Search

The prevalence and mortality of sepsis in Internal Medicine Units (IMUs) is poorly understood as most of the data derive from studies conducted in Intensive Care Units. Aim of SEpsis Management in INternal medicine Apulia (SEMINA) study was to determine the prevalence of sepsis and the characteristics and outcomes of patients with Sepsis-3 criteria admitted in Apulia's Internal Medicine Units for over six months.The SEpsis Management in INternal medicine of Apulia study was a prospective, multicentre, observational study. Adult admissions to the 13 Apulia Region's Internal Medicine Units between November 15, 2018 and May 15, 2019 were screened for sepsis according to the Sepsis-3 criteria. Medical data were collected in electronic case report form.Out of 7,885 adult patients of the Internal Medicine Units, 359 (4.55%) fulfilled the inclusion criteria, and 65 of them (18.1%) met the septic shock criteria. The patients enrolled were elderly, suffering from chronic poly-pathologies and from cognitive and functional impairment. The respiratory system was the most common site of infection and the most common pathogens isolated from blood cultures were Staphylococcus spp., E. coli, Klebsiella spp., Enterococcus spp. and Acinetobacter spp. The in-hospital fatality rate was 31.2% and was significantly higher for septic shock. Sequential Organ Failure Assessment score, dementia and infections from Acinetobacter spp. were independent risk factors for mortality.A high prevalence of sepsis and a high fatality rate were detected in Apulia Region's Internal Medicine Units. The high fatality rate observed in our study could be related to the underlying diseases and to the vulnerability of elderly patients admitted to our Internal Medicine Units.

Due to early metastasis and delayed diagnosis, lung cancer is the leading cause of cancer-related deaths. Although the most common metastasis sites are brain, bone, lung, adrenal glands, liver, and extra-thoracic lymph node, soft tissues, such as skeletal muscles, skin, and subcutaneous tissues, can also be undermined. This article aims to report the first case of an asymptomatic radial extensor muscle metastasis generating from a lung adenocarcinoma that was diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).

Mycoplasma pneumoniae infection is frequent but generally mild or self-limiting. Approximately 10% of cases develop clinical signs of pneumonia with "atypical" radiographic pattern. However, mycoplasma pneumoniae can be responsible for a variety of extrapulmonary manifestations, potentially involving all systems and apparatuses. Although exact pathophysiological mechanisms are not completely known, these could be secondary to direct invasion of the target organ, immunological damage due to molecular mimicry or vascular obstruction. A 45-year-old man was admitted to Internal Medicine Unit because of fever, dry cough and fatigue lasting 15 days. Fever disappeared after starting clarithromycin. About 72 h after admission the patient complained of right calf pain and tachypnea. The presence of anti-mycoplasma antibodies suggested mycoplasma pneumoniae infection. Moreover, a diagnosis of venous thrombo-embolism was performed. Given the absence of classical risk factors for thrombosis, patient was investigated for inherited and acquired thrombophilia and tested positive for antiphospholipid antibodies. A review of the English literature on the association between m. pneumoniae and pulmonary embolism will be provided in order to underline the possible pathogenetic role of antiphospholipid antibodies in this setting. Clinicians should outweigh risk and benefits for LMWH prophylaxis case by case considering these adjunctive pro-thrombotic mechanisms in patients m. pneumoniae infection.

Prior cardiovascular event and kidney dysfunction are both strong risk factors for coronary artery disease. The aim of this study is to assess coronary atherosclerotic burden in a large population of patients undergoing coronary angiography, according to prior cardiovascular event or chronic kidney disease.We evaluated 700 consecutive patients who underwent coronary angiography (CA). Serum creatinine to estimate glomerular filtration rate (eGFR) was measured. Clinically significant coronary artery disease (CAD) was defined by the presence of a coronary lesion resulting in a luminal stenosis50%. For the purpose of the study, the whole population was divided into 4 subgroups according to the presence/absence of eGFR60 ml/min/1.73 m2 or prior cardiovascular event: eGFR≥60/no event (Group A), eGFR≥60/yes event (Group B), eGFR60/no event (Group C), eGFR60/yes event (Group D).As expected, patients in group D had the worst clinical and biochemical profile. These patients also presented the highest values of urinary albumin creatinine ratio (ACR, p0.001) and the lowest values of eGFR (p0.01). One-hundred-ninety-six patients had three-vessel disease. Patients who had undergone PCI procedure showed a lower eGFR as compared to patients who had not (p=0.009). Considering group A as reference, the risk of having three-vessel disease was increased in group B (OR= 2.09; 95% CI 1.37-3.19), in group C, (OR= 1.80; 95% CI 1.04-3.14), and finally in group D (OR= 3.35; 95% CI 2.01-5.58). The risk carried by group C was not significantly different from that carried by Group B: OR= 0.86; 95% CI 0.5-1.5.In our study, low eGFR seems to have the same excess risk of prior CV event.

