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.

Bile secretion and liver microsomal mixed function oxidase system in mice with griseofulvin-induced hepatic protoporphyria.

Administration of 2.5% griseofulvin in the diet to male CD1 mice produced protoporphyria and cholestasis. Protoporphyria became evident as early as after 10 days of treatment, whereas cholestasis, expressed in terms of total bile flow reduction, developed only after 45 days of griseofulvin. Bile flow impairment was due both to the length of treatment and to the severity of liver protoporphyria. Griseofulvin administration was also associated with a significant modification of the relative amounts of hepatic microsomal cytochromes P-450 and b5, a loss in concentration/mg of protein of cytochrome P-450 and a concomitant increase of b5. Despite these changes, the activity of aniline hydroxylase expressed per mg of microsomal protein, assessed in vitro, was not modified.

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.

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.

3-Hydroxy-3-methylglutaric acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster.

3-Hydroxy-3-methylglutaric acid (HMGA) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) and strongly reduces cholesterol biosynthesis both in vitro and in vivo. Since the effects of this compound on biliary lipid composition are hitherto unknown, we have investigated whether it prevents dietary cholesterol induction of saturated bile in the hamster. Female Golden Syrian hamsters have been divided into four groups and treated for 10 weeks as follows: I) Standard diet, containing 0.8 mg cholesterol/g food; II) Standard diet plus HMGA (100 mg/kg b.w./day per os); III) Lithogenic diet containing 2.4 mg cholesterol/g food; IV) Lithogenic diet plus HMGA as above. The results indicate that HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia. Inhibition of hepatic cholesterogenesis at the level of mevalonate synthesis by HMGCoAR and reduction of intestinal cholesterol absorption may be responsible for these effects.

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.

Problematic bile duct stones: polyvalent treatment.

BACKGROUND: The availability of different methods for the non-surgical treatment of complicated bile duct stones makes it possible to choose the most appropriate therapy on the basis of the particular characteristics of each individual case and a careful evaluation of their related risks/benefits/costs. METHODS: The present study involved 26 patients treated using different techniques; in some cases, after the failure of the first approach, one of the alternative treatments was adopted. Twenty-one of the patients had isolated stones that were large (> 20 mm in diameter: 11 cases), impacted (5) or upstream of a stenotic tract; five had multiple stones (two of whom had undergone previous biliodigestive anastomosis and two had Caroli's disease). The initial treatment in 24/26 cases was chemical litholysis with a 2:1 v/v association of monooctanoin and methyl tert-butyl ether. RESULTS: Total dissolution was obtained in nine cases and partial dissolution leading to subsequent elimination (spontaneous or by means of a basket and/or saline washout) in eight. In the seven patients in whom chemolitholysis was unsuccessful, clearance was obtained surgically (6 cases) or by means of extracorporeal shockwave lithotripsy (ESWL). The remaining two patients were successfully treated by means of first-choice ESWL and saline washout.

Treatment of intrahepatic calculi in Caroli's disease by non-invasive saline washout.

The case of a 59 year old pluriparous woman who underwent cholecystectomy and exploration of the main biliary pathway for cholecystic and common bile duct stones is described. Postoperative T-tube cholangiography showed a voluminous saccular dilatation stacked with calculi located on the left main hepatic duct. The patient was immediately transferred to our Centre, and a T-tube was used to introduce a guidewire/M 0.035 (Terumo, Tokyo, Japan) at the bottom of the cystic dilatation. A 6.0F drainage catheter (Angiomed, Germany) was placed over the subsequently withdrawn guidewire and a 60-minute saline washout was administered (625 ml). Subsequent cholangiography showed the total clearance of the cyst; papillotomy and a second saline washout led to some of the larger stones, which had remained in a prepapillary location, being made to flow easily into the duodenum. Discharged five days after admission, the patient is well one year later and has not experienced any further disturbance; an ERCP has shown the persistence of the biliary clearance. When the circumstances allow it, this noninvasive treatment of intrahepatic calculi is proposed before undertaking any surgical or invasive procedure.

Mono-octanoin and methyl tert-butyl ether mixture for bile duct stones.

