Clusterin silencing restores myoblasts viability and down modulates the inflammatory process in osteoporotic disease.

BACKGROUND: Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. METHODS: Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. RESULTS: We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p < 0.001). CLU treatment of isolated OP and OA myoblasts showed: modulation of proliferation, morphological changes, increase of histone H4 acetylation and induction of myogenin (MYOG) activation in OP myoblast only. In OP condition, functional knockdown of CLU by siRNA restores proliferative myoblasts capability and tissue damage repair, carried out by an evident upregulation of Transglutaminase 2 (TGM2). We also observed downmodulation of CX3CR1 expression with consequent impairing of the inflammatory infiltrate recruitment. CONCLUSIONS: Results obtained suggest a potential role of CLU in OP by influencing myoblasts terminal differentiation, epigenetic regulation of muscle cell differentiation and senescence. Moreover, CLU silencing points out its role in the modulation of tissue damage repair and inflammation, proposing it as a new diagnostic marker for muscle degeneration and a potential target for specific therapeutic intervention in OP related sarcopenia.

Femoral cortical index: an indicator of poor bone quality in patient with hip fracture.

BACKGROUND: Osteoporosis is a common disease in elderly, characterized by poor bone quality as a result of alterations affecting trabecular bone. However, recent studies have described also an important role of alterations of cortical bone in the physiopathology of osteoporosis. Although dual-energy X-ray absorptiometry (DXA) is a valid method to assess bone mineral density, in the presence of comorbidities real bone fragility is unable to be evaluated. The number of hip fractures is rising, especially in people over 85 years old. AIMS: The aim is to evaluate an alternative method so that it can indicate fracture risk, independent of bone mineral density (BMD). Femoral cortical index (FCI) assesses cortical bone stock using femur X-ray. METHODS: A retrospective study has been conducted on 152 patients with hip fragility fractures. FCI has been calculated on fractured femur and on the opposite side. The presence of comorbidities, osteoporosis risk factors, vitamin D levels, and BMD have been analyzed for each patient. RESULTS: Average values of FCI have been 0.42 for fractured femurs and 0.48 at the opposite side with a statistically significant difference (p = 0.002). Patients with severe hypovitaminosis D had a minor FCI compared to those with moderate deficiency (0.41 vs. 0.46, p < 0.011). 42 patients (27.6%) with osteopenic or normal BMD have presented low values of FCI. DISCUSSION AND CONCLUSION: A significant correlation among low values of FCI, comorbidities, severe hypovitaminosis D. and BMD in patients with hip fractures has been found. FCI could be a useful tool to evaluate bone fragility and to predict fracture risk even in the normal and osteopenic BMD patients.

The implantable cardioverter defibrillator in congestive heart failure patients in primary prevention: assessment of neuropsychological impact.

AIM: Cognitive impairment, anxiety and depression have been described in patients with congestive heart failure (CHF). The aim was to analyse the prevalence of cognitive impairment and anxiety-depression in an in-hospital CHF population before discharge attempting to correlate with the presence of an implantable cardioverter defibrillator (ICD). METHODS: All subjects underwent a mini mental state examination (MMSE), geriatric depression scale (GDS), hospital anxiety and depression scale test (HADS). RESULTS: Three-hundred and eighteen CHF patients (age 71.6 years, 195 males) were analysed. The mean New York Heart Association class (NYHA) was 2.9±0.8, left ventricular ejection fraction (LVEF) was 43.4±15.8%; brain natriuretic peptide (BNP) plasma level was 579.8±688.4 pg/mL. In 9.6% a pathological MMSE score emerged; a depression of mood in 18.2% and anxiety in 23.4% of patients were observed. An ICD was implanted in 43 (14.2%) CHF patients for primary prevention of cardiac sudden death. Patients in ICD group demonstrated a higher prevalence of renal impairment (creatinine 1.7±0.7 vs. 1.2±0.8 mg/dL; P=0.0001), lower LVEF (24.9±8.9 vs. 46.2±14.6% P=0.0001) and higher BNP (717.1±538 vs. 345.4±448.6 pg/ml; P=0.0001) but similar 6-minute walking test (338.6±81.3 vs. 345.3±114.9 m; P=0.8). An ICD intervention was registered in 9 (20.9%) patients. Although clinical parameters seemed to describe a sicker population in ICD implanted patients, from neuropsychological tests did not emerge any significant differences (P=NS for MMSE, GDS and HADS). CONCLUSION: ICD-implanted CHF patients for primary prevention did not reveal a worsening in anxiety and depression of mood demonstrating a similar cognitive performance in comparison with non-ICD implanted.

