[Narration in clinical medicine: why and how?]. / Narrare la medicina clinica. Perchè? Come?

During the years of their medical schooling, physicians ought to be trained in narration. The health care organization as a whole should be encouraged to allow narration to play a role in everyday practice. Narration is an important means to bringing clinical medicine closer to the understanding and proper care of the patient and to observance of the related ethical principles.

Dome-like behaviour at Mt. Etna: The case of the 28 December 2014 South East Crater paroxysm.

On the 28 December 2014, a violent and short paroxysmal eruption occurred at the South East Crater (SEC) of Mount Etna that led to the formation of huge niches on the SW and NE flanks of the SEC edifice from which a volume of ~3 × 106 m3 of lava was erupted. Two basaltic lava flows discharged at a rate of ~370 m3/s, reaching a maximum distance of ~5 km. The seismicity during the event was scarce and the eruption was not preceded by any notable ground deformation, which instead was dramatic during and immediately after the event. The SO2 flux associated with the eruption was relatively low and even decreased few days before. Observations suggest that the paroxysm was not related to the ascent of volatile-rich fresh magma from a deep reservoir (dyke intrusion), but instead to a collapse of a portion of SEC, similar to what happens on exogenous andesitic domes. The sudden and fast discharge eventually triggered a depressurization in the shallow volcano plumbing system that drew up fresh magma from depth. Integration of data and observations has allowed to formulate a novel interpretation of mechanism leading volcanic activity at Mt. Etna and on basaltic volcanoes worldwide.

Ancient Ethiopian genome reveals extensive Eurasian admixture throughout the African continent.

Characterizing genetic diversity in Africa is a crucial step for most analyses reconstructing the evolutionary history of anatomically modern humans. However, historic migrations from Eurasia into Africa have affected many contemporary populations, confounding inferences. Here, we present a 12.5× coverage ancient genome of an Ethiopian male ("Mota") who lived approximately 4500 years ago. We use this genome to demonstrate that the Eurasian backflow into Africa came from a population closely related to Early Neolithic farmers, who had colonized Europe 4000 years earlier. The extent of this backflow was much greater than previously reported, reaching all the way to Central, West, and Southern Africa, affecting even populations such as Yoruba and Mbuti, previously thought to be relatively unadmixed, who harbor 6 to 7% Eurasian ancestry.

Role of S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis.

Recent studies have established the clinical efficacy of S-adenosyl-L-methionine (SAMe) in the treatment of cholestasis associated with hepatic diseases, pregnancy and the administration of estrogen-containing oral contraceptives. In 4 clinical trials involving a total of 639 patients with cholestasis due to acute or chronic liver disease, SAMe in an intravenous dose of 800 mg/day or an oral regimen of 1.6 g/day for 2 weeks was superior to placebo in relieving the symptom of pruritus and in restoring serum total bilirubin and serum alkaline phosphatase towards normal. The drug is also effective in intrahepatic cholestasis of pregnancy (ICP), with intravenous administration of 800 mg/day for 2 weeks producing a substantial reduction in pruritus and an improvement in abnormal liver function indices. Moreover, SAMe treatment decreases the incidence of premature labour. SAMe appears to be the first safe and effective approach to the treatment of this syndrome, and also protects against the adverse hepatic effects of small doses of estrogen in patients with a history of ICP by normalising liver biochemistry and the oversaturated biliary lipid composition of the gallbladder bile. In animal models, SAMe reverses the pathological liver changes induced by xenobiotics such as taurolithocholate and alpha-naphthyl-isothiocyanate (ANIT) and the antipsychotic chlorpromazine. Several cooperative mechanisms appear to underlie the anticholestatic action of SAMe, the most important being the restoration of normal hepatocyte membrane fluidity and Na+, K+ ATPase activity, through a reversal of the reduction in phospholipid methylation produced by hepatotoxic agents. In addition, SAMe may act by promoting trans-sulphuration pathway reactions and consequently improving the detoxifying capacity of this metabolic system.

Alterations of glucose metabolism in chronic liver disease.

