F. Rodríguez-Moreno

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.

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.

Chronic Alcoholic Myopathy and Nutritional Status

To investigate the prevalence of alcoholic myopathy and its relationship to the nutritional status, we performed a muscle biopsy on the vastum lateralis of 60 consecutive hospitalized alcoholic patients using a Tru-Cut needle, processing it for light microscope and ultrastructural analysis. The nutritional status was assessed by anthropometric measurements such as midarm circumference, triceps skinfold and midarm muscle area, and serum albumin. The hallmark of chronic alcoholic myopathy, fiber muscle atrophy, was present in 33% of the patients, necrosis scarcely being observed (1.5%). Ultrastructural alterations as lipid and glycogen accumulation or mitochondrial and myofibrillar alterations were nonspecific and observed in nearly all the cases where atrophy was present. Malnutrition was frequent in our patients: 39% and 34% showed a triceps skinfold and a midarm muscle area, respectively, under the fifth populational percentile. Patients with muscle fiber atrophy or ultrastructural changes showed a worse nutritional status, not only regarding muscle protein (assessed by midarm muscle area or creatininuria and explained by fiber atrophy), but also regarding fat stores assessed by triceps skinfold. Toxic effect of ethanol and malnutrition may act synergistically leading to chronic alcoholic myopathy.

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.

Combined effects of ethanol and protein deficiency on hepatic iron, zinc, manganese, and copper contents.

The present study has been performed in order to establish the relative and combined roles of ethanol and malnutrition on liver Fe, Zn, Cu, and Mn alterations in alcoholic male adult Wistar rats, and also the relationships between these alterations and histomorphometrically determined hepatocyte and nuclear areas, perivenular fibrotic rim area, and total amount of fat present in the liver. Four groups of 8 animals each were fed: (1) a nutritionally adequate diet (C); (2) a 36% ethanol-containing (as percent of energy), isocaloric diet (A); (3) a 2% protein-containing, isocaloric diet (PD); and (4) a 36% ethanol, 2% protein-containing, isocaloric diet (A-PD), respectively, following the Lieber-DeCarli model. Ethanol-fed, protein-deficient animals showed the highest liver Fe, and the lowest Zn and Cu values, although differences in liver Zn, Mn, and Cu values were not significantly different between PD and A-PD groups. Statistically significant differences of these parameters were observed between the A and the A-PD groups, and between the A and PD groups, except for liver iron. Except for liver Mn, differences between C and A groups were statistically significant. These alterations correlated with liver fibrosis and steatosis, serum albumin, and weight loss, except for liver Mn, which was not correlated with fibrosis or steatosis. Thus, protein deficiency seems to enhance ethanol-induced liver Fe, Zn, and Cu alterations, whereas protein deficiency, but not ethanol, seems to play a major role on liver Mn alterations.

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.

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 Childs C patients, whereas no correlation was found between t-PA and thrombomodulin and hepatic function derangement. PAI-1 activity was normal in our patients.

Subjective Nutritional Assessment and Short-term Prognosis

To analyze the relationship between the subjective assessment of nutritional status and anthropometric parameters, as well as the prognostic value of the subjective evaluation, the nutritional status of 280 patients was evaluated as follows on admission to a semi-intensive care unit: temporal muscle atrophy, Bichats fat atrophy, upper and lower extremities muscle atrophy and subcutaneous fat atrophy. Each parameter was categorized into three degrees of severity and a nutritional score (NS) was obtained. We have also determined the mid-upper arm circumference (MUAC), the triceps skinfold (TSF), the mid-arm muscle area (MAMA), serum albumin and transferrin. During the hospital admission 88 patients died. We found a good concordance (82%) between subjective and objective (anthropometric data, fifth percentile criteria) assessments. Those patients who died showed significant lower values of MUAC, MAMA, TSF, serum albumin and transferrin; and higher neutrophil count, alpha-1-antitrypsin, ferritin, BUN and als...

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.

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.