[Professional drivers and psychoactive substances consumption: results from medical surveillance at the workplace in Piedmont region]. / Guida professionale e consumo di sostanze stupefacenti, risultati relativi ala sorveglinza sanitaria nella regione Piemonnte.

BACKGROUND: The use of psychoactive substances has been shown to be a risk factor for accidents in professional drivers. According to an approved Italian law, in order to detect dependency at the workplace the occupational health physician is called to assess the use of illicit drugs among professional drivers. The main purpose of this study was to investigate the use of psychoactive substances among professional drivers. METHODS: From July to December 2008, rapid urine screening test was carried out on 198 professional drivers. All positive results from the screening stage were verified by specialized laboratories. RESULTS: We found 4 workers with a positive rapid urine screening test (7.1%), one of which was positive only for benzodiazepines and another positive test was not confirmed by specialized laboratory. By only considering illegal substances detected, 6.1% of the drivers tested positive. In this study, the high number of consumers among professional drivers ranged from 31 to 35 years old. Cannabis (THC) was the most frequently detected substance (seen in 10 over 12 cases,), after that was methadone (2/12 cases) and cocaine (1/12 case). We only had one case where more than one substance was found in the same subject (THC and cocaine). Five (41.7%) were former drug-addicts and public Pathological Addiction Services (Ser.T.) had previously followed them. CONCLUSIONS: Our results highlight the problem of drug consumption among professional drivers in Piedmont region. Health education and medical surveillance in workplace drug-testing may improve worker and third parties safety.

Comparison between immunoradiometric and fluorimetric brain natriuretic peptide determination in patients with congestive heart failure.

UNLABELLED: This study compared two different methods, namely the immunoradiometric (IRMA) and fluorimetric (FIA), in order to determine plasma brain natriuretic peptide (BNP) in congestive heart failure (CHF) patients. METHODS: CHF in-patients underwent echocardiography and plasma BNP determination using both two methods. The echocardiograms analysed left ventricular end-systolic (LVESV) and end-diastolic (LVEDV) volumes and systolic dysfunction [left ventricular ejection fraction (LVEF) <50%]. RESULTS: Seventy-three (71% males, age 67 ± 9.6 yr) patients were enrolled, 31.5% affected by valvular heart disease. The mean LVEF was 39.8 ± 14.1%; in 26 (35%) a hypertensive etiology emerged. The immunoradiometric assay (IRMA) BNP was found to be significantly lower than the FIA determination 116.5 ± 149 pg/ml vs 267.3 ± 285.6 pg/ml; p=0.0001) and the two methods were closely correlated (r=0.89; p=0.00001). Logistic regression demonstrated a significant correlation between BNP, LVEF, and LVESV/LVEDV (r=-0.45, p=0.0003; r=-0.48, p=0.00001; r=0.22 p=0.003; r=0.34 p=0.0001; r=0.13 p=0.02; r=0.28 p=0.001 IRMA and FIA, respectively). IRMA BNP and FIA BNP significantly increased according to the worsening functional class [from 34.3 ± 60.2 pg/ml in NYHA (New York Heart Association) I to 555.5 ± 273.1 pg/ml in NYHA IV; from 86.1 ± 162.1 pg/ml in NYHA I to 1070 ± 42.2 pg/ml in NYHA IV, respectively]. In severe systolic dysfunction (LVEF<30%), receiver operating characteristic analysis revealed a satisfactorily sensitivity and specificity using a cut-off point of 50.6 pg/ml with IRMA and 243 pg/ml with FIA. In mild systolic dysfunction (LVEF<50%), a good sensitivity and specificity using a cut-off point of 42 pg/ml with IRMA and 182 pg/ml with FIA emerged. CONCLUSIONS: In CHF patients both BNP methods correlated with NYHA class, LVEF, and ventricular volumes.