The prevalence of glucose intolerance has been studied by oral glucose tolerance test in 670 patients affected by chronic liver disease. The glycometabolic status was evaluated by criteria given by WHO in 1980. Sixty-nine subjects appeared to be affected by chronic persistent hepatitis and 140 by chronic active hepatitis. In these patients the prevalence of diabetic responses (DR) did not differ much from that of the general population in our geographic area. In contrast, a markedly higher frequency of DR appeared in a cirrhotic group of 401 patients compared to non-cirrhotic subjects. The cirrhotics, divided according to different disease stages, showed a higher DR frequency in decompensated patients than in well compensated patients, the prevalence reaching 63% in the former subgroup. The coincident presence of hepatocarcinoma - documented in 60 other cirrhotic patients - does not modify the prevalence of diabetes. Other risk factors for diabetes such as age, sex, and family history have been considered. Our results suggest that: (1) all these factors seem not to play a major role in the pathogenesis of alterations of glucose metabolism in patients suffering from chronic liver disease, and therefore (2) liver cirrhosis by itself might be a risk factor in the disturbance of glucose tolerance.

Plasma clearance of nicotinic acid and rifamycin-SV, and their interaction in Gilbert's syndrome: application of a compartmental model.

The bicompartmental kinetics of nicotinic acid (NA) and rifamycin-SV (R-SV)--2 organic anions that probably share a common hepatic uptake mechanism--were studied in 7 cases of Gilbert's syndrome (GS) and in 7 healthy controls matched for sex and age. In GS the NA and R-SV uptake constants (K21) were significantly decreased. In GS patients, simultaneous loads of NA and R-SV, the latter at increasing doses, produced: 1) a progressive lowering only of R-SV K21; and 2) an increase in R-SV hepatic plasma reflux (K12). Changes in biliary excretion ( Kee ) and hepatocellular pool (Ke) of both NA and R-SV probably depend on the rates of uptake and reflux constants of the two anions. The study of the parameters of compartmental kinetics of NA and R-SV confirms that the two organic anions, which have different metabolic routes and/or a different affinity for intracellular carriers, share common uptake mechanisms.

Impaired plasma clearance of nicotinic acid and rifamycin-SV in Gilbert's syndrome: evidence of a functional heterogeneity.

Patients with Gilbert's syndrome (GS) have impaired clearance by the liver of some organic anions. We looked for possible differences in hepatic clearance of nicotinic acid (NA) and rifamycin-SV (R-SV) among GS patients, and examined the effect produced by these anions on the plasma levels of unconjugated bilirubin (UCB). Two subgroups of GS patients, GS1 and GS2, were differentiated according to their ability to handle R-SV and NA. Compared with a control group, the alteration of the half-life both of NA and R-SV was less marked in GS1 than in GS2. UCB plasma concentration after NA and R-SV loading was more greatly increased in GS2 than in GS1 patients. In addition, a striking correlation was found in all subjects studied between UCB and the half-life of NA and R-SV. These related alterations of plasma UCB and plasma half-life or organic anions suggests a common defect of hepatic uptake. It is hypothesized that this defect is located at the level of a hepatic plasma membrane carrier.

Familial clustering of heterogeneous chronic unconjugated hyperbilirubinemia.

This study concerns the family of a girl affected by type 2 Crigler-Najjar syndrome; a brother and a sister died of kernicterus a few months after birth. The father and two living siblings had moderate unconjugated hyperbilirubinemia. The patient's liver uridine-diphospho-glucuronyl-transferase activity (UDPGT) was markedly reduced. All the family members underwent nicotinic acid (NA) load to test hepatic uptake capacity. This test, and NA half-life were normal in the patient and in her mother, and altered in the other relatives. The extent of the hyperbilirubinemic response to NA load, and of the NA half-life, together with physical examination over a one-year period were in good agreement with the diagnosis of Gilbert's syndrome in the patient's father and siblings. Our conclusion is that different impairments of hepatic handling of organic anions may be present in members of families with non-hemolytic bilirubinemia.

A review of the studies on the clinical use of S-adenosylmethionine (SAMe) for the symptomatic treatment of intrahepatic cholestasis.

