Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Staphylococcus aureus as source of catheter‐related bloodstream infection evaluated by PFGE and rep‐PCR typing in a Brazilian hospital

Staphylococci are a common cause of catheter‐related bloodstream infection (CR‐BSI), and epidemiological typing is an important tool for effective infection control. This study evaluated by PFGE and rep‐PCR whether Staphylococcus aureus strains isolated from skin and catheter tips were related to specimens isolated from blood. A prospective observational study, carried out in a clinical surgical ward at a Brazilian hospital between September 2000 and November 2002, investigated non‐tunneled central venous catheters from 179 patients. S. aureus isolates were mainly obtained from blood (41.4%), while coagulase‐negative staphylococci strains were more often isolated from the skin at the catheter insertion site (49.7%) and from the catheter tip (57.5%). Among the 21 strains isolated from 9 patients at 2 or 3 sites simultaneously, 9 were methicillin‐resistant S. aureus (MRSA) and 12 were methicillin‐susceptible S. aureus (MSSA). Seven patients harbored the same S. aureus strain isolated from the skin, blood and/or catheter tip cultures. MRSA isolates belonged to one PFGE pattern (type A‐ subtypes A₁, A₂ and A₃), and to two rep‐PCR patterns (a and b). MSSA isolates were distinguished in five PFGE (B to F) and in three rep‐PCR (c, d and e) patterns. Both PFGE and rep‐PCR methods indicated that the skin at the catheter insertion site was the origin of CR‐BSI caused by S. aureus.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Mucosa‐associated lymphoid‐tissue lymphoma. Should we perform a colonoscopy in multiorgan involvement?

Mucosa‐associated lymphoid tissue (MALT) lymphoma is the most frequent non‐Hodgkin lymphoma in the gastrointestinal tract, but colon involvement has only been reported in multiorgan lymphoma. We present a rare case of a woman with MALT involvement of eye conjunctiva, tonsils, stomach, duodenum and colon. In selected cases like this, with multiorgan involvement, we recommend performing colonoscopy, with biopsies for immunohistochemistry with CD10 and cyclin D1 for differential diagnosis with other entities with different prognosis, such as follicular lymphoma, and mantle cell lymphoma, respectively.     

Esophageal P-Synchronous Pacing

An esophageal electrode can be employed to provide atrial sensing which then can be used to change from temporary right ventriculor (VVI) pacing to P-synchronous (VAT) pacing. Two cases of postoperative aortic valve replacement, each with new complete heart block (CHB) and dopamine dependency, are presented. In both cases, establishment of P-synchronous pacing resulted in improved hemodynamic status characterized by successful weaning from dopamine and maintenance of adequafe cardiac output (CO).     

Valve Resistance in Mitral Stenosis

To evaluate the value and the determinants of valve resistance in mitral stenosis, 95 patients with pure mitral stenosis were examined by Doppler echocardiography during their clinical follow-up, measuring cavity dimensions, left ventricular function, mitral area (by planimetry and pressure half time), mean transmitral pressure gradient, aortic flow, and pulmonary artery systolic pressure. The mitral resistance was calculated as mean transmitral pressure gradient/aortic flow ratio. To graduate the severity of the morphological abnormalities in valvular structure, we used a point score system with evaluation of leaflet and subvalvular thickness, calcification, and valvular mobility. The functional class was determined according to NYHA classifcation. In this study, both mitral area (r = -0.79, P < 0.001 and r_p= -0.60, P < 0.001) and mitral score (r = 0.68, P < 0.001 and r_p= 0.25, P = -0.013) were independent determinants of mitral resistance. In multivariate analysis, mitral resistance and female gender were selected by multiple linear regression analysis as determinants of pulmonary artery systolic pressure, and mitral area and pulmonary artery systolic pressure were selected by logistic linear regression analysis as determinants of NYHA functional class. In patients with moderate or severe mitral stenosis, the estimated probability for III and IV NYHA functional class considering mitral area 1 cm² or below went from 51.1–86.4% when mitral resistance below or above 130 dynes.sec.cm,⁻⁵ respectively, was considered together. Thus, mitral valve resistance should be used as a complement to the mitral area method in assessment of mitral stenosis, adding the effects of the reduction in mitral area and the damage in mitral valve apparatus.     

TRANSURETHRAL RESECTION OF PARTIALLY OBSTRUCTED EJACULATORY DUCTS: SEMINAL PARAMETERS AND PREGNANCY OUTCOMES ACCORDING TO THE ETIOLOGY OF OBSTRUCTION

Purpose

We determine how transurethral resection of the ejaculatory ducts performed for infertility affects seminal parameters and pregnancy outcomes in patients with partial ejaculatory duct obstruction due to a congenital or acquired etiological factor.

Materials and Methods

Based on history and physical examination, hormonal profiles, semen analyses, transrectal ultrasonography and vasography findings partial ejaculatory duct obstruction was diagnosed in 14 men a mean of 30 years old who presented for infertility evaluation. Patients were grouped according to congenital or acquired cause of obstruction. Transurethral resection of the ejaculatory ducts was performed using the standard resectoscope loop technique. Clinical outcome was assessed by postoperative analyses of seminal parameters and pregnancy reports.