Paradoxical embolism represents a rare condition occurring when a thrombus originating from venous system produces pulmonary embolism and systemic embolization through an intracardiac or pulmonary shunt. The evidence of a thrombus entrapped in a patent foramen ovale (PFO) is an even more rare condition. There is uncertainty about the optimal treatment strategy.A 58-year-old male patient was admitted to our Internal Medicine Unit with the diagnosis of bilateral bronchopneumonia. During hospitalization, the co-occurrence of chest pain and amaurosis led us to hypothesize a paradoxical embolism.Transthoracic echocardiography showed the presence of a thrombus stuck over the interatrial septum. A contrast-enhanced chest CT scan showed multiple pulmonary embolisms and brain CT scan documented a hypodense area, of ischemic significance, in the left occipital lobe near tentorium. In order to prevent further embolization, emergency cardiac surgery (right atriotomy, removal of thrombus and closure of the PFO, pulmonary thrombectomy) was performed without complications.Although rare, the evidence of a thrombus stuck in a patent foramen ovale represents a clinical emergency. The optimal therapeutic approach is still debated. The surgical correction seems to be a safe and effective option for these patients.

Pathological, genetic, biochemical and pharmacological studies support the hypothesis that brain accumulation of oligomeric species of beta-amyloid (Abeta) peptides may cause Alzheimer's disease (AD). Drugs currently used for the treatment of AD produce limited clinical benefits and do not treat the underlying causes of the disease. In the last 10 years, new therapeutic approaches targeting Abeta have been discovered and developed with the hope of modifying the natural history of the disease. Several active and passive immunotherapy approaches are under investigation in clinical trials with the aim of accelerating Abeta clearance from the brain of the AD patients. The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Abeta monoclonal antibodies, that is being tested in two large late-stage trials. Compounds that interfere with proteases regulating Abeta formation from amyloid precursor protein (APP) are also actively pursued. Unfortunately, the most biologically attractive of these proteases, beta-secretase, that regulates the first step of the amyloidogenic APP metabolism, was found to be particularly problematic to block and only one compound (CTS21166) has reached clinical testing so far. Conversely, several inhibitors of gamma-secretase, the protease that regulates the last metabolic step generating Abeta, have been identified, the most advanced being LY-450139 (semagacestat), presently in Phase III clinical development. Compounds that stimulate alpha-secretase, the enzyme responsible for the non-amyloidogenic metabolism of APP, are also being developed one of them, EHT-0202, has recently started a Phase II study. Furthermore, brain penetrant inhibitors of Abeta aggregation have been identified and one of such compounds, PBT-2, has produced encouraging neuropsychological results in a recently completed Phase II study. With all these anti-Abeta approaches in clinical testing, we will know in few years if the Abeta hypothesis of AD is correct.

Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes.Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment.Compared with controls, patients showed lower levels of protein sulphydrils (28.9 +/- 7.1 vs. 65.6 +/- 1.8 nmol mg(-1) prot) and accumulation of carbonyls (4.7 +/- 1.7 vs. 1.4 +/- 0.1 nmol mg(-1) prot). Phosphatidylethanolamine level was lower in stage III-IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4.25 +/- 0.55 in the I-II stage and 2.89 +/- 0.44 in the stage III-IV vs. 1.61 +/- 0.30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P0.05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r=0.66, P0.05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters.This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.

