Reversible impairment of myocardial function in Hanta virus infection - direct viral effect?
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Biomedical subjects
Publications and source records attributed to M Azizi.
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INTRODUCTION: Cardiac resynchronization therapy (CRT) using coronary sinus (CS) leads is a new method for the therapy of congestive heart failure (CHF). Because the intervention is more complex than regular pacemaker implantations, information on the feasibility and side effects of this method are of interest. METHODS: From 1999 to June 2005, CRT implantations were attempted in 244 patients (pts; mean age 64+/-12 years, range 14-90 years), 82% were male, 44% had coronary artery disease, 29% were in atrial fibrillation, 71 had preexisting pacemakers. RESULTS: In 97% of the pts the intervention was successful (27% of the systems with defibrillation capabilities). In 285 interventions, 255 CS leads were positioned according to CS vein anatomy in 130 posterolateral, 97 anterolateral and 28 anterior side branches (16 patients received 2 CS leads). Over-the-wire leads were used in 88%, 71% were additionally preshaped. We observed no mortality but 37 complications (12.5%): CS dissection in 9, CS perforation in 1, ventricular fibrillation in 4, asystole in 5, pulmonary edema in 1, pneumothorax in 2, need for early CS lead revision in 19 (dislodgement n=7, phrenic nerve stimulation n=12) and infection with explantation in 2 cases. An improvement in NYHA functional class was found in 88% of pts (only 55% if anterior lead position). CONCLUSION: Perioperative complications during CS lead implantation occur in 10-15% of cases. Most patients responded well to CRT. Patients should be informed about the possible need for a reoperation. During implantation, immediate defibrillation and stimulation capabilities must be available. Anterior lead positions should be avoided.
This report illustrates the case of a patient with an implantable cardioverter defibrillator (ICD) who during physiotherapy with transcutaneous electrical stimulation of the lumbar musculature perceived a shock discharge by the ICD. Analysis of the stored electrogram showed inappropriate therapy due to electromagnetic interference with the external stimulation. Patients as well as physiotherapists should be informed about this potential interaction to avoid such iatrogenic, inappropriate ICD therapy.
BACKGROUND: Acute studies in cardiac resynchronization therapy (CRT) showed that hemodynamic effects may depend on the coronary sinus (CS) lead position. However, there are no data on the longterm effect of CS lead position. METHODS: In 45 heart failure patients with left bundle branch block and QRS >150 ms (age 59+/-10 years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular pacemakers were implanted. CS leads were positioned in posterior (P, n=15), lateral (L, n=19) or, if no other option available, anterior (A, n=11) side branches. Before and 6 months after implantation, clinical state, echocardiography, brain natriuretic peptide (BNP) and right heart catheterization were evaluated. RESULTS: Baseline parameters were similar between groups. After 6 months, there were 32/34 responders in groups P and L compared to 7/11 responders in group A (94 vs groups P and L: Arterial pressure +8 and +9% vs +2%; PCWP -23 and -15% vs -4%, pulmonary pressure -18 and -12% vs -3% (p<0.01 for A vs P+L); cardiac index +21 and +12% vs +11% (p=0.03 for A vs P). BNP was reduced by 55, 35, and 27% (p=0.05 for A vs P). Ejection fraction increased in P and L by 40 and 41%, respectively, but only by +19% in A (p<0.03 for A vs P+L). CONCLUSION: Chronic CRT improves ejection fraction, BNP and hemodynamic measurements predominantly in patients with lateral and posterior CS lead positions. Anterior lead positions should be avoided.
BACKGROUND: A leaf gauge and an anterior jig may be used to assist the recording of a reproducible jaw position for restorative and prosthodontic treatment. This study investigated possible condylar displacement using an opto-electronic jaw-tracking device and a leaf gauge or anterior jig. The effect of a leaf gauge and anterior jig on jaw muscle electromyography was also examined. METHODS: Five healthy adults without symptoms of temporomandibular disorders were selected. Condylar displacement during clenching were recorded simultaneously with electromyographic activity of superior and inferior heads of the lateral pterygoid, anterior and posterior temporalis, masseter, and suprahyoid muscles. Subjects were trained to bite at maximum and half-maximum bite-force using an anterior jig incorporating a force transducer. RESULTS: No consistent condylar displacement was observed in x, y and z axes between different bite-forces although there was a trend towards superior displacement. Comparison of maximum intercuspal clench and maximum clench on a leaf gauge and an anterior jig produced significant decrease in anterior temporalis activity (p < 0.05), whilst an anterior jig with maximum clench significantly decreased posterior temporalis muscle activity. CONCLUSION: Within the limits of this pilot study, no consistent change in condylar position was identified with these appliances.
