Water-soluble vitamins in severe liver disease

Biochemical deficiency of thiamine, vitamin B6, ascorbic acid or nicotinic acid occurred in 71% and 88% of patients with fulminant hepatic failure (FHF) and decompensated chronic liver disease (DCLD) respectively. Transient high plasma vitamin B6 concentrations in FHF were followed by low levels later in the illness. Although patients with DCLD of alcoholic aetiology tended to have lower circulating levels of vitamins than those with non-alcoholic DCLD, the prevalence of abnormally low concentrations did not differ. Decreased dietary nutrient intake and alcohol appeared to be less important determinants of biochemical vitamin deficiency than the presence of liver disease per se. Finally, urinary excretion of these vitamins or their major metabolites in patients with severe liver disease correlated poorly with circulating levels of vitamins.     

Neuropathic beriberi as a complication of surgery of morbid obesity

We describe a women of 22 years of age who had had a vertical gastroplasty (as treatment for morbid obesity). She was admitted to hospital with a 4 week history of nausea and vomiting of food. Treatment with intravenous dextrose, without vitamin supplements was started. One week later she complained of diplopia, paresthesia and weakness of the limbs. All investigations proved to be normal. A deficiency state was suspected, probably Wernicke's encephalopathy, although no alterations were seen in her mental state. We started treatment with high doses of parenteral thiamine, other vitamins and a suitable diet. The treatment was followed by complete recovery. Few neurological complications have been described in association with vertical gastroplasty. The commonest are polyneuropathies. The probable deficiency origin of these is considered. We emphasise the importance of vitamin supplements following the surgical treatment of morbid obesity to avoid the development of deficiency states. Wernicke's encephalopathy is due to thiamine deficiency. It may be associated with any type of malnutrition, not only with chronic alcoholism. The full clinical triad which is diagnostic of this condition is only present in one third of the cases. When the condition is suspected on clinical grounds treatment should be started early to avoid the occurrence of irreversible secuelae.     

Biosynthesis of a cyclic tautomer of (3-methylmaleyl)acetone from 4-hydroxy-3,5-dimethylbenzoate by Pseudomonas sp. HH35 but not by Rhodococcus rhodochrous N75

Vitamin E is one of the most important lipid-soluble antioxidant nutrients. Severe vitamin E deficiency can have a profound effect on the central nervous system. Cystic fibrosis, chronic cholestatic liver disease, abetalipoproteinemia, short bowel syndrome, isolated vitamin E deficiency syndrome and other malabsorption syndromes all may cause varying degrees of neurologic deficits due to related vitamin deficiencies. The classic abnormalities in vitamin E deficiency progress from hyporeflexia, ataxia, limitations in upward gaze and strabismus to long-tract defects, profound muscle weakness and visual field constriction. Patients with severe, prolonged deficiency may develop complete blindness, dementia and cardiac arrhythmias. Treatment must be tailored to the underlying cause of vitamin E deficiency and may include oral or parenteral vitamin supplementation. The more advanced the deficits, the more limited the response to therapy. Therefore, a good neurologic examination and periodic serum vitamin E levels are essential in patients at risk of vitamin E deficiency.     