Performance of influenza rapid antigen testing in influenza in emergency department patients.

BACKGROUND: The use of rapid antigen tests to triage specimens for polymerase chain reaction (PCR) testing from emergency department patients with influenza-like illness during surveillance for novel influenza viruses has been suggested. OBJECTIVE: To measure the observed sensitivity and specificity for a widely used rapid antigen test (Binax) using a PCR-based assay (Medical Diagnostic Laboratories). METHODS: Nasopharyngeal samples were taken with flocked swabs (Copan Diagnostics) from patients presenting to the emergency department of a community hospital. Samples were analysed using a rapid antigen and a PCR-based test. PCR testing was used as the criterion reference. Sensitivity and specificity were calculated for influenza and influenza A. Positive predictive values were calculated over a range of possible prevalence. RESULTS: Samples from 566 unique patients were tested using both methods. Sensitivity was 69.1% (95% CI 58.9% to 78.1%) and specificity was 97.7% (95% CI 95.8% to 98.8%) for the detection of any influenza and 75.3% (95% CI 64.7% to 84.0%) and 97.8% (95% CI 95.9% to 98.9%), respectively, for influenza A only. The resultant positive predictive value ranges from 23% to 77% when the prevalence ranges from 1% to 10%. CONCLUSION: When planning early outbreak surveillance, provision of adequate PCR testing capacity rather than triaging specimens using rapid antigen testing for influenza is advisable.

B-type natriuretic peptide levels and insulin resistance in patients with severe ischemic myocardial dysfunction.

B-type natriuretic peptide (BNP) is an important clinical parameter of severity in congestive heart failure (CHF). Recent findings suggest a close relation between lipid and glucose metabolism and the natriuretic peptide axis, even if conflicting data exist on the relationship between natriuretic peptide levels and insulin resistance (IR). Thus, we sought to investigate potential relations between BNP level and IR in 134 patients with severe ischemic myocardial dysfunction [mean+/-SD: age =64.8+/-9.6 yr, male/female =104/30; body mass index (BMI) =25.5+/-4.05 kg/m2, 26.1% diabetics; ejection fraction (EF) = 30.2+/-7.7%]. In univariate analysis, an inverse relationship between BNP levels and EF% was observed (R=-0.43, p=0.0006). Moreover, we found an inverse association between BNP levels and BMI (R=-0.27, p=0.036), and also between BNP and homeostasis model assessment of insulin resistance (HOMA-IR) (R=-0.27, p=0.039). In multivariate analysis, EF% and HOMA-IR were significantly and independently associated with logarithmically transformed BNP levels (beta=-0.40, p=0.019 and beta=-0.26, p=0.042, respectively; R2=0.36). In conclusion, in patients with severe ischemic myocardial dysfunction EF and IR are independently associated with BNP levels explaining about 1/3 of the variability of this parameter. Multiple potential mechanisms may underlie this association, but it seems now clinically important to take into account also metabolic features when interpreting plasma natriuretic peptide concentrations obtained for diagnostic or prognostic purposes.

[Peculiarities and aims of first aid training in the road haulage sector]. / Peculiarità e obiettivi della formazione degli addetti al primo soccorso nel settore dell'autotrasporto.

BACKGROUND: Four years after the law concerning first aid in the workplace was passed in Italy (inter-ministerial decree 388/2003), which is a useful tool in improving safety at work, it is necessary to organize first aid courses specifically for those working in the road haulage sector which would also be effective in case of traffic accidents. In view of the characteristics of the working environment in this sector (the road) and of the working conditions (generally workers are isolated and far from the company's headquarters), it would be necessary to organize ad hoc first aid courses at the workplace for the category of professional drivers. OBJECTIVES AND METHODS: The aim of this article is to discuss some possible organizational aspects of first aid in the road haulage sector, such as: number of workers responsible for first aid, how to train workers for specific risks of traffic accidents, the requirements for teachers responsible for first aid and course targets that must be achieved. RESULTS AND CONCLUSIONS: A good level of training, achieved during the first aid course at the workplace, might therefore be useful to improve road safety and increase the quality of basic and advanced first aid in road traffic injuries.

[Professional driving and safety, a target for occupational medicine]. / Guida professionale e sicurezza, un approccio obiettivo che coinvolge anche la medicina del lavoro.

