Plasma levels and vascular effects of vasopressin in patients undergoing coronary artery bypass grafting.

OBJECTIVE: Recent studies have suggested that endogenous vasopressin (AVP) acts as a spasmogen during coronary artery bypass grafting (CABG). Given that AVP could induce vasospasm in the grafted vessel, we assessed the release of this peptide during and after CABG, and explored ways of counteracting its contractile effect on the internal mammary artery (IMA). METHODS: Plasma levels of AVP were determined by radioimmunoassay in 16 patients before, during and after CABG. Using isometric force recording techniques, we also investigated the mechanisms involved in the contractile effect of AVP in ring preparations of IMA specimens taken from 95 patients. RESULTS: Plasma AVP levels peaked after the start of cardiopulmonary bypass (CPB) and correlated well with serum osmolality (Pearson's r=0.9490; P<0.0001; n=16). An inverse correlation was observed between plasma AVP levels recorded at this stage and the maximal contraction induced in vitro by AVP in vascular rings from the same patients (Pearson's r=-0.6968; P<0.01; n=16). No change in the AVP response was produced by endothelium removal, exposure to the NO precursor (3 x 10(-4)M L-arginine), inhibition of nitric oxide (NO) synthase (3 x 10(-5) M L-NAME) or soluble guanylate cyclase (3 x 10(-6) M 1H-[1,2,4]oxadiazol [4,3,-alpha]quinoxalin-1-one (ODQ)), removal of the superoxide anion (100 U/ml superoxide dismutase (SOD) plus 1200 U/ml catalase) or hydroxyl radical (10(-4) M deferoxamine), or specific alpha1 - (10(-6) M prazosin) or endothelin (10(-5) M bosentan) receptor antagonism. In contrast, adenylate cyclase activation (3 x 10(-8) M forskolin) reduced the contractile response to AVP, while prostanoid synthesis (3 x 10(-6) M indomethacin) inhibition and blockade of Ca2+ -activated potassium channels (KCa) (10(-3) M tetraethylammonium (TEA)) enhanced AVP contraction. Age, gender and smoking also modified the AVP response. CONCLUSION: Our findings suggest a role for AVP as a modulator of vascular tone in human IMA. The effect of AVP is dependent on prostanoids and Ca2+ -activated K+ channels, so its dysfunction in pathophysiological cardiovascular processes could mean that AVP, among other factors, produces vasospasm in IMA grafts.     

CD10 is expressed in a subset of chromophobe renal cell carcinomas.

CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.     

Unbalanced X-chromosome inactivation in haemopoietic cells from normal women

We studied X-chromosome inactivation patterns in blood cells from normal females in three age groups: neonates (umbilical cord blood), 25–32 years old (young women group) and >75 years old (elderly women). Using PCR, the differential allele methylation status was evaluated on active and inactive X chromosomes at the human androgen receptor (HUMARA) and phosphoglycerate kinase (PGK) loci. A cleavage ratio (CR)  3.0 was adopted as a cut-off to discriminate between balanced and unbalanced X-chromosome inactivation. In adult women this analysis was also performed on hair bulbs. The frequency of skewed X-inactivation in polymorphonuclear (PMN) cells increased with age: CR  3.0 was found in 3/36 cord blood samples, 5/30 young women and 14/31 elderly women. Mathematical analysis of patterns found in neonates indicated that X-chromosome inactivation probably occurs when the total number of haemopoietic stem cell precursors is 14–16. The inactivation patterns found in T lymphocytes were significantly related to those observed in PMNs in both young ( P  < 0.001) and elderly women ( P  < 0.01). However, the use of T lymphocytes as a control tissue for distinguishing between skewed inactivation and clonal proliferation proved to be reliable in young females, but not in elderly women, where overestimation of the frequency of clonal myelopoiesis may appear.     

Rehabilitation of Fecal Incontinence After Sphincter-Saving Surgery for Rectal Cancer: Encouraging Results

Purpose  Some patients, having undergone sphincter-saving operations for rectal cancer, may suffer from fecal incontinence. This study was designed to evaluate the results of rehabilitative treatment in patients with fecal incontinence after sphincter-saving operations and to identify the negative factors that influence therapeutic success. Methods  Between January 2000 and June 2007, 88 incontinent patients (54 women; age range, 47–73 years; 69 had received a low anterior rectal resection; 19 a straight coloanal anastomosis) were included in the study. After a preliminary clinical evaluation, including the Wexner Incontinence Scale score, anorectal manometry was performed. All 88 patients underwent rehabilitative treatment according to the “multimodal rehabilitative program” for fecal incontinence. At the end of program, all 88 patients were reassessed by means of a clinical evaluation and anorectal manometry; their results were compared with the clinical and manometric data from ten healthy control subjects. Postrehabilitative Wexner Incontinence Scale scores were used for an arbitrary schedule of patients divided into three classes: Class I, good (score ≤3); Class II, fair (score >3 to ≤6); Class III, poor (score >6). Results  After rehabilitation, there was a significant improvement in the overall mean Wexner Incontinence Scale score (P < 0.03) for both surgical operation types (low anterior rectal resection: P < 0.05; coloanal anastomosis: P < 0.02). Only 21 patients (23.8 percent) were symptom-free, and 37 (42 percent) were considered Class III. A significant postrehabilitative direct correlation was found between: 1) Wexner Incontinence Scale score and degree of genital relaxation (rρ _s 0.78; P < 0.001); 2) Wexner Incontinence Scale score and irradiation (rρ _s 0.72; P < 0.01); and 3) Wexner Incontinence Scale score and pelvic (rρ _s 0.65; P < 0.01) or anal surgery (rρ _s 0.68; P < 0.01). No significant differences were found between prerehabilitative and postrehabilitative anal pressures in low anterior rectal resection and coloanal anastomosis patients. Conclusions  After rehabilitation, some patients become symptom-free, many patients show an improvement in the Wexner Incontinence Scale score, and others exhibit the highest grades of fecal incontinence. Genital relaxation, radiotherapy, and previous pelvic, and/or anal surgery are impeding factors to rehabilitative success.     