Vitamin B 12 deficiency: early diagnosis in ambulatory care medicine

Many patients suffer from vitamin B12 deficiency and are thus exposed to irreversible sequelae if diagnosis occurs at a late stage. This prospective study undertaken by eight practitioners over a period of 12 months concerns early diagnosis. Blood vitamin B12 levels were measured in 152 patients presenting macrocytosis detected by systematic MCV analysis at the time of a blood test, a neuropathy or a recent cognitive, affective and behavioural problem, and were found to be lowered (< or = 175 pmol/l) in 54 patients of whom 43 had undergone vitamin B12 test treatment for 6 months. Haematological, neurological and psychiatric evaluation was carried out before and after treatment, and a diagnosis of deficiency was recorded in 24 patients based on unequivocal response to therapy. Improvement was greatest haematologically in 12 patients, neurologically in 6 patients and psychiatrically in 6 other patients, with 4 patients showing a combination of all modes. These 24 patients (mean age 69 years) suffered from numerous pathologies which were liable to complicate diagnosis in some of them: neurological (46%), psychiatric (37%), chronic alcoholism (33%), folic acid deficiency (29%), and diabetes (17%). The only diagnostic element used as a criterion of deficiency was an extremely low level of vitamin B12 (< or = 75 pmol/l). Marked macrocytosis or a combination of haematological and neuropsychiatric signs are strong indicators, but only improvement under treatment allowed a diagnosis to be made in the majority of patients. Macrocytosis was, however, not present in 6 of the 12 neuropsychiatric patients. The study thus identified a high proportion of patients with vitamin B12 deficiency who additionally presented, in equal proportions, both haematological and neuropsychiatric symptoms. Neither the clinical examination nor the vitamin B12 level in general permit early diagnosis based on a high probability index and long-term follow-up. Simpler methods for early diagnosis are therefore needed.     

Clinical relevance of thiamine status amongst hospitalized elderly patients

BACKGROUND: The prevalence and the consequences of thiamine deficiency among elderly patients admitted to acute geriatric wards are not known. OBJECTIVES: (1) To assess the prevalence of thiamine deficiency in patients admitted to a geriatric ward compared to age-matched ambulatory outpatients; (2) to identify their diseases and problems associated with thiamine deficiency, and (3) to determine the relationship between the thiamine status and the cognitive and functional status of these patients. MATERIALS AND METHODS: 118 aged hospitalized patients (83 +/- 7 years; mean age +/- SD) were prospectively enrolled on admission to the geriatric ward. Their cognitive status was assessed using the Mini-Mental State Examination (MMSE) and their ability to perform their activities of daily living (ADL) using ADL scales. The effect of exogenous thiamine pyrophosphate (TPP) addition on the blood transketolase (TK) activity (TPP TK effect) served to estimate thiamine deficiency. Socioeconomic data, diseases and treatment were identified as potential associated risk factors. This group of hospitalized patients was divided according to their thiamine status to characterize the conditions associated with thiamine deficiency. Thirty-five outpatients without any functional or cognitive impairment served as a control group. RESULTS: Of 118 inpatients, 46 (39%) presented with a TPP TK effect of >15%, and 6 with values of >22%, indicating moderate and severe thiamine deficiency, respectively. Only 6 of 30 outpatients (20%) exhibited a TPP TK effect of >15% and none of them reached values of >18%. Although it tended to be lower in outpatients, the mean TPP TK effect did not statistically differ from the mean of inpatients. Thiamine-deficient inpatients comprised a larger proportion of institutionalized subjects than nondeficient inpatients (87 versus 47%, p < 0.001). Functional status, cognitive functions and the occurrence of delirium did not differ according to their thiamine status. By contrast, thiamine-deficient inpatients exhibited a higher proportion of Alzheimer's disease, depression, cardiac failure and falls. Furosemide was more frequently taken by thiamine-deficient patients. CONCLUSIONS: Severe thiamine deficiency remained quite low among the hospitalized elderly. The prevalence of moderate thiamine deficiency approached 40%. Institutionalized subjects were at particular risk of developing thiamine deficiency. Its clinical relevance on functional status and on cognitive function remained not significant. By contrast, a high proportion of falls, Alzheimer's disease, depression, cardiac failure and furosemide use could have been related to thiamine deficiency.     

