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The very high prevalence of haemorrhoids in the most economically developed countries is contrasted with their low prevalence in rural communities in developing countries. Traditional concepts of causation are shown to be no longer tenable. It is argued from epidemiological, clinical and experimental evidence that the fundamental cause of piles is straining at viscid stools which are the result of fibre-depleted diets. [ABSTRACT FROM PUBLISHER]

There are two main types of hemorrhoids—vascular and mucosal. Vascular piles, occurring most commonly in young men, are caused by straining at defecation, when the anal sphincter relaxes, subjecting the anorectal tissues to a high pressure gradient. The superior hemorrhoidal plexus is filled initially by blood which is forced at very high pressure from the superior rectal venous radicles lying in the lower part of the ampulla of the rectum. Distention of the plexus is limited and is confined to the veins of the upper part of the anal canal by a tube-valve mechanism which also has a similar, but less direct, effect on the inferior rectal veins.Mucosal piles, usually found in pregnant women and the aged, are caused by deterioration of the function of the anal sphincter muscle.There is no evidence that any other etiologic factor is of significance in the causation of piles. [ABSTRACT FROM AUTHOR]

D-Fen-induced hyperthermia has been shown to coincide with an enhanced depletion of 5-HT and 5-hydroxyindole acetic acid (5-HIAA). Because these observations have relied on D-Fen exposure at multiple environmental temperatures, some have questioned the validity of the findings. Therefore, this experiment was designed to determine if the correlation between elevated body temperature and 5-HT depletion could be observed when D-Fen exposure occurred in one warm environment (28 degrees C) and to determine if a hyperthermia-enhanced glial-cell response could be evoked by D-Fen exposure. Hyperthermia-enhanced 5-HT and 5-HIAA depletion resulting from D-Fen exposure was dependent on body temperature during drug exposure. In the frontal cortex, 5-HT concentrations ranged from 3 to 45% of control values. Likewise, in the striatum and hippocampus, 5-HT concentrations ranged from 13 to 53% and 6 to 40%, respectively. The 5-HIAA concentrations had a wider range than the 5-HT concentrations for each brain region. In the frontal cortex, striatum and hippocampus, 5-HIAA ranged from 0 to 93%, 15 to 72% and 0 to 83% of control, respectively. In spite of the substantial reductions in 5-HT, there was no detectable glial-cell response. D-Fen-induced hyperthermia does not appear to cause generalized damage to neurons in the frontal cortex, striatum and hippocampus.

Recent findings indicate that elevations in body temperature during acute d-fenfluramine (Fen) exposure enhance long-term 5-HT depletion. Therefore, we hypothesized that when repeated exposure to d-Fen produced repeated elevations in body temperature, 5-HT reductions would be greater in comparison to a single d-Fen exposure. Groups of animals were exposed to d-Fen for 1 or 4 days in a 28 degrees C environment. Exposure to d-Fen in the 28 degrees C environment induced an increase in body temperature and resulted in a long-term decrease in brain 5-HT. However, brain 5-HT was not different between the two groups. An additional experiment revealed that if the initial exposure to d-Fen does not induce elevations in body temperature, then long-term 5-HT depletion can be prevented. We conclude that the central nervous system rapidly adapts to the 5-HT depleting action of d-Fen thereby preventing further decreases in 5-HT concentrations from d-Fen exposure. In addition, this rapid adaptation circumvented the hyperthermia-enhanced 5-HT depletion that results from d-Fen exposure in a warm environment.

d-Fenfluramine (d-Fen) has been demonstrated to alter body temperature (BT), decrease 5-hydroxytryptamine (5-HT) and decrease 5-HT plasma membrane transporters (PMT) in rats. Therefore, experiments were designed to test whether a correlation existed between elevated BT and brain 5-HT depletions. It was hypothesized that d-Fen would induce hyperthermia if the environmental temperature was elevated. Experiments were conducted to determine 1) the dose-response of d-Fen on BT in a 28 degrees C environment, 2) the acute effect of d-Fen on long-term depletion of 5-HT and 5-HT PMT in a 4 degrees C, 22 degrees C or 28 degrees C environment and 3) the effect of a 22 degrees C environment vs. a 28 degrees C environment on the plasma levels of d-Fen and d-norfenfluramine. d-Fen produced a dose-dependent elevation of BT in the 28 degrees C environment, decreased BT in the 4 degrees C environment and had no effect on BT in the 22 degrees C environment. Exposure to d-Fen in the 4 degrees C or 22 degrees C environment reduced 5-HT and 5-HT PMT concentrations compared with control. However, greater reductions of 5-HT and 5-HT PMT concentrations occurred in the 28 degrees C environment. Conversely, the plasma levels of d-Fen and d-norfenfluramine were not altered. Thus these experiments demonstrate that increased BT during d-Fen exposure occurs at elevated environmental temperatures without altering the plasma concentrations of the drug and results in an enhanced long-term depletion of brain 5-HT and 5-HT PMT.