BACKGROUND: Road traffic injuries constitute one of the main causes of death and disability in Italy and in the European Union. Occupational medicine should pay special attention to the field of road transport because every year a large number of road accidents occur with fatal outcomes. Via health surveillance the occupational physician can play an important role in the prevention of such events. OBJECTIVES: The aim of the article is to summarize the results of the most recent studies on the main risk factors for road transport safety and discuss possible strategies of health surveillance, according to the recent indications of the European Agency for Safety and Health at Work, Bilbao. METHODS: A review of the literature was made. RESULTS AND CONCLUSIONS: The scientific literature provides a large amount of interesting information on the most important risk factors for road accidents, such as drinking and drug abuse, sleepiness and other medical conditions, or excessive speed. The presence of numerous and varied hazards for road transport safety requires, as suggested by the Bilbao Agency, the adoption of occupational health measures, including risk assessment, health education, technical and environmental prevention, health surveillance and clinical interventions (diagnosis and rehabilitation of occupational accidents). Moreover, the paper stresses the need to strengthen collaboration between occupational health physicians and other medical specialists.

[Neurally-mediated syncope and occupational accidents: prevention strategies and case report]. / Sincope neuromediata e infortuni sul lavoro: strategie preventive e considerazioni su un caso clinico.

A bus driver came to our observation after an occupational traffic accident due to a syncopal event. The positive result of the tilt testing demonstrated the neurally-mediated nature of the syncope. The accident involved approximately 40 people (all the bus passengers), fortunately without severe injuries or deaths. The described episode indicates the need for a procedural algorithm, commonly approved, applicable in the field of prevention, for those occupational categories with severe accident risk. Indeed, the possibility exists to identify at least a part of the subjects predisposed to neurally-mediated syncope. Fundamental steps for such screening are history taking (looking for previous events, familiarity), the physical examination (useful, for example, to exclude orthostatic hypotension or carotid sinus syncope), and, in particular, the tilt testing, a diagnostic investigation recommended for all the workers who have had a previous syncope and are at high occupational accident risk. Moreover, the reported case recalls the need to strengthen the collaboration between the cardiologist and the occupational health physician.

[Syncope and professional driving: the role of the occupational physician]. / Sincope e guida professionale, il ruolo del medico del lavoro.

BACKGROUND: Road traffic injuries constitute one of the main causes of death and disability in Italy and in the European Union. Although much scientific evidence exists on the important role of complete loss of consciousness in the dynamics of motor vehicle accidents, at present there is no specific legislation in Italy. Occupational medicine should take particular care in this field, because every year a large number of accidents with fatal outcomes occur among truck drivers. Via health surveillance, the occupational physician can play an important role in the prevention of such events. OBJECTIVES AND METHODS: The aim of this article is to discuss some possible strategies of health surveillance, comparing the current Italian regulations with the recent guidelines of the European Society of Cardiology (ESC) Task Force regarding the association of syncope and road transport. RESULTS AND CONCLUSION: Current Italian legislation does not include specific prescriptions in case of syncope in truck drivers. This deficiency leads to a lack of information for occupational physicians in order to define unanimous judgements of work fitness. The authors attempted to apply the ESC guidelines on syncope and truck driving to the Italian situation. Four cases of syncope were described, in which the judgement of work fitness for truck drivers proved to be especially complex and stressed the need for cooperation between occupational health physicians and cardiologists.

First pulmonary case reported in Argentina of infection with mycobacterium szulgai, a rare pathogen.

Mycobacterium szulgai is a rare pathogen. Nontuberculous mycobacteria usually produce disease in people with some kind of immunosuppression or another predisposing condition. A case of pulmonary Mycobacterium szulgai infection is described.

Prognostic role of B-type natriuretic peptide in patients with diabetes and acute decompensated heart failure.

