Prevalence and mortality of heavy drinkers in a general medical hospital unit.

This study was performed in order to analyse the prevalence, clinical characteristics and mortality of heavy drinkers among hospitalized patients during a 2-year period. Chronic excessive alcohol consumption (daily intake >80 g of ethanol for males and >40 g for females) was found in 278 of 2913 hospital admissions and was strongly associated with the male sex (90.69%). Heavy drinkers were significantly younger than other admissions (15 and 10 years for men and women, respectively), but showed similar mortality rates to other admissions, despite a much earlier age at death (19.5 years for men and 22 years for women). There was a trend towards higher mortality rates among severe alcoholic women than severe alcoholic men and non-alcoholic women. Liver cirrhosis was the entity most frequently observed in the heavy drinkers, and was significantly more prevalent in alcoholic women.

[The efficacy of antiretroviral treatment in patients with human immunodeficiency virus infection. A study of 807 patients]. / Eficacia del tratamiento antirretroviral en pacientes con infección por el virus de la inmunodeficiencia humana. Estudio de 807 pacientes.

BACKGROUND: The natural history of HIV infection and its related diseases has changed after the introduction of new potent antiretroviral therapies (HAART). We have performed this study to analyse in our hospital the natural history of HIV infection in relation to the therapeutics advances. PATIENTS AND METHODS: We have exhaustively revised the clinic records of all the 807 adult HIV-infected patients followed at the HUC from January 1985 to December 1999. RESULTS: The incidence of most opportunistic diseases, new AIDS cases, hospital admissions and deaths decreased as from 1997. Patients who started antiretroviral therapy with HAART had lower incidence of AIDS, hospital admissions and deaths than patients with other therapy modalities. Survival of patients placed on HAART was better than that of patients who received different therapy modalities (p < 0.001), independently on the intensity of immunosuppression and AIDS diagnosis. Multivariate analysis showed that HAART therapy was the best protector factor, decreasing the risk of progression to death (p < 0.001). CONCLUSIONS: HAART therapy leads an important improvement of survival of HIV infected patients, independently an the intensity of immunosuppression and slows HIV progression, decreasing the number of new AIDS cases, hospital admissions and deaths.

Relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism.

This study was performed to analyze the relative and combined effects of ethanol and protein deficiency on bone histology and mineral metabolism in 4 groups of 7 animals each which were pair-fed during 8 weeks with 1) a nutritionally adequate diet; 2) a 36% (as energy) ethanol containing isocaloric diet; 3) a 2% protein, isocaloric diet; and 4) a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Another group of five rats were fed ad libitum the control diet. The first and second lumbar vertebrae were removed after sacrifice, and processed for histomorphometrical analysis of undecalcified bone samples. Blood and 24-h urine were also collected. Protein malnutrition, but not ethanol, leads to osteoporosis and reduced osteoid synthesis, whereas ethanol and protein malnutrition both lead to impaired bone mineral apposition and increased urinary hydroxyproline excretion. These changes are accompanied by an increase in serum parathormone and serum 1,25 dihydroxy vitamin D3, a slight hypomagnesemia, hypercalciuria and hyperphosphaturia; protein deficiency plays an independent role in these alterations, whereas both ethanol and protein deficiency exert independent effects on decreasing serum testosterone levels; this last alteration may contribute to the bone changes mentioned before.

Valor pronóstico del estado de nutrición y de las citoquinas proinflamatorias (IL-1, FNTa e IL-6) en pacientes graves / Prognostic value in nutritional assessment and cytokine (IL-1, FNTa e IL-6) in critically ill patients