Mycoplasma pneumoniae is a common respiratory pathogen in community acquired pneumonia. In severe cases extrapulmonary manifestations of the disease may be prominent. Proof of infection is found, though usually delayed, through serologic methods. A calculated therapy of community acquired pneumonia, especially in younger patients with interstitial infiltrates, should therefore include effective treatment for Mycoplasma pneumoniae. Macrolide antibiotics are the most commonly used antibiotics in the treatment of mycoplasma infection, alternatives include ketolides, quinolones and tetracyclines.
One to 10 per cent of healthy adult individuals do not produce protective levels of anti-hepatitis B surface (HBs) antibodies, following a standard vaccination protocol. Lack of an HBs antigen (Ag)-specific T-cell repertoire is amongst the possible defects, which may lead to humoral unresponsiveness and is the main objective of this study. We analysed TcR BV (T-cell receptor beta chain variable) gene usage in T lymphocytes from nine healthy adult responders and six nonresponders to recombinant HB vaccine, before and after booster vaccination. CD4+ and CD8+ T-cell populations were isolated from peripheral blood mononuclear cells by magnetic beads, and the expression of TcR BV genes in each population was investigated by reverse transcription polymerase chain reaction and hybridization with specific probe. When the usage of each TcR BV gene within CD4+ and CD8+ T cells of the responders was compared with that of nonresponders, statistically significant difference (P < 0.01) was noted for BV5S2-3 gene family in CD4+ T cells of nonresponders. Furthermore, individual vaccinees were shown to overexpress several TcR BV genes. To characterize the T-cell repertoire and determine their clonal nature, analysis of CDR3 length polymorphism was performed. Our results show that T-cell response to HBsAg is generally oligoclonal and involves multiple BV families. Furthermore, overexpressed individual TcR BV genes and CDR3 length distributions in response to HBsAg are subject-dependent. In conclusion, our results are not in line with the notion that defective TcR repertoire may be an explanation for unresponsiveness to recombinant HBsAg vaccine.
Blood pressure (BP) response to infused angiotensin II (Ang II) has been widely used to characterize hypertensive subjects. High cholesterol levels have recently been found to enhance this response in young men, suggesting an important new link between atherosclerosis and hypertension. The present study assessed the familial resemblance of the BP response following an Ang II infusion and measured the factors affecting the trait in a large set of hypertensive men and women. After a low-salt diet for 7 days a 30-min infusion of Ang II was administered to 218 white hypertensive patients (28 singletons, 80 sibling pairs, 10 trios). Age and gender were significantly correlated to the Ang II systolic but not to the diastolic BP response. Conversely, cholesterol level and especially low-density lipoprotein (LDL) were correlated to both systolic and diastolic changes. Multivariate analysis showed that age, gender, and LDL were the three parameters that explained the systolic BP change whereas plasma LDL remained the only variable significantly correlated to the diastolic BP change. Significant familial resemblances in the Ang II induced systolic and diastolic BP response were observed, especially in female pairs. On this limited number of subjects, suggestive evidence for association and linkage was found between the trait, A1166C, and (CA)n repeat polymorphisms of the Ang II type 1 receptor (AT1R) gene. In conclusion, the Ang II induced BP change is strongly related to plasma LDL in hypertensive men and women, stressing the importance of the lipid profile as a contributor to BP regulation. Familial resemblance of this intermediate phenotype is sex dependent and may be partly explained by polymorphisms of the AT1R gene.
1. Angiotensin I-converting enzyme (ACE) has two homologous active N- and C-terminal domains and displays activity towards a broad range of substrates. The tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) has been shown to be hydrolysed in vitro by ACE and to be a preferential substrate for its N-terminal active site. This peptide reversibly prevents the recruitment of pluripotent haematopoietic stem cells and normal early progenitors into the S-phase. 2. Angiotensin I-converting enzyme inhibitors, given as a single dose to normal subjects or during long-term treatment in hypertensive patients, result in plasma AcSDKP levels five- to six-fold higher and urine concentrations 40-fold higher than those of control subjects and/or patients. Thus, AcSDKP is a natural peptide hydrolysed by the N-terminal domain of ACE in vivo. In addition, ACE may be implicated in the process of haematopoietic stem cell regulation by permanently degrading this natural circulating inhibitor of cell entry into the S-phase. 3. Besides hydrolysis by ACE, the second very effective mechanism by which AcSDKP is cleared from plasma is glomerular filtration. Because of its high sensitivity and specificity, the measurement of AcSDKP in plasma and urine provides a valuable tool in screening specific inhibitors of the N-terminal domain of ACE and in monitoring ACE inhibition during chronic treatment. 4. The long-term consequences of AcSDKP accumulation are not known. During chronic ACE inhibition in rats, AcSDKP levels slightly increase in organs with high ACE content (kidneys, lungs). To significantly increase its concentration in target haematopoietic organs (the extracellular fraction of bone marrow), AcSDKP has to be infused on top of a captopril-based treatment. 5. A selective inhibitor of the N-domain of ACE in vitro and in vivo has been identified recently. The phosphinic peptide RXP 407 does not interfere with blood pressure regulation, but does increase, dose dependently, plasma concentrations of AcSDKP in mice, in contrast with lisinopril, which affects the metabolism of both AcSDKP and angiotensin I. N-Terminal-selective ACE inhibitors may be used to selectively control AcSDKP metabolism in target haematopoietic organs. This new therapeutic strategy may be of value for protecting haematopoietic cells from the toxicity of cancer chemotherapy.