BACKGROUND: Several studies have reported the prognostic value of natriuretic peptides, but their predictive value in patients with diabetes mellitus is unknown. The aim of the study was to test the hypothesis that measurement of brain natriuretic peptide (BNP) levels in ambulatory patients with congestive heart failure (CHF) and diabetes can predict the occurrence of cardiovascular events at 6-month follow-up. METHODS: We enrolled 145 consecutive patient with diabetes [age 72 +/- 9 years, hypertension (21%), ischaemic heart disease (52%), atrial fibrillation (22%), preserved left ventricular function (29%)] seen in the outpatient heart failure clinic after an acute episode of cardiac failure. RESULTS: The median (25th/75th interquartile range) BNP concentrations at discharge were 186 (75-348) pg/ml. At 6-month clinical follow-up 10/145 (7%) subjects had died and 31/145 (21%) had been readmitted because of cardiac decompensation. BNP values of 200 and 500 pg/ml were found to have the best compromise between sensitivity (88 and 46%, respectively) and specificity (71 and 89%, respectively) for predicting events at 6 months. Multivariate Cox regression analysis identified only two parameters as predictors of events: serum creatinine [hazard ratio (HR) = 3.3; P = 0.02], and BNP plasma level BNP cut-off values (HR = 3.8; P = 0.03 for 201-499 pg/ml and HR = 7.7; P = 0.001 for > or = 500 pg/ml). CONCLUSION: These results suggest that BNP and serum creatinine are strong predictors of clinical events in patients with diabetes and CHF. In these patients, clinical outcome might be stratified by plasma BNP levels.

A novel hemoglobin-adenosine-glutathione based blood substitute: evaluation of its effects on human blood ex vivo.

Chemically modified hemoglobin (Hb) solutions are under current investigation as potential red cell substitutes. Researchers at Texas Tech University have developed a novel free Hb based blood substitute product. This blood substitute is composed of purified bovine Hb cross-linked intramolecularly with o-adenosine-5'-triphosphate and intermolecularly with o-adenosine, and conjugated with reduced glutathione (GSH). In this study, we compared the effects of our novel blood substitute and unmodified (U) Hb, by using allogenic plasma as the control, on human blood components: red blood cells (RBCs), platelets, monocytes (Mo), and low-density lipoproteins (LDLs). The pro-oxidant potential of both Hb solutions on RBCs was examined by the measurement of osmotic and mechanical fragility, conjugated dienes (CD), lipid hydroperoxides (LOOH), thiobarbituric acid reactants (TBAR-S), isoprostanes (8-iso PGF2alpha) and intracellular GSH. The oxidative modification of LDLs was assessed by CD, LOOH, and TBAR-S, and the degree of apolipoprotein (apo) B cross-linking. The effects of Hb on platelets have been studied by monitoring their responses to the aggregation agonists: collagen, ADP, epinephrine, and arachidonic acid. Monocytes were cultured with Hb solutions or plasma and tested for TNF-alpha and IL-1beta release, then examined by electron microscopy. Results indicate that native UHb initiates oxidative stress of many blood components and aggravates inflammatory responses of Mo. It also caused an increase in RBC osmotic and mechanical fragility (p < 0.001). While the level of GSH was slightly changed, the lipid peroxidation of RBC increased (p < 0.001). UHb was found to be a stimulator of 8-iso PGF2alpha synthesis, a potent modulator of LDLs, and an effective potentiator of agonist induced platelet aggregation. Contrarily, our novel blood substitute did not seem to induce oxidative stress nor to increase Mo inflammatory reactions. The osmotic and mechanical fragility of RBCs was similar to that of the control. Such modified Hb failed to alter LDLs, increase the production of 8-iso PGF2alpha, but markedly inhibited platelet aggregation. The effect of this novel blood substitute can be linked with the cytoprotective and anti-inflammatory properties of adenosine, which is used as a cross-linker and surface modifier, and a modification procedure that lowers the hemoglobin pro-oxidant potential.

Comparison of thrombolytic therapy and primary coronary angioplasty with liberal stenting for inferior myocardial infarction with precordial ST-segment depression: immediate and long-term results of a randomized study.