Objetivo: En el pronóstico del paciente hospitalizado influyen, entre otros factores, el estado de nutrición, la intensidad de la reacción de fase aguda (RFA) y la gravedad de la enfermedad. Estos tres factores están estrechamente interrelacionados: la enfermedad, a través de la RFA mediada por citoquinas, produce desnutrición, más intensa cuanto más grave es la enfermedad. Nuestro objetivo es analizar en que medida los mencionados factores están relacionados con la mortalidad y cuáles de ellos tienen valor predictivo independiente. Método: Se ha estudiado a 119 pacientes ingresados consecutivamente en una unidad de cuidados intermedios, en los que se realizó una valoración nutricional objetiva y subjetiva, determinaciones bioquímicas nutricionales, reactantes de fase aguda y citoquinas IL-1, FNTa e IL-6. La gravedad de la enfermedad se valoró a través de la existencia de insuficiencia de órganos. Se consideró como único punto final el fallecimiento o el alta hospitalaria del paciente. Resultados: Se relacionaron con mayor mortalidad un peor estado de nutrición, tanto los antecedentes de alimentación deficiente, como una peor valoración nutricional subjetiva, la elevación de la IL-6, el aumento del porcentaje de neutrófilos, el descenso de los linfocitos, de la hemoglobina, de la transferrina y la anergia al PPD; también la existencia de alguna de las siguientes complicaciones o insuficiencia de órganos: sepsis, ventilación mecánica, shock, insuficiencia renal aguda y alteraciones de la coagulación. En el análisis multivariante (regresión logística) sólo las variables nutricionales, la existencia de sepsis y los datos de insuficiencia de órganos mostraron valor pronóstico independiente, mientras que la IL-6 era desplazada por los datos de fallo de órganos. Conclusión. De cara al pronóstico, la gravedad de la enfermedad y el estado de nutrición aportan información independiente, mientras que la IL-6 queda desplazada, probablemente debido a su estrecha relación con la respuesta inflamatoria y la existencia de fallo de órganos (AU)

Relative and combined effects of ethanol and protein deficiency on strontium and barium bone content and fecal and urinary excretion.

Strontium metabolism has attracted considerable interest because of to its interaction with calcium, the bone alterations detected after treatment with strontium, and its potential value as a paleodietary indicator. The effects of ethanol on strontium and barium metabolism-another divalent cation which also accumulates in bone--is largely unknown. Based on this fact, we have determined bone content and fecal and urinary excretion of Ba and Sr in four groups of eight animals each pair-fed for 8 wk with (1) a nutritionally adequate diet, (2) a 36% (as energy) ethanol-containing isocaloric diet, (3) a 2% protein, isocaloric diet, and (4) a 36% ethanol, 2% protein isocaloric diet, following the Lieber-DeCarli model. Five additional rats were fed with the control diet ad libitum. We have found that ethanol tends to decrease and a low protein diet to increase bone strontium content; the decrease in bone strontium in the ethanol-fed rats is accompanied by an increase in the absolute excretion of strontium in urine. Ethanol also decreases bone barium content, but the effect of ethanol on urinary barium excretion is opposite that of strontium, a decrease. Thus, we conclude that ethanol alters both barium and strontium metabolism and bone deposition.

[Prognostic value of the nutrition status and pro-inflammatory cytokines (IL-1, TNF-alpha and IL-6) in critically ill patients]. / Valor pronóstico del estado de nutrición y de las citoquinas proinflamatorias (IL-1, FNT alpha e IL-6) en pacientes graves.

OBJECTIVE: Prognosis of hospitalized patients depends on the status of nutrition, the intensity of the biologic inflammatory response or acute phase response (APR), triggered by cytokine, and the illness severity. These factors have been shown closely related, as cytokine causes malnutrition and organ failure. AIM: to analyze which of these factors are related to mortality and, by multivariate analysis, which of them have an independent predictive value. METHOD: We include 119 patients admitted to a semi-intensive care unit. Nutritional assessment was performed by mid arm anthropometrics, serum albumin, transferrin, IGF-I, and subjective nutritional evaluation; we also determine acute phase proteins and cytokine IL-1, TNF alpha and IL-6. Severity of illness was assessed by organ failure. The only end point considered was death or survival until discharge of hospital. RESULTS: The following data were related to increased mortality: impaired alimentary habits and nutritional subjective assessment, raised serum levels of IL-6 and neutrophil differential count, decreased lymphocyte count, hemoglobin and serum transferrin levels, a negative PPD and the presence of sepsis, shock or organ failure. At multivariate analysis (stepwise logistic regression) only nutritional variables, sepsis and organ failure data showed an independent predictive value, whereas IL-6 was displaced by organ failure data. CONCLUSION: Regarding prognosis, severity of illness and nutritional status have independent predictive value, whereas IL-6 was displaced, probably because it is closely related to the inflammatory response and to organ failure.

Relative and combined effects of ethanol and protein deficiency on zinc, iron, copper, and manganese contents in different organs and urinary and fecal excretion.