Whether fatty infiltration of the liver influences the generation of reactive oxygen species (ROS) during reperfusion is unclear. Thus, this study aimed to compare the ROS formation that occurs during postanoxic reoxygenation in isolated normal and fatty livers.Isolated livers from fed Sprague-Dawley rats with normal or fatty livers induced by a choline-deficient diet were reperfused at 37 degrees C for 60 min with an oxygenated medium containing 10 microM of lucigenin after 1 hr of warm ischemia. Superoxide anion generation was assessed by the chemiluminescence (CLS) signal emitted from the organ surface. The hepatic content of malondialdehyde (MDA) and glutathione was determined at the end of reperfusion. Tissue injury was evaluated by the liver histology and the alanine aminotransferase (ALT) release in the perfusate.CLS started rapidly with reoxygenation and it diffused to the whole organ in both groups. However, CLS emission was significantly higher in fatty liver (after 10 min: 812.425+/-39.898 vs. 294.525+/-21.068 photons/cm2/sec; P0.01). A greater concentration of MDA was measured at the end of reoxygenation in fatty liver. Finally, the liver histology and the ALT release indicated a greater injury in steatotic than normal liver.The CLS technique allows a direct visualization and comparison of ROS generation from the organ surface. Fatty infiltration increases ROS generation in the liver during postischemic reoxygenation, likely leading to the greater lipid peroxidation observed in these experiments. The increased oxidative stress may contribute to the reduced tolerance of steatotic livers to ischemia-reperfusion injury.

The reason why some hepatitis C virus carriers with normal aminotransferase activity present, during time, an activation of the disease, is unknown. The aim of this study was to assess the oxidative balance in such patients and to evaluate its possible role on the severity of disease.Histology, glutathione and malondialdehyde were determined in the liver of 30 HCV-RNA positive patients with persistently normal aminotransferase. Patients were followed-up for 18 months with plasmatic determinations of aminotransferase, ferritin, glutathione, malondialdehyde, carbonyl and sulphydryl protein levels (every 2 months) and serum HCV-RNA (every 3 months).Four subjects had normal histology, whereas the remaining 26 showed mild/moderate chronic hepatitis. Hepatic glutathione and malondialdehyde concentrations were normal in 16 patients and clearly altered in the other 14. The hepatic redox state did not correlate with histology whereas it correlated with plasmatic oxidative markers. During the study, aminotransferase flared up in 11 patients, 9 of these (82%) having at enrollment an altered hepatic oxidative balance. Patients with aminotransferase elevation showed increased blood indices of oxidative stress, which occurred earlier than aminotransferase flare-ups. No oxidative stress was observed in the remaining subjects.This study suggests that symptom-free HCV carriers with impaired redox state have a higher risk of aminotransferase flare-up; therefore the impaired oxidative balance may have a prognostic significance on disease activity.

Oxidative damage to lens proteins is a major factor leading to cataract formation. It is of pathogenic importance to determine a threshold of protein oxidation over which opacification of the lens takes place.Sixty-two lenses extracted from patients affected by idiopathic senile, diabetic, or myopic cataract were studied. Clear lenses were obtained from subjects undergoing enucleation (n = 10) or vitrectomy for giant retinal tears (n = 9), and were age- and sex-matched to those with cataract. The content of carbonyls and sulfhydryls (P-SH) in proteins in the lens was assessed using spectrophotometric assay.An age-associated inverse relation (P0.01) was noted in the content of P-SH, the concentrations of which were also inversely related (P0.03) to the content of protein carbonyls. These changes were more pronounced in cataracts than in clear lenses and in diabetic and myopic cataracts when compared with senile cataracts. The drop of P-SH concentration occurred earlier in diabetic and in myopic cataracts than in senile cataracts. The accumulation of protein carbonyls2 nmol/mg protein and the decrease of P-SH below 12 to 10 nmol/mg protein were always accompanied by lens opacification.Idiopathic senile, diabetic, and myopic cataractogenesis appear to be dependent on oxidative damage to lens proteins. This damage occurs earlier in myopic and diabetic patients. Values of P-SH below and protein carbonyls above their specific threshold were found to be predictive for the presence of cataract. Because increased oxidation was observed in clear lenses removed from myopic and diabetic subjects, oxidation may be involved in the pathogenesis of these forms of human cataract.

