Growth and lung function in Asian patients with cystic fibrosis.

BACKGROUND: The incidence of cystic fibrosis (CF) in Asians is rare. How these patients fare in terms of morbidity and mortality in the UK compared to their non-Asian peers is not well documented. AIMS: To retrospectively study annual reviews of 31 Asian CF patients from three London paediatric CF centres. METHODS: Disease severity was assessed by lung function, age at first infection with Pseudomonas aeruginosa, and body mass index (BMI). The Asian children were compared with 143 matched non-Asian patients with CF. Matching criteria used were same sex and treatment centre as the Asian index patient. In addition, the controls were matched so that their date of birth, date of diagnosis, and date at annual review were within 12 months of the index patient. RESULTS: There was no significant difference in age at diagnosis or age at annual review between the Asian and non-Asian children. Mean Z-scores for FEV1 and FVC were significantly lower for the Asian girls. There was no significant difference in Z-scores for BMI between the Asian children and their controls. Age at first isolation of Pseudomonas aeruginosa in Asian girls was significantly later than for their controls (8.3 years compared to 5.6 years for non-Asian girls). CONCLUSIONS: While the Asian boys' lung function seems comparable with that of their non-Asian peers, the Asian girls emerge as a potentially vulnerable group and more work is required to discover why this is the case.

Does the pineal gland have a role in the psychological mechanisms involved in the progression of cancer?

Psychological factors, e.g., depression and psychological stress have been implicated in the progress of cancer. Similarly, the pineal gland and its principal secretion, melatonin, are known to influence the initiation and progress of cancer. Furthermore, changes in melatonin secretion have been linked with psychological stress and depression, and both the pineal gland and the cerebral cortex act via the limbic system in producing their effects. Both psychological stress and melatonin affect the immune system, as does the hypothalamus and the autonomic nervous system. The pineal gland has both a direct effect on cancer, and via the immune system. Psychological treatment and melatonin treatment have both been found to alleviate the course of cancer clinically. It is thus hypothesized that the pineal gland, and melatonin, are involved in the mechanism of psychological effects in the promotion of the progress of cancer.

Changes in pineal sympathetic innervation are not significant in the hyperproliferative effects of pinealectomy on the intestinal crypts.

OBJECTIVES: To observe the effect of changes in the pineal sympathetic innervation on the crypt cell proliferation rate in the rat small intestine, and compare these with the effect of pinealectomy to determine the role of the sympathetic innervation in the effect of pinealectomy. METHODS: The effect of bilateral ablation of the superior cervical ganglion, and that of pinealectomy on the crypt cell proliferation rate in the rat small intestine was determined, using a stathmokinetic technique. RESULTS: Pinealectomy was associated with a considerably increased crypt cell proliferation rate, whereas superior cervical ganglionectomy was associated with a slightly decreased rate. CONCLUSIONS: It appears likely that changes in pineal melatonin production cannot be correlated directly with the effects of pinealectomy on the crypts, although melatonin production was not measured in this case. The role of loss of the non-adrenergic innervation of the pineal in the effect of pinealectomy needs to be examined. There is also other experimental evidence that melatonin-free extracts of the pineal, containing as yet unidentified substances, can influence mitotic activity in some tissues, so the possible role of these substances in the effects of pinealectomy should also be considered. Furthermore, the superior cervical ganglion itself has an extra-pineal role. Changes in pineal sympathetic innervation are not significant in the hyperproliferative effects of pinealectomy on the intestinal crypts.

The effect of pinealectomy on the crypts of defunctioned rat colon.

Previously it has been found that 6 months after pinealectomy hyperplasia occurred in the crypt cells of the rat small bowel and colon. It is also known that defunctioning a loop of colon, using a colostomy, results in crypt cell hypoplasia, emphasizing the prime importance of luminal factors in the control of crypt cell proliferation. To determine if the effects of pinealectomy on the colon could be modified by the absence of colonic luminal contents, the crypt cell kinetic effects of combined pinealectomy and defunctioning of a colonic loop by colostomy for 6 months were examined by using a stathmokinetic technique. It was found that the hypoproliferative effect of defunctioning a loop of colon was largely but not completely overridden by the hyperproliferative effect of pinealectomy. However, previously it has been found that in the rat small bowel, the hypoproliferative effects of defunctioning a loop were completely overridden by the effect of pinealectomy. This and other evidence suggests that the role of the pineal in the control of crypt cell proliferation in the colon may possibly be different from its role in the small bowel. There is other evidence of possible involvement of the pineal in carcinoma of the colon and it is possible that its role in the colon may be to prevent excessive mitotic activity, which is known to be present in the early stages of carcinoma. The Pineal gland may have a role in modulating the usual mechanisms of crypt cell mitotic control.