A new litholytic mixture of mono-octanoin (MO) and methyl tert-butyl ether (MTBE) in a ratio of 2:1 (v/v) was employed in 42 patients with bile duct stones, 29 of them failures after papillotomy. Twenty-two of these patients had complicated stones. The new solvent mixture was given for 4-6 h/day and 2-3 ml were instilled every 30 min. Gentle aspiration and instillation were alternated so as to "stir" the preparation around the stones. Perfusion was given for up to six days. The mixture contributed to success in 37 cases (88%), 19 of them with complicated stones. Total dissolution was attained in 18 cases, and in the other 19 cases clearance was achieved after partial lysis followed by easy crushing with a basket. The mean volume of solvent perfused (+/- SD) was 84.9 +/- 39 ml (range 25-150), the mean duration of treatment was 16.5 +/- 7.4 h (range 5-30). Hospital stay averaged 4.6 +/- 1.6 days (range 2-7). There were five failures: in one patient eight large concretions were eliminated only after extracorporeal shock wave lithotripsy (ESWL). Two were re-operated and pigment stones were found. The last two refused alternative treatments. Side effects were minimal and easily managed by withdrawal of a few ml of bile. Treatment with the new solvent may be indicated as first-instance therapy in place of ESWL, laser endoscopy, electrohydraulic or mechanical lithotripsy for patients with complicated biliary stones, or in cases in which endoscopic papillotomy has failed.

Predictive factors for cholelithiasis complications.

BACKGROUND: Cholelithiasis is a benign disease that is very frequently encountered throughout the world. Its surgical mortality is usually minimal (0.1%), but the risk is considerably greater (2-10%) in patients developing complications particularly if they are elderly. The identification of possible predictive signs of complications is therefore crucial for the indication of preventive surgery. METHODS: The present study retrospectively examined 490 patients admitted to hospital because of complicated and uncomplicated cholelithiasis in order to establish the existence of previous (clinical or instrumental) symptoms that may be predictive of the course of the disease. The analysis of some variables (age, sex, pregnancy, diet, ethanol consumption, smoking, previous/concomitant diseases, and blood chemistry and instrumental test results) and the specific symptoms of cholelithiasis made it possible to identify two potential risk factors: an age of more than 60 years and the onset of biliary colic. RESULTS: The risk of developing complications is 3.2 times greater in patients aged more than 60 years than in those who are younger, and 3.3 times greater in symptomatic than in asymptomatic patients. Statistical analysis also revealed that the risk of complications is about ten times greater in patients with both risk factors than in those with neither. CONCLUSIONS: In conclusion, the indication for surgery must be considered absolute in symptomatic patients aged more than 60 years and relative to younger symptomatic patients.

Double-blind placebo-controlled clinical trial of microporous cholestyramine in the treatment of intra- and extra-hepatic cholestasis: relationship between itching and serum bile acids.

In order to investigate the effectiveness of microporous cholestyramine in the pharmacological management of intra- and extrahepatic cholestasis, a double-blind placebo-controlled study was carried out in 10 patients. Microporous cholestyramine or placebo 3 g t.i.d. were given orally over a four-week period. The active drug resulted statistically superior to the placebo in reducing itching intensity (p less than 0.01) and serum bile acids (p less than 0.01). A positive linear relationship between itching and serum bile acids (p less than 0.01) was also demonstrated.

Effect of a concomitant treatment with ethynylestradiol and ascorbic acid on bile secretion in female hamsters.

The administration of large doses (5 mg/kg b.wt./day) of ethynylestradiol to adult female hamsters did not induce cholestasis or modifications of bile lipid composition. These findings are in contrast with the data of other authors who in different experimental conditions described the sensitivity of hamsters to the estrogen-induced hepatobiliary toxicity. Ascorbic acid alone or added to ethynylestradiol did not impair bile secretion. However, it significantly increased the plasma levels of radioactivity tested 24 hours after the oral administration of a tracer dose of radiolabelled ethynylestradiol. These results confirm previous data showing in humans the capability of ascorbic acid to favour the rise of plasma concentrations of ethynylestradiol.

Dissolution of bile duct stones with monooctanoin: in vitro study.