The relative contribution of protein deficiency to the altered metabolism of certain trace elements in chronic alcoholics is not well defined, so this study was performed to analyse the relative and combined effects of ethanol and protein deficiency on liver, bone, muscle, and blood cell content of copper, zinc, iron, and manganese, and also on serum levels and urinary and fecal excretion of these elements in four groups of eight animals each that were pair-fed during 8 weeks with a nutritionally adequate diet, a 36% (as energy) ethanol-containing isocaloric diet, a 2% protein isocaloric diet, and a 36% ethanol 2% protein isocaloric diet, respectively, following the Lieber-DeCarli model. Five additional rats were fed ad lib the control diet. Protein malnutrition, but not ethanol, leads to liver zinc depletion. Both ethanol and protein malnutrition cause muscle zinc depletion and increase urinary zinc and manganese excretion, whereas ethanol also increases urinary iron excretion and liver manganese content. No differences were observed regarding copper metabolism.

Coagulation inhibitors in alcoholic liver cirrhosis.

In the present study we have analyzed the relationship between coagulation inhibitors (antithrombin III, protein C and S, thrombomodulin), liver function impairment, and plasma activity of the endothelium-derived proteins plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 27 alcoholic cirrhotic patients and 25 controls. Cirrhotics showed decreased values of all the mentioned parameters except for thrombomodulin, PAI-1, and t-PA. Thrombomodulin and t-PA levels were higher in cirrhotics. No relationship was observed between thrombomodulin and t-PA or PAI-1. Protein C and antithrombin III levels were significantly lower in Child's C patients, whereas no correlation was found between t-PA and thrombomodulin and hepatic function derangement. PAI-1 activity was normal in our patients.

Zinc, copper, manganese, and iron in chronic alcoholic liver disease.

Ethanol consumption and/or liver damage may alter liver content of several trace elements, as iron, zinc, copper, and manganese. This alteration may play a role on ongoing liver fibrogenesis. Based on these facts we have determined liver, serum, and urinary Mn, Cu, Zn, and Fe levels in a group of alcoholic cirrhotics and noncirrhotics with normal renal function, comparing them with those of controls. We have observed low liver zinc and high liver copper--this last in relation with histomorphometrically determined total amount of liver fibrosis--and manganese contents in cirrhotics, together with increased excretion of zinc and iron and decreased excretion of manganese. Zinc, iron, and copper excretion kept a relation with data of severity of cirrhosis, including mortality in the case of urinary copper, independently of the use of diuretics. Thus, liver copper and urinary iron, zinc, and copper excretion seem to be related with data of severity of chronic alcoholic liver disease. Low urinary manganese excretion may play a role on liver manganese overload.

Haemoperitoneum secondary to rupture of retroperitoneal variceal.

A 45-year-old alcoholic male patient presented with hypovolemic shock and intense anemia (Hemoglobin 04.7 g/dl), and was operated on. A bleeding retroperitoneal varix located near the right colon was responsible for the clinical picture and was sutured. After operation the patient developed haemodynamic instability and pneumonia a situation which was reverted with intensive medical therapy. The patient is now doing well.

[Caroli's disease, congenital hepatic fibrosis and renal polycystosis: a little frequent association]. / Enfermedad de Caroli, fibrosis hepática congénita y poliquistosis renal: una asociación poco frecuente.

We report the case of a woman with Caroli's syndrome (Caroli's disease and congenital hepatic fibrosis) and adult polycystic kidney disease. Whereas the association of these two entities with autosomal-recessive-polycystic kidney disease has been widely reported, its association with adult-polycystic kidney disease is very infrequent.

Relative and combined effects of propylthiouracil, ethanol and protein deficiency on liver histology and hepatic iron, zinc, manganese and copper contents.

The present study was performed in order to discern the effects of propylthiouracil (PTU) on ethanol and/or protein deficiency-mediated liver histological changes and liver Fe, Zn, Cu and Mn alterations in male adult Wistar rats. The study was performed on 64 animals divided into eight groups, fed with the Leiber-DeCarli control, 36% ethanol-2% protein- and 36% ethanol-2% protein-containing diets, without and with PTU, respectively. PTU was administered at a concentration of 0.05%, an amount which rendered the animals hypothyroid. Two further groups of 5 animals each, with and without PTU respectively, were allowed to consume the control diet ad libitum. Animals treated with PTU showed significantly less fibrosis, but more fat, than animals without PTU. Liver fibrosis was inversely correlated with liver zinc, liver content of this element being higher in the PTU-treated and the ethanol or protein deficiency groups. PTU also reversed ethanol-mediated hepatocyte ballooning and also led to a reduction in nuclear areas.