OBJECTIVES: The aim of the study was to compare randomly assigned primary angioplasty and accelerated recombinant tissue plasminogen activator (rt-PA), in patients with "high-risk" inferior acute myocardial infarction (ST-segment elevation in the inferior leads and ST-segment depression in the precordial leads). BACKGROUND: The ST-segment depression in the precordial leads is a marker of severe prognosis in patients with inferior myocardial infarction. The comparative outcome of treatment with primary angioplasty or lysis with accelerated rt-PA has not been investigated. METHODS: One hundred and ten patients within 6 h of symptoms were randomized to either treatment. To assess the in-hospital and 1-year outcome of both treatments the following results were compared: death or nonfatal infarction, recurrence of angina, left ventricular ejection fraction (LVEF), and the need for repeat target vessel revascularization (TVR). RESULTS: In patients treated with angioplasty (55) and rt-PA (55) the rate of in-hospital mortality and reinfarction was 3.6% versus 9.1% (p=0.4). Recurrence of angina was 1.8% versus 20% (p=0.002), new TVR was used in 3.6% versus 29.1% (p=0.0003), and the LVEF (%) at discharge was 55.2+/-9.5 versus 48.2+/-9.9 (p=0.0001). There were no hemorrhagic strokes, no emergency coronary artery bypass graft (CABG) and identical (5.5%) need for blood transfusions. At 1 year, the incidence of death, reinfarction or repeat TVR was 11% in the percutaneous transluminal coronary angioplasty (PTCA) group versus 52.7% in the rt-PA group (log-rank 22.38, p < 0.0001). CONCLUSIONS: Primary angioplasty is superior to accelerated rt-PA in terms of both myocardial preservation and reduction of in-hospital complications in patients with inferior myocardial infarction and precordial ST-segment depression. Primary angioplasty also yields a better long-term event-free survival.

[Primary angioplasty in acute inferior myocardial infarct with anterior ST-segment depression: the long-term follow-up]. / Angioplastica primaria nell'infarto miocardico acuto inferiore con sottoslivellamento anteriore del tratto ST: follow-up a lungo termine.

BACKGROUND: Concomitant anterior ST-segment depression is a marker of severe prognosis in inferior myocardial infarction. PATIENTS AND METHODS: Prospective observational study in patients with inferior acute myocardial infarction and ST-segment depression > or = 4 mm in the anterior leads, who were treated with primary angioplasty. Angiography was performed at hospital discharge and at six months, and a clinical follow-up was obtained at one year after the infarction. RESULTS: Sixty-three patients were included in the study. Pre-hospital and in-hospital delay were 147 +/- 70 minutes (20-355) and 54 +/- 11 minutes (18-80), respectively. Angioplasty was successful in all patients and 48 stents were implanted in 36 patients (57%). Angiography was performed at hospital discharge in 55 patients (87%) and showed a TIMI grade 3 coronary flow in the infarct-related artery in all cases. The left ventricular ejection fraction was 0.55 +/- 0.09 (0.4-0.8). One patient (1.6%) died before discharge, two (3.2%) had ischemic complications (one had non-fatal reinfarction, another had recurrent angina at rest), and three (4.9%) had local vascular complications. At the six-month follow-up, none of the patients had died. One had suffered reinfarction (1.6%) and another had been readmitted for recurrence of angina at rest (1.6%); none had symptoms of stable angina. The ejection fraction was 0.56 +/- 0.12 and eight patients (14%) showed angiographic restenosis. At twelve months, two patients had died (1.6%) and five (8%) had required readmission to hospital. CONCLUSIONS: Primary angioplasty yielded favorable results in this group of patients. Our data confirm the efficacy of primary angioplasty for the treatment of acute myocardial infarction, with a low rate of clinical (3.2%) and angiographic (14%) restenosis at six months, and a high rate (87%) of event-free survival at one year follow-up.

Ambulatory 24-hour blood pressure monitoring: correlation between blood pressure variability and left ventricular hypertrophy in untreated hypertensive patients.

