Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot study

Malignancy associated primary thiamine deficiency has been documented in several experimental tumours, sporadic clinical case reports, and in a number of patients with fast growing haematological malignancies. Thiamine status was assessed prospectively in 14 untreated B-chronic lymphocytic leukaemia (CLL) patients, and in 14 age matched control patients with non-malignant disease. Patients with any known cause of absolute, relative, or functional thiamine deficiency were excluded. High (>15%) thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, was found in five out of 14 CLL patients (35.7%) and in none of the controls (p=0.057). Mean (SD) TPPE in the thiamine deficient patients group was 21.6 (3.4)%. In all the patients, thiamine deficiency was subclinical. No correlates for the thiamine deficiency have been found save for an increment of more than 20% in the total leucocyte count over the preceding three months, which was found in all five thiamine deficient patients compared with only one of the nine non-thiamine deficient CLL patients. Thus, CLL patients may be prone to develop primary thiamine deficiency possibly promoted by the increased leucocytes span, which may increase thiamine consumption. Since even subclinical thiamine deficiency may be detrimental to the patient's clinical course, and in view of the theoretical danger of thiamine promoted tumour cell proliferation, further large scale studies are warranted to confirm this observation, and to elucidate the issue of thiamine supplementation to CLL patients.     

多维元素片中维生素B1和维生素B2的含量测定

目的建立多维元素片中维生素B1和维生素B2含量的测定方法。方法采用Hypersil ODS2色谱柱（200mmx4．6mm，5μm），流动相为离子对溶液（己烷磺酸钠1．4g，冰醋酸5mL，三乙胺2mL，用水定容至1000mL）-甲醇（80：20），流速为1．0mL／min，检测波长为280nm。结果维生素B1质量浓度在20．03～100．16μg／mL范围内与峰面积呈线性关系（r=0．9999），平均回收率为98.40％，日内、日间RSD均小于0．83％；维生素B2质量浓度在19.8l～99.04μg／mL范围内与峰面积呈线性关系（r=1．0000），平均回收率为97.37％，日内、日间RSD均小于1．77％。结论高效液相色谱法可用于多维元素片的质量控制。     

Wernicke's encephalopathy induced by hyperemesis gravidarum

A report is presented on a patient with Wernicke's encephalopathy secondary to hyperemesis gravidarum. The 25-year-old female presented 11 weeks into pregnancy with prolonged vomiting. Neurological examination 8 weeks later demonstrated obtunded sensations, nystagmus and ataxia of gait. MR imaging revealed bilateral lesions in the mediodorsal nuclei of thalami, in the hypothalamus and in the periaqueductal gray matter (1). The neurological signs and the MRI findings pointed to a diagnosis of Wernicke's encephalopathy. The patient was treated with intramuscular vitamin B1 followed by oral thiamine until the end of pregnancy. The subsequent course of the pregnancy was uncomplicated, and resulted in the delivery of a healthy 2970 g male infant. A review of the literature published during the last 30 years revealed an additional 20 cases of Wernicke's encephalopathy induced by hyperemesis gravidarum. Only half of these pregnancies resulted in the birth of a normal infant.     

Pyrithiamine-induced thiamine deficiency results in decreased Ca2+-dependent release of glutamate from rat hippocampal slices

Alterations of excitatory amino acids in brain may be of pathophysiological significance in thiamine-deficiency encephalopathy. The present study was undertaken to evaluate the effects of thiamine deficiency induced by the central thiamine antagonist, pyrithiamine, on the glutamate content of glutamatergic nerve terminals. Electrically-stimulated, Ca²⁺-dependent release of glutamate from hippocampal slices obtained from symptomatic pyrithiamine-treated rats was significantly decreased compared to pair-fed controls. Possible explanations for the decreased neurotransmitter pool of glutamate in thiamine-deficient rat brain include decreased synthesis of glutamate as a result of decreased activities of the thiamine-dependent enzyme -ketoglutarate dehydrogenase or increased release of glutamateper se. There is evidence to suggest that the latter mechanism with ensuing excitotoxic neuronal damage could be involved in the pathogenesis of selective neuronal death in thiamine deficiency. Similar mechanisms could be implicated in Wemicke's encephalopathy in humans.     

