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Biomedical subjects

R Tritapepe

Publications and source records attributed to R Tritapepe.

At least 37 records · Page 2Linked to original sources

Non-invasive treatment for retained common bile duct stones in patients with T tube in situ: saline washout after intravenous ceruletide.

The combination of ceruletide-induced relaxation of the sphincter of Oddi plus flushing with saline has recently been proposed as a novel procedure for the treatment of residual common bile duct (CBD) stones. In this study we have administered intravenous ceruletide (2 ng kg-1 body weight min-1 for 1 h) plus intraductal saline (800-3000 ml, infused at a rate that kept biliary pressure below 30 cmH2O) to a group of 14 patients. The treatment induced the passage of residual stones in 11 subjects (79 per cent) with complete clearance in 7 (50 per cent). The majority of the cleared concretions (11/15) had a diameter less than 10 mm. No severe side-effects were recorded during the treatment. Four of the seven subjects who exhibited incomplete CBD clearance underwent a short cycle of mono-octanoin administration in order to reduce the size of residual radiolucent stones. This course of treatment was followed by another attempt with intravenous ceruletide and saline washout which gave a successful response in an additional three cases. These data indicate that the combination of ceruletide and flushing is a safe and inexpensive method for treatment of residual stones. The procedure is feasible for both radiolucent and radio-opaque stones and is mainly eligible for small concretions of diameter less than 10 mm. Larger (greater than 10 mm) radiolucent stones may be partially dissolved with mono-octanoin and then eliminated by the washout technique.

Adult↗

Spontaneous and polyclonal Ig secretion by circulating B cells after surgery.

Abnormalities of the immune response are commonly observed after surgery. In many cases, they are part of a physiologic rather than of a pathologic response to trauma. In this study we show that after elective surgery in otherwise healthy subjects the B cell compartment is deeply affected, as documented by the appearance, 7 days after the intervention, of circulating lymphoblastoid B cells spontaneously secreting in vitro IgG and IgA antibodies. Analogous lymphoblastoid B cells have been described after in vivo immunization and represent a sensitive marker of the B cell response against the immunizing antigen. To better understand the origin of the reaction, we have analyzed the specificity of the antibodies secreted in culture supernatants. We show that the antibody response is polyclonal, since low titers of antibodies against several different bacterial antigens--such as tetanus toxoid, pneumococcal capsular polysaccharides (PCPs), and the lipopolysaccharides (LPSs) of several enteropathogenic strains of Escherichia coli--are detected. This response seems to reflect the previous immunologic experience of the single patient and to be caused by antigens released from traumatized tissues or absorbed through breaches in skin or mucous membranes.

Adolescent↗

Prevention of S-adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women.

Women with past histories of intrahepatic cholestasis of pregnancy (ICP) exhibit a congenital exaggerated sensitivity to estrogens, which may express as abnormal hepatic reactivity to oral contraceptive intake and increased risk of developing gallbladder disease. Since previous investigations have shown that S-adenosylmethionine (SAMe) is effective in antagonizing ICP, we wondered whether its administration to subjects with previous ICP could 1) protect them from a challenge with ethynylestradiol (EE) or 2) normalize the cholesterol saturation index (CSI). To test the first hypothesis, six women volunteered to receive EE (0.1 mg/day orally for 1 wk) and, after 3 months, the same EE dose plus oral SAMe (800 mg/day for 1 wk). EE significantly increased serum values of transaminases, conjugated bilirubin, and total bile acids with respect to basal values. In the rechallenge with EE plus SAMe, liver function tests did not differ from basal levels and were significantly lower than the values obtained after EE. In the second experiment, we gave oral SAMe (800 mg/day for 2 wk) to seven women with previous ICP who exhibited cholesterol supersaturation of duodenal bile. Both subjects were nonpregnant and nonobese and had cholecystograms negative for gallstones. Bile CSI decreased from a basal value of 1.35 +/- 0.07 to 0.98 +/- 0.08 after SAMe (p less than 0.01). These findings indicate that SAMe protects women with previous ICP from EE-induced liver toxicity and normalizes bile CSI in the same subjects who secrete lithogenic bile. The data support the belief that SAMe acts as a physiological antidote against estrogen hepatobiliary toxicity in susceptible women.

