Effect of opioid antagonists on sex hormone secretion.

BACKGROUND: Endogenous opioids have roles in various functions in different parts of the body, including intestinal motility, suppression of pain, reinforcement of behavior, and regulation of the hypothalamic-pituitary-gonadal axis. The endogenous opioid system is also recognized to be involved in the negative-feedback regulation of the release of LH and testosterone. AIM: The reviewed articles herein show the development of the current model of this regulation, the evidence supporting it, and also the observed effects of opioid antagonist (naloxone, naltrexone, and nalmefene) on the system. MATERIALS AND METHODS: Review of the studies published during the years 1979-1996 (no significant studies made after that). Search from databases Pubmed, SciFinder, and Medline with search words opioid antagonists, hormones, LH, testosterone, and GnRH, in different combinations. RESULTS/CONCLUSIONS: Opioid antagonists seem to increase the secretion of GnRH in the hypothalamus which then causes a pulsatile release of LH in the pituitary and secretion of testosterone. According to the experiments, the frequency of pulses and concentration of LH and testosterone in plasma seem to increase. These effects are seen in both men and women (at early follicular phase). More research is needed to investigate the consequences of these effects in general.

Work-related accidents and daylight saving time in Finland.

BACKGROUND: Recent research has indicated that transitions into and out of daylight saving time (DST) unbalance the physiological circadian rhythm and may lead to sleep disturbance. Sleep deprivation may have negative effects on motivation, attention and alertness and thus it is possible that transitions into and out of DST may increase accident rates. AIMS: To explore the impact of DST transitions on the number of occupational accidents in Finland. METHODS: For the study, we analysed all occupational accidents that happened in Finland 1 week before and 1 week after DST transitions during the years 2002-06. RESULTS: Transitions into and out of DST did not significantly increase the number of occupational accidents. CONCLUSIONS: It seems that sleep deprivation after DST transition is not harmful enough to impact on occupational accident rates.

Functional, global and cognitive decline correlates to accumulation of Alzheimer's pathology in MCI and AD.

BACKGROUND: Cognitive, global and functional instruments have been extensively investigated for correlations with neuropathological changes such as neurofibrillary tangles (NFTs), plaques, and synapse loss in the brain. OBJECTIVE: Our objective is to correlate the functional, global and cognitive decline assessed clinically with the neuropathological changes observed in a large prospectively characterized cohort of mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: We examined 150 subjects (16 MCI and 134 AD) that were prospectively assessed and longitudinally followed to autopsy. MCI subjects clinically met Petersen criteria for single or multi-domain amnestic MCI. AD subjects clinically met NINCDS-ADRDA criteria for probable or possible AD. All subjects received the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and the Mini Mental State Examination (MMSE) ante-mortem. Plaque and tangle counts were gathered for hippocampus, entorhinal cortex, frontal, temporal and parietal cortices. Braak staging was performed as well. RESULTS: The GDS, FAST and MMSE correlated with plaque counts in all regions. The GDS, FAST and MMSE correlated with tangle counts in in all regions. The three instruments also correlated with the Braak score. The MMSE and GDS correlate better than the FAST in most regions. CONCLUSIONS: Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress from MCI through AD.

Functional ability correlates with cognitive impairment in Parkinson's disease and Alzheimer's disease.

BACKGROUND/AIMS: Previously we have shown that functional declines in Parkinson's disease (PD) and Alzheimer's disease (AD) correlate to global measures of cognitive decline. We now determine if the correlation between cognitive impairment and functional ability in PD is similar to that in AD using individual cognitive measures. METHODS: 93 PD subjects and 124 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and a neuropsychological battery. RESULTS: In PD subjects, the FAST and GDS correlated significantly with Rey Auditory Verbal Learning Test (AVLT), Controlled Oral Word Association (COWA), Animal Fluency, and Stroop but not with Clock Draw or Judgment Line Orientation (JLO). In AD/MCI subjects, FAST and GDS correlated with all neuropsychological components except Stroop. In the AD/MCI group, the UPDRS significantly correlated with the FAST, GDS, MMSE, and all neuropsychological parameters except the Stroop. In the PD group, the motor UPDRS significantly correlated significantly with FAST, GDS, MMSE and all neuropsychological parameters except Digit Span, Stroop, Clock Draw and JLO. CONCLUSIONS: Similar to AD, functional decline in PD correlates with multiple measures of cognitive impairment. Some differences between PD and AD may be explained by the influence of motor disability and declines in visuospatial function in PD.

Soy in hypercholesterolaemia: a double-blind, placebo-controlled trial.

