BILIARY HYPERPRESSURE IN RAT EXTRAHEPATIC CHOLESTASIS ALTERS HORSERADISH PEROXIDASE BILIARY EXCRETION

1. The authors investigated the effect of two extrahepatic cholestasis models (one by bile duct ligation and the other by choledocho-jugular fistula) on the hepatic clearance of horseradish peroxidase in male Sprague-Dawley rats divided into four groups. 2. In groups A (n = 5 rats) and B (n = 5), bile duct ligation was performed, while a choledocho-jugular fistula was created in groups C (n = 5) and D (n= 7). A 10 mg intravenous bolus of horseradish peroxidase was injected after 24 h (groups A and C), 48 h (groups B and D) or 1 h (Group E; five sham-operated rats). Serum and bile samples were then serially collected for 2 h. 3. In all groups, serum horseradish peroxidase levels increased soon after injection and then rapidly decreased, the curves being similar. Biliary excretion increased for 30 min and then slowly decreased. The highest horseradish peroxidase biliary concentrations and outputs were found in Group B followed by Group A; both groups had significantly higher levels than Group E. No difference was found between horseradish peroxidase biliary excretion of groups C and D and that of sham-operated rats. 4. When each group was considered separately, sampling times correlated with the corresponding ratios of bile/ plasma HRP. Significant differences were found between the relative slopes of groups A, B and E, but not between those of groups C, D and E. 5. In conclusion, bile duct obstruction greatly affects the plasma-bile transfer of fluid phase markers, such as horseradish peroxidase, while single retention, caused by choledocho-jugular fistula, has no influence. The increased biliary hyperpressure related to the duration of cholestasis may account for the degree of horseradish peroxidase transfer which, in turn, probably depends on an enhanced paracellular passage.     

Ampicillin-Sulbactam versus Cefoxitin for Prophylaxis in High-Risk Patients Undergoing Abdominal Surgery

This double-blind study compared ampicillin-sulbactam 3 g versus cefoxitin 2 g in 136 adult patients at risk for developing an infection after abdominal surgery. Separate randomization schedules were used for colorectal, upper gastrointestinal/biliary, and other abdominal procedures. Study antibiotics were administered within 30 minutes before incision and repeated 6 hours later. Patients having colorectal surgery received a third dose of antibiotic 6 hours after the second. Efficacy evaluations were made on 123 patients, 62 in the ampicillin-sulbactam group and 61 in the cefoxitin group. The overall postoperative infection rates were 12.9% for ampicillin-sulbactam and 9.8% for cefoxitin (p>0.05); one wound infection occurred in each group. Adverse events were experienced by 13.2% of the ampicillin-sulbactam and 19.1% of the cefoxitin recipients (p>0.05). Cost-minimization analysis revealed that ampicillin-sulbactam was a cost-effective alternative to cefoxitin for the prevention of infection after abdominal surgery.     

The callous elbow and aging of the upper arm

The author describes his surgical approach to the problems of the aging upper arm and elbow region. Surgery at an appropriate age can prevent the progressive wrinkling of the elbow which is further aggravated by aging of the upper arm. The author's operation is aimed at correcting both portions of the arm anatomy at the same time.     

Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.     

Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.

The anatomic response to intravitreal bevacizumab injection in three patients with aggressive, posterior retinopathy of prematurity is described. In all cases, the worse eye was treated with a single intravitreal injection of 0.75 mg of bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all injected eyes showed regression of the tunica vasculosa lentis and iris vessel engorgement and disappearance of iris rigidity. In addition, plus disease and retinal proliferation began to regress. None of the eyes required additional treatment. Follow-up of up to 10 months     

Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.     

Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.