[Serum laminin in chronic alcoholic liver disease: its value in the estimation of the degree of fibrosis]. / Laminina sérica en la hepatopatía crónica alcohólica: su valor en la estimación del grado de fibrosis.

AIM: To determine the clinical and prognostic value of serum laminin in chronic alcoholic liver disease and to discern whether laminin, alone or in combination with serum N-terminal type III collagen propeptide, and/or biochemical parameters, is useful in estimating the histomorphometrically determined amount of fibrosis. STUDY DESIGN: Prospective. PATIENTS: 121 (80 of them cirrhotics), 107 followed up for a variable periods ranging from 1 to 1440 days. RESULTS: Serum laminin was higher in cirrhotic patients belonging to Child's C group and, in cirrhotic patients, it significantly correlated with Pugh's score (r = 0.32, p < 0.01), prothrombin activity (r = 0.23, p < 0.05), serum albumin (r = -0.35, p < 0.001) and bilirubin (r = 0.30, p < 0.01), and also with the degree of fibrosis (r = 0.49, p < 0.001). Serum laminin over 3.5 U/ml were associated to higher mortality rates in the total population (Log rank test = 4.9, p = 0.022), but not in cirrhotics. Stepwise multiple regression analysis showed that laminin is useless in the estimation of liver fibrosis in cirrhotics, although in non-cirrhotic alcoholics, serum laminin together with alkaline phosphatase and GGT roughly estimates the amount of liver fibrosis (r = 0.72, p < 0.001, standard error = 7.29). CONCLUSIONS: Laminin is not useful in estimating the total amount of fibrosis neither in prognostic assessment of cirrhotics. However, serum laminin-values over 3.5 U/ml were associated with higher mortality rates in patients with chronic alcoholic liver disease, and serum laminin together with alkaline phosphatase and GGT correlated with the amount of fibrosis in the non-cirrhotic subgroup.

Relative and combined effects of propylthiouracil, ethanol and protein deficiency on muscle.

A hypermetabolic state with increased oxygen consumption has been described in alcoholic hepatitis, playing a major role in ethanol-induced liver damage. Based on its ability to decrease oxygen consumption, propylthiouracil (PTU) has been proposed as a therapeutic agent in this context. On the other hand, several muscle changes have been described in hypothyroidism, including both atrophy and hypertrophy of muscle fibres. The aim of this experimental study was to analyse the effects of PTU on the alcohol-induced changes in muscle fibre size and proportion, also taking into account the presence or absence of protein deficiency. The study was performed on 64 male Wistar rats divided into eight groups, fed with: (1) Lieber-DeCarli control diet: (2) an isocaloric 36% ethanol-containing diet: (3) an isocaloric 2% protein-containing diet: (4) an isocaloric 36% ethanol 2% protein-containing diet, without and with PTU, respectively. Right gastrocnemius muscle was removed 2 months later and histochemical and morphometric studies were performed. Type IIb fibre atrophy was observed both in the alcoholic and protein-deficient animals, but not in the PTU-treated animals. The combination of protein deficiency and ethanol led to a more marked type IIb atrophy, with PTU reversing this effect. Malnutrition led to a decrease in type I fibre diameter: ethanol and PTU caused an increase in its size and PTU reversed the effect of protein deficiency. Proportion of type IIb fibres decreased in the three experimental groups without PTU with respect to the control, especially in the alcoholic protein-deficient animals. PTU-treated animals, especially those fed a low-protein diet, showed a more marked reduction in type IIb fibre proportion than that presented by the groups without PTU. However, an increase in type I fibre proportion was observed in the PTU-treated animals, especially marked in those fed a low-protein diet. Thus, PTU seems to ameliorate ethanol-induced changes on type IIb muscle fibres.

Transient hemolytic anemia after transjugular intrahepatic portosystemic stent shunt.

Management of variceal bleeding secondary to portal hypertension constitutes a challenging issue, particularly in child's C cirrhotic patients. Recently, transjugular placement of self-expanding metallic stents in the liver (TIPS), creating a shunt between the portal and hepatic branches has provided a safe and promising therapeutic approach in this clinical situation. We report here the case of a 66-year-old male cirrhotic patient who developed a moderately severe clinical picture of Coombsnegative hemolytic anemia (serum hemoglobin, 93 g/l, serum bilirubin 160.74 umol/L (9.4 mg/dl), indirect 6.3 mg/dl (107.73 umol/L); serum LDH 1220 mu/l, reticulocytes, 5.1%, serum ferritin 1221 micrograms/l, schistocytes in peripheral blood smear) the week after undergoing a TIPS, suggesting the development of microangiopathic hemolytic anaemia secondary to red blood cell disruption by passing through the metallic network of the stent.