Adult↗

Effects of iron overload on bile secretion and hepatic porphyrin metabolism in ethinyl estradiol-treated rats.

We investigated the effects of ethinyl estradiol (5 mg/kg body wt daily for 5 days, orally) and/or iron sorbitol (50 mg/kg body wt daily for 5 days, i.m.) on bile flow, bile salt independent fraction (BSIF), hepatic delta-aminolevulinate synthase (ALA-S) and uroporphyrinogen decarboxylase (URO-D) in female rats. Ethinyl estradiol administration was associated with a significant decrease of bile flow and BSIF and an increase in URO-D activity in comparison to control values. Iron alone did not modify biliary parameters, but significantly increased the activity of ALA-S. Combined treatment with ethinyl estradiol plus iron partially corrected the reduction of BSIF and restored the activity of ALA-S and URO-D to control levels. Thus iron appears to exert a partially protective effect against ethinyl estradiol-induced cholestasis. No porphyrinogenic effect was observed.

Animals↗

Methyl tert-butyl ether fails to dissolve retained radiolucent common bile duct stones.

Methyl tert-butyl ether (MTBE) has been recently proposed as a new therapeutic modality for the dissolution of cholesterol gallstones. To further evaluate efficacy and tolerability of this new litholytic agent, we have administered MTBE to 3 patients with nonobstructive radiolucent common bile duct stones after recent surgery. Methyl tert-butyl ether (8-11 ml/day) was infused after aspiration of bile via a Teflon catheter inserted through the postoperative T tube. Gentle aspiration and reinfusion were performed continuously to generate stirring. The total amount of MTBE retrieved during the entire procedure was equivalent to approximately 30% of the volume infused. In all cases, MTBE failed to dissolve the radiolucent stones, which were then dissolved with continuous infusion of monooctanoin via the biliary catheter. The characteristic odor of MTBE was detected on the breath of the patients, and nausea and somnolence developed during the treatment. Serum hepatic and pancreatic enzymes did not change after MTBE. In the third subject, who received 11 ml/day of MTBE for 2 consecutive days (total of 22 ml), histologic evidence of duodenitis was found around the papilla. In our opinion, the lack of efficacy of MTBE in dissolving retained radiolucent common bile duct stones was mainly related to its leakage from the common bile duct into the duodenum and the ensuing local chemical toxicity and systemic absorption. As MTBE needs a persistent stone-solvent contact to exert its litholytic action and, at the same time, its toxicity prevents the infusion of larger doses, MTBE use should be restricted to stones placed in closed chambers, such as the gallbladder.

Aged↗

Appearance of spontaneously Ig secreting B cells in human peripheral blood after surgery.

Lymphoblastoid B cells, spontaneously secreting specific antibodies of IgG and IgA classes, are constantly detected after in-vivo immunization and represent a sensitive marker of a recent antigenic exposure. In this study we demonstrate that surgical trauma is followed, at a well-defined time after surgery, by the appearance of circulating lymphoblastoid B cells spontaneously secreting IgG and IgA. The kinetics and the functional behaviour of this B cell subset are identical to those of lymphoblastoid B cells observed after in-vivo immunization. Our data indicate that surgical trauma activates a humoral immune response. Antigens released by traumatized tissues or encountered through breaches in skin or mucous membranes might initiate the reaction.

Adolescent↗

Inhibition of lymphocyte function by a naturally occurring nucleoside: 5'-methylthioadenosine (MTA).

The link between immunodeficiencies and nucleoside metabolism is exemplified by the inherited deficiencies of adenosine deaminase and purine nucleoside phosphorylase which are associated with an abnormal development of the immune system. In this report we show that high doses of methylthioadenosine (MTA), a natural purine nucleoside, inhibit both the mitogen-induced blastogenesis of human peripheral blood lymphocytes (PBL) and the pokeweed mitogen (PWM)-driven in vitro immunoglobulin synthesis by PBL in a non-toxic and reversible fashion. Our data support the view that both T and B cells are sensitive to MTA inhibition and that PWM-driven Ig production is more affected by MTA than the mitogen-induced PBL proliferation. The observation that MTA causes an evident inhibition of in vitro PWM-driven Ig secretion when added four days after the start of the cultures suggests that MTA can exert its activity not only on proliferation but also on differentiation of B cells.