S-Adenosylmethionine (SAMe) proved to be effective in antagonizing bile secretion impairment induced by a wide range of hepatotoxins, including ethynylestradiol, taurolithocholate, chlorpromazine and alpha-naphthyl-isothiocyanate. The anticholestatic activity of SAMe may result from its role in the intermediate metabolism as this molecule is involved in transmethylation and transsulfuration reactions. Clinical experience, carried-out on more than 1,000 cholestatic patients, supports preclinical data. In particular, controlled clinical trials have documented that intravenous SAMe (800 mg/day) induced a significant decrease of biochemical parameters of cholestasis (serum total and conjugated bilirubin, serum total bile salts, and aminotransferases), as well as a significant improvement of pruritus in women with ICP compared with placebo. In addition, other studies provided the evidence that both parenteral (800 mg/day) and oral SAMe (1600 mg/day) significantly improves subjective (pruritus, fatigue, and general discomfort) and objective (serum total and conjugated bilirubin, and serum alkaline phosphatase) parameters of cholestasis in patients with intrahepatic cholestasis complicating chronic liver diseases compared with placebo. In all these trials, SAMe treatment has been well tolerated at the same extent as placebo. In conclusion, experimental and clinical investigations indicate that SAMe represents an effective and safe approach to the management of intrahepatic cholestasis.

Hypotensive effect of the association atenolol-chlorthalidone in hypertensive diabetics.

The authors conducted a clinical investigation in twenty-five patients affected with essential hypertension of mild or moderate grade associated with type II diabetes mellitus, the purpose being to assess the effect of 8 weeks of combined treatment with atenolol (100 mg) and chlorthalidone (25 mg) on arterial blood pressure, heart rate, and glycaemia. It is, indeed, generally known that both beta-blockade agents and diuretics can interfere with carbohydrate metabolism. The results indicate that 92% of the patients treated in this trial had significant reduction of systolic and diastolic blood pressure readings, in the absence of bradycardia or other adverse effects. Glycaemia values were lower at the end of treatment, probably as a result of better diet control during the trial, as suggested by the general tendency to body-weight reduction.

Enterococcus lactic acid bacteria strain SF68 and lactulose in hepatic encephalopathy: a controlled study.

Forty cirrhotic patients with non-advanced hepatic encephalopathy were randomly allocated into groups which were given orally either two capsules three times daily of a preparation of Enterococcus lactic acid bacteria strain SF68 or 30 ml lactulose four times daily. The patients were evaluated over a 10-day course of treatment and for 10 days post-treatment. The Enterococcus SF68 preparation proved to be as effective as lactulose in lowering blood ammonia, and in improving mental state and psychometric performance. Moreover, the effects of Enterococcus SF68, contrary to that of lactulose, persisted longer after treatment withdrawal. Some patients reported diarrhoea and abdominal pain with lactulose. Lactulose is a standard therapy in the treatment of patients with hepatic encephalopathy. In this study, however, the use of the Enterococcus SF68 preparation was shown to offer advantages over lactulose in these patients.

[Nutritional problems in cirrhotic patients. Evaluation of dietetic aspects]. / Problemi nutrizionali nei pazienti cirrotici. Valutazione degli aspetti dietetici.

The aim of the study was to evaluate: a) the influence of the diagnosis of liver cirrhosis on the alimentary behaviour of cirrhotic patients; b) the compliance and the effect during observation-time of a personalized diet; c) the modifications, induced by the diet, of some clinical and biochemical parameters, specifically of these correlated to hepatic encephalopathy in 20 non-alcoholic cirrhotic patients. They were entered the study, in stage A-B of liver disease, according to Child-Pugh criteria. No patients received a previous specific dietetic prescription. After the collection of the alimentary intake before and after the diagnosis of liver disease, we prescribed normoprotein and hyposodium diets, reducing or increasing the caloric intake for the patients who were not at their ideal weight. From our study it stands out that the diagnosis induced all patients to reduce their caloric intake, especially of lipids. The appropriate dietetic prescription followed by short run controls led to a general improvement of the evaluated parameters, which was not kept during the following months; as a matter of fact, at the long run control all patients tended to return to their previous alimentary habits, neglecting, in the course of time, the diets they had been prescribed. We can, consequently, maintain that the cirrhotic needs a steady clinical and dietetic control since he seems to undervalue the prescribed therapies.