The history of healing; beriberi: 'kind of paralysis'

Beriberi began to attract increasing attention in the second half of the 19th century, mostly due to the large numbers of victims among Dutch military personnel in the Netherlands East Indies. A study, carried out in Atjeh in 1886 by the Japanese Sugenoya and F. J. Cornelissen, led to the conclusion that there existed a beriberi bacillus which they could make visible in stained microscopical preparations. An extensive disinfection campaign in all barracks followed, but its benefits were a matter of debate. Inadequate nutrition in the investigators' eyes was only a predisposing factor. A.G. Vorderman (1844-1902) assumed a connection between rice feeding and beriberi in prisoners; he reported that the disease coincided with a diet of polished white rice. Beriberi could be prevented by providing the prisoners with 'red rice' (unpolished rice). However, red rice was regarded as inferior and status-lowering so that substitution of red for white rice in the rations was impossible. The concept of a 'lacking substance' (thiamine, vitamin B1) was hesitatingly accepted in the Netherlands. C. Winkler and C. Eijkman, for instance, refused until the early twenties of this century to exclude the possibility of a bacterial infection as the cause. As known, Eijkman in 1929 was awarded the Nobel prize for his contribution to vitamin research.     

Disturbance of consciousness associated with hypophosphatemia in a chronically alcoholic patient

A 69-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and oliguria. Emergency laboratory examination revealed metabolic acidosis, hypoglycemia, hyponatremia, mild liver dysfunction, acute renal failure and rhabdomyolysis. After administration of fluids and nutrients and continuous hemodiafiltration, he recovered from all signs and symptoms except for disturbance of consciousness after 7 days. Since severe hypophosphatemia persisted, we administered adequate phosphates, and then his level of consciousness normalized. We discuss the relationships among alcohol abuse, hypophosphatemia and disturbance of consciousness, and recommend that hypophosphatemia be considered a potential cause of disturbance of consciousness in alcoholic patients.     

On vitamin B1 metabolism in avitaminosis and its correction with thiamine and taurine

The levels of phosphate esters and the activities of thiamine biotransformation enzymes in the blood and tissues of albino rats were studied during oxythiamine-induced B1 deficiency and after metabolic correction with thiamine and taurine. Among thiamine phosphates, the most informative indicators of thiamine deficiency were shown to be triphosphate esters and free thiamine diphosphate. The biosynthetic enzymes thiamine kinase and thiamine diphosphate kinase played a decisive role in maintaining the initial rate and in recovering the physiologically active forms of vitamin B1. The activation of hydrolytic enzymes of thiamine phosphate esters occurred by producing abundant free thiamine diphosphate and thiamine triphosphate. Within the first hours, taurine favoured the acceleration of phosphoester biosynthesis and, accumulating in the tissues, inhibited vitamin phosphorylation reactions.     

A neglected lesbian health concern: cervical neoplasia

OBJECTIVE: The role of a deficiency of vitamin B1 in the development of alcoholic complaints is confined to the case of the Wernicke-Korsakov syndrome. Findings concerning a deficiency of thiamine in alcoholics in comparison with normal persons are contradictory and there are no differentiated tests in the case of delirium tremens. In this study the vitamin B1 absorption in patients with delirium tremens was of interest in connection with the presence or absence of hallucinations and autonomic symptoms. METHOD: Male patients (N = 70) with delirium tremens were compared with a group of 13 controls. The controls and patients were hospitalized in order to ensure abstinence from alcohol. The examination of the delirium patients was carried out with their consent after termination of the delirium tremens and again on discontinuance of drug therapy. In the case of 33 delirium patients the absorption of thiamine was tested again 4 weeks after the first examination. RESULTS: The absorption of vitamin B1 was in general only minimally lower in the case of the delirium patients in comparison with the nonalcoholics. The results showed, however, a considerably greater range of scattering of vitamin B1 absorption in the delirium patients. The absorption conditions showed marked improvement in the 4 weeks after delirium. The extent of absorption of vitamin B1 showed no influence on the duration of delirium. The patients with visual hallucinations, however, showed lower thiamine absorption than patients without such symptoms, whereas no dependence of autonomic symptoms on vitamin B1 absorption was seen. CONCLUSIONS: The disturbed absorption conditions in the delirium patients were obvious at the time of the examination as demonstrated by the wide range of absorption values. Improvement or near normal conditions were registered 4 weeks after the delirium. The absorption conditions had possibly already improved during the few days of alcohol abstinence in the course of the delirium treatment. The reduced vitamin B1 absorption of patients suffering from visual hallucination corresponds to observations of alcoholic hallucinosis.     