Global risk stratification in primary hypertension: the role of the kidney

OBJECTIVE: Microalbuminuria and a reduction in creatinine clearance are well known, independent predictors of unfavourable cardiovascular prognosis. Our aim was to evaluate the impact of renal damage on global risk stratification in 459 non-diabetic, untreated hypertensive patients (64% men, mean age 47.3 years). METHODS: Renal damage was defined as creatinine clearance < 60 ml/min per 1.73 m2 (Cockcroft-Gault formula) or the presence of microalbuminuria (albumin to creatinine ratio). Cardiac and vascular organ damage was assessed by ultrasound scan. We evaluated the impact of renal damage, left ventricular hypertrophy and carotid atherosclerosis on risk stratification as recommended by the 2007 European Society of Hypertension-European Society of Cardiology Guidelines. RESULTS: The prevalence of renal damage, microalbuminuria and creatinine clearance < 60 ml/min per 1.73 m2 was 24, 12 and 13%, respectively. There was no correlation between albuminuria and estimated creatinine clearance, and only 0.9% of patients showed microalbuminuria and reduced creatinine clearance simultaneously. The presence of renal damage entailed a 3.3 times higher risk of having cardiovascular abnormalities. Based on routine work-up, 58% of our study patients were classified as high-very high risk. The simultaneous evaluation of albuminuria and creatinine clearance resulted in a significant change in risk stratification, since 68% of patients were classified in the high-very high risk class. The search for left ventricular hypertrophy or carotid atherosclerosis by ultrasonography did not improve risk stratification significantly as compared to the assessment of renal damage. CONCLUSIONS: Our findings support the assessment of renal abnormalities as the first step when evaluating target organ damage for cardiovascular risk assessment in hypertensive patients.     

Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients

BACKGROUND/AIM: Cefotaxime is considered the first-choice antibiotic for empirical treatment in cirrhotic patients developing bacterial infections. It has been suggested that amoxicillin-clavulanic acid could be an alternative to cefotaxime, particularly in patients developing bacterial infections while on prophylactic norfloxacin. The aim of the present study was to compare amoxicillin-clavulanic acid with cefotaxime in the treatment of bacterial infections in cirrhosis. METHODS: Ninety-six hospitalized cirrhotic patients with suspicion of bacterial infection were prospectively included and randomized into two groups: one group (n=48) received amoxicillin-clavulanic acid, first intravenously 1 g-0.2 g every 8 h, and then orally 500 mg-125 mg every 8 h, and the other group (n=48) received intravenous cefotaxime 1 g every 6 h. Patients were stratified for previous prophylaxis with norfloxacin and ascitic fluid infection. RESULTS: Sixteen patients were excluded from the analysis because bacterial infection was not demonstrated or because of secondary peritonitis. Therefore, 38 patients from the amoxicillin-clavulanic acid group and 42 from the cefotaxime group were finally analyzed. There were 24 ascitic fluid infections in each group. Infection resolution (86.8% vs 88%, 95% CI: -0.15 to 0.13, p NS), spontaneous bacterial peritonitis resolution (87.5% vs 83.3%, 95% CI: -0.15 to 0.24, p NS), duration of treatment, incidence of complications, time of hospitalization and hospital mortality were similar in both groups. Considering patients on prophylactic norfloxacin, infection resolution was also similar (100% vs 83.3%, 95% CI: -0.04 to 0.37, p NS). No adverse events were observed in either of the two groups. The cost of antibiotics was statistically lower in the amoxicillin-clavulanic acid group (p<0.001). CONCLUSIONS: Amoxicillin-clavulanic acid is as effective as cefotaxime in the treatment of bacterial infections in cirrhotic patients, but is less expensive and can be administered orally. These results suggest that amoxicillin-clavulanic acid is an effective alternative to cefotaxime for the empirical treatment of bacterial infections in cirrhosis.     

A case of primary toxoplasmosis in an immunocompetent patient

CASE REPORT: A case of an immunocompetent patient presenting primary systemic toxoplasma infection involving the eye (condition seen in less than 3% of primary infections). The patient showed reactivation of this primary focus two years later. DISCUSSION: Diagnosis of toxoplasm retinitis is based on a typical lesion consisting in an area of active retinitis adjacent to an inactive corioretinal scar. Differential diagnosis must consider other causes of retinal coroiditis in primary infection cases: sarcoidosis, tuberculosis, syphilis as well as viral and fungal infections. Ocular toxoplasmosis was confirmed by serum tests.