We describe the specific identification of Leishmania species in Iran using PCR DNA amplification of kDNA. For this purpose, we designed a pair of primers--upstream 5' TCGCAGAACGCCCCTACC 3' and downstream 5'-AGGGGTTGGTGTAAAATAGGC 3'--specific for conserved sequences of kDNA of Leishmania. Using this primer, we identified 3 different amplified fragments from the kDNA of the WHO reference Leishmania species. Two bands at 620 and 850 bp were identified for L. major (MRHO/IR/64/Nadim-1 strain) and only 1 band at 620 bp was identified for L. major (P strain). Therefore, we could differentiate 2 Leishmania species. Also, 1 band at 830 bp was identified for L. tropica (MHOM/Sudan/58/OD strain). We determined the sequence analysis of 2 DNA bands (620 and 850 bp) obtained from kDNA of L. major (MRHO/IR/64/Nadim-1). A total of 157 bp from the 5' site and 234 bp from the 3' site were sequenced and showed about 28% homology between 620 and 850 bp fragments. This technique could amplify as little as 1 fg of DNA and was used to differentiate kDNA samples isolated from Iranian patients with cutaneous leishmaniasis. These data indicate that the primer used for PCR amplification of kDNA is specific and can be used for diagnostic and epidemiological purposes.
Palpation of the radial pulses is an important technique in traditional Chinese medicine. Two double-blind randomized trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitized subjects) and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform were measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-min acupuncture period. In sensitized patients, arterial diameter significantly increased during real acupuncture, compared with the sham group (+7.5 +/- 2.8 vs. -2.9 +/- 2.7%, respectively; P < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time course of blood pressure, radial artery distensibility, and pressure waveform. Our results demonstrate that real acupuncture is associated with an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.
The phosphinic peptide RXP 407 has recently been identified as the first potent selective inhibitor of the N-active site (domain) of angiotensin-converting enzyme (ACE) in vitro. The aim of this study was to probe the in vivo efficacy of this new ACE inhibitor and to assess its effect on the metabolism of AcSDKP and angiotensin I. In mice infused with increasing doses of RXP 407 (0.1--30 mg/kg/30 min), plasma concentrations of AcSDKP, a physiological substrate of the N-domain, increased significantly and dose dependently toward a plateau 4 to 6 times the basal levels. RXP 407 significantly and dose dependently inhibited ex vivo plasma ACE N-domain activity, whereas it had no inhibitory activity toward the ACE C-domain. RXP 407 (10 mg/kg) did not inhibit the pressor response to an i.v. angiotensin I bolus injection in mice. In contrast, lisinopril infusion (5 and 10 mg/kg/30 min) affected the metabolism of both AcSDKP and angiotensin I. Thus, RXP 407 is the first ACE inhibitor that might be used to control selectively AcSDKP metabolism with no effect on blood pressure regulation.
Palpation of the radial pulses is one of the most important techniques in traditional Chinese medicine. Two double-blind randomised trials of the effects of real and sham acupuncture on radial artery hemodynamics were conducted in 19 patients regularly exposed to acupuncture (sensitised subjects), and in 8 healthy subjects devoid of previous exposure (naive subjects), respectively. Radial artery diameter and pulse waveform was measured with a high-resolution echotracking system and aplanation tonometry, respectively, before and during a 20-minute's acupuncture period. In sensitised patients, arterial diameter significantly increased during real acupuncture, compared to the sham group (+7.5 +/- 2.8% vs -2.9 +/- 2.7%, respectively; p < 0.01). By contrast, in naive subjects, arterial diameter did not change during real or sham acupuncture. In both populations, no significant difference was observed between real and sham acupuncture, concerning the time-course of blood pressure, radial artery distensibility and pressure waveform. Our results demonstrate that real acupuncture can determine an objective vasodilatation of the radial artery in patients regularly exposed to acupuncture, but not in naive subjects.