Selenium deficiency associated with cardiac dysfunction in three patients with chronic respiratory failure

We encountered three patients with chronic respiratory failure who had heart failure of cardiac arrhythmias and low levels of serum selenium. All three had tracheostomies and had received long-term parenteral nutrition that had not included selenium. All three also had refractory cardiac dysfunction, which was manifested in edema, heart failure, and various tachycardias. We suspected that selenium deficiency had caused their cardiac dysfunction. Serum selenium concentrations were found to be much lower than normal in all three, so 100 micrograms/day of selenium was administered in addition to their tube feedings. Cardiac function improved after replacement of selenium. These cases show the need for preventing selenium deficiency in patients with chronic respiratory failure during long-term administration of parenteral nutrition.     

Sunlight, cholesterol and coronary heart disease

We investigated the relationship between geography and incidence of coronary heart disease, looking at deficiency of sunlight and thus of vitamin D as a factor that might influence susceptibility and thus disease incidence. Sunlight deficiency could increase blood cholesterol by allowing squalene metabolism to progress to cholesterol synthesis rather than to vitamin D synthesis as would occur with greater amounts of sunlight exposure, and the increased concentration of blood cholesterol during the winter months, confirmed in this study, may well be due to reduced sunlight exposure. We show evidence that outdoor activity (gardening) is associated with a lower concentration of blood cholesterol in the summer but not in the winter. We suggest that the geographical variation of coronary heart disease is not specific, but is seen in other diseases and sunlight influences susceptibility to a number of chronic diseases, of which coronary heart disease is one.     

Glucose-6-phosphate dehydrogenase deficiency in an 81-year-old

In a 81-year-old woman, who for many years had been treated with iron and vitamin B12 injections because of a 'tendency to anaemia', congenital haemolytic anaemia on the basis of glucose-6-phosphate dehydrogenase (G6PD) deficiency was diagnosed. The iron and vitamin medication was discontinued and after a blood transfusion because of signs of heart failure, the patient could leave the hospital in good condition. After instruction with regard to provocative factors, like eating of broad beans, no more haemolytic events occurred. Of her children and grandchildren, 2 sons and 1 granddaughter were G6PD deficient.     

Corticosteroid therapy in cardiac sarcoidosis

Corticosteroid treatment of cardiac sarcoidosis is not conclusive, although sarcoid granulomas in the heart may be more responsive to steroid therapy than in other organs. Healing of sarcoidosis lesions in the heart results in fibrosis and sinning of the myocardium, which may lead to aneurysm formation causing congestive heart failure or sudden death. Congestive heart failure is the leading cause of death in patients with cardiac sarcoidosis in Japan. It is reasonable to initiate steroid therapy as soon as the diagnosis of cardiac sarcoidosis is established in order to prevent fibrosis. Early initiation of steroid therapy with conventional treatment for specific cardiac manifestations (antiarrhythmic therapy, pacemaker implantation and heart failure medication) should bring improvement in the left ventricular systolic and diastolic function with prevention from malignant arrhythmias. Systemic disorder represents a contraindication to organ transplantation, but heart transplantation is now a feasible treatment for patients with end-stage cardiac sarcoidosis with congestive heart failure.     

