Relationship between P-glycoprotein expression and p53 status in high-grade osteosarcoma.

The transcription of MDR1 gene may be increased by mutation or loss of function of p53 gene. In this study, we investigated whether in osteosarcoma, the p53 status is correlated with overexpression of the MDR1 gene product P-glycoprotein. The relationship between P-glycoprotein expression and p53 status was analyzed by immunohistochemistry in 64 primary and 11 metastatic high-grade osteosarcomas. In the same series, we also assessed the nuclear accumulation of MDM2 protein, whose binding to p53 protein provides an alternative mechanism of p53 inactivation. No association was found between mutant-p53 and MDM2 nuclear accumulation either with P-glycoprotein expression or with clinical course. Only increased expression of P-glycoprotein in tumor cells was significantly associated with a poor outcome, further supporting the adverse prognostic value of this marker in osteosarcoma.

The effects of levosulpiride on gastric and gall-bladder emptying in functional dyspepsia.

BACKGROUND: 50% of patients with functional dyspepsia have delayed gastric emptying. Levosulpiride is an orthopramide drug that stimulates gastrointestinal motility. Aim of our study was to evaluate the effect of levosulpiride on symptoms and gastric and gall-bladder emptying, in dyspeptic patients. METHODS: Thirty adult patients, treated for 20 days with levosulpiride (75 mg/day) or placebo, were evaluated in a randomized double-blind study. Symptoms were assessed by a cumulative index and overall intensity (visual analogue line). Gastric and gall-bladder emptying were evaluated by epigastric impedance (liquid meal) and real-time ultrasonography (mixed meal). RESULTS: Levosulpiride, with respect to placebo, accelerated the mean gastric half-emptying time of liquids (P < 0.05), gastric emptying (P < 0.001 at 180 min; P < 0.05 at 240 min), and gall-bladder emptying (P < 0.05 at 60 and 120 min) emptying after a solid-liquid mixed meal. Both the mean cumulative index (P < 0.05) and the overall intensity (P < 0.025) of dyspeptic symptoms were reduced significantly by levosulpiride. CONCLUSIONS: Our results showed that levosulpiride can be usefully employed in patients affected by functional dyspepsia.

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study.

BACKGROUND: Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated. AIM: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components. METHODS: One hundred and twenty-eight patients (68 males, 60 females, age 22-80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the 13C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities. RESULTS: All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT. CONCLUSIONS: (i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

P-glycoprotein expression in osteosarcoma: a basis for risk-adapted adjuvant chemotherapy.

Previous reports on osteosarcomas treated with multi-agent chemotherapy have shown that P-glycoprotein expression is a reliable prognostic indicator. The current thinking is that, of the several agents used for the treatment of osteosarcoma, only doxorubicin is involved in drug resistance mediated by P-glycoprotein. This study examines the relationship of P-glycoprotein expression to clinical outcome in osteosarcomas, treated only with doxorubicin in addition to surgery, to determine if the prognostic significance of P-glycoprotein expression reflects the ability of osteosarcoma to respond to this drug. The expression of P-glycoprotein in tumor specimens was assessed by immunohistochemistry in 37 nonmetastatic, operable osteosarcomas treated at a single institution with doxorubicin as a single adjuvant drug. The P-glycoprotein status was analysed in relation to the length of event-free survival. A widespread pattern of P-glycoprotein expression in tumor cells at diagnosis was significantly associated with a higher rate of systemic relapse (p < 0.001). On comparison of this group of patients with a similar series of 92 patients, all treated with multi-agent chemotherapy plus surgery of the primary lesion and previously analysed for P-glycoprotein status, only P-glycoprotein-positive, doxorubicin-resistant tumors consistently benefited from the addition of drugs other than doxorubicin (p < 0.001). Osteosarcomas with different abilities to respond to adjuvant chemotherapy can be identified by the expression of P-glycoprotein in tumor cells at the clinical onset. P-glycoprotein status may serve as a basis for risk-adapted, individualized therapeutic regimens. Standard programs are sufficient for P-glycoprotein-negative osteosarcomas, whereas P-glycoprotein-positive tumors may benefit from the use of more intensive therapeutic approaches.