The role of GSH in the detoxification of reactive metabolites of oxygen and xenobiotics, in gene expression, and as a source of cysteine is well established. Because decreased circulating and intracellular concentrations of GSH might be of pathogenetic relevance in several clinical conditions, there is a growing interest in pharmacological interventions to correct a deranged sulfhydryl status. In this study, the disposition and the effect of S,N-diacetylcysteine monoethyl ester (DACE) on sulfhydryls were investigated after i.v. and intraduodenal (i.d.) administrations to rats. DACE was rapidly hydrolyzed and deacetylated to N-acetylcysteine and cysteine in plasma. High concentrations of cysteine were attained in the circulation and in the liver after i.v. and i.d. administrations of 5 mmol/kg DACE, and physiological levels of GSH in the liver and in plasma increased by 30 and 300%, respectively, with i.v. and i.d. administrations. Incubation of peripheral blood mononuclear cells with 1 mM DACE resulted in higher intracellular concentrations of cysteine and GSH after 24 h than incubations with equimolar concentrations of cysteine, N-acetylcysteine, or oxothiazolidine carboxylic acid, respectively. It is concluded that DACE provides an efficient delivery system for cysteine that markedly increases intra- and extracellular cysteine and GSH after i.v. and i.d. administrations. Because its uptake into cells is probably not dependent on an active transport process, DACE results in higher intracellular concentrations of cysteine than those resulting from other prodrugs of cysteine and cysteine itself. The compound may thus have advantages over other compounds for the correction of a deranged sulfhydryl status.

Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics.Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients.Fasting gallbladder volume was significantly (P0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019).Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.

Although it is well known that chronic ethanol abuse produces sexual dysfunction and impaired spermatogenesis, the mechanisms of ethanol-induced testicular alterations are not fully explained. Therefore, the aim of this study was to investigate the mechanisms of testicular oxidative damage in rats given drinking water containing 3% ethanol for 8 weeks. Control rats were pair-fed with saccharose. The mean daily ethanol intake was 4.05 g kg(-1), corresponding to the consumption of 41 of wine (10% alcohol) or 0.71 of whiskey (40% alcohol) by a man of 70 kg body wt. Exposure to ethanol caused a significant depletion in the testicular levels of glutathione (GSH), protein containing sulfhydryl groups, tocopherol and ascorbic acid, and an increase in the concentrations of malondialdehyde (index of lipid peroxidation) and carbonyl proteins (index of protein oxidation). Other effects were decreases in the concentration of adenosine 5'-triphosphate and in the activity of glutathione peroxidase, and an increase in the activity of alcohol dehydrogenase. In summary, this study shows that in the rat, daily consumption of ethanol in the drinking water increases lipid and protein oxidation. In addition to impaired antioxidant defence, an imbalance in energy production may also play a role in the toxic reaction to alcohol.

Oxidative modification of proteins is of great importance because of their biological role in transport, enzyme activity, immune response and membrane fluidity. This study investigated the redox status of proteins in plasma, erythrocyte and erythrocyte ghosts of chronic alcoholics; a comparison with subjects affected by chronic viral hepatitis and healthy controls was also performed. Compared to the other groups, chronic active alcoholics showed significant increase of plasma, erythrocyte and erythrocyte ghost concentrations of carbonyl proteins, marker of protein oxidative damage. Also, a significant correlation was noted between daily alcohol intake and plasma levels of carbonyl proteins. The incubation of fresh human plasma with acetaldehyde, but not with ethanol, led to a significant increase of the carbonyl protein production. In conclusion, plasma, erythrocyte and membrane proteins are oxidatively modified in active chronic alcoholics; these changes seem to be related to acetaldehyde rather than ethanol toxicity.