[Chronic liver disease exacerbated during alpha-interferon treatment]. / Hepatopatía crónica exacerbada tras tratamiento con alpha-interferón.

A 27 year old male patient was referred to our clinical unit because of marked elevation of serum bilirubin (up to 15.3 mg/dl), ASAT (563 U/l) and ALAT (845 U/l) were detected after institution of therapy with alpha interferon. The patient had been previously treated because of persistent slight elevation of serum transaminases, serological markers of hepatitis B virus and hepatitis C virus being both negative. Liver histology was consistent with chronic active hepatitis. Antinuclear, anti smooth muscle and antimitochondrial autoantibodies were all negative, although anti smooth muscle antibodies became positive (1/40) after interferon therapy. The drug was withdrawn, prednisone was instituted, and transaminases and bilirubin values returned to normality.

Alcoholic hypogonadism: hormonal response to clomiphene.

To investigate the androgen, weak androgen, estrogen, and gonadotrophin response to clomiphene in alcoholics, we determined in 63 male patients (25 with and 38 without liver cirrhosis) serum testosterone, sexual hormone binding protein (SHBG), dehidroepiandrosterone, androstenedione, LH, FSH, prolactin, and estradiol levels, on the first and the sixth day after admission, and after a course of 8 days of clomiphene 200 mg/day. The same test was performed on 15 healthy volunteers. Cirrhotic patients showed decreased basal testosterone levels and a loss of the circadian rhythm with recovery after clomiphene. Although basal testosterone levels in noncirrhotic alcoholics did not differ from those of the controls, there was a significant improvement after withdrawal. SHBG levels were higher in both groups of alcoholics than in controls, pointing to a worse degree of hypogonadism, because only the free hormone is active. Before the clomiphene test, serum LH and FSH levels were nonsignificantly higher in both groups of alcoholics than in the control group. After clomiphene both LH and FSH increased. Androstenedione and estradiol showed a (parallelism) similar behavior in alcoholic and in cirrhotic groups, showing in both cases higher levels than in the control group, and an increase after clomiphene, perhaps reflecting peripheral conversion of androgens to estrogens. Because clomiphene has no effect on the adrenal cortex, the increase of androstenedione after clomiphene points to its testicular origin (directly or after testosterone conversion) and not to an adrenal one. The highest serum estradiol levels were observed in cirrhotics with ascites or gynecomastia. We have not found any relation between serum hormone levels and alcohol intake nor with nutritional status.

Cytokine levels in acute alcoholic hepatitis: a sequential study.

Chronic alcoholic liver disease is associated with several immunological alterations: depressed T-cell function, low serum gamma-interferon, and high serum tumour necrosis factor (TNF-alpha) and interleukin levels. Therefore, macrophage activity seems to be enhanced. Some cytokines, such as TNF-alpha, exert adverse effects on chronic alcoholic liver disease, so that protracted activation of macrophages with continuous TNF-alpha production may aggravate alcoholic hepatitis. Based on these facts we have sequentially determined serum levels of TNF-alpha, 1 beta interleukin (IL-1 beta), gamma-interferon and neopterin--a macrophage product--at admission, and at the end of the first, third and sixth weeks after admission, of 43 patients affected by alcoholic hepatitis, and of 20 age-matched sanitary workers as controls. Our patients showed higher levels of neopterin and lower levels of IL-1 beta and gamma-interferon than the controls; TNF-alpha levels in our patients were almost significantly higher than in controls. TNF-alpha levels at admission were higher in the patients who died (P = 0.025). TNF-alpha and neopterin levels showed no trend to normalization in patients who died, with higher levels of neopterin at first and third weeks and higher TNF-alpha and gamma-interferon levels at first week. Using logistic regression analysis, serum TNF-alpha levels at admission showed significant (P = 0.045), independent effects on mortality, as well as serum neopterin (P = 0.0026) at the first week. Thus, enhanced macrophage activity, measured by serum levels of TNF-alpha and neopterin seems to be related to a worse prognosis in alcoholic hepatitis.

Nutritional assessment of drug addicts.

OBJECTIVE: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. DESIGN: Cross-sectional prospective study. SETTING: Detoxication unit and internal medicine unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. RESULTS: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. CONCLUSIONS: Many drug addicts suffer from calorie and protein malnutrition. This mainutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.