[Diabetic neuropathy. I). Peripheral neuropathy]. / La neuropatia diabetica. I). Neuropatia periferica.

This is the first of a series of reports on diabetic neuropathy. Peripheral or somatic diabetic neuropathy is discussed with reference to its major symptoms: central, peripheral and amyotrophic mononeuropathies, symmetrical and asymmetrical polyneuropathies, peripheral arthropathy and finally diabetic cachexia. The various theories on the pathogenesis of peripheral neuropathy are presented. Finally data on 173 type I and II diabetics are presented. These patients, treated in outpatients departments, were paired by sex, weight and age with an equal number of non-diabetic subjects. The results of the survey largely confirm report in the literature. The importance of continuous medical surveillance for the identification and hence prevention of diabetic neuropathy is emphasized. This is particularly necessary since we have still much to learn about the natural history of the disease and for the moment the therapeutic approaches to the various neuropathies concerned are both tentative and symptomatic.

[Evaluation of the arterial share of portal flow using a scintigraphic technique in patients with liver cirrhosis. Correlations with other parameters of portal hypertension]. / Valutazione della quota arteriosa di flusso portale mediante tecnica scintigrafica in pazienti con cirrosi epatica. Correlazione con altri parametri di ipertensione portale.

This study aimed to measure in semiquantitative terms the arterial-venous ratio of the portal flow using a scintigraphic technique, by means of a simple intravenous injection of a 99mTcDiethylHIDA bolus, a method which was found to be extremely simple and non-invasive, with a good degree of repeatibility. The percentage of arterialisation of the portal flow was found to be higher in cirrhotic patients compared to non-hepatopathic subjects, and among cirrhotic patients it was correlated with the severity of disease, the presence and degree of esophageal varices, and the presence of porto-systemic shunts, assessed using the ammonium chloride test.

Role of delta infection in the progression to chronicity of acute HBsAg positive hepatitis.

A previous study of 159 consecutive cases of HBsAg+ acute viral hepatitis, observed from the onset of disease and seen between May 1977 and May 1980, revealed a higher frequency of evolution to chronicity in the region of Naples than that reported for other areas. This suggested that environmental factors might influence the chronically rate. We investigated 125 HBsAg+ acute hepatitis cases for whom sera were available: 35 patients who remained HBsAg+ at the two-year control (28 chronic hepatitis and 7 healthy carriers) and 90 who recovered and seroconverted HBsAg---- anti-HBs during follow-up. At the onset of disease, all patients who cleared HBsAg showed IgM anti-HBc positivity and 48 were also HBeAg positive; no patient was anti-delta positive. On the contrary of the 28 chronic cases only 7 were IgM anti-HBc+ (6 under 13 years old), while 21 were IgM anti-HBc- but anti-delta+. This study demonstrates that not all HBsAg+ acute hepatitis cases are due to HBV and that in our area, superinfection by the delta agent is responsible for most cases of chronic HBsAg positive hepatitis.

[The pharmacological therapy of intrahepatic cholestasis]. / Terapia farmacologica della colestasi intraepatica.

Changes in liver membrane fluidity constitute one of the most important factors in the pathogenesis of experimental and human cholestasis. These alterations could partly be correlated with a defect in the methylation of membrane phospholipids and with a modification in the cholesterol/phospholipids ratio, which in turn may result from a decrease in the ademethionine hepatic levels and from a dysfunction of the enzymes involved in the ademethionine synthesis or in methylation processes, where ademethionine is a crucial factor. On the basis of these considerations, several trials have proved the protective effect of ademethionine in cholestasis and in hepatic disease with different etiology. As regard human pathology the efficacy of ademethionine was demonstrated firstly in intrahepatic cholestasis of pregnancy or estrogen-induced and later on in hepatic diseases with different etiology. These results are particularly encouraging since very few are the drugs effective in the treatment of intrahepatic cholestasis, which represents indeed a crucial element in hepatic diseases.