To test whether impaired glutathione redox status may be related to lens oxidative damage in humans, we measured glutathione (total and oxidised forms) and malondialdehyde, a lipid peroxidation product, in clear lenses and diabetic and non-diabetic cataracts. Diabetic cataracts were divided into 2 subgroups with either intact or abnormal haemo-ocular barrier as evaluated by preoperative iridography. Decreased total glutathione values were observed in cataractous (diabetic and non-diabetic) as compared to clear lenses (p0.001), whereas enhanced oxidised glutathione levels were found in diabetic caracts as compared to non-diabetic ones and clear lenses (p0.001). Malondialdehyde concentrations were significantly higher in all types of cataracts, especially myopic and diabetic ones, than in clear lenses (p0.001). Moreover, malondialdehyde levels in diabetic lenses were inversely correlated with total glutathione (r = 0.80; p0.001) and linearly correlated with oxidised glutathione values (r = 0.76; p0.001). Finally, glutathione redox status was found to be more seriously impaired in lenses from diabetic patients with abnormal than intact haemo-ocular barrier. These data suggest a contributory role of lipid peroxidation and glutathione oxidation and consumption in the pathogenesis of cataract, especially in diabetic lenses with haemo-ocular barrier abnormality.

A prospective blind study was performed to compare sonographic with postoperative findings of gallstone burden in 34 patients (10 males, 24 females; mean age 52 years). Gallstone size was assessed in single calculi (n = 15) by measuring the largest diameter by ultrasonography (US). The ellipsoid algorithm was used to estimate US volume for both single and multiple gallstones. After cholecystectomy, diameters were measured in single stones; stone volume was assessed by the ellipsoid formula (single stones) and fluid displacement (single and multiple stones). Stone volumes assessed by the ellipsoid formula and fluid displacement correlated closely (r = 0.98; p0.0001, n = 15). In the case of single gallstones, the mean length assessed by US was 25.3 +/- 3.2 mm and compared well with the value measured "in vitro" (24.8 +/- 3.1 mm). A highly significant and positive relationship existed between the sonographic size and the true stone size (r = 0.93; p0.0001, n = 15). Stone volumes assessed "in vivo" and by fluid displacement were comparable and correlated for both single (US: 6.6 +/- 1.3 vs fluid displacement: 5.8 +/- 1.4 ml; r = 0.79; p0.0005, n = 15) and multiple stones (US: 3.8 +/- 0.8 vs fluid displacement: 3.7 +/- 0.8 ml; r = 0.85; p0.0001, n = 19).(ABSTRACT TRUNCATED AT 250 WORDS)

Crystalline lactulose (Laevolac Cristalli, CAS 4618-18-2), a pure form of the disaccharide widely employed in the therapy of complications of liver cirrhosis, was administered, after a pharmacological wash-out of 10 days and following a randomized design, to 10 cirrhotic patients for 30 days at the dosage of 60 g/d, while another 10 subjects with similar characteristics received no treatment. Besides the parameters usually monitored for the evaluation of liver function and state of hepatic encephalopathy, immunological patterns such as lymphocyte subpopulations CD3, CD4, CD8, CD16(NK), CD25 and antibacterial activity against Ty2 strain of Salmonella typhi were evaluated. At the end of the study (day 30) a significant decrease of blood ammonia was observed, as expected, only in the group treated with lactulose with respect to the control group, as well as a significant increase of CD16 and antibacterial activity (1/3); an enhanced level of CD25, although not significant, was also noticed in the treated group with respect to the control group. These findings seem to show an effect of activation on cell-mediated immune system depressed during liver cirrhosis, produced by lactulose. Further studies are needed to confirm these data and to clarify the possible mechanisms involved.

