[Mortality in alcoholic withdrawal syndrome].
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Biomedical subjects
Publications and source records attributed to E González-Reimers.
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The island of Gran Canaria was inhabited in pre-Hispanic times by people of North African origin who arrived on the island towards the second half of the first millennium BC. In previous studies, we reported that there are some differences between the coastal inhabitants from Gran Canaria, mainly buried in tumuli, and those from the central mountains, mainly buried in caves. For example, the prevalence of auricular exostoses is higher among the population interred in coastal tumuli when compared with the inland population. This finding may be explained by the practice of marine activities, as supported by chroniclers' reports, by archaeological data, and by bone trace-element analysis, which point to a more intense consumption of marine products by the inhabitants of the coastal regions. Dental caries epidemiology is one of the most important ways in which the diet of past populations can be reconstructed. The purpose of this study is to assess the prevalence and intensity of caries among the pre-Hispanic population of Gran Canaria, in order to increase our knowledge about the dietary habits of these people, and to search for differences among the population buried in caves and that buried in tumuli. We studied a total of 791 individuals. Sex was estimated in 561 cases, and age at death, following Brothwell's criteria, in 549. We found that 66.95% of individuals buried in caves and 58.91% of those buried in tumuli showed at least one carious lesion. The proportion of carious teeth was significantly higher among the population buried in caves (median = 15.71%, interquartile range (IR) = 0-33.33%) than among the population buried in tumuli (median = 6.25%, IR = 0-20%, P = 0.001). Type of burial is the main factor associated with the proportion of carious teeth.These data suggest that the population buried in caves had a different dietary pattern from that of those buried in tumuli.
A chronic form of myopathy has been described in alcoholics, characterized by atrophy of type II fibers, due both to reduced protein synthesis and increased protein breakdown. Increased production of reactive oxygen species could probably play a role in increased protein breakdown. In addition, treatment with zinc might be beneficial, since it acts as a cofactor of several enzymes involved in the synthesis of proteins and antioxidants as copper-zinc-superoxidedismutase (SOD) and selenium dependent glutathione peroxidase (GPX). Based on these facts, we analyze the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in form of zinc sulphate, on muscle changes in 8 groups of adult Sprague-Dawley rats fed following the Lieber-de Carli model during 5 weeks. We also study the association between muscle histological changes and the activity of GPX, SOD and lipid peroxidation products (MDA), with hormones such as IGF-1, and with trace elements involved in antioxidant systems and/or in lipid peroxidation, such as selenium, copper, zinc, and iron. We found type IIa and IIb fiber atrophy in the alcoholic animals, especially in the low-protein fed ones. This effect was mainly due to protein deficiency. Zinc played no role at all. Muscle iron increased in ethanol, low protein fed rats, either with or without zinc, and was directly related with muscle MDA levels, which in turn were related with muscle atrophy, as was also found for serum IGF-1 levels. Ethanol was the main responsible for all these changes, although protein undernutrition also played an independent role in MDA levels. A positive interaction between ethanol and protein deficiency on serum IGF-1 was also detected. These results suggest that both protein deficiency and ethanol contribute to muscle atrophy observed in alcoholized rats; this atrophy is associated with increased lipid peroxidation and muscle iron overload. Treatment with zinc sulphate confers no benefit.
