Influence of sleep disruption and calorie restriction on biological markers for depression.

The hypothesis that the dexamethasone suppression test (DST) and rapid-eye-movement (REM) latency test are not biological markers for depressive illness but artifacts arising from dietary and sleep disturbances that accompany depression was examined in 28 normal volunteers. The restriction of calorie intake with moderate weight loss reproduced a pattern of response to dexamethasone closely resembling that claimed to be diagnostic of depressive illness. The shortened REM latencies claimed as a diagnostic marker were replicated in volunteers by mimicking the sleep pattern commonly found in depression. These changes could not be explained by the induction of mood disorder in the subjects. The results put in question the diagnostic value of the DST and REM latency tests in clinical practice, where sleep disorder and poor appetite, with reduced calorie intake, are the common accompaniments of depressive illness.

Impact of a handicapped child on mental health of parents.

In a cross sectional study the mental health of parents of physically and mentally handicapped preschool children was compared with that of parents of healthy preschool children. The social networks of the parents with handicapped children were also studied to determine factors that might influence psychiatric morbidity. The mothers of the handicapped children showed significantly more psychiatric morbidity than the control mothers, but the fathers did not show the same deleterious effect on mental health.

Circadian rhythms of epinephrine and norepinephrine in man.

The diurnal rhythms of plasma epinephrine and norepinephrine were investigated in a group of normal young men. Sleep, posture, illumination, and food intake were monitored. Plasma epinephrine demonstrated a statistically significant diurnal rhythm, with a mean amplitude of 14 +/- 1.6 (+/- SE) pg/ml superimposed on a mean level of 43 +/- 5.3 pg/ml. The trough occurred at 03.20 h +/- 35 min. Plasma norepinephrine had a significant diurnal rhythm, with a mean amplitude of 111 +/- 19 pg/ml superimposed on a mean level of 413 +/- 25 pg/ml, with the trough occurring at 02.20 h +/- 30 min. There was a significant correlation between the two rhythms at zero phase shift, with a pooled value for the group of r = 0.49. Epinephrine levels had no direct relationship to sleep or posture, whereas norepinephrine levels were significantly higher with upright posture and higher when the men were awake than when asleep. Our results indicate that circadian variations in the sympathetic-adrenal medullary system are not explained by a single controlling influence and that the norepinephrine rhythm can be accounted for as a direct response to changes in posture and sleep, whereas the epinephrine rhythm is probably controlled by a circadian oscillator.

Postmenopausal flashes: studies of chronological organisation.

The times of occurrence of climacteric flashes were recorded by three women over a period of one month. The mean intervals between flashes were 130 +/- 5, 142 +/- 6 and 67 +/- 3 min (mean +/- S.E.) for the three women. The flashes did not occur simply randomly in time. Following a flash, a period of suppression of the ability to flash again was apparent. No mathematical model was derived which satisfactorily described the incidence of flashing in all three women. However, models assuming suppression of the ability to flash immediately following a flash gave the best fits to our data. This suggest that there is an inhibitory feedback mechanism mediating partial suppression of flashing for at least 30 min after a flash.

A study of 24-hour profiles of plasma met-enkephalin in man.

Met-enkephalin has recently been demonstrated to circulate in human plasma and using this highly specific extracted radioimmunoassay the fluctuations of plasma Met-enkephalin in man were studied over 24 h. The subjects were 6 healthy volunteers. Following a 24 h adaptation period in the metabolic ward and sleep laboratory, an i.v. catheter was inserted. Blood samples were taken at hourly intervals through the day and at 30 min intervals between 23.00 h and 07.00 h. Sleep was monitored polygraphically. There was no regular rhythm discernible in plasma Met-enkephalin levels throughout the 24 h, nor was there any relationship with sleep or food intake. In a further 3 subjects beta-LPH and beta-endorphin levels as estimated by N- and C-terminal beta-LPH radioimmunoassay were elevated on waking compared with 01.00 h, suggesting a nyctohemeral rhythm. In contrast to the correlated circadian fluctuations in beta-LPH, ACTH and beta-endorphin levels therefore, the lack of circadian rhythmicity and dissociation of plasma Met-enkephalin from plasma levels of the former group of peptides suggests control mechanisms for the secretion of Met-enkephalin are quite different and adds support to the concept of separate Met-enkephalin precursors.

Studies of diurnal changes in plasma renin activity, and plasma noradrenaline, aldosterone and cortisol concentrations in man.

Diurnal studies were performed on ten normal volunteers taking a normal sodium diet. Half-hourly blood samples were taken throughout 25 h and assayed for plasma renin activity (PRA) and the plasma concentrations of noradrenaline, aldosterone and cortisol. Sleep was recorded polygraphically and scored by standard criteria. Circadian rhythms were demonstrated for plasma cortisol, aldosterone and noradrenaline concentrations, but not for plasma renin activity. The nadir of the rhythm for the noradrenaline concentration appeared to be related to sleep itself rather than to any chronological index. Only PRA was effected by the stage of sleep, falling sharply during periods of REM sleep. Plasma cortisol and aldosterone concentrations showed a positive correlation over the 24 h. There was, however, no correlation between PRA and plasma aldosterone concentrations, except when the subjects arose after their night's recumbency. Plasma noradrenaline concentration did not correlate with the concentration of any of the other hormones measured.

Liver cell cancer--intervention studies.