An increased lipid peroxidation, due to the altered intracellular ratio between free radicals and antioxidant systems, has been recently related to diabetes. To study the possible relationship between lipid peroxidation and metabolic control, we measured the plasma concentrations of malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, in poorly and well controlled Type 2 diabetic patients. A significant increase in plasma malondialdehyde concentrations was found in poorly controlled diabetics when compared to well controlled patients (p0.001) and to healthy normoglycaemic subjects (p0.001), whereas no significant difference was observed between the two latter groups. Plasma MDA/Cholesterol and MDA/triglyceride ratios were both higher in poorly controlled diabetics than in well controlled (p0.005) and in normal subjects (p0.01 and p0.02 for MDA/CHOL and MDA/TG respectively). In diabetic patients a positive correlation was found between plasma MDA levels and mean daily blood glucose (p0.01), plasma fructosamines (p0.001), HbA1 (p0.05) and plasma triglycerides (p0.05), while no significant correlation was shown between plasma malondialdehyde and total cholesterol. Malondialdehyde levels were followed-up for 7 days running (T1-T7) in five poorly controlled diabetics, treated with conventional insulin therapy. This group showed normalized plasma lipid peroxide values (0.486 +/- 0.13 mumol/l, T5, M +/- SEM) 72 h after the restoration of glycaemic control (145 +/- 25 mg/dl, T2, M +/- SEM). These results confirm the increase of lipid peroxidation during Type 2 diabetes. The correlation with the degree of metabolic imbalance suggests a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes.

It is well known that lipid peroxidation may be initiated or exaggerated by conditions leading to hepatic GSH depletion or altered GSH/GSSG ratio. In our study we evaluated the effects of GSH administration on hepatic, bile and plasma GSH, GSSG and MDA in rats depleted of the tripeptide by a prolonged. fasting. An exteriorized biliary-duodenal fistula was established and GSH or saline solution was administered i.p. for a period of 6h. Rats treated with GSH exhibited an increased GSH and decreased GSSG biliary excretion. Whereas in control rats an opposite pattern was observed, namely enhanced GSSG and decreased GSH biliary excretion. While hepatic GSH and GSSG concentrations were comparable in the two groups, a significant increase in liver and plasma MDA production was found in controls compared to GSH treated rats. Our data suggest a protective role of GSH against the production of lipoperoxidation as evidenced by the decrease of hepatic, biliary and plasma MDA levels and by a decreased percentage of biliary GSSG. In addition, the significant increase of biliary GSH excretion, observed in rats treated with GSH compared to controls, may be due to an increased supply of the tripeptide which is known to be preferentially excreted into bile in the reduced form.

Fasting hypoglycemia is frequently observed in patients with Multiple Sclerosis (S.M.) showing orthostatic hypotension and defective thermoregulation, although they never complicate in hypoglycemic coma. The aim of this study was to evaluate glucose homeostasis in S.M. patients. Both insular and counter-insular regulating mechanisms were investigated by determination of glucose, insulin, C-peptide and cortisol plasmatic levels during OGTT, and subsequently by evaluating glucagon plasmatic levels after arginine administration (30 g., i.v.). Our results suggest that the increased susceptibility of S.M. patients to undergo fasting hypoglycemia could be related to some alterations in counter-insular mechanisms, generally included among neurovegetative modifications in S.M. patients and probably due to orthosympathetic function impairment.

Increased 2-3 Diphosphoglycerate levels in cirrhotic patients have been reported. Previous studies did not show significant changes in 2-3 DPG in anaemic cirrhotic patients when compared to non anaemic cirrhotic patients, but the role played by alkalosis and/or hypoxia has not been investigated. To study this question, haematic 2-3 DPG was measured in 8 male patients with liver cirrhosis (histologically diagnosed) together with PO2, PCO2, pH and Hct. 2-3 DPG was also measured in 6 healthy male volunteers. We found a significant increase in blood 2-3 DPG of cirrhotic patients compared to control subjects (5,55 +/- 0,4 vs 2,18 +/- 0,3 mmol/l erythrocytes respectively, p less than 0,001) in agreement with previous studies. PO2 levels and Hct value did not show important changes, whereas PCO2 and pH resulted to be very altered when compared to normal values, even though we could not correlate these values with blood 2-3 DPG. We conclude that the genesis of 2-3 DPG increase is multifactorial, however an alteration in acid-base equilibrium seems to play a more important role than hypoxia.

