated with a reduced risk of in-hospital mortality when compared with patients not treated with RAS modifiers (OR: 0.66, 95% CI: 0.36 to 1.20, p = 0.172). Conversely, ARBs users showed a 59% lower risk of death (OR: 0.41, 95% CI: 0.20 to 0.84, p = 0.016) even after allowance for several prognostic markers, including age, oxygen saturation, occurrence of severe hypotension during hospitalization, and lymphocyte count (adjusted OR: 0.37, 95% CI: 0.17 to 0.80, p = 0.012). The discontinuation of RAS modifiers during hospitalization did not exert a significant effect (p = 0.515). Conclusions: This prospective study indicates that exposure to ARBs reduces mortality in hospitalized patients with COVID-19

Development and Feasibility of a Smartphone, ECG and GPS Based System for Remotely Monitoring Exercise in Cardiac Rehabilitation

Background Despite its efficacy and cost-effectiveness, exercise-based cardiac rehabilitation is undertaken by less than one-third of clinically eligible cardiac patients in every country for which data is available. Reasons for non-participation include the unavailability of hospital-based rehabilitation programs, or excessive travel time and distance. For this reason, there have been calls for the development of more flexible alternatives. Methodology and Principal Findings We developed a system to enable walking-based cardiac rehabilitation in which the patient's single-lead ECG, heart rate, GPS-based speed and location are transmitted by a programmed smartphone to a secure server for real-time monitoring by a qualified exercise scientist. The feasibility of this approach was evaluated in 134 remotely-monitored exercise assessment and exercise sessions in cardiac patients unable to undertake hospital-based rehabilitation. Completion rates, rates of technical problems, detection of ECG changes, pre- and post-intervention six minute walk test (6 MWT), cardiac depression and Quality of Life (QOL) were key measures. The system was rated as easy and quick to use. It allowed participants to complete six weeks of exercise-based rehabilitation near their homes, worksites, or when travelling. The majority of sessions were completed without any technical problems, although periodic signal loss in areas of poor coverage was an occasional limitation. Several exercise and post-exercise ECG changes were detected. Participants showed improvements comparable to those reported for hospital-based programs, walking significantly further on the post-intervention 6 MWT, 637 m (95% CI: 565–726), than on the pre-test, 524 m (95% CI: 420–655), and reporting significantly reduced levels of cardiac depression and significantly improved physical health-related QOL. Conclusions and Significance The system provided a feasible and very flexible alternative form of supervised cardiac rehabilitation for those unable to access hospital-based programs, with the potential to address a well-recognised deficiency in health care provision in many countries. Future research should assess its longer-term efficacy, cost-effectiveness and safety in larger samples representing the spectrum of cardiac morbidity and severity

Plasma leptin and insulin-like growth factor I levels during acute exacerbations of chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Recent studies have provided evidence for a link between leptin and tumor necrosis factor-alpha (TNF-α). Insulin-like growth factor I (IGF-I) mediates the metabolic effects of growth hormone (GH). The GH axis is believed to be suppressed in chronic obstructive pulmonary disease (COPD). The aim of this study is to find out whether acute exacerbations of COPD are followed by changes in plasma leptin and insulin-like growth factor I (IGF-I) levels and furthermore, whether these changes are related to systemic inflammation.</p> <p>Methods</p> <p>We measured serum leptin, IGF-I, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6) and interleukin 8 (IL-8) levels in 52 COPD patients with acute exacerbation on admission to hospital (Day 1) and two weeks later (Day 15). 25 healthy age-matched subjects served as controls. COPD patients were also divided into two subgroups (29 with chronic bronchitis and 23 with emphysema). Serum leptin and IGF-I were measured by radioimmunoassay and TNF-α, IL-1β, IL-6 and IL-8 were measured by ELISA.</p> <p>Results</p> <p>Serum leptin levels were significantly higher and serum IGF-I levels significantly lower in COPD patients on Day 1 than in healthy controls (p < 0.001). A positive correlation was observed between leptin and TNF-α on Day 1 (r = 0.620, p < 0.001). Emphysematous patients had significantly lower IGF-I levels compared to those with chronic bronchitis both on Day 1 and Day 15 (p = 0.003 and p < 0.001 respectively).</p> <p>Conclusion</p> <p>Inappropriately increased circulating leptin levels along with decreased IGF-I levels occured during acute exacerbations of COPD. Compared to chronic bronchitis, patients with emphysema had lower circulating IGF-I levels both at the onset of the exacerbation and two weeks later.</p

Pedometer use and self-determined motivation for walking in a cardiac telerehabilitation program: a qualitative study

