NF-kappaB expression and apoptosis are increased from adenoma to poorly differentiated adenocarcinoma tissues. Apoptosis is correlated with suppression of Bcl-2 expression, but appears to proceed through a p53- and Bax-independent pathway. Activation of NF-kappaB may play an important role in colorectal tumour progression.
Erythrocyte transketolase activity and its stimulation in vitro by the addition of thiamine pyrophosphate (TPP effect) was measured in 64 normally nourished alcoholics with well-compensated liver disease and in 20 control subjects. Biochemical evidence of thiamine deficiency as judged by low transketolase activity was found in 19 alcoholics (29.7%). In 5 of these 19 patients the TPP effect was abnormally high, indicating depleted thiamine stores. IN the other 13 patients the TPP effect was either normal or low, suggesting a deficiency or an inability to use the transketolase apoenzyme, probably as a result o long-standing thiamine deficiency or the presence of liver disease. a further eight patients (12.5%) had normal transketolase activity but a low TPP effect, perhaps reflecting failure of hte coenzyme TPP to recombine with the transketolase apoenzyme in the presence of normal thiamine stores. There was no relationship between transketolase activity and the daily alcohol consumption, the duration of alcoholism, or the histological severity of the liver disease. Thiamine should be given routinely to alcoholics even if their diet appears adequate and their liver disease is minimal or well compensated.
Summary The incidence of macrocytosis, defined as a mean corpuscular volume (MCV) of > 95 fl and large red cells on peripheral blood film, was determined in 303 alcoholics with liver disease (95 females: 208 males), 60 non‐alcoholics with chronic liver disease (44 females: 16 males) and 35 control subjects (15 females: 20 males). Macrocytosis was found in 70.3% (213/303) of alcoholics with liver disease and in 23.3% (14/60) of non‐alcoholics with liver disease, P < 0.001. MCV values > 100 fl were seen in 49.5% (150/303) of alcoholics, but in only 3.3% (2/60) of non‐alcoholics, P < 0.001. Macrocytosis was more frequent in female, 86.3% (82/95) than in male alcoholics 63.0% (131/208), P < 0.001. Serum folate values < 3 μg/1 were found in 14.5% (44/303) of alcoholics and in 11.7% (7/60) of non‐alcoholics. Low serum folate values were found in 183% (39/213) of alcoholics with macrocytosis and in 35.9% (28/78) of those with macrocytic anaemia. Twenty alcholics with pre‐cirrhotic liver disease were followed over three months. Macrocytosis was present in 85.0% (17/20) at the outset and in 40% (8/20) 3 months later. The changes in MCV were independent of alcohol intake and serum folate values. Macrocytosis is a useful diagnostic indicator of alcoholism. MCV values > 100 fl in patients with liver disease almost invariably indicate alcohol‐related disease. In the short‐term, changes in MCV are of little use in monitoring alcohol intake.
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