Neuronal cell death in Wernicke's encephalopathy: pathophysiologic mechanisms and implications for PET imaging

Thiamine deficiency in humans is associated with Wernicke's encephalopathy (WE) which is characterized neuropathologically by neuronal loss in selective brain regions. Pyrithiamine-induced thiamine-deficiency in the rat results in lesions which are similar in nature and distribution to those seen in human WE. Several mechanisms have been implicated in the pathogenesis of neuronal loss in thiamine deficiency including, (i) impaired cerebral energy metabolism, (ii) focal lactic acidosis, (iii) NMDA-receptor mediated excitotoxicity and (iv) blood-brain barrier breakdown. WE is difficult to diagnose during life and a large number of cases are missed by routine clinical neurological evaluation. Recently, non-invasive diagnostic procedures such as CT and MRI have been used for the evaluation of acute and chronic WE. Autoradiographic studies reveal that increased densities of binding sites for the astrocytic ligand³H-PK11195 closely parallel the topographic distribution of reactive gliosis and neuronal loss in selective brain regions of pyrithiamine-induced thiamine-deficient rats. In contrast, binding sites for the neuronal ligand³H-Ro15-1788 show poor regional correlation with neuronal loss in thiamine deficiency. Both of these ligands are available, and have been used in PET assessment of various disorders in humans. The results of autoradiographic studies suggest that¹¹C-PK11195 may offer a useful PET ligand for the assessment of brain damage in WE in humans.     

High thiamine diphosphate level as a protective factor for Alzheimer’s disease

Objectives Thiamine diphosphate (TDP) is an indispensable coenzyme for three key enzymes in glucose metabolism. Reduced TDP levels in patients with Alzheimer’s disease (AD) has been widely demonstrated and is a diagnostic biomarker for the disease. In this study, we further explored the correlation between altered TDP metabolism and AD along with other risk factors.

Methods A 1:1 case-control study was employed with 90 AD patients and 90 control subjects with normal-range cognitive abilities as assayed by the Mini Mental Status Evaluation. Age (≤2 years variation), gender, and educational background were strictly matched. Levels of the main thiamine metabolites in whole blood samples, including TDP, thiamine monophosphate, and thiamine, were assayed using high-performance liquid chromatography. Apolipoprotein E genotypes, haemoglobin, and several metabolic factors (fasting glucose, uric acid, triglyceride, and total cholesterol) associated with AD were also measured.

Results The odds ratio of TDP level for AD was 0.95 (with TDP level as a continuous variable) or 0.09 (with TDP level as a dichotomized variable with a cut-off value of 99.48 nmol/L). Blood TDP levels were significantly decreased in female AD patients compared to male AD patients. No correlations were identified between TDP levels and several metabolic factors (fasting glucose, uric acid, triglyceride, and total cholesterol).

Conclusions TDP is a protective factor for AD and its protective efficacy may be independent of other metabolic factors. The difference of TDP levels between genders may be another possible explanation for the higher prevalence of AD in females.     

Nutritional Heart Disease and Cardiomyopathies: JACC Focus Seminar 4/4

This JACC Focus Seminar provides an overview of and highlights recently published research on cardiomyopathies and nutritional heart disease that have a higher prevalence in tropical regions. The development of tropical cardiomyopathies and nutritional cardiovascular disease (CVD) is complicated by high rates of poverty, fragmented health care systems, and suboptimal access to health care because of socioeconomic inequalities, leading to the fact that children, adolescents, and young adults are disproportionally affected. Such tropical cardiomyopathies and nutritional CVD that have not been prevalent in high-income countries in the past decades are now reemerging. When treating migrants or refugees, it is important for attending physicians to consider the burden of endemic diseases in the countries of origin and the likelihood that such patients might be affected. In this review, the authors propose an approach for adequate diagnostic work-up leading to appropriate care for those with suspected or confirmed tropical cardiomyopathies and nutritional CVD.