Ethanol consumption leads to bone alterations, mainly osteoporosis. Ethanol itself may directly alter bone synthesis, but other factors, such as accompanying protein malnutrition--frequently observed in alcoholics, chronic alcoholic myopathy with muscle atrophy, alcohol induced hypogonadism or hypercortisolism, or liver damage, may all contribute to altered bone metabolism. Some data suggest that zinc may exert beneficial effects on bone growth. Based on these facts, we analyzed the relative and combined effects of ethanol, protein malnutrition and treatment with zinc, 227 mg/l in the form of zinc sulphate, on bone histology, biochemical markers of bone formation (osteocalcin) and resorption (urinary hydroxyproline excretion), and hormones involved in bone homeostasis (insulin growth factor 1 (IGF-1), vitamin D, parathormone (PTH), free testosterone and corticosterone), as well as the association between these parameters and muscle fiber area and liver fibrosis, in eight groups of adult Sprague Dawley rats fed following the Lieber de Carli model during 5 weeks. Ethanol showed an independent effect on TBV (F=14.5, p<0.001), causing it to decrease, whereas a low protein diet caused a reduction in osteoid area (F=8.9, p<0.001). Treatment with zinc increased osteoid area (F=11.2, p<0.001) and serum vitamin D levels (F=3.74, p=0.057). Both ethanol (F=45, p<0.001) and low protein diet (F=46.8, p<0.01) decreased serum osteocalcin levels. Ethanol was the only factor independently related with serum IGF-1 (F=130.24, p<0.001), and also showed a synergistic interaction with protein deficiency (p=0.027). In contrast, no change was observed in hydroxyproline excretion and serum PTH levels. No correlation was found between TBM and muscle atrophy, liver fibrosis, corticosterone, or free testosterone levels, but a significant relationship was observed between type II-b muscle fiber area and osteoid area (rho=0.34, p<0.01). Osteoporosis is, therefore, present in alcohol treated rats. Both alcohol and protein deficiency lead to reduced bone formation. Muscle atrophy is related to osteoid area, suggesting a role for chronic alcoholic myopathy in decreased bone mass. Treatment with zinc increases osteoid area, but has no effect on TBV.
This study was performed to determine the levels of lead (Pb) and cadmium (Cd) in 63 bone samples of the prehispanic population of the island El Hierro, comparing them with the values obtained on 98 prehispanic samples from Tenerife, Fuerteventura, Gran Canaria, and La Palma, all of them in the Canary Islands, and with eight modern samples who served as controls. Prehispanic individuals from El Hierro showed the lowest bone Pb values of all the archipelago (0.72+/-1.01 mg/kg), significantly different (F=6.9, p<0.001) from the values obtained for the population of other islands such as Tenerife (4.87+/-5.36 mg/kg) or Fuerteventura (4.45+/-7.85 mg/kg) and also from those of the modern population (30.53+/-14.62 mg/kg). On the other hand, bone Cd, although slightly lower in the ancient population groups, was not significantly different when compared with the modern one. In addition, no differences were observed in bone Cd among the ancient population of the different islands. Bone lead but not cadmium kept an inverse significant relationship with the distance of the burial site both to south Spain (r=-0.31) and Atlantic Morocco (r=-0.28, p<0.001 in both cases).
Both lead and cadmium exposures derive from natural sources and also from industrialisation and certain habits, such as cigarette smoking in the case of cadmium. Some of these sources only affect human beings. The aim of this study was to determine the levels of lead and cadmium in bone samples of 16 prehispanic inhabitants of Gran Canaria, 24 prehispanic domestic animals (sheep, goat and pigs) from this island, 8 modern individuals, and 13 modern domestic animals. We found that modern individuals showed higher bone Cd values (mean=516.7+/-352.49 microg/kg, range=167.20-1125 microg/kg) than prehistoric ones (mean=85.13+/-128.96 microcg/kg, range=2.97-433 microg/kg). Values of prehistoric individuals did not differ from those of the prehistoric animals (mean=70.54+/-46.86 microg/kg, range=11.06-216.50 microg/kg), but were higher than those of the modern animals (mean=7.31+/-10.35 microg/kg, range=0-35.62 microg/kg). In the same way, modern individuals and modern animals showed approximately 7-fold higher bone Pb than ancient individuals and ancient animals, respectively. Ancient animals showed significantly lower Pb values than all the other groups, whereas modern animals showed Pb values comparable to those of the ancient individuals. A significant correlation was observed between bone Pb and Cd (r=0.61, P<0.001). Since bone cadmium accumulation leads to osteoporosis, we have also tested the relationship between histomorphometrically assessed trabecular bone mass and bone cadmium both in modern and ancient individuals. No significant relationship was found between these two parameters.
Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation-which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)-may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl(4)) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl(4) to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl(4)-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.
We report the case of a 39-year-old male patient affected by type B Niemann-Pick disease, in whom pulmonary involvement became evident 15 years after the initial diagnosis. Pulmonary involvement was discovered incidentally during the evaluation of a dry cough and exertional dyspnoea which occurred in the context of an acute febrile, self-limiting illness. In this case, the pulmonary involvement is clinically mild, with minimal alteration of the diffusing capacity for carbon monoxide (DL(CO)), despite moderate fibrosis and widespread infiltration of both alveoli and interstitium by sea blue histiocytes.
In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.
Bone mineral density (BMD) assessed by double-energy X-ray absorptiometry (DEXA) accurately estimates the bone mass in living individuals, and is thus the method usually employed in the diagnosis and follow-up of osteopenia. It is preferred, in clinical settings, to the more invasive and destructive histomorphometrical assessment of trabecular bone mass in undecalcified bone samples. This study was performed in order to examine the value of DEXA-assessed BMD at the proximal end of the right tibia, either alone or in combination with the cortico-medullary index at the midshaft point of the right tibia (CMI), in the diagnosis of osteopenia in a prehistoric sample composed of 95 pre-Hispanic individuals from Gran Canaria. Age at death could be estimated in 34 cases. Diagnosis of osteopenia was performed by histomorphometrical assessment of trabecular bone mass (TBM) in an undecalcified bone section of a small portion of the proximal epiphysis of the right tibia. A high prevalence of osteopenia was found among the population of Gran Canaria. Both TBM and BMD were significantly lower in the older individuals than in younger ones, and BMD was also significantly lower in female individuals. BMD was moderately correlated with TBM (r = +0.51); the correlation was higher if CMI was included (multiple r = +0.615). BMD values lower than 0.7 g/cm2 showed a high specificity (>93%) at excluding normal TBM values. These methods were prospectively applied in a further sample of 21 right tibiae from Gran Canaria, Tenerife, and El Hierro. The results were similar to those obtained in the larger sample. Thus, DEXA-assessed BMD combined with CMI (noninvasive procedures) may be useful in detecting osteopenia in ancient populations.
Chronic alcoholics frequently show associated malnutrition. Both ethanol and malnutrition exert profound changes on zinc and copper metabolism. In this study, we found higher hair zinc and copper values in 43 male alcoholics than in 39 controls. Hair copper was significantly related to the amount of ethanol consumed, whereas hair zinc was higher in consumers of distilled beverages. No relation was observed between hair zinc and copper and nutritional status, kind of diet consumed, style of life, and liver cirrhosis. Consequently, hair zinc and copper levels are related only with alcohol intake.
We studied 174 patients with SIRS criteria, 45 with sepsis, eight with severe sepsis and 13 with septic shock. Serum TNF-alpha, IL-6, IL-8 and IL-10 levels were raised in SIRS patients, even in those cases in which an infection could not be documented, and more intensely in severe sepsis and in patients who died (11%). The slope of the regression line between IL-10 and TNF-alpha was sharper in patients with severe sepsis and in those who died; an imbalance between pro- and anti-inflammatory cytokines may be related to poor prognosis. Increased IL-6 and IL-10, decreased muscle mass, raised BUN and low body temperature were all independently related to prognosis.
