A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels. METHODS: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant). RESULTS: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration. CONCLUSION: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

[Hepatic iron, iron depletion and response to therapy with peg-Interferon and Ribavirin in chronic hepatitis C. Pilot study]. / Ferro epatico, ferrodeplezione e risposta alla terapia con peg-Interferone e Ribavirina nell'epatite cronica C. Studio pilota.

AIM: To estimate whether pretreatment serum iron levels, the HIC (hepatic iron concentration) and the distribution of hepatic iron identify the long-term "responders" and "non-responders" to therapy with peg-IFN and RBV, and whether the addition of phlebotomy could increase the likelihood of therapeutic response. PATIENTS AND METHODS: 45 subjects with chronic hepatitis C were taking peg-IFN alpha-2a 180 microg once a week and RBV 1000 mg/die. The "responders" continued therapy with peg-IFN plus RBV, while, the "non-responders" were subjected to phlebotomy. After two weeks and subsequently every month the patients were subjected to blood test and clinical appraisal. RESULTS: Hepatic iron storage meaningfully conditions the outcome of therapy with peg-IFN and RBV, its reduction by phlebotomy favourably correlates with response to treatment and, at last, the semiquantitative histological appraisal would have to be included in the pre-treatment work-up of patients with chronic hepatitis C. CONCLUSIONS: The study results, even though obtained on a small size of cases, allow to conclude that serum corporeal iron evaluation underestimates the real hepatic iron concentration; the hepatic iron concentration, in turn, negatively conditions the response to therapy with peg-IFN and RBV (by reducing the percentage of the fast virological response). Lastly, iron removal by phlebotomy favourably correlates with the response to treatment.

Meaning of elevated CA 19-9 serum levels in chronic hepatitis and HCV-related cirrhosis.

AIM: Carbohydrate 19-9 antigen (CA 19-9) has been used in the diagnosis and follow-up of gastrointestinal tumors. However, a remarkable reduction of specificity has been described in subjects with chronic diseases. Elevated CA 19-9 serum levels have been described in non neoplastic liver diseases, such as hepatic cirrhosis, where they correlate with the fibrosis grade and the disease severity. The aim of the study is to evaluate CA 19-9 levels in chronic hepatitis patients (CH) and hepatic cirrhosis patients, Hepatitis C Virus (HCV)-correlated. Our goal was to establish whether elevated CA 19-9 levels can be considered a non casual event in chronic liver disease and whether a correlation can be found between CA 19-9 levels and the severity of the disease. METHODS: 116 patients have been recruited (76 m, 40 f, average 54 years); 56 patients were affected by CH and 60 by hepatic cirrhosis (Child A). All patients were HCV+, genotype 1b. Patients positive to CA 19-9 high levels were subjected to abdominal echography, EGDS, colonscopy, abdominal CT. RESULTS: Fifty two percent presented high levels of CA 19-9. None was affected by intestinal or pancreatic neoplasia, or colestatic icterus. CA 19-9 levels were elevated in 46% of patients with chronic hepatitis, and in 54% in patients with hepatic cirrhosis. Furthermore, CA 19-9 levels in hepatic cirrhosis compared to CA 19-9 levels in chronic hepatitis was statistically significant (P>0.007). CONCLUSION: Increased serum levels of CA 19-9 are frequent in chronic viral hepatitis; this often does not indicate a contemporary neoplastic disease and correlates in a statistically significant way (P>0.007) with the severity of the disease.

[A case of overlap syndrome: autoimmune idiopathic hepatitis/pulmonary idiopathic hypertension]. / Un caso di Overlap Sindrome: epatite autoimmune/ipertensione polmonare idiopatica.

In medical practice we frequently encounter autoimmune syndromes, called "overlap-syndromes," which are of difficult nosographic classification because of the presence of sero-immunologic and clinical features common to various diseases having an autoimmune pathogenesis. Some of these syndromes have already been extensively described in scientific literature such as, for example, the presence of clinical and biohumoral alterations with hepatic and extrahepatic involvement, in the course of viral and autoimmune chronic hepatitis. The described clinical case can be classified as a new "overlap syndrome": Type 1 autoimmune hepatitis (AIH)/Primary pulmonary hypertension (PPH). Although the presence of pulmonary hypertension has been extensively described in the course of various connective tissue diseases (S.L.E., Mixed Connective Tissue Disease, Scleroderma, Hashimoto's Thyroiditis, Sjögren's Syndrome), in recent scientific literature, the association is quite rare. The interest in the described clinical case lies both in the possibility to classify it in the context of a more complex "overlap syndrome" AIH/PPH and in the correlated diagnostic and therapeutic implications. Therefore, in cases of primary pulmonary hypertension, a thorough immunological and hepatic functionality study is always recommended in order to ensure an early diagnosis and a prompt AIH treatment, thus warding off the risk of a rapid progression in cirrhosis.

[HAV infection in patients with chronic hepatitis C]. / Infezione da HAV in pazienti con epatite cronica HCV-correlata.

AIM: In most cases, hepatitis A virus (HAV) infection causes a self-limiting benign acute hepatitis which confers permanent acquired immunity. However, in patients with pre-existing chronic hepatitis, HAV superinfection can cause acute hepatitis with severe progression leading to a fulminant form or linked to the risk of a rapid deterioration of hepatic function. For such a reason, some Authors recommend anti-HAV vaccination for subjects with HCV-correlated chronic hepatitis before the initiation of peg-Interferon and Ribavirin treatment. Subsequently, the real prevalence of IgG anti-HAV antibodies in patients with HC HCV-related and in healthy subjects from Eastern Sicily has been verified. PATIENTS AND METHODS: In 254 subjects affected by HC HCV-related it has been carried out the research of antibodies IgG and IgM anti HAV. The control group was formed by 685 non hepatopathic subjects, subdivided in range of ages. RESULTS: 97.64% out of the patients affected by HC HCV related exhibit antibodies IgG anti HAV, while only 2.36% of them was negative. The prevalence of infection in the control group has been stratified in relation to different ranges of age of the people taken into consideration. CONCLUSIONS: The results obtained in this study performed in our geographical area, let us to suggest that it is not necessary the anti HAV vaccination during the phase of pre-treatment for HC HCV-related.