BACKGROUND: Exercise-based cardiac rehabilitation reduces morbidity and mortality. Walking is a convenient activity suitable for people with cardiac disease. Pedometers count steps, measure walking activity and motivate people to increase physical activity. In this study, patients participating in cardiac telerehabilitation were provided with a pedometer to support motivation for physical activity with the purpose of exploring pedometer use and self-determined motivation for walking experienced by patients and health professionals during a cardiac telerehabilitation program. METHODS: A qualitative research design consisting of observations, individual interviews and patient documents made the basis for a content analysis. Data was analysed deductively using Self Determination Theory as a frame for analysis and discussion, focusing on the psychological needs of autonomy, competence and relatedness. Twelve cardiac patients, 11 health professionals, 6 physiotherapists and 5 registered nurses were included. RESULTS: The pedometer offered independence from standardised rehabilitation since the pedometer supported tailoring, individualised walking activity based on the patient’s choice. This led to an increased autonomy. The patients felt consciously aware of health benefits of walking, and the pedometer provided feedback on walking activity leading to an increased competence to achieve goals for steps. Finally, the pedometer supported relatedness with others. The health professionals’ surveillance of patients’ steps, made the patients feel observed, yet supported, furthermore, their next of kin appeared to be supportive as walking partners. CONCLUSION: Cardiac patients’ motivation for walking was evident due to pedometer use. Even though not all aspects of motivation were autonomous and self determined, the patients felt motivated for walking. The visible steps and continuous monitoring of own walking activity made it possible for each individual patient to choose their desired kind of activity and perform ongoing adjustments of walking activity. The immediate feedback on step activity and the expectations of health benefits resulted in motivation for walking. Finally, pedometer supported walking made surveillance possible, giving the patients a feeling of being looked after and supported. TRIAL REGISTRATION: Current study is a part of The Teledi@log project

Controlled human exposures to ambient pollutant particles in susceptible populations

Epidemiologic studies have established an association between exposures to air pollution particles and human mortality and morbidity at concentrations of particles currently found in major metropolitan areas. The adverse effects of pollution particles are most prominent in susceptible subjects, including the elderly and patients with cardiopulmonary diseases. Controlled human exposure studies have been used to confirm the causal relationship between pollution particle exposure and adverse health effects. Earlier studies enrolled mostly young healthy subjects and have largely confirmed the capability of particles to cause adverse health effects shown in epidemiological studies. In the last few years, more studies involving susceptible populations have been published. These recent studies in susceptible populations, however, have shown that the adverse responses to particles appear diminished in these susceptible subjects compared to those in healthy subjects. The present paper reviewed and compared control human exposure studies to particles and sought to explain the "unexpected" response to particle exposure in these susceptible populations and make recommendations for future studies. We found that the causes for the discrepant results are likely multifactorial. Factors such as medications, the disease itself, genetic susceptibility, subject selection bias that is intrinsic to many controlled exposure studies and nonspecificity of study endpoints may explain part of the results. Future controlled exposure studies should select endpoints that are more closely related to the pathogenesis of the disease and reflect the severity of particle-induced health effects in the specific populations under investigation. Future studies should also attempt to control for medications and genetic susceptibility. Using a different study design, such as exposing subjects to filtered air and ambient levels of particles, and assessing the improvement in biological endpoints during filtered air exposure, may allow the inclusion of higher risk patients who are likely the main contributors to the increased particle-induced health effects in epidemiological studies

Reduced costs with bisoprolol treatment for heart failure - An economic analysis of the second Cardiac Insufficiency Bisoprolol Study (CIBIS-II)

Background Beta-blockers, used as an adjunctive to diuretics, digoxin and angiotensin converting enzyme inhibitors, improve survival in chronic heart failure. We report a prospectively planned economic analysis of the cost of adjunctive beta-blocker therapy in the second Cardiac Insufficiency BIsoprolol Study (CIBIS II). Methods Resource utilization data (drug therapy, number of hospital admissions, length of hospital stay, ward type) were collected prospectively in all patients in CIBIS . These data were used to determine the additional direct costs incurred, and savings made, with bisoprolol therapy. As well as the cost of the drug, additional costs related to bisoprolol therapy were added to cover the supervision of treatment initiation and titration (four outpatient clinic/office visits). Per them (hospital bed day) costings were carried out for France, Germany and the U.K. Diagnosis related group costings were performed for France and the U.K. Our analyses took the perspective of a third party payer in France and Germany and the National Health Service in the U.K. Results Overall, fewer patients were hospitalized in the bisoprolol group, there were fewer hospital admissions perpatient hospitalized, fewer hospital admissions overall, fewer days spent in hospital and fewer days spent in the most expensive type of ward. As a consequence the cost of care in the bisoprolol group was 5-10% less in all three countries, in the per them analysis, even taking into account the cost of bisoprolol and the extra initiation/up-titration visits. The cost per patient treated in the placebo and bisoprolol groups was FF35 009 vs FF31 762 in France, DM11 563 vs DM10 784 in Germany and pound 4987 vs pound 4722 in the U.K. The diagnosis related group analysis gave similar results. Interpretation Not only did bisoprolol increase survival and reduce hospital admissions in CIBIS II, it also cut the cost of care in so doing. This `win-win' situation of positive health benefits associated with cost savings is Favourable from the point of view of both the patient and health care systems. These findings add further support for the use of beta-blockers in chronic heart failure