Alcoholism is related to malnutrition and low levels of several vitamins that take part in the metabolism of homocysteine. The objective of the study was to analyze the prevalence of hyperhomocysteinemia in patients with heavy alcohol intake and the factors on which it depends. Included in the study were 103 hospitalized heavy drinkers (i.e., patients with an intake of alcohol greater than 80 g per day). Serum homocysteine, folate, and vitamin B(12) levels, plasma vitamin B(6) levels, and CT677 polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were determined. We also recorded the intensity of alcoholism, the status of nutrition, and the existence of liver cirrhosis. Determination of biochemical data was repeated after 15 days of withdrawal. Serum homocysteine levels were found to be significantly elevated, whereas serum folate and plasma B(6) levels were significantly decreased. Serum homocysteine levels were significantly higher in those heavy drinkers who showed the TT polymorphism of MTHFR, with a prevalence of hyperhomocysteinemia of 84.2% in the homozygote TT, 54.3% in the heterozygote CT, and 31.6% in the normal CC genotype. Serum homocysteine inversely correlated with serum folate, serum B(12), and plasma B(6) levels. We did not find any relation between serum homocysteine and intensity of alcoholism, nutritional status, or liver cirrhosis. Serum folate levels were significantly decreased in heavy drinkers, mainly depending on irregular feeding and malnutrition. After 15 days of withdrawal, serum homocysteine levels significantly decreased, whereas folate, B(12), and B(6) levels significantly increased. The conclusion is that heavy drinkers show a high prevalence of hyperhomocysteinemia related to low levels of folate, B(6), and B(12) and to the TT polymorphism of MTHFR.
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It is generally believed that auricular exostoses are due to prolonged exposure to cold water, so their existence in ancient remains may inform us about economic activities in the past. This study was performed to analyze the prevalence of auricular exostoses among 150 pre-Hispanic individuals of different islands of the Canary archipelago. Individuals from Gran Canaria (6/26), Fuerteventura (1/15), and Tenerife (2/64), but not from El Hierro (0/45), showed auricular exostoses, thus supporting the hypothesis of a greater reliance on fishing and shellfishing in the former 3 islands.
In this study, we determine bone strontium, barium, and calcium, as well as zinc, copper, and iron, in prehispanic samples belonging to adult individuals from the two main funerary caves from La Palma (Espigón and Barranco Porto), comparing them with our own modern controls. We have found that the Ba/Sr molar ratio of the individuals from Barranco Porto are significantly lower than that of the individuals from Espigón, thus suggesting a consumption of a marine-based diet by the former.
To establish their ability to predict malnutrition, irregular feeding, alcoholic intake, derangement of social and familial links and organic complications (liver cirrhosis) were assessed in 181 hospitalized male alcoholic. BMI was under 18.5 kg/m(2) in 8.9%, between 18.5-20 kg/m(2) in 8.9%, 20-25 kg/m(2) in 42%, 25-30 kg/m(2) in 32.2% and over 30 kg/m(2) in 8.2% of patients. Malnutrition was related to the intensity of ethanol intake, development of social or familial problems, irregularity of feeding habits and cirrhosis with ascites. Irregularity of feeding habits was also related to heavy drinking and to social or familial derangement. By logistic regression analysis, the only variables which independently predict malnutrition were irregular feeding habits and liver cirrhosis with ascites. In a second step, irregular feeding was dependent on social or familial troubles and daily intake of ethanol. So, malnutrition related to alcoholism seems multifactorial in its pathogenesis.
This study has been performed in order to define standards usable to determine the sex of prehispanic individuals from the Canary Islands from their skeletal remains. Osteometric information at the right tibia was obtained from 59 complete skeletons from Gran Canaria, housed in the Museo Canario (Las Palmas), 45 males and 14 females (this constitutes the totality of complete prehispanic skeletons known from Gran Canaria). The parameters measured were: tibial length, proximal and distal epiphyseal breadth, transverse and anteroposterior diameter, perimeter at the nutrition foramen levels and minimum shaft perimeter. These parameters were subjected to different SPSS discriminant function analysis, combining all of them, or only the proximal or distal ones, without tibial length, etc., in order to obtain functions usable even if only bone fragments are available. Transverse diameter, proximal epiphyseal breadth and minimum shaft perimeter showed the highest discriminant power. The functions obtained showed high average accuracies, ranging from 94.9 to 98.3%, with female accuracies of 100%. The functions obtained were further applied to a test prehispanic population (ten males and ten females) from El Hierro. Overall accuracies of the functions when applied to this population ranged from 65 to 94.7%, with female accuracies ranging 80% to 100%.