Results

Transurethral resection of the ejaculatory ducts significantly improved semen quality (ejaculate volume and percentage of sperm motility) in all patients in the congenital group, while all but 1 (83%) had an improved sperm count. Pregnancy was achieved via sexual intercourse by 66% of the patients an average of 5.7 months postoperatively. Of the acquired etiological factor group 37.5% had improved semen quality after transurethral resection of ejaculatory duct and 12.5% achieved pregnancy via sexual intercourse. Postoperative complications occurred at a similar rate in each group (33%). However, complications in the congenital etiology group were minor, while 25% of the men in the acquired group had significant impairment of seminal parameters after transurethral resection of the ejaculatory ducts.

Conclusions

Semen quality improvement and pregnancy outcome after transurethral resection of the ejaculatory ducts for partial ejaculatory duct obstruction differ significantly according to the main etiological cause of obstruction. An equivocal diagnosis of partial obstruction and technical problems during transurethral resection of the ejaculatory ducts may contribute to failure. However, in some cases the reason for failure remains unclear.     

p53 OVEREXPRESSION AND HUMAN PAPILLOMAVIRUS INFECTION IN TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER: CORRELATION WITH HISTOLOGICAL PARAMETERS

Seventy-nine transitional cell carcinomas (TCCs) of the urinary bladder (25 grade 1, 22 grade 2, and 32 grade 3 tumours) were examined for p53 overexpression by immunohistochemistry with a monoclonal antibody and for human papillomavirus (HPV) infection by the polymerase chain reaction (PCR). Positive immunostaining for p53 was detected in 40·5 per cent of the cases; the percentage of positive cases was significantly lower in low-grade (G1 and G2) TCCs than in high-grade (G3) tumours (10·6 per cent vs. 84·4 per cent; P <0·0001). The overall rate of HPV infection was 32·9 per cent; 20·3 per cent of the cases were positive for HPV 16, 3·8 per cent for HPV 18, and 8·9 per cent for both. Consensus primers as well as type-specific primers for HPV types 6, 11, and 33 failed to detect any additional case with HPV infection. The prevalence of HPV 16 and/or HPV 18 infection was significantly higher in low-grade than in high-grade tumours (44·7 per cent vs. 15·6 per cent; P =0·0061). p53-positive cases were more common among papillary, deeply infiltrating tumours, and HPV-positive cases among papillary, non-infiltrating lesions. According to these data, p53 overexpression and HPV 16/18 infection are common findings in bladder TCC and there appears to be an inverse correlation of p53 overexpression and of HPV infection with tumour aggressiveness. The possibility of different molecular pathways in superficial low-grade and in invasive high-grade tumours is suggested.     

Ventricular Endocardial Right Bifocal Stimulation in the Treatment of Severe Dilated Cardiomyopathy Heart Failure with Wide QRS

PACHÓN, J.C., et al. : Ventricular Endocardial Right Bifocal Stimulation in the Treatment of the Severe Dilated Cardiomyopathy Heart Failure with Wide QRS. The QRS widening by ventricular conventional pacing impairs the systolic and diastolic functions and increases mitral regurgitation. The aim of this study was to compare conventional pacing to an alternative stimulation mode with a narrower QRS using two leads in the RV. Thirty‐nine (25 men, 14 women; mean age 60.1 ± 15.1 years ) dilated cardiomyopathy patients (Chagas' disease [n = 17], coronariopathy [n = 9], AV ablation for tachycardiomyopathy [n = 3], and other [n = 10] ) with cardiac failure (NYHA 3.1 ± 0.8 ), pacemaker indication, and chronic AV block (22 AF) had endocardial pacemaker implantations (27 Biotronik, 12 Guidant). Two RV leads (one septal, one conventional [RV apex] were connected, respectively, to the atrial and ventricular pacemaker plugs. After clinical stabilization they were studied under three stimulation modes in the same session: AAI (septal), VVI (conventional), and ventricular endocardial right bifocal stimulation (VERBS) (DDT/DVI/DDD = AV interval = 15/10 ms). In comparison to conventional pacing, VERBS increased ejection fraction (0.124), cardiac output (19.5%), and peak filling rate (31.0%), and decreased QRS duration (24.7%), left atrium area (11.9%), mitral regurgitation area (32.3%), the diastolic transmitral flow (E/A relation) (19.3%), and the propagation flow time (18.0%) from the mitral valve to the left ventricular apex (tE_col), (P < 0.05). The quality‐of‐life showed an impressive score reduction of 50.4%. The septal stimulation alone showed a less expressive benefit. In severe dilated cardiomyopathy with classic pacemaker indication, VERBS showed significantly better performance than the septal or the conventional stimulation alone. There was a good systolic and a remarkable diastolic improvement causing an important reduction in the quality‐of‐life score.