Mono-octanoin (Mo) is the drug of choice in the topical litholytic treatment of residual gallstones following cholecystectomy. Although this drug does not produce significant side effects, it requires a lengthy period of treatment (15-20 days). The purpose of this study was to verify the in vitro efficacy of the mixture Mo + 10% H2O vs pure Mo in human cholesterol stones. The findings indicate that this mixture can reduce dissolution time by 15.8% and increase the dissolution rate by 27.9% vs pure Mo. A further significant reduction (p = 0.0001) in dissolution times can be obtained by constant exchange of the solvent at the surface of the stone (stirring).

[Primary therapy after radical removal of sinus pilonidal]. / Guarigione per prima intenzione dopo intervento radicale di asportazione del sinus pilonidalis.

The successful closure of the operative wound after removal of the Sinus pilonidalis, is linked, in our opinion, to the application of certain measures that should be taken during surgery. Specifically: 1) careful haemostasis, 2) correct positioning of effective deep drainage with exit into the left gluteal region, 3) diligent suture of the deep layers, 4) correction of tension at operative wound level. Two-year follow-up of 29 of 32 operated patients did not reveal relapses.

[Treatment of residual and recurrent biliary calculi: the surgical option]. / Il trattamento dei calcoli biliari residui e ricorrenti: la scelta chirurgica.

Retained and recurrent bile duct stones can be treated with a variety of non-surgical methods. The list includes endoscopic papillotomy, chemical dissolution, by T-tube extraction, percutaneous or extracorporeal lithotripsy. The various attempts at non-surgical therapy are described in two patients with retained bile duct stones before biliary clearance was achieved by re-operation. The failure of oral dissolution using biliary acids, endoscopic papillotomy and by T-tube extraction, led to a delay of 6 and 8 months respectively in the elimination of the retained stones in each patient. Surgical re-exploration proved relatively simple due to the long interval after the first operation, and the stones were removed without particular difficulties. The paper underlines the importance of the choice of treatment for use in cases of secondary common bile duct calculi, evaluated on the basis of a correct assessment of the cost/benefit, risk/benefit ratios.

[A new therapeutic approach to retained biliary calculi. Results in 6 patients]. / Nuovo approccio terapeutico ai calcoli biliari residui. Risultati in sei pazienti.

A new three-phase therapeutical approach to retained biliary stones (RBS) is designed to shorten the long treatment times with Monooctanoin (Mo). In the first phase, the litholytic agent is infused to soften the stones. In the second one the calculi are crushed, and in the last complete elimination of the fragmentary stones into the duodenum is obtained after 1-2 flushings with ceruletide. In 6 patients a complete clearance of the stones was obtained (success 100%) together with a reduction in the litholytic agent dose (52%) and the infusion time (62%), in comparison with the results of using Mo. alone.

[A comparative evaluation of the efficacy of the excisional new attachment procedure (ENAP) relative to root planing in the etiological phase of periodontal therapy]. / Valutazione comparativa dell'efficacia della excisional new attachment procedure (ENAP) nei confronti della levigatura radicolare nella fase etiologica della terapia parodontale.

BACKGROUND: In the present study, the effectiveness of root planing has been compared to the excisional new attachment procedure (ENAP) during the etiological phase of periodontal therapy, after the supragingival scaling, in order to establish if a technique offering an easy access to the subgingival areas could reduce the need for a surgical phase in the periodontal treatment. METHODS: Twenty-seven patients, affected by moderate periodontitis, participated in this study; in each of them root planing was performed in a half of the oral cavity (control site) and the ENAP in the other half (test site). The main clinical parameters of periodontal health (probing depth--PD-, attachment loss--AL-, plaque index--PlI- and gingival index--GI-) were evaluated before and 1, 2 and 6 months after the periodontal treatment. RESULTS: The results of the study showed that the parameters related with the amount of plaque and with the conditions of the marginal gingival tissue were not influenced by the different treatments used. Better improvements were found in PD and AL values in teeth treated by ENAP compared to those treated by root planing; this result is explained by a better access to the roots offered by the ENAP. CONCLUSIONS: We can conclude that, within the limits of the present study, the ENAP can reduce the need for a further surgical treatment of the periodontal patient.