p21/WAF1/CIP1 EXPRESSION IN NORMAL MUCOSA AND IN ADENOMAS AND ADENOCARCINOMAS OF THE COLON: ITS RELATIONSHIP WITH DIFFERENTIATION

The immunoreactivity of p21 was evaluated in normal mucosa and in adenomas and adenocarcinomas of the human large bowel. In normal mucosa, p21 immunoreactivity was seen in the superficial third of the crypts (maturation compartment) and in surface (terminally differentiated) epithelium, and was mutually exclusive with Ki67/MIB1 reactivity. These data show that p21 expression is inversely related to proliferation and directly related to terminal differentiation. In adenomas, p21-reactive cells were frequently clustered in the superficial areas and were non-reactive for MIB1. In adenocarcinomas, p21 staining was heterogeneous: high p21 expression (19 cases) was associated with lower stage and lack of p53 overexpression. p21-reactive cells were devoid of MIB1 immunoreactivity, but no relationship could be found between p21 and MIB1 labelling indices. p21 heterogeneity may be related to alterations in the p53-dependent induction pathway: high p21 expression was associated with low to absent p53 reactivity, with presumed normal p53 function; low p21 expression was associated with p53 overexpression, with presumed p53 alteration resulting in loss of function.     

Early Conduction Disorders Following Percutaneous Aortic Valve Replacement

Background: Percutaneous aortic valve replacement (PAVR) may be an alternative therapy for patients with severe aortic stenosis who are denied valve surgery because of age and comorbidity. Data are few regarding the incidence of early conduction disorders (CD) after PAVR. We examined the incidence and characteristics of CD in the immediate postoperative period after PAVR, and the need for permanent pacemaker (PPM) implantation.
Methods and Results: Between June 2007 and June 2008 30 patients (mean age = 82.1 ± 8.5 years) underwent PAVR in our institution. The incidence of new, postoperative CD, diagnosed by 12-lead or 24-hour Holter electrocardiogram, was 68.0%. Left bundle branch block was the most common conduction abnormality, with an incidence of 45.8%. The incidence of complete atrioventricular block requiring PPM implantation was 20%.
Conclusions: We observed a higher incidence of early conduction disorders and need for PPM implantation after PAVR than generally reported after surgery. Whether this observation is clinically important requires larger prospective studies and follow up.     

Mycobacterium tuberculosis chaperonin 10 and N-truncated fragments Their synthesis and purification by the isoelectric focusing technique carried out in solution

The Mycobacterium tuberculosis chaperonin 10 protein and fragments corresponding to sequences 59-99, 51-99 and 26-99 were synthesised by the solid-phase methodology using a double coupling protocol and without the aid of capping agents. After the final acid cleavage using the low TFMSA-high HF protocol the polypeptides were purified by either the ion exchange chromatography/RP-HPLC combination or the isoelectric separation carried out in solution and followed by semi-preparative RP-HPLC. Comparison of the results obtained through the two approaches indicated that in general the isoeletricfocusing/HPLC combination was superior both in terms of recovery of final material and its purity. The advantages found were as follows: (i) Unlike ion exchange chromatography, no tailoring of the separation conditions is required. (ii) Several consecutive focusings can be carried out in progressively narrower pH gradients. This increases the separation resolution without the need of changing other separation parameters, (iii) Very little manipulation is needed, and each focusing requires 3-5 h. (iv) Full compatibility with non-ionic denaturants such as 8 M urea. This increases solubility so that using the ROTOFOR instrument described here 50-100 mg crude polypeptide can be processed daily. Thus the isoelectric focusing technique carried out in solution is a valid and inexpensive alternative to ion exchange chromatography. © Munksgaard 1997.     

Antipyrine clearance in chronic and neoplastic liver diseases: A study of 518 patients

Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 ± 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 ± 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 ± 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 ± 0.174 mL/min per kg) was similar to that of the healthy group (0.489 ± 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r²= 0.10, P= 0.01) and prothrombin time (r²= 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.     