Ewing's sarcoma of bone: relation between clinical characteristics and staging.

Patients with metastatic Ewing's sarcoma of bone have a poor prognosis. A relation between clinical characteristics and presence of metastatic disease at diagnosis in patients with Ewing's sarcoma of bone was investigated. Data from 618 patients [136 (22%) with metastases at diagnosis] registered at the authors' institution between April 1972 and December 1997 were collected. The distribution of several clinical and hematologic parameters in patients with metastases and those without metastases was analyzed, and clinical risk factors of metastatic disease at presentation were analyzed by means of multivariate logistic regression analysis. All the variables significant at the univariate analysis (age, fever, site, volume, lactic dehydrogenase, anemia, and interval between onset of symptoms and diagnosis) were considered in the multivariate analysis. Pelvic location of the tumor, high level of lactic dehydrogenase, presence of fever, an interval between onset of symptoms and diagnosis less than 3 months, and age older than 12 years were found to be risk factors of clinically evident metastatic disease. In the subset of patients with no risk factors the rate of metastatic disease at presentation was only 4%; in case of contemporary presence of two factors it was 23%, although it was almost double (44%) if three or four factors were present. Only six patients were positive for five factors and all of them had metastases at presentation. The parameters identified are clinical markers of Ewing's sarcoma having a particularly aggressive metastatic behavior.

Neoadjuvant chemotherapy for osseous malignant fibrous histiocytoma of the extremity: results in 18 cases and comparison with 112 contemporary osteosarcoma patients treated with the same chemotherapy regimen.

Eighteen patients with high grade malignant fibrous histiocytoma (MFH) of bone and 112 patients with high grade osteosarcoma (OS) of the extremity were treated with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2 cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good histologic response to preoperative chemotherapy (90% or more tumor necrosis) was significantly higher in patients with osteosarcoma than in patients with MFH (74% vs 28%; p < 0.003). However, at a median follow-up of 38 months (range 25-61), the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%, OS 70.5%; p = ns). In patients with MFH, no local recurrences were registered, whereas in the osteosarcoma group there were 6 local relapses (5.%). The effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has been assessed during the last 15 years. The results of the present study seem to indicate that, in spite of a usually poor histologic response to preoperative treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.

[Acupuncture and labor]. / Agopuntura e travaglio di parto.

Results obtained in delivery room with simple acupuncture methods without electrical stimulation are presented. The Author tried successfully to speed up the labours and to induce labours at the end of gestation.. Easy application of the method and the good results obtained require a deeper study and a larger groups of patients.

[Alcoholism and HCV-antibody association. Effects on the course and severity of chronic liver disease]. / Etilismo e HCV-anticorpo positività associati. Effetti sul decorso e la gravità delle epatopatie croniche.

BACKGROUND: The authors evaluated the role of the association alcohol-hepatitis C virus on the course and severity of chronic liver disease; they also regard the researches of many authors on this subject. MATERIALS AND METHODS: 280 consecutive patients, suffering from chronic liver disease and admitted to the Department of Medical Hydrology of Rome University ''La Sapienza'' are studied. Fifty-nine of them were affected by chronic alcoholic liver disease without evidence of hepatitis virus infection (AC-), 58 were alcoholic and positive for HCV antibody (AC+), 163 positive for HCV antibody and non alcoholic (NAC+). They are divided according to the diagnosis into chronic hepatitics, cirrhotics and those affected with hepatocarcinoma; among them 193 patients, age and sex matched, are evaluated as regards the course and severity or the chronic liver disease. RESULTS: In the total of 280 patients the hepatic damage arises significantly faster in the alcoholic and anti-HCV positive than in other patients. In the age and sex matched, in alcoholic and HCV positive patients the hepatocarcinoma significantly prevailed (AC-: 8.2%, NAC+: 9.4%, AC+: 19%; p=0.04). The three groups of cirrhotics did not show a significant difference with respect to the severity of the disease evaluated according to Child-Pugh criteria. CONCLUSIONS: Our research confirms the role of the association of HCV virus infection and alcoholism on the severity and impairment of chronic liver disease.