The field studies leading to possible intervention procedures are reviewed. Currently the most promising form of intervention is the prevention of aflatoxin contamination of foodstuffs. It is essential that these are monitored and their efficacy in lowering the incidence of liver cancer measured. The association of liver cancer with hepatitis B infection may be a confounding factor and the impact of this on the study population must also be considered. The imminent production of vaccines for hepatitis B infection may provide an alternative or additional mode of intervention. The possibilities for intervention in liver cell cancer appear one of the brighter prospects for primary prevention of a cancer.

Multiple cases of Burkitt's lymphoma and other neoplasms in families in the North Mara District of Tanzania.

In an area of Tanzania in which Burkitt's lymphoma (BL) is endemic, five families are described in which multiple cases of BL were found or BL occurred with other neoplasms. The patients include two brothers and one half-brother with BL, two brothers with BL, a woman with nasopharyngeal carcinoma (NPC) whose daughter had BL, a boy with BL whose sister developed chronic myelogenous leukaemia (CML), and a man with CML whose son developed BL. The two full-sib pairs with BL is significantly more than would be expected to have arisen by chance and the association of BL with NPC and CML among close relatives is remarkable in view of the rarity of the last two neoplasms in the study area. It is suggested that genetic factors may be important. It is suggested that genetic factors may be important in determining susceptibility to the three malignancies in this population, but the possibility that the clustering of cases within families may be due to local environmental factors cannot be excluded.

A relationship between plasma renin activity and the rapid eye movement phase of sleep in man.

The possible influence of the central nervous system on renin release was investigated by simultaneously monitoring the PRA and the changes of the sleep-wake cycle. Nine normal volunteers were studied, 2 of whom were subjected to an acute sleep reversal procedure. PRA exhibited marked intra- and intersubject variability. No consistent diurnal or ultradian rhythm was observed. The nocturnal variation in PRA, however, was associated with changes in the stage of sleep. The rapid eye movement (REM) phase correlated with a decrease in PRA. In the 9 subjects, 26 measurements were made during REM, all but 2 of which showed a drop compared to the level obtained in the immediately preceding sleep stage (P less than 0.001), by two-tailed t test). The mean decrease in PRA accompanying REM was 407 pg/ml.h, and the mean time for PRA to decrease by half after REM onset was 33 min, with a SE of 8 min. The sleep reversal procedure confirmed that REM was associated with decreased PRA even when sleep occurred at an unaccustomed time. REM is demonstrated by these findings to be temporally associated with a suppression of PRA. The rate of decrease of PRA after REM onset closely approximates the most recent estimations of PRA half-life, which suggests that REM onset is associated with a virtual cessation in renin production.

The circadian variation of immunoreactive lipotrophin and its relationship to ACTH and growth hormone in man.

There is a clear circadian rhythm of plasma immunoreactive LPH in man with the trough occurring between 22.00 h and 03.00 h and the peak between 07.00 h and 08.00 h, immediately after waking. At all times circulating LPH and ACTH levels follow each other closely. However, no correlation was observed between LPH levels and either plasma GH or the stage of sleep.

Environmental chemical carcinogens and liver cancer.

An appraisal is made of these chemical carcinogens available in the human environment that have been implicated in the etiology of liver cancer. The possible role of mycotoxins is discussed in detail, in particular the association between the aflatoxins and liver cancer in Africa and the Far East.

Decision on the control of a dietary carcinogen -- aflatoxin.

The sequence of events is described whereby decisions are made by the scientific community and national or international legislative bodies in evaluating a dietary carcinogen. This is proposed on the basis of experience gained from the aflatoxins. Suspicion arose first after the deaths of large numbers of poultry and fish; the agent was soon identified as aflatoxins. This was followed by laboratory investigations of their toxic and carcinogenic effects in experimental animals, which showed them to be the most potent liver carcinogen known to experimentalists. Field studies were established to assess a possible association with liver-cell cancer in humans, and a significant correlation was found. An intervention programme was therefore set up to lower exposure and to observe the trend of cancer incidence. Aflatoxins are found in many cereals and nuts exposed to humidity; thus, the staple foods of most of the developing world are at risk. The severity of the economic problem for some countries if prejudice should continue to develop against peanuts as a basis for animal feeds is illustrated. Decisions about control of aflatoxins thus fall into two groups: control measures to prevent contaminated foods from reaching the populations of industrialized countries, and primary prevention for the millions in the developing world. Regulatory actions have been taken in various industrialized countries, but their effect is to make developing countries safeguard exports and still to ignore the hazard within the country. The main problem is thus protection of food supplies, for the indigenous populations of those countries that grow and consume the bulk of the susceptible cereals, by improved husbandry.

Hepatitis B and primary hepatocellular carcinoma in a European population.

The prevalence of serological markers of active of past hepatitis-B virus (H.B.V.) infection was determined in 80 Greek patients with primary hepatocellular carcinoma (P.H.C.), 160 age and sex matched controls and 40 patients with metastatic liver cancer (M.L.C.). The relative risk of the various patterns of H.B.V. serological markers for P.H.C. was calculated. Active H.B.V. infection, as indicated by positive tests for hepatitis-B surface antigen (HBsAg), or antibody to hepatitis-B core antigen (anti-HBc) without antibody to HBsAg) (anti-HBs), was associated with P.H.C. (relative risk 10.4) but not with M.L.C. (relative risk 1.2). Patients without markers and those who had recovered from hepatitis B (anti-HBs-positive) had approximately the same low risk for P.H.C. (relative risk 0.8). Active infection was more common in P.H.C. patients with co-existing cirrhosis than in those without cirrhosis (67% versus 26%). Thus the relationship between active hepatitis B and P.H.C. seen in African and Asian populations is now seen in a European Caucasian population with different racial, environmental, and dietary circumstances.