To study the effect of chronic ethanol consumption on biliary excretion of acetaminophen, male Sprague-Dawley rats were pair-fed a nutritionally adequate liquid diet containing either ethanol or isocaloric carbohydrate for 4-6 weeks. One day after bile duct cannulation, acetaminophen (250 mg/kg body weight) was given ip and drug metabolism was studied for 5 hr. Biliary excretion of acetaminophen and its principal metabolites was significantly decreased in rats fed alcohol chronically when compared to pair-fed controls. Although no difference was found in the urinary excretion of the drug, the total elimination (biliary + urinary) was significantly depressed in the alcohol-fed animals. The decreases in hepatic glutathione content and in biliary glutathione concentration (after acetaminophen injection) were significantly greater in ethanol-fed rats than in controls. These data support the possibility that diminished hepatic glutathione and biliary excretion of the drug may contribute to the increased hepatotoxicity of acetaminophen after chronic alcohol feeding.

To investigate the role played by plasmatic lipids in the altered erythrocyte deformability observed in cirrhotic patients we studied 15 patients with liver cirrhosis (histologically diagnosed) and 10 healthy volunteers. Erythrocyte filtration time, plasmatic free and esterified cholesterol and phospholipids were measured in all subjects. The erythrocyte filtration time resulted to be significantly increased in cirrhotic patients (35'' +/- 3, 35 M +/- SEM) when compared to control subjects (26'' +/- 2, 53: M +/- SEM) (t = 2,078 p less than 0,05). This increase correlated in cirrhotic patients (but not in control subjects) with free/esterified cholesterol ratio (p less than 0,01) as well as free cholesterol/phospholipid ratio (p less than 0,001). Our results confirm that decreased erythrocyte deformability in cirrhotic patients which is accompanied by altered erythrocyte morphology is due, at least in part, to the altered lipids blood levels.

To study beta-cells response during liver cirrhosis, OGTT (0.75 g/kg b.w.) was performed in 7 cirrhotic patients (histologically diagnosed). An impaired glucose tolerance was observed in all the subjects: basal plasma glucose was 0.74 g/l +/- 0.05 (M +/- SEM); at 90 min was 1.50 g/l +/- 0.10, and at 180 min was 1.10 g/l +/- 0.17. Plasma insulin peak was delayed at 90 min (78.2 microU/ml +/- 27.7); two patients showed basal hyperinsulinemia. C peptide concentration reached the peak at 120 min (3.6 ng/ml +/- 0.5), in agreement with Gragnoli and coll. Plasma insulin concentration did not correlate with hepatic laboratory findings. All the patients had severe liver disease, including esophageal varices; in 4 patients ascites was observed. The results show that impaired glucose tolerance in patients with liver cirrhosis is not directly related to the degree of the disease and confirm the decreased insulin catabolism and peripheric resistance.

In a further attempt to tackle the question of the doctor-patient relationship in rheumatology, this time more comprehensively and from a different angle, the mistakes a doctor may make in daily practice are indicated. In effect, since the doctor's himself a kind of "drug", only his "correct administration" will effectively solve certain of the patient's psychological problems.

The observation of several cases triggers a review of psychological pain in rheumatology. Such situations require a thorough grounding on the part of the rheumatologist who must work with the psychiatrist and clinical psychologist in the treatment of such patients. The importance of teamwork and the need for clinical psychologists and psychiatrists in rheumatology wards is emphasised and the approach and treatment techniques to be adopted for patients suffering from so-called psychological pain are outlined. Essentially, the first (approach) stage involving several phases will be followed by a second stage to be evaluated by the team in an attempt to provide the patient with the most appropriate treatment.

Rats treated acutely with ethanol showed a significant increase in biliary bilirubin secretion and in serum bilirubin levels (compared to saline treated controls); no difference was found in bile acid secretion. In rats fed ethanol chronically (36% of total energy for 4-6 weeks) there was a significant increase in the secretion of bilirubin and bile acids when compared to pair fed controls. We observed this effect either in the presence or in the absence of alcohol in the blood at the time of the experiment. The presence of ethanol in the blood, however, resulted in higher biliary and serum bilirubin levels. The increase in bile acid secretion involved selectively di- (but not tri-) hydroxy bile acids. Since increased secretion of unconjugated bilirubin favors pigment gallstones formation, it can be postulated that ethanol contributes to the pathogenesis of cholelithiasis by enhancing the biliary secretion of the pigment.