Front crawl stroke in swimming: Phase durations and self-similarity.

Human movements, such as walking and running, are able to generate rhythmic motor patterns, with the consequent appearance of hidden time-harmonic structures. Such harmonic structures are represented (at comfortable speed) by the occurrence of the golden ratio as ratio of durations of specific walking and running gait sub-phases. Preliminary experimental evidences suggest that front crawl swimming may behave, under this point of view, like walking and running. This paper aims to demonstrate that a mathematical connection between the golden ratio and the front crawl swimming stroke actually exists, at a pace that plays the role of the comfortable speed in walking and running. Generalized Fibonacci sequences are used to this purpose. They rely on the durations of aggregate phases of the front crawl swimming stroke with a clear physical meaning, while characterizing self-similarity of front crawl strokes in its simple nature and enhanced (stronger) variant. Experimental data on front crawl swimmers illustrate the theoretical derivations, suggesting that the pace playing the role of the comfortable speed in walking and running is the middle/long-distance one, while showing that the self-similarity level increases with the swimming technique and the enhanced self-similarity is associated with the performance of top-level swimmers.

High doses of alpha-interferon are required in chronic hepatitis due to coinfection with hepatitis B virus and hepatitis C virus: long term results of a prospective randomized trial.

OBJECTIVE: Coinfection with hepatitis B (HBV) and hepatitis C (HCV) viruses is associated with a more severe liver disease, increased frequency in the development of hepatocellular carcinoma, and resistance to interferon (IFN) therapy when performed with the standard dosages used in single infections. In the attempt to verify whether the outcome of IFN therapy in patients with hepatitis B and hepatitis C coinfection can be improved, we have planned a prospective, randomized trial with medium to high dosages of interferon three times a week for 6 months. METHODS: Thirty patients with HBV-HCV coinfection, and chronic hepatitis were randomized to receive either 6 or 9 MU alpha-interferon three times a week for 6 months. Patients were HBsAg positive, anti-HBe positive, HBV DNA negative by dot blot (6/30 positive by polymerase chain reaction), and anti-HCV-positive, HCV RNA positive. Pretreatment and posttreatment liver biopsies were performed. RESULTS: Five patients treated with 9 MU IFN consistently cleared HCV RNA and HBV DNA, whereas none of those treated with 6 MU reacted in a similar fashion (p = 0.045). Responders showed significant improvement of histological activity index in comparison with nonresponders (mean Ishak score pretreatment versus posttreatment p = 0.002). Long term follow-up showed that none of the patients treated with high doses developed cirrhosis whereas 4/14 treated with low doses did develop cirrhosis. CONCLUSION: Even though the percentage was not very high, the sustained response, the striking histological improvement, and the lack of development of cirrhosis achieved in these patients, indicate that with HBV-HCV coinfection, a trial with high doses of interferon is strongly recommended.

Hormonal therapy with megestrol in inoperable hepatocellular carcinoma characterized by variant oestrogen receptors.

Variant liver oestrogen receptor transcripts in hepatocellular carcinoma are associated with aggressive clinical course and unresponsiveness to tamoxifen. To evaluate the impact on survival and on tumour growth of megestrol (progestin drug acting at post-receptorial level) we enrolled 45 patients with HCC characterized by variant liver oestrogen receptors in a prospective, randomized study with megestrol vs. placebo. Presence of variant oestrogen receptors was determined by RT/PCR. 24 patients were randomized to no treatment and 21 to therapy with megestrol 160 mg day(-1). Results were analysed by Kaplan-Meier and Cox methods. Survival of hepatocellular carcinoma characterized by variant oestrogen receptors was extremely poor (median survival 7 months); megestrol significantly improved survival (18 months) (P = 0.0090). Tumour growth at one year was significantly slowed down in megestrol-treated patients (P = 0.0212). Bilirubin levels, presence of portal thrombosis, HBV aetiology and treatment were identified at univariate analysis as factors significantly associated with survival; at multivariate analysis, only megestrol therapy (P = 0.0003), presence of HBV infection (P = 0.0009) and presence of portal vein thrombosis (P = 0.0051) were factors independently related with survival. (1) Megestrol slows down the aggressive tumour growth of patients with hepatocellular carcinoma characterized by variant estrogen receptors and (2) is also able to favourably influence the course of disease, more than doubling median survival.

Natural history of inoperable hepatocellular carcinoma: estrogen receptors' status in the tumor is the strongest prognostic factor for survival.