[Crenotherapy in sports medicine: the state of the art]. / La crenoterapia nella medicina sportiva: lo stato dell'arte.

The existing relationship linking thermal and sport medicine has developed with time. This is shown by the established beneficial effects of thermal treatments (mineral waters, mud baths, balneotherapy, aerosol applications) in a wide range of sport and non-sport related injuries. The muscle fatigue syndrome is a condition particularly worrisome for sports practising individuals. This condition impairs the cardiovascular system, as well as hematologic, renal and gastrointestinal functions, acting via biochemical and metabolic modifications of the organism, which have effects also on the psyche of the subject. The treatment of this syndrome includes the use of specific mineral waters, which underscores that the correct hydration of the organisms is a precondition to achieve high performance levels. Traumas involving muscles and skeletal segments, and precocious arthrosis occur with higher frequency in sportsmen after continuous and intense stresses. Within the scope of rheumatology, mud-baths and balneotherapy have curative and rehabilitative potentials leading to a reduction, and often a disappearance, of pain with a faster recovery of the locomotory system. The gastrointestinal system is a target of psychic as well as physical stresses displaying symptoms or diseases which may be favourably addressed with the aid of mineral waters. This treatment has proved effective in secretory and motility dysfunctions of the biliary tree allowing a rapid functional recovery. Mineral water treatments are successfully employed in the treatment of urologic disturbance and ORL and dermatological pathologies, where local applications such as mud baths, balneotherapy, showers and aerosols, play a critical role.

[Current therapeutic methods in primary sclerosing cholangitis]. / Moderni orientamenti di terapia della colangite sclerosante primitiva.

The authors synthesize the main etiopathogenetic, physiopathologic and clinic findings of CSP and describe the pharmacs employed in the treatment of disease: corticosteroids, cyclosporin, penicillamine, colchicine, tacrolimus, metotrexate, hydrophylic bile salts. They outline the poor or none therapeutic activity of the majority of these and stress the improvement of some clinical parameters after prolonged use of hydrophilic bile salts. However none of the used pharmacs can stop the pathologic course of the disease. At the end authors remember the usefulness of liposoluble vitamins to prevent carential syndromes.

[The treatment of chronic viral hepatitis with recombinant alpha-2 interferon: meta analysis and clinical contribution]. / La terapia delle epatiti virali croniche con interferone alpha 2-ricombinante: metanalisi e contributo clinico.

The Authors have developed a work of meta-analysis on the employment of IFN in the virus-correlated chronic hepatitis. They have examined World literature on: virus causing chronic hepatitis, type and duration of the treatment, criteria in the choice of the observed patients, clinical effects, effects on the virus, effects on the isto-pathologic situation. Have been considered the useful actions at the end of the treatment and in the follow-ups, so to evaluate the permanence of favourable effects. Have been also reminded the main collateral effects, even about frequency and intensity, as the various Authors relate. There are quite clear data indicating: efficacy in B-correlated chronic hepatitis greater than in C-correlated ones, greater efficacy in the treatments with Interferon with duration of more then 6 months in chronic hepatitis C. Doses greater than those generally employed appear not to give better results. The Authors moreover show the results of a clinical survey they made on patients with chronic hepatitis HBsAg+/HBeAg+ (treated with IFN-alpha 2r 5 MU t.i.w. for six months) and chronic hepatitis anti-HCV+ (treated with IFN-alpha 2r 3 MU t.i.w. for six months). The results confirm the efficacy of IFN in B-correlated chronic hepatitis (50% of sustained response) and its scarce efficacy in C-correlated chronic hepatitis for treatment shorter than 12 months (9.1% of sustained response).