A transketolase assembly defect in a Wernicke-Korsakoff syndrome patient

Thiamine deficiency, a frequent complication of alcoholism, contributes significantly to the development of damage in various organ systems, including the brain. The molecular mechanisms that underlie the differential vulnerabilities to thiamine deficiency of tissue and cell types and among individuals are not understood. Investigations into these mechanisms have examined potential variations in thiamine utilizing enzymes. Transketolase is a homodimeric enzyme containing two molecules of noncovalently bound thiamine pyrophosphate. In the present study, we examined a his-tagged human transketolase that was produced in and purified from Escherichia coli cells. Previous findings demonstrated that purified his-transketolase had a Km app for cofactor and a thiamine pyrophosphate-dependent lag period for attaining steady-state kinetics that was similar to transketolase purified from human tissues. Interestingly, the time of the lag period, which is normally independent of enzyme concentration, was found herein to be dependent on the concentration of the recombinant protein. This atypical behavior was due to production in E. coli. Generation of the normal, enzyme concentration-independent state required a cytosolic factor(s) derived from human cells. Importantly, the required factor(s) was found to be defective in a Wernicke-Korsakoff patient whose cells in culture show an enhanced sensitivity to thiamine deficiency.     

Investigation of the selenium status of aborted calves with cardiac failure and myocardial necrosis

Lesions of heart failure, specifically cardiac dilation or hypertrophy along with a nodular liver (chronic passive congestion) and ascites, have been found in 4-5% of aborted bovine fetuses. In this study, a group of 22 such fetuses was compared with groups of aborted fetuses without lesions of heart failure and with nonaborted fetuses obtained from a slaughterhouse. The fetuses were necropsied, tissues were taken for histopathology, and samples were collected for routine bacteriologic and virologic examinations. Liver and kidney tissue was saved for selenium analysis. Histopathologic examinations of myocardium of fetuses with cardiac failure revealed myocardial necrosis and mineralization in 7 fetuses, lymphocytic myocarditis in 5 fetuses, myocardial fibrosis in 5 fetuses, or no microscopic lesions in 5 fetuses. Mean liver selenium levels were 5.5 mumol/kg in the fetuses with heart lesions, 6.5 mumol/kg in the fetuses without heart lesions and 7.5 mumol/kg in fetuses from the slaughterhouse; these differences were statistically significant. The results suggest that selenium deficiency in bovine fetuses may cause myocardial necrosis and heart failure. This study also provides data on normal liver and kidney selenium levels in bovine fetuses from the analyses of 19 nonaborted fetuses.     

Incidence of primary malignancies other than breast cancer among women treated with radiation therapy for benign breast disease

In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.     

Myosin heavy chain gene expression in human heart failure

Two isoforms of myosin heavy chain (MyHC), alpha and beta, exist in the mammalian ventricular myocardium, and their relative expression is correlated with the contractile velocity of cardiac muscle. Several pathologic stimuli can cause a shift in the MyHC composition of the rodent ventricle from alpha- to beta-MyHC. Given the potential physiological consequences of cardiac MyHC isoform shifts, we determined MyHC gene expression in human heart failure where cardiac contractility is impaired significantly. In this study, we quantitated the relative amounts of alpha- and beta-MyHC mRNA in the left ventricular free walls (LVs) of 14 heart donor candidates with no history of cardiovascular disease or structural cardiovascular abnormalities. This group consisted of seven patients with nonfailing (NF) hearts and seven patients with hearts that exhibited donor heart dysfunction (DHD). These were compared with 19 patients undergoing cardiac transplantation for chronic end-stage heart failure (F). The relative amounts of alpha-MyHC mRNA to total (i.e., alpha + beta) MyHC mRNA in the NF- and DHD-LVs were surprisingly high compared with previous reports (33.3+/-18.9 and 35.4+/-16.5%, respectively), and were significantly higher than those in the F-LVs, regardless of the cause of heart failure (2.2+/-3.5%, P < 0.0001). There was no significant difference in the ratios in NF- and DHD-LVs. Our results demonstrate that a considerable amount of alpha-MyHC mRNA is expressed in the normal heart, and is decreased significantly in chronic end-stage heart failure. If protein and enzymatic activity correlate with mRNA expression, this molecular alteration may be sufficient to explain systolic dysfunction in F-LVs, and therapeutics oriented towards increasing alpha-MyHC gene expression may be feasible.     