Clinical course in hepatocellular carcinoma may be very different. We prospectively evaluated 96 patients with hepatocellular carcinoma unsuitable for radical therapy to investigate factors that could influence survival. Clinical, pathologic, and molecular data of patients were analyzed by univariate and multivariate analysis. The overall actuarial probability of survival at year 1, 2, 3, 4, 5, and 6 was 72%, 41%, 38%, 24%, 20%, and 9%. At univariate analysis, alpha-fetoprotein (AFP) (P =.0082); alkaline phosphatase (P =.0281); bilirubin (P =.0076); etiology (P =.0001); increment of tumor mass at month 3 (P =.0051); type of estrogen receptor (ER) in the tumor (P =.0000); prothrombin time (P =.0003); and portal vein thrombosis (P =.0000) had prognostic significance. At multivariate analysis, only type of ER (P =.0000) and bilirubin (P =.0030) showed independent predictive value for mortality. Survival was significantly longer in patients with wild-type estrogen receptors (P =.0000). Cumulative probability of survival at year 1, 2, 3, 4, 5, and 6 was 94%, 66%, 52%, 43%, 35%, and 18% for wild-type and 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients alive after 4 years). Hepatitis B surface antigen (HBsAg)-positive patients with variant ERs had a median survival of 8 months versus 45 months in anti-hepatitis C virus-positive patients with wild-type ERs (P =.0001). In conclusion, (1) the presence of variant liver ER transcripts in the tumor was the strongest negative predictor of survival in inoperable hepatocellular carcinoma; (2) their presence was associated with spontaneous survival significantly worse than in patients with wild-type estrogen receptors; and (3) HBsAg-positive patients with variant receptors were characterized by the worst survival.

Variant liver estrogen receptor transcripts already occur at an early stage of chronic liver disease.

Variant estrogen receptors may be found in hepatocellular carcinoma and may influence its natural history. Because it is not known whether their occurrence is an early or a late event during the course of chronic liver disease or whether they cluster in some subgroups of patients, we investigated a series of patients in different stages of chronic liver disease. One hundred eleven consecutive patients were studied for variant estrogen receptor transcripts by reverse-transcription polymerase chain reaction of RNA extracted from liver biopsy specimens. In chronic active hepatitis, variant estrogen receptor transcripts were coexpressed with wild-type significantly more often in men than in women (P = .029) and in hepatitis B surface antigen (HBsAg)-positive subjects than in subjects positive for antibody to hepatitis C virus (P = .0006). In hepatocellular carcinoma, again in men (P = .004) and in HBsAg-positive patients (P = .0015), the variant estrogen receptor transcript was overexpressed or remained the only one expressed. Patients with liver cell dysplasia presented with the same estrogen receptor pattern than patients with hepatocellular carcinoma. This further reinforces the significance of liver cell dysplasia as a preneoplastic condition. The significantly higher occurrence of variant estrogen receptor in men (especially in HBsAg-positive men) already at an early stage of disease, like chronic active hepatitis, suggests that the alteration of estrogen receptors, favoring uncontrolled proliferation and development of hyperplasia, might constitute a prominent mechanism facilitating neoplastic transformation especially in men.

Chronic administration of ursodeoxycholic and tauroursodeoxycholic acid changes microsomal membrane lipid content and fatty acid compositions in rats.

We studied the effect of oral supplementation with ursodeoxycholate (UDCA) or tauroursodeoxycholate (TUDCA) on the lipid content and fatty acid composition of rat hepatic microsomes. UDCA and TUDCA significantly increased the total amount of lipids with the exception of cholesteryl-esters. UDCA significantly increased the triglycerides and phosphatidylethanolamine (PE) microsomal content, and decreased the cholesterol/phospholipids and the phosphatidylcholine (PC)/PE ratio. Both treatments increased the percentage oleic acid and of polyunsaturated fatty acids (PUFA) in each class of lipids. UDCA and TUDCA had a different action on PUFA microsomal molar percentage of phospholipids: UDCA increased the relative percentage of PUFA in the PE fraction, while TUDCA increased the relative percentage of PUFA in the PC fraction. These changes in the hepatic lipid content and composition might in part explain both cytoprotective action of these hydrophillic bile acids and their effect on membrane fluidity.

Long-term follow-up of hepatitis C virus (HCV) infection in liver transplant patients.