Clinical manifestations of gallstone disease: evidence from the multicenter Italian study on cholelithiasis (MICOL).

Despite the many efforts to delineate the clinical manifestations of gallbladder disease, the precise symptom complex associated with gallstones is still a matter of debate, and even the existence of gallstone-specific symptoms has been questioned. We carried out a large population-based cross-sectional study (MICOL) to identify symptoms significantly related to gallstones. Fourteen centers throughout Italy enrolled 29,504 subjects aged 30 to 69 years. All subjects were administered an ultrasonographic examination of the upper abdomen and a precoded questionnaire. All subjects were divided into 4 groups: 25,374 (86.0%) gallstone-free subjects (GF), 1,832 (6.2%) patients with gallstones not previously diagnosed (GNPD), 638 (2.2%) patients with gallstones previously diagnosed (GPD), 1,660 (5.6%) patients with a history of cholecystectomy for gallstones (CC). In logistic regression analysis, pain at epigastrium and, even more, pain at right hypocondrium were significantly associated with gallstones. For pain at right hypocondrium, this association progressively increased from GNPD (OR = 1.60, 95% CI = 0.97-2.65) to GPD (OR = 8.77, 95% CI = 5.27-14.61) to CC (OR = 59.40, 95% CI = 43.87-80.42). Absence of heartburn combined with right hypocondrium or epigastrium pain and intolerance to fried or fatty food were also significantly related to gallstones. We also found some pain characteristics significantly associated with gallstones, i.e., pain radiated to the right shoulder, forcing the patient to rest, occurring soon after meals or unrelated to meals, not relieved by bowel movements, and frequently accompanied by gallstone-related morbidities. We developed a probability tree reporting the cumulative probability of having gallstones for each combination of those symptoms and characteristics of pain significantly associated with gallstones. In conclusion, we have identified symptoms and signs significantly associated with gallstones. We have shown that there is an increase in frequency and severity of these symptoms and signs across the different stages of gallstone disease. We have proposed a complex of symptoms and signs significantly associated with gallstones that might help physicians in clinical decision making.

The risk of adenomatous polyps in asymptomatic first-degree relatives of persons with colon cancer.

BACKGROUND & AIMS: Increasing evidence indicates that inherited susceptibility is important in the pathogenesis of colorectal neoplasia. The aim of this study was to clarify whether having only one first-degree relative with colorectal cancer increases the risk of developing adenomatous polyps and whether total colonoscopy is an appropriate screening measure in these patients. METHODS: The frequency of such a history was evaluated in 397 asymptomatic patients who underwent total colonoscopy. Of these patients, 155 had colorectal polyps and the remaining 242 did not have polyps. RESULTS: Among polyp cases, 27 of 155 (17.4%) had a positive history; among those without polyps, 12 of 242 (5.0%) had a positive history. Alternatively expressed, 27 of 39 patients (69%) with family history and 128 of 358 patients (36%) without family history had adenomas. The estimated risk for polyps associated with family history was 1.9. Among polyp cases, 14 of 27 patients (51.9%) with family history and 32 of 128 patients (25.0%) without family history had only proximal polyps (chi 2 test; P = 0.006; odds ratio, 3.2), In the same groups, frequency of high-grade dysplasia was 8 of 27 patients (29.6%) and 16 of 128 patients (12.5%), respectively (chi 2 test; P = 0.04; odds ratio, 2.9). CONCLUSIONS: Relative to subjects with no family history, asymptomatic patients with one first-degree relative with colorectal cancer had nearly double the risk of developing adenomatous polyps, greater frequency of severely dysplastic lesions, and significantly higher frequency of proximal polyp location. This suggests that total colonoscopy screening is indicated in these subjects.