The long-term effect of pinealectomy on the crypts of the rat gastrointestinal tract.

Previously it has been found that rat small bowel crypt cell hyperplasia occurred several weeks after pinealectomy. To determine if this effect was longer-lasting (because of the possible role of the pineal in bowel malignancy) the crypt cell proliferation rate was determined in rat small bowel and colon 6 months after pinealectomy, using a stathmokinetic technique. Although the hyperproliferative effect of pinealectomy was well maintained in the small bowel crypts after 6 months, the hyperproliferative effect in the colonic crypts was much less marked. There is no obvious explanation for these findings, although it is possible that regional differences in levels of gut neuropeptides or melatonin are involved. The mechanism of the effect of pinealectomy on the crypts remains unexplained--in particular, why the effect is so prolonged.

The effect of pinealectomy and autonomic denervation on crypt cell proliferation in the rat small intestine.

Previously it has been found that pinealectomy in rats was associated with increased small bowel crypt cell proliferation. The hypothalamus is thought to play a role in the neural control of crypt cell proliferation and the pineal gland is known to be functionally connected with this component of the autonomic nervous system. Consequently, the effect on crypt cell mitotic rate of pinealectomy with autonomic denervation of the rat small bowel (local sympathectomy and truncal vagotomy) was observed to determine the possible importance of the autonomic nervous system in the mediation of the effects of pinealectomy on the crypts. It was found that interruption of either the vagal or sympathetic nerve supply to the small intestine both significantly decreased the usual hyperproliferative effect on the crypt cells observed after pinealectomy. It is suggested that the overall effect of the pineal gland is to suppress the crypt cell proliferation rate and that this effect is mediated, at least to some extent, by (1) the direct connections between the pineal gland and the hypothalamus, (2) the connections between the hypothalamus and the vagal and sympathetic innervation of the gut, and (3) the influence of the autonomic innervation on the activity of the enteric plexuses in relationship to the crypts. The pineal may have a role in modulating the local control mechanism of crypt cell proliferation. Its exact role in the control of crypt cell proliferation has not yet been defined.

Effect of septal and fornix lesions on rat small bowel crypt cell kinetics.

The septum and fornix are known to modulate the functional activity of the hypothalamus. Since the hypothalamus has been shown to influence crypt cell mitotic rate, it was considered possible that the septum and fornix might have a similar influence. Using a stathmokinetic technique, bilateral fornix and septal lesions were found to be associated with a marked increase in rat small bowel crypt cell mitotic rate. There was no associated significant change in food intake. It appears possible that the effects of the septal and fornix lesions may have been mediated via their influence over the functions of the hypothalamus.

The effect of bilateral amygdaloid nucleus lesions on rat small bowel crypt cell kinetics.

Previous investigators have found that central nervous system lesions, in particular lesions of the hypothalamus, may increase the crypt cell mitotic rate in the rat small bowel. Since the amygdaloid nuclei form part of the limbic system (the "visceral brain") and have functional neural connections with the hypothalamus the effect of bilateral electrocoagulation lesions of the amygdaloid nuclei on crypt cell mitotic rate in the rat small bowel was investigated, using a stathmokinetic technique. Bilateral amygdaloid lesions were found to be associated with a marked increase in crypt cell mitotic rate in the proximal jejunum and distal ileum. Consideration of the neural connections of the amygdaloid nuclei suggests that these effects may possibly be mediated via the hypothalamus and the autonomic nervous system. The effects of lesions of other parts of the limbic system on crypt cell mitotic rate will be published subsequently.

The effect of pinealectomy and jejunal loop diversion on rat small bowel crypt cell kinetics.

Previously, it was found that diversion of an isolated loop of jejunum into the colon was associated with a significantly diminished crypt cell proliferation rate in the isolated loop, probably principally because of the diminished amount of nutrient available to the diverted mucosa. It has also been shown previously that removal of the pineal gland is associated with a considerable increase in the jejunal crypt cell mitotic rate. In the present investigation it was found that following pinealectomy, whilst the rise in crypt cell proliferation elsewhere in the rat small intestine was maintained at the expected level, the mitotic rate in the crypts of an isolated jejunal loop attached to the colon was also increased to a similar level, despite the fact that this isolated loop was in contact with a considerably diminished level of luminal nutrients. Thus, the expected hypoproliferative effects of jejunal isolation were overridden by the hyperproliferative effects of pinealectomy and the effects of pinealectomy appeared to be independent of the particular changes in luminal environment produced in this experiment. The significance of these findings is discussed in the light of the available literature.