Attenuated cardiac sympathetic responsiveness during dynamic exercise in patients with heart failure

BACKGROUND: Cardiac norepinephrine (NE) spillover is increased in patients with chronic heart failure. This elevation is partly due to augmented NE release but also to reduced capacity for cardiac NE removal processes. In patients with mild to moderate heart failure, it is not known whether the described alteration in cardiac sympathetic function also affects cardiac NE spillover during intense sympathetic activation and whether other organs respond in proportion to the heart. METHODS AND RESULTS: Twenty-two patients with heart failure and 15 age-matched healthy subjects were studied. Whole-body and regional (NE) spillovers from the heart and kidneys were assessed at baseline and during supine cycling exercise (10 minutes) with the use of steady-state infusions of tritiated NE (isotope dilution). Cardiac performance was evaluated by means of catheterization of the right side of the heart. Cardiac NE spillover was higher (P < .05) at baseline in the patient group than in healthy subjects, whereas renal and whole-body NE spillovers were similar between the study groups. During exercise, cardiac NE spillover increased 13-fold (P < .05) in healthy subjects but only 5-fold (P < .05) in the cardiac failure group, the latter reaching a lower peak value (P < .05). In contrast, there was no difference between the study groups in either renal or whole-body NE spillover responsiveness to exercise. CONCLUSIONS: Patients with mild to moderate heart failure demonstrated a selective attenuation of cardiac sympathetic responsiveness during dynamic exercise. This attenuation may convey reduced inotropic and chronotropic support to the failing heart.     

Value of digoxin in heart failure and sinus rhythm: new features of an old drug?

Digoxin has been a controversial drug since its introduction >200 years ago. Although its efficacy in patients with heart failure and atrial fibrillation is clear, its value in patients with heart failure and sinus rhythm has often been questioned. In the 1980s, reports of some large-scale trials indicated that digoxin, with or without vasodilators or angiotensin-converting enzyme inhibitors, reduced signs and symptoms of congestive heart failure and improved exercise tolerance. This beneficial influence was mainly found in patients with more advanced heart failure and dilated ventricles, whereas the effect in those with mild disease appeared to be less pronounced. In the last few years, new data have shown that digoxin may also have clinical value in mild heart failure, either when used in combination with other drugs or when administered alone. As neurohumoral activation has increasingly been recognized to be a contributing factor in the disease progression of chronic heart failure, the modulating effects of digoxin on neurohumoral and autonomic status have received more attention. Also, there is evidence that relatively low doses of digoxin may be at least as effective as higher doses and have a lower incidence of side effects. Further, the recognition that the use of digoxin too early after myocardial infarction may be harmful and the development of other drugs, in particular angiotensin-converting enzyme inhibitors, have obviously changed the place of digoxin in the treatment of chronic heart failure. The large-scale survival trial by the Digitalis Investigators Group (DIG), whose preliminary results have recently been presented, has shown that although digoxin has a neutral effect on total mortality during long-term treatment, it reduces the number of hospital admissions and deaths due to worsening heart failure. The potentially new features of the old drug digoxin are discussed in this review.     

Hemolysis and schizocytosis, malabsorption and the "folate trap": unusual semiological peculiarities associated with vitamin B12 deficiency

INTRODUCTION: Hemolysis and red cell fragmentation accompanying vitamin B12 deficiency may misdirect the diagnosis. Signs of malabsorption and abnormalities related to folic acid metabolism characterized by discrepancies between folic acid normal serum levels and erythrocytic folic acid levels may also exist. EXEGESIS: We report the occurrence of hemolysis and red cell fragmentation mimicking microangiopathic hemolytic anemia, malabsorption and folic acid deficiency in the course of vitamin B12 deficiency. Appropriate replacement therapy corrected all abnormalities. CONCLUSION: An association between hemolysis, malabsorption and folic acid deficiency should lead physicians to search for signs of vitamin B12 deficiency.