Doppler ultrasonographic evaluation of splanchnic blood flow in coeliac disease.

BACKGROUND: Current knowledge on splanchnic haemodynamics in coeliac disease is limited and incomplete. AIM: To evaluate splanchnic arterial and venous blood flow in coeliac disease. METHODS: In 22 coeliac (13 untreated, nine treated) patients and in nine healthy subjects the following variables were assessed: vessel diameter and mean flow velocity in portal vein, splenic vein, superior mesenteric vein, and superior mesenteric artery. Peak systolic velocity, end diastolic velocity and pulsatility index were also determined in the superior mesenteric artery. Five patients of the untreated group were re-evaluated after nine months on a gluten free diet. RESULTS: Significant differences in haemodynamic variables between the three groups were shown only in the superior mesenteric artery. An increase in both mean flow velocity and end diastolic velocity and a reduction in pulsatility index occurred in untreated patients compared with treated patients (p < 0.002; p < 0.04; p < 0.035) and with healthy controls (p < 0.001; p < 0.025; p < 0.0003). Similar results were obtained for the five patients evaluated before and after treatment (p < 0.03; p < 0.02; p < 0.03), in whom the mean flow velocity in the superior mesenteric vein also decreased after treatment (p < 0.05). No significant differences were noted between treated coeliac patients and healthy controls. CONCLUSIONS: In untreated coeliac disease there is a hyperdynamic mesenteric circulation that decreases after treatment.

Alpha interferon treatment may prevent hepatocellular carcinoma in HCV-related liver cirrhosis.

BACKGROUND/AIMS: The aims of alpha-interferon treatment for chronic viral liver infections are clearance of the virus and healing of the disease. Hepatocellular carcinoma is a complication of viral cirrhosis; but it is not yet known whether treatment of viral cirrhosis with alpha-interferon prevents this complication. METHODS: The incidence and the risk (Cox regression analysis) of developing hepatocellular carcinoma were calculated in 347 patients with hepatic cirrhosis; 227 (34 hepatitis B virus and 193 hepatitis C virus related) were treated with alpha-interferon and 120 (28 hepatitis B virus and 92 hepatitis C virus) did not receive this treatment, in order to evaluate the efficacy of alpha-interferon in the prevention of hepatocellular carcinoma. In all patients, the cirrhosis was well compensated (Child A). RESULTS: Over mean follow-up periods of 49 months for hepatitis B virus and 32 months for hepatitis C virus, 20/347 patients (6/62 hepatitis B virus and 14/285 hepatitis C virus) developed hepatocellular carcinoma. The risk of developing this tumor was significantly greater in males (p < 0.007) and in patients not treated with alpha-interferon (p < 0.01). The Relative Risk of developing hepatocellular carcinoma increased significantly (p < 0.0002) with each passing year. In patients with hepatic cirrhosis secondary to hepatitis B virus infections, the risk did not seem to be modified by alpha-interferon treatment, even though a greater, but not significant risk (Relative Risk = 4.9; p = 0.3) was calculated for untreated patients; in contrast, in hepatitis C virus-related cirrhosis, this risk was reduced by a factor of 4.0 (p = 0.04). The tumor developed only in non-responder patients regardless of virus type. After adjustment for confounding factors (sex, age, alcohol consumption, cigarette smoking), a statistically significant (p < 0.025) effect of interferon treatment in preventing hepatocellular carcinoma was still demonstrated when responders were matched with controls, but not when responders were compared with non-responders. CONCLUSIONS: These results show that, in addition to its ability to halt the progression of viral-induced liver disease, alpha-interferon is also of benefit in patients with hepatitis C virus cirrhosis who respond to this treatment by lowering their risk of developing hepatocellular carcinoma.

Acquired gallstone opacification during cholelitholytic treatment with chenodeoxyholic, ursodeoxycholic, and tauroursodeoxycholic acids.