The influence of carbon monoxide (CO) on chronic spinal nerve lesion induced spinal cord neurodegeneration was examined using immunohistochemical expression of the constitutive isoform of its synthesising enzyme, hemeoxygenase-2 (HO-2) in a rat model. Spinal nerve lesion at L-5 and L-6 level was produced according to the Chung model of neuropathic pain and rats were allowed to survive for 8 weeks. Sham operated rats, in which the spinal nerves were exposed but not ligated, served as controls. Ligation of spinal nerves in rats resulted in an upregulation of HO-2 expression which was most pronounced in the ipsilateral gray matter of the spinal cord compared to the contralateral side. In these rats, morphological investigations showed distorted neurons, membrane disruption, synaptic damage and myelin vesiculation. Sham operated rats did not show an upregulation of HO-2 expression and the structural changes in the spinal cord were absent. These observations strongly suggest that spinal nerve lesion is associated with an increased production of CO which is somehow contributing to the neurodegenerative changes in the spinal cord, not reported earlier.
The development of angiotensin-converting enzyme inhibitors and selective angiotensin type 1 (AT1)-receptor antagonists has provided new insights into understanding the mechanism of the renin-angiotensin system (RAS) in the pathophysiology of cardiovascular disease. There is good evidence from meta-analyses that shows that inhibition of the RAS achieves organ protection features that go beyond blood pressure control. Candesartan cilexetil, a new angiotensin II receptor antagonist, is characterised by its tight binding to and slow dissociation from the AT1 receptor, and high antagonistic potency, resulting in long-lasting antagonistic effects. It is anticipated that these pharmacological characteristics may bring additional benefits to patients, not only for the management of essential hypertension but also for the management of end-organ damage.
BACKGROUND: Additive hemodynamic effects of combined blockade of the renin-angiotensin system by an angiotensin I converting enzyme inhibitor and an angiotensin II antagonist have been observed in sodium-depleted normotensive volunteers and in patients with congestive heart failure. OBJECTIVE: To investigate whether the same additive hemodynamic effects occur in patients with hypertension and to verify the safety of such an approach. DESIGN: Multicenter, randomized, double-blind, parallel-group, pilot study. PATIENTS: 177 patients with mild-to-moderate hypertension [diastolic blood pressure (DBP): 95-115 mmHg after a 4-week placebo run-in period] were included in the study. INTERVENTION: Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily was administered for 6 weeks. The effects of this therapeutic regimen was compared with similar groups of patients who received either 50 mg losartan daily or 10 mg enalapril daily. MAIN OUTCOME MEASURES: 24-hour ambulatory mean DBP and clinic DBP measured at trough after 6 weeks of treatment. RESULTS: 24-hour ambulatory mean DBP did not significantly differ between treatment groups although the combination tended to lower BP more. The combination therapy was more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012], and more effective than enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28 patients, higher plasma active renin and angiotensin I levels during blockade by the combination therapy were observed. This finding confirmed that the combination of the two agents inhibited the renin-angiotensin system to a greater extent than did either agent alone. CONCLUSION: A combination of 10 mg enalapril daily and 50 mg losartan daily safely induces a supplementary, although modest, fall in clinic DBP in patients with mild-to-moderate essential hypertension.
The aldosterone response to infused angiotensin II (Ang II) in patients receiving a low-salt diet has been described as an important phenotype for genetic studies on human hypertension. The objectives of the present study were to determine the parameters that influence this intermediate phenotype as a quantitative trait and to assess the importance of its familial resemblance in hypertensive sibling pairs. Two hundred one white hypertensive subjects (95 families: 84 pairs and 11 trios) were selected in 3 centers. The patients followed the same protocol, which included a 4-week withdrawal period of antihypertensive therapy, a 1-week period on a low-salt diet, and a 30-minute infusion of Ang II. The increase in the aldosterone level was greater in women than in men (29.1+/-16.2 versus 18.2+/-9.6 ng/dL, P<0.0001). A strong relationship was found with age (r=-0.54, P<10(-4)) and plasma renin activity (r=0.32, P<10(-4)) in women but not in men. Weak correlations of the aldosterone response to Ang II were observed for the whole set of sibling pairs (r=0.11, NS). Conversely, strong sibling correlations were found among brother-brother pairs (r=0.40, n=36) and among sister-sister pairs as soon as age or menopausal status was considered. Similar results were obtained when the Ang I-aldosterone response was analyzed as a qualitative trait (kappa=0. 35, P<0.008 in brother-brother pairs). We conclude that age, gender, and plasma renin are strong determinants of the aldosterone response to Ang II, with strong sibling correlations in men and postmenopausal women. These relationships will have to be considered in future linkage and association studies.