BACKGROUND: Left ventricular hypertrophy (LVH) appears to be poorly correlated with clinical measurements of blood pressure: a better correlation may be observed with data from 24 h ambulatory blood pressure monitoring (ABPM). The aim of this study was to compare the results of non-invasive ABPM in a population of patients with essential hypertension who had never been treated, subdividing them based on the presence or absence of LVH in the transthoracic echocardiogram (LVMI, left ventricular mass index > 135 g/m2 in males and > 110 g/m2 in females). METHODS: Eighty hypertensive patients with mild or moderate hypertension underwent routine blood tests, a 24 h ABPM and a transthoracic echocardiogram. Based on the ABPMs, we analyzed average 24 h systolic and diastolic blood pressure (BP), average daytime (6 a.m.-10 p.m.) and nighttime (10 p.m.-6 a.m.) systolic and diastolic BP, average morning (6-12 a.m.) BP and the number of dipper or non-dipper patients. The echocardiographic study included the calculation of left ventricular mass using Devereux's formula according to the Penn convention, analysis of the patterns of left ventricular geometry and a study of left ventricular diastolic function. RESULTS: Thirty-five (43.7%) patients had LVH at the echocardiographic study. In 52 subjects, the clinical history showed at least one BP measurement > 140/90 mmHg in the year prior to our observation. The average age was 48 +/- 11, without any significant correlation to LVMI (r = 0.13). The magnitude of the S-wave in V1 and the R-wave in V5 and the magnitude of the tallest R-wave and S-wave in the electrocardiogram analysis had a significant correlation with LVMI (r = 0.23 and r = 0.26, respectively). The echocardiogram revealed a normal left ventricular geometry in 43.8% of hypertensive patients, concentric remodeling in 13.8%, concentric hypertrophy in 16.2% and eccentric hypertrophy in 26.2%. The isovolumic relaxation time (IVRT) and A-wave were significantly correlated with LVMI (r = 0.49 and r = 0.33, respectively). LVMI had a significant correlation with systolic BP at ABPM (24 h systolic BP r = 0.34; daytime systolic BP r = 0.35; nighttime systolic BP r = 0.28; 6-12 systolic BP r = 0.29) but not with diastolic BP. Dipper patients represented 76.3% of the population, without any difference in LVMI between dippers and non-dippers (p = 0.09). Dipper patients had a higher prevalence of normal left ventricles as compared with non-dippers (p < 0.0001). White-coat hypertension was observed in 7.5% of hypertensive patients. CONCLUSIONS: The prevalence of LVH in our population was high (43.7%) and some parameters related to diastolic left ventricular function (IVRT, A-wave) were correlated with LVMI. Systolic ambulatory BP was significantly correlated with LVMI, while diastolic BP was not.

An improved blood substitute. In vivo evaluation of its renal effects.

Nephrotoxicity of free hemoglobin (Hb) based blood substitutes still awaits full elucidation. Previous reports attributed Hb passage through the renal glomeruli to a tendency of the Hb tetramer to dissociate into dimers. Now it has become more evident that the Hb tetramer is able to extravasate. It appears that the electrical charge of proteins plays an important role, with electronegativity and a low isoelectric point favoring intravascular persistence. This effect was utilized in the development of an improved blood substitute, comprising Hb reacted with o-ATP and o-adenosine, to form an intra- and intermolecularly cross linked product, which is reduced with glutathione. The modification reagents possess the desired pharmacologic activities and produce an increase in the electronegative charges on the Hb surface. All Hb polymers and chemically modified tetramers present in this solution have a uniform electronegative charge, with a pl of 6.1-6.2. In this present study, unmodified bovine Hb and an improved blood substitute were used for the replacement of 40% of the total blood volume in rats. The nephrotoxic effect was investigated by the determination of urinary output, glomerular filtration rate (GFR), fractional excretion of sodium (FENa), potassium (FEK), and chloride (FECl), urine/plasma osmolality ratio, and urine N-acetyl-beta-D-glucosaminidase (NAG) level. The free Hb and non heme protein contents in the urine were analyzed by using isoelectric focusing and size exclusion liquid chromatography methods. The results indicate that unmodified Hb is nephrotoxic. An initially elevated urinary output was followed by a significant oliguria associated with decreased GFR, FEK, and FECl and elevated FENa and NAG. Severe hemoglobinuria was associated with proteinuria. Analysis of urine from unmodified Hb treated rats revealed the presence of Hb tetramers. Histopathological examination of the kidneys showed cytoplasmic vacuolization of proximal tubular epithelium. On the contrary, an improved blood substitute did not produce any nephrotoxic reactions. It was found that this Hb solution did not pass through the renal glomerular barrier and was not present in urine samples. In conclusion, such a chemical and pharmacological alteration of Hb molecules reduced their interaction with renal glomeruli and suspended nephrotoxicity.