OBJECTIVES: The appearance of gallstone opacification during oral bile acid administration indicates that stones are no longer susceptible to dissolution and represents, therefore, a definitive treatment failure. Ursodeoxycholic acid (UDCA) has been imputed to facilitate gallstone opacification; however, data regarding the comparative occurrence of gallstone opacification during UDCA and chenodeoxycholic acid (CDCA) administration are not yet available. Our objectives were to evaluate the frequency of acquired opacification in gallstone patients taking UDCA and in gallstone patients taking CDCA, to verify whether or not gallstone opacification is a peculiar side effect of UDCA treatment and, further, to evaluate gallstone opacification in gallstone patients receiving tauro-UDCA (TUDCA) to verify whether the administration of the more soluble tauroconjugate might prevent the deposition of calcium salts on the stone surface. METHODS: 106 gallstone patients on UDCA, 125 gallstone patients on CDCA, and 31 gallstone patients on TUDCA were evaluated. Before treatment, all patients had radiolucent gallstones as assessed by oral cholecystography; further cholecystographic evaluations were performed every 6 months during treatment. RESULTS: The frequency of gallstone opacification was 13.2% (14/106) in UDCA patients, 8.8% (11/125) in the CDCA patients, and 12.9% (4/31) in the TUDCA patients. The differences were not statistically significant (p = NS). Sex, stone size, dose of bile acid, and duration of treatment were not significantly related to an increased frequency of gallstone calcification in any of the treatment groups. The frequency of gallstone opacification appeared to be higher in older patients. CONCLUSIONS: 1) UDCA rich bile is not a major predisposing factor for acquired gallstone opacification; 2) the administration of TUDCA does not prevent gallstone opacification; 3) opacification could be related to the natural history of gallstone disease.

Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome.

BACKGROUND: Increased levels of P-glycoprotein occur in some osteosarcomas. In this study we determined the relation between P-glycoprotein status and outcome in patients with high-grade osteosarcoma. METHODS: P-glycoprotein status was determined immunohistochemically in specimens of osteosarcoma of the extremities (stage II) from 92 patients who were treated with surgery and chemotherapy. The P-glycoprotein status was analyzed in relation to the length of event-free survival. RESULTS: The presence of increased levels of P-glycoprotein in the osteosarcoma was significantly associated with a decreased probability of remaining event-free after diagnosis (P = 0.002). In a multivariate analysis, P-glycoprotein status (P = 0.001) and the extent of tumor necrosis after preoperative chemotherapy (P = 0.04) were independent predictors of clinical outcome. The risk of adverse events was increased substantially (rate ratio, 3.37; 95 percent confidence interval, 1.60 to 7.10) among patients with increased levels of P-glycoprotein in tumor cells, as compared with patients who did not have increased levels of P-glycoprotein in tumor cells. CONCLUSIONS: In patients with high-grade osteosarcoma treated with surgery and chemotherapy, the presence of increased levels of P-glycoprotein in tumor cells is associated with a significantly increased risk of adverse events and is independent of the extent of necrosis after preoperative chemotherapy.

Treatment of chronic sporadic-type non-A, non-B hepatitis with lymphoblastoid interferon: gamma GT levels predictive for response.