OBJECTIVE: To study whether Abacor, a product based on isolated soy protein with high and standardised levels of isoflavones and cotyledon soy fibres, was more effective in lowering total and LDL cholesterol than placebo. DESIGN: Randomised, placebo-controlled, double-blind, parallel group, single centre study. SETTING: Primary care in Joensuu, North Karelia, Finland. SUBJECTS: Subjects were screened from the patient database of the health centre; 30 were randomised to the Abacor group and 30 subjects to placebo. Eight subjects were withdrawn, six from the active group, two from the placebo group. INTERVENTION: The preparations were given as two daily liquid supplements in addition to the subjects' regular diets for 6 weeks. RESULTS: Abacor showed a statistically significant lipid-lowering effect as compared to placebo, although an unexpected reduction was seen in the placebo group. The estimated difference between active treatment and placebo was 0.25 mmol/l (95% CI 0.01, 0.50; P=0.049) for total cholesterol, corresponding to reductions of 8.3 and 5.1%, respectively. The difference in reduction of LDL-cholesterol was 0.27 mmol/l (95% CI 0.06, 0.49; P=0.014) and corresponded to a reduction of 13.2% in the active treatment group, and 8.0% in the placebo group. Abacor showed a rapid onset of effect, as compared with placebo. During a wash-out period of 4 weeks after treatment, the subjects returned to pre-treatment cholesterol levels. CONCLUSION: Added to a regular diet, Abacor significantly reduced LDL-cholesterol and total cholesterol. These beneficial effects occurred within 6 weeks of treatment.

Uterine findings by transvaginal sonography during percutaneous estrogen treatment in postmenopausal women.

OBJECTIVES: To evaluate the effect of hormone replacement treatment (HRT) with percutaneous estradiol and cyclical peroral medroxyprogesterone acetate (MPA) every month or every third month on the uterus and endometrium of postmenopausal women. METHODS: Uterine size and endometrial thickness were measured by transvaginal sonography in 159 postmenopausal women before HRT, and after 6 and 12 months on HRT during 9-12 days of the MPA administration periods. RESULTS: During HRT, uterine size and endometrial thickness increased. The percentage increase in uterine diameter varied between 3.8% and 19.6%, and endometrial thickness varied between 28.7% and 76.4%, being greater in the group receiving MPA every third month than in the groups receiving MPA every month. Myomas grew during the first 6 months on HRT but increased no further during the next 6 months on HRT. CONCLUSIONS: The increases in uterine size, myomas and endometrial thickness during HRT were moderate and not problematic and occurred mainly during the first 6 months on HRT.

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline.

A new doxycycline formulation consisting of enteric-coated doxycycline hyclate pellets in capsules is aimed at reducing gastrointestinal adverse reactions related to doxycycline therapy. In this randomised, double-blind, 3-way crossover study, adverse reactions caused by short term treatment with enteric-coated doxycycline hyclate pellets in capsules were compared with placebo and doxycycline monohydrate tablets. The latter are generally considered to be better tolerated than older formulations of doxycycline hyclate. 111 healthy volunteers completed the study. They were given 150mg of doxycycline once daily over 3 consecutive days with a washout of 4 to 10 days between the study periods. The medication was administered after an overnight fast (10 hours) with 200ml of tap water. An upright position was maintained for 1 hour and no food was allowed for 2 hours after drug administration. Participants recorded adverse reactions daily. Adverse reactions were reported by 66% of the subjects during treatment with doxycycline monohydrate, while 43% reported adverse reactions during treatment with enteric-coated doxycycline hyclate and 30% during placebo. Compared with the 2 other groups, doxycycline monohydrate caused significantly more adverse reactions in general, and abdominal pain, nausea and vomiting in particular. It is concluded that enteric-coated doxycycline hyclate pellets in capsules have significantly better gastrointestinal tolerability compared with doxycycline monohydrate.

Effect of intravenous diclofenac or indomethacin on the emergence from anaesthesia for tonsillectomy.

We evaluated the effects of a single dose of diclofenac (75 mg) or indomethacin (50 mg) on intraoperative events and on the early recovery phase. The study was performed in a randomised, double-blind, placebo-controlled fashion in 63 adult patients scheduled for elective tonsillectomy. Study infusions started intravenously immediately after the induction of general anaesthesia with thiopentone; maintenance was with N2O/O2 and halothane. After intubation with the aid of suxamethonium, the patients breathed spontaneously via a Bain coaxial system. Perioperative events (bleeding tendency, bleeding, need for pain medication, physical recovery) were recorded with the aid of a questionnaire applied to the anaesthesia nurses and estimation of vigilance, attention, concentration, short-term memory, and simple motor speed during recovery was with the aid of three neuropsychological tests (thumb tapping test, digit span test and homogenic interference test). No significant differences between the three groups were found in systolic and diastolic arterial pressures, the results of the questionnaire, and those of the neuropsychological tests. The ability to keep the head elevated for at least 5 s recovered significantly later (P < 0.05) and heart rate levels in the indomethacin group were significantly lower (P < 0.001) than in the other two groups. No enhanced bleeding during the perioperative period was observed. Diclofenac and indomethacin in the doses used in our study have only a marginal effect on the patient's emergence from anaesthesia.

Photosynthesis of a Scots pine shoot: a comparison of two models of shoot photosynthesis in direct and diffuse radiation fields.

Two models of shoot photosynthesis, the needle surface element model (SEM) and needle volume element model (VEM), were tested against empirical data obtained from measurements of the photosynthetic response of twelve Scots pine (Pinus sylvestris L.) shoots in direct and diffuse radiation. The models assume that shoot photosynthesis is obtained as the integrated response of either all needle surface area elements (SEM) or all needle volume elements (VEM) of the shoot. The models differ in that needles are treated as optically black in SEM, whereas in VEM radiation penetrates into the needle. The photosynthetic response of a surface/volume element was described as a