QUALITY OF LIFE ASSESSMENT IN PATIENTS WHO UNDERGO SACRAL NEUROMODULATION IMPLANTATION FOR URGE INCONTINENCE: AN ADDITIONAL TOOL FOR EVALUATING OUTCOME

PURPOSE: We investigated the impact of sacral neuromodulation on quality of life and assessed the importance of quality of life for determining the success of sacral neuromodulation in patients with detrusor hyperactivity, including instability and hyperreflexia. We also compared it with parameters documented in a voiding diary. MATERIALS AND METHODS: From May 1998 to December 2000, 82 female and 31 male patients 17 to 79 years old (mean age 51.1) with urge incontinence (63), urgency/frequency (5), voiding disturbance (41) and pelvic pain (4) resistant to conservative treatment were enrolled in a national prospective registry after showing a positive response to percutaneous nerve evaluation testing. Of the patients 47 who were 32 to 79 years old (mean age 59.2) with urge incontinence due to detrusor instability and 16 who were 27 to 51 years old (mean age 51.5) with hyperreflexia were asked to complete a validated self-reporting incontinence domain specific quality of life questionnaire before, and 3, 6, 9, 12, 18, 24 and 36 months after implantation. RESULTS: Compared with baseline the quality of life index significantly improved at each followup, which strongly correlated with the decrease in the number of incontinence episodes. CONCLUSIONS: Evaluating quality of life may be an additional useful tool for assessing the results of sacral neuromodulation for urge incontinence. Our study confirms that sacral neuromodulation is effective therapy for urge incontinence that can have a positive effect on patient quality of life.     

Biventricular Pacing via a Persistent Left Superior Vena Cava: Report of Four Cases

GASPARINI, M., et al .: Biventricular Pacing via a Persistent Left Superior Vena Cava: Report of Four Cases. Persistence of left superior vena cava (LSVC) is an uncommon finding during pacemaker implantation, which may be particularly relevant in performing LV transvenous pacing. Rarely, it is further complicated by the presence of atresia of the coronary sinus ostium (CSO). This article reports the authors experience with biventricular pacing (Biv-P) in this unusual clinical setting. From October 1999 to April 2002, 158 patients underwent biventricular pacing. In four of them (mean age 62.2 years), the presence of a persistent LSVC draining into the coronary sinus (CS) was detected at implantation, associated with atresia of the CSO in two patients. A common characteristic was the angiographic finding of a large CS with few tributaries. The LV leads were successfully positioned in the middle cardiac vein in three patients and in a posterolateral vein in one patient. All vessels were large and their cannulation via downstream CS catheterization required the lead to be manipulated through sharp angles. Mean fluoroscopic exposure and procedural times were not significantly different from the overall Biv-P population. In all patients, at a mean follow-up of 11 months, sensing and capture threshold remained stable and a significant decrease in NYHA functional class and increase in LVEF were noted. The direct lead placement in large CS tributaries in the presence of persistent LSVC was feasible and safe. The leads remained stable up to a mean follow-up of nearly 1 year. (PACE 2003; 26[Pt. II]:192–196)     

Cavotricuspid Isthmus Ablation and Subcutaneous Monitoring Device Implantation in a 2‐Year‐Old Baby with 2 SCN5A Mutations,Sinus Node Dysfunction,Atrial Flutter Recurrences,and Drug Induced Long‐QT Syndrome: A Tricky Case of Pediatric Overlap Syndrome?

We describe the case of 2‐year‐old baby with compound heterozygosity for paternal and maternal alleles mutation of α‐subunit of the cardiac sodium channel (SCN5A), sinus node dysfunction, atrial flutter recurrences, and drug induced long‐QT syndrome. In this setting, we chose at first to perform linear ablation of cavotricuspid isthmus resulting in a bidirectional isthmus block. As a second step, we decided to implant a miniaturized loop recorder that, with a minimally invasive procedure, permits us to follow the development of the disease in order to define the future strategy. After 8 months follow‐up, automatic daily loop‐recorder transmissions disclose the complete absence of any arrhythmia along with asymptomatic ventricular pauses due to sinus node dysfunction. Echocardiography shows normal findings, in particular no left ventricular dysfunction.