The aim of this study was to evaluate the efficacy of human lymphoblastoid interferon-alpha treatment in chronic sporadic-type non-A, non-B hepatitis. We also aimed to determine if histological or liver function data could predict either response or relapse. Sixty patients with chronic sporadic-type non-A, non-B hepatitis were randomized in two groups of 30. One group was treated with interferon-alpha (3 MU thrice weekly) for one year; the other group was untreated controls. The treated group was followed for another year after interferon withdrawal. Liver function tests were performed during treatment. Liver biopsy was carried out before and a year after randomization. We evaluated rate of response [normalization of alanine aminotransferase (ALT) levels for at least three consecutive months] and rate of relapse (ALT rebound after therapy suspension). We also looked at possible predictive factors for response and relapse. In the treatment group the rate of response was 55% (16/29). No control patient exhibited ALT normalization. Among the responders, 31% (5/16) relapsed after interferon withdrawal. Low gamma GT and female sex are positive predictive factors of response (P < 0.01 and P < 0.02 respectively). Presence of portal and periportal inflammation at the second liver biopsy was correlated with relapse (P < 0.05). In conclusion, human lymphoblastoid interferon-alpha treatment for one year is beneficial in patients suffering from chronic sporadic-type non-A, non-B hepatitis. Low pretreatment gamma GT levels and female sex are positive predictors of response in this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)

Weekend therapy for the treatment of Helicobacter pylori infection.

OBJECTIVES: The aim of the present study was to evaluate the efficacy and the safety of a short-term regimen (weekend therapy) in the cure of Helicobacter pylori infection and to analyze the factors that may influence the success of the treatment. METHODS: Seventy-one patients with gastric colonization by a tinidazole sensitive H. pylori strain (34 duodenal ulcer and 37 nonulcer dyspepsia) received omeprazole 40 mg o.m. for 7 days (from Monday to Sunday) and bismuth 240 mg q.i.d. + amoxicillin 1000 mg/q.i.d. + tinidazole 500 mg q.i.d. for only 2 days (Saturday and Sunday). Endoscopy, histology, culture, urease test, and susceptibility studies were done at entry and 30 days after treatment. RESULTS: Successful eradication was obtained in 84% of patients. The percentage of eradication was higher in duodenal ulcer patients (94%) than in those with nonulcer dyspepsia (74%; p < 0.05), and in patients who received the treatment during hot weather (94%) than in those who received the treatment during cold weather (74%; p < 0.05). Side-effects were induced by the treatment in 17% of patients, and these were all not severe, self-limiting, short-lasting, and did not require specific treatment. CONCLUSIONS: These data suggested that weekend therapy with high doses of drugs represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection, particularly in patients with duodenal ulcer. Furthermore, they also confirm the relevant role that short-term treatments may play in the therapeutic approach to H. pylori infection, and highlight some important aspects influencing short-term schedules.

Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well).

OBJECTIVE: Dieting obese subjects are at risk of developing gallstones. A gallbladder motor dysfunction could have a pathogenetic role. The principal aim of this study was to evaluate the long term effects of two very low calorie diets differing in fat content on gallbladder emptying and gallstone formation in obese subjects. DESIGN AND SUBJECTS: Gallbladder emptying in response to meals (breakfast, lunch and dinner) in two different diet regimens (3.0 vs 12.2 g of fat/d) was evaluated by ultrasonography in 32 gallstone-free obese patients on different days, before and during (at 45 d intervals) one or two 6-month weight reduction diets (for the first three months: 2.24 MJ (535.2 kcal), 3.0 g fat/d vs 2.415 MJ (577.0 kcal), 12.2 g fat/d; for the second three months, the same low calorie diet of 4.194 MJ (1002 kcal)/d for both groups). In 10 subjects, bile analysis was also performed. RESULTS: Twenty-two (69%) subjects concluded the study, eleven in each group, and a significant weight loss was achieved by all subjects. Gallstones (asymptomatic) developed in 6/11 (54.5%) (P < 0.01) of subjects following the lower fat diet, but in none with the higher fat regimen. In the dieters during the first three months (very low calorie phase) the higher fat meals always induced a significantly greater gallbladder emptying than the lower fat meals. The cholesterol saturation index initially increased significantly and then decreased, without difference between the two groups. CONCLUSION: In the obese during rapid weight loss from a very low calorie diet, a relatively high fat intake could prevent gallstone formation, probably by maintaining an adequate gallbladder emptying, which could counterbalance lithogenic mechanisms acting during weight loss.