Obesity and related diseases: an epidemiologic study in eastern Sicily.

AIM: The aim of this study was to investigate the prevalence of obesity in a non selected cohort of adult subjects living in eastern Sicily. METHODS: Out of 2 296 examined subjects, 834 (36.3%) were affected by obesity. Of these, only 160 (19.1%) were affected by obesity alone while 674 (80.9%) showed other associated pathologies. RESULTS: The prevalence of arterial hypertension, diabetes mellitus, hepatic steatosis, hyperdyslipidemia and renal failure was significantly higher (P = 0.000) than in a control group of non-obese subjects comparable for sex and age. CONCLUSIONS: In a large part of obese patients, the presence of insulin resistance was observed suggesting that this alteration can play a pivotal role in the development of some important metabolic and cardiovascular complications related to obesity.

[Mezlocillin in short-term obstetrico-gynecologic prophylaxis]. / La mezlocillina nella profilassi ostetrico-ginecologica short-term.

The present study examines a sample of 98 patients aged 18-77 (mean age 57) and awaiting obstetric or gynaecological surgery who were given short-term prophylaxis with mezlocillin. The overall success rate was 83.67%, partial success 14.28% (against 81% in the controls). In addition to the benefits of a shorter hospital stay and lower operating costs, the treatment produced no side effects.

Clinical experimental considerations on the presence of set uterine pacemakers.

The authors studied the physiology of human uterine muscle contraction. Clinical experimental results obtained from elementary electrophysiological, electrohysterographic and pharmacological studies using PGs suggested that uterine muscle contraction does not originate in "pacemaker" areas. These data also showed that the electric phenomenon is not propagated along preferential "rails".

A new cervical perfusion method for induction of labor with prostaglandins.

PIP: 144 patients aged 18-41 were observed to study a new method of cervical perfusion of prostaglandins (PGs) to induce labor and missed abortion. 46 patients were primigravidae, 86 had a normal pregnancy, and 58 had missed abortion. Duration of gestation was 37-42 weeks, and duration of amenorrhea in case of missed abortion was 16-34 weeks. Induction of labor with oxytocin had been unsuccessful in all patients. A new technique of local perfusion of PGs directly into the cervix was attempted. In pregnant women 10 mg of PGF2alpha was diluted in 1000 ml of saline and infused; the initial concentration of 1-2 mcg/minute was increased every 2 hours. In cases of missed abortion 40 mg of PGF2alpha was diluted in 800 ml of saline; initial concentrations ranged from 5 to 10 mcg/minute and were increased every 2 hours. Mean delivery time was 6 hours 50 minutes; mean abortion time was 9 hours 55 minutes. 6 patients underwent cesarean section. When the uterine activity was analyzed in terms of amplitude and frequency of contractions it showed a maximum from 1 1/2 hours from beginning of labor, up to the 3rd hour of observation. In patients with missed abortion the maximum activity was recorded after the 2nd hour. Cardiotocographic curves, fetal heart rate, and clinical tests were normal. There were no complications, but only vomiting in 4 patients, and mild diarrhea in 9 patients. Labor was immediate in all patients, the latent phase exceeding 6 minutes in only 1 case; a contractile response was normally obtained after 30-40 seconds. In patients with incomplete abortion, the basal tone increased more rapidly than in pregnant patients while staying within the limits of safety. There were no pathologic or other changes in the genital organs at check up. Further studies on the effectiveness and safety of PGs are needed.^ieng

[The effect of methergoline and of a synthetic estrogen on plasmatic prolactin levels and on postpartum lactation]. / Effetto della metergolina e di un estrogeno di sintesi sui livelli di prolattina plasmatica e sulla montata lattea nel post-partum.

PIP: 30 women who, for various reasons, did not wish to breastfeed were treated with 12 mg of methergoline a day, for 5 days, while a second group of women were treated, for the same purpose, with 450 mg of resorcilic acid lactone for 5 days. In the first group not only lactation was totally suppressed, but plasma prolactin levels were significantly reduced. In the second group lactation was inhibited, but prolactin levels remained the same.^ieng

HGH behaviour at term of pregnancy and during puerperium.

Human growth hormone (HGH) has been measured in the plasma of 30 subjects at term of pregnancy, at 96 and at 144 h after delivery. The subjects were then selected into three groups: 10 were studied in basal conditions, 10 were given pyridoxine, 10 were given enantate testosterone and valerianate estradiol. In the first group the correlation index (t of Student) was not significant showing the lack of correlation among the tested averages. IN the second group the index of Student was weakly significant (t = 2.36, p less than 0.05). In the third group the Authors found a high representative correlation between the term of pregnancy and the 144th hour after delivery (t = 3.81, p less than 0.01) and between the 96th and 144th hour after delivery (t = 2.95, p less than 0.01).

Hormone profile of T3, T4 at the end of pregnancy and during puerperium.

The Authors have studied the T3, T4 and TBG behaviour at the end of pregnancy and after 96 h and 144 h from delivery in 25 pregnant women. The patients have been randomly divided into two groups: the first was studied in basal conditions and the second after administration of enantate testosterone and valerianate estradiol. In the first group T3 and T4 values increased slightly. A higher increase was noticed from the 96th to the 144th h from delivery. In the second group T3 and T4 values were discording.