Chronic hepatitis represents a frequent event after orthotopic liver transplantation (OLT). To ascertain the influence of HCV infection on the clinical and histological outcome of these patients, we have investigated the long-term outcome of 22 patients with end-stage chronic liver disease undergoing liver transplant focusing the attention on the role of different HCV genotypes in determining recurrence and severity of post-OLT liver disease. For all patients blood samples taken before OLT and 3 months, 1, 2 and 3 years after OLT were tested for antiHCV antibodies by two different enzyme-linked immuno-assays and by recombinant immuno-blot II and for the presence and type of HCV RNA by nested PCR (5' untranslated region and core gene primers). Of the 16 pre-OLT antiHCV-positive patients, 14 (87.5%) had recurrence of HCV infection while 2 cleared HCV. Pre-OLT genotype recurred in 11 of these 14 patients (2 genotype I) 8 genotype II - in 1 case associated with genotype III - and 1 genotype IV). Of the 6 pre-OLT antiHCV-negative patients, only 1 (16.6%) became persistently HCV-infected, with genotypes I and II. The recurrence of genotype II strictly related with development of severe chronic hepatitis while genotype I and IV were associated with milder forms of liver disease and were more easily cleared.

Selection of more pathogenic hepatitis C virus genotype II during long-term follow-up of interferon-treated patients.

The behavior of hepatitis C virus (HCV) infection with regards to type and number of HCV genotypes (tested with genotype-specific nested polymerase chain reaction) was evaluated in 60 patients with anti-HCV-positive chronic active hepatitis without cirrhosis [17 untreated and 43 subjects undergoing single or repeat courses of interferon (IFN) therapy] during a mean follow-up period of 76 +/- 18 months. In untreated patients (2 genotype I, 6 genotype II, 9 mixed infections) 4 out of 9 mixed infections selected for genotype II at the end of follow-up. Of the 43 treated patients 10 were long-term responders with histological remission, 6 were short-term responders, and 22 did not respond. Fifteen of the latter patients received another course of IFN therapy, and only 3 patients responded. Eight of the 10 responders had infection with a single genotype (4 gt I, 3 gt II, 3 gt III). After IFN therapy, all but 2 patients cleared the HCV infection. The responders to the second IFN course (1 gt I, 1 gt II, 1 gt III) remained viremic. Of the short-term responders, 2/6 patients had genotype II and 4 had a mixed infection (3 gt II +/- I and 1 gt II +/- III); gt III became prevalent in the latter in all but one patient. Of the nonresponders 18/24 had more than one genotype, 5 were genotype II at baseline and one had genotype I. At the end of the follow-up period 15/18 with mixed infection had selected for gt II (P < 0.01 vs. untreated patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Presence of HCV RNA in serum of asymptomatic blood donors involved in post-transfusion hepatitis (PTH).

To study the causes of residual posttransfusion hepatitis, serum from implicated donors was tested by PCR for the presence of HCV RNA. Of 20 anti HCV negative donors, 4 were HCV RNA positive and thus, infective. The results suggest that higher-level investigations are necessary for prospective donors who present blood enzyme abnormalities or other questionable characteristics.

HCV RNA in serum of asymptomatic blood donors involved in post-transfusion hepatitis (PTH).

A group of blood donors involved in post-transfusion hepatitis was investigated for the presence of the anti-HCV antibody and of HCV RNA as a more direct infection marker. RNA was extracted from serum, reverse transcribed and amplified using primers which belonged to the non structural region. The amplified product of the PCR reaction was 582 base pairs. Seven (25.9%) of the 27 blood donors examined were found anti-HCV-positive by ELISA; five (71.4%) of these were HCV RNA positive. Among the 20 anti-HCV-negative blood donors, four (20.0%) were HCV RNA positive. ALT levels were below 45 UI/l in 18 donors, while the other nine had ALTs over the limit accepted for transfusion. The anti-HCV-negative HCV RNA-positive blood donors had normal ALTs. Our study offers a direct explanation for the substantial proportion of residual cases of anti-HCV-positive post-transfusion hepatitis and suggests the necessity of creating a register of blood donors who have at some time presented blood enzyme abnormalities and for whom second level investigations such as HCV RNA should be used.

Effect of ursodeoxycholic acid treatment on alanine aminotransferase and gamma-glutamyltranspeptidase serum levels in patients with hypertransaminasemia. Results from a double-blind controlled trial.

The ability of ursodeoxycholic acid (UDCA, 600 mg/day) to lower alanine aminotransferase (ALT) blood levels in blood donors rejected for donation because of fluctuating hypertransaminasemia was evaluated in a randomized, controlled, double-blind clinical trial vs. placebo. All subjects with ALT values at least twice the normal upper limit in at least two out of three previous checks (the last one not more than 1 month previously) were admitted to the study. Checks were carried out 1, 2 and 3 months after the admission. 59 out of 65 patients completed the study. Although all patients were asked to abstain from alcohol, more than 50% of them in both groups had basal gamma-glutamyltransferase (gamma-GT) values higher than normal. After 1 month of treatment and throughout its duration, UDCA was effective in lowering ALT in all patients (30% decrease with respect to the basal value) and, especially, in lowering gamma-GT in those patients with elevated levels (50% decrease with respect to the basal value). This decrease was significantly different from the spontaneous 10% decrease of the ALT and gamma-GT levels observed in the placebo group. 3 months after suspension of therapy a rebound of both ALT and gamma-GT to values comparable to the basal ones or even higher was found only in UDCA-treated patients. We conclude that the short-term administration of UDCA is free of hepatotoxic effects and could be useful in lowering ALT and gamma-GT serum levels. The real significance of UDCA treatment in the natural history of chronic liver diseases deserves further investigation.

Sex differences in the hepatic uptake of sulphobromophthalein in the rat.

Sex difference in the hepatic uptake of sulphobromophthalein (BSP) was investigated in male and female rats in three different experimental models. In the intact animal the BSP plasma disappearance rate was significantly higher (P less than 0.01) in females than in males when 0.15 or 1.5 mumol/kg body wt. was injected. Comparable values were found at the highest BSP dose (15 mumol/kg body wt.) used. In the perfused liver, the first-pass hepatic extraction and the uptake velocity were significantly higher (P less than 0.001) in female rats at low BSP doses (0.3-750 mumol/g of liver) whereas identical values were found at higher concentrations. In hepatocytes isolated by collagenase perfusion, the BSP uptake occurs via two different uptake sites in both sexes. The Km of the high affinity sites was lower in females than in males (3.67 +/- 0.58 vs 7.24 +/- 0.68 mumol/l, P less than 0.001) whereas Vmax. showed comparable values (2.70 +/- 0.36 vs 2.47 +/- 0.45 nmol of BSP/mg of protein, NS). In contrast, no difference was found in the kinetic parameters of the low affinity sites (Km 50.6 +/- 31.1 vs 61.0 +/- 17.5 mumol/l; Vmax. 21.9 +/- 13.2 vs 25.0 +/- 3.6 nmol of BSP/mg of protein, mean +/- SD, NS, females and males respectively). Taken together these data show that low doses of BSP are taken up by the liver more efficiently in female than in male rats and are consistent with a sex-related difference in the affinity but not in the number of the BSP high affinity uptake sites.

Gastrointestinal endoscopy and HBV infection: no evidence for a causal relationship. A prospective controlled study.

The importance of the different endoscopic procedures in the transmission of hepatitis B was investigated prospectively by following up for 6 months all HBV-negative patients endoscoped from April to October 1981. A group of patients admitted in the same period to our unit constituted the control group. Controls were obtained after 1, 3, and 6 months from endoscopy. Infection rate was 1% for the control group and 0.45% for the endoscopy group. The difference is not statistically significant. These results strongly support the view, already present on an uncontrolled basis in the literature, that transmission of hepatitis B is not associated with gastrointestinal endoscopy.

Susceptibility of chronic symptomless HBsAg carriers to ethanol-induced hepatic damage.

To investigate the susceptibility of chronic symptomless HBsAg carriers to the hepatotoxic effect of ethanol 296 such carriers were followed up for 3 1/2 years with repeated biochemical and clinical examinations. A control group of HBsAg-negative blood donors matched by age, sex, occupation, duration and type of ethanol intake, and state of nutrition were followed up for the same period. Chronic symptomless HBsAg carriers seemed to be at risk of hepatic abnormalities when drinking an amount of ethanol which was harmless for HBsAg-negative subjects (less than 80 g). It may therefore be advisable to suggest complete abstinence from ethanol for HBsAg carriers.

Decreased insulin receptors but normal glucose metabolism in Duchenne muscular dystrophy.

Compared to matched controls, 17 patients with Duchenne muscular dystrophy showed decreased insulin binding to monocytes due to decreased receptor concentration. These patients showed no signs of altered glucose metabolism and retrospective analysis of the clinical records of a further 56 such patients revealed no modification in carbohydrate metabolism. These data suggest that reduced insulin receptor number does not produce overt modifications of glucose metabolism in Duchenne muscular dystrophy.