Adenosine↗

S-adenosyl-L-methionine protection against alpha-naphthylisothiocyanate-induced cholestasis in the rat.

The effect of S-adenosyl-L-methionine (SAMe) on cholestasis induced by alpha-naphthylisothiocyanate (ANIT) was studied in rats. SAMe significantly attenuated both bile flow impairment and elevated values of serum bilirubin, glutamic pyruvic transaminase and alkaline phosphatase in ANIT-treated animals. These results suggest that SAMe protects the rat liver against the toxic effects of ANIT.

1-Naphthylisothiocyanate↗

HMGCoA reductase and cholesterol 7 alpha-hydroxylase in human liver.

The activities of HMGCoA reductase and cholesterol 7 alpha-hydroxylase were assayed in liver biopsies of patients with or without cholestyramine treatment. The active dephosphorylated form of HMGCoA reductase and the activity of cholesterol 7 alpha-hydroxylase were under the detection limits in untreated subjects. After cholestyramine treatment activities of both enzymes were stimulated and the active form of HMGCoA reductase became detectable in four out of the five tested patients. In two subjects who received cholestyramine, the effect of exogenously added [4-14C] cholesterol on cholesterol 7 alpha-hydroxylase was tested. In the presence of Tween 80, the detergent by which [14C]cholesterol was suspended, the enzyme activity was profoundly inhibited and synthesis of 7 alpha-hydroxycholesterol was extremely low.

Adult↗

Decreased blood levels of ethanol and acetaldehyde by S-adenosyl-L-methionine in humans.

In view of the protective effects of SAM on alcohol-induced fatty liver degeneration, an investigation has been carried out to see if this compound accelerates the clearance of ethanol and acetaldehyde in humans. Both parameters were significantly lower after SAM, indicating the capability of exogenous SAM to favour the inactivation of ethanol without increasing blood levels of acetaldehyde.

Acetaldehyde↗

Effect of 3-hydroxy-3-methylglutaric acid administration on bile lipid composition in humans.

The effects of the lipid-lowering agent 3-hydroxy-3-methylglutaric acid (HMGA) on serum lipids and on biliary lipid composition were evaluated in a double-blind, placebo-controlled study in normolipidemic volunteers. After 4 weeks of HMGA administration (1 g three times a day orally) serum total cholesterol showed a significant decrease with regard to both pretreatment values and corresponding values of controls. The bile lipid molar percentage composition and the cholesterol saturation index showed no modification after HMGA and did not differ from the values obtained in the placebo group. These findings indicate that HMGA exerts no adverse effects on bile lipid composition in humans, differing from other hypolipidemic drugs currently in clinical use, which increase the bile cholesterol saturation index.

Adult↗

S-adenosyl-L-methionine antagonizes oral contraceptive-induced bile cholesterol supersaturation in healthy women: preliminary report of a controlled randomized trial.

Recent experimental investigations have shown that S-adenosyl-L-methionine (SAMe) reverses estrogen-induced bile secretion impairment. The mechanism of this action seems to be related to the capability of SAMe both to inactivate catecholestrogens by methylation reaction and to methylate membrane phospholipids increasing the liver plasma membrane fluidity reduced by the estrogens. Aim of this investigation was to know whether SAMe also prevents oral contraceptive-induced cholesterol supersaturation of gallbladder bile in humans. To six healthy nonobese women whose bile cholesterol saturation index increased from a mean basal value of 0.77 (SD 0.22) to 1.20 (SD 0.38) (p less than 0.01) after two cycles of treatment with oral contraceptives containing 50 micrograms ethynylestradiol, plus 250 micrograms d-norgestrel, 200 mg SAMe per os tid was administered in addition to the oral contraceptive for other two cycles. The bile cholesterol saturation index decreased to 0.88 (SD 0.26) (p less than 0.05 versus oral contraceptive value). These results indicate that SAMe antagonizes biliary lipid changes induced by estrogen-progestin containing oral contraceptive and suggest its potential usefulness in women on oral contraceptive treatment to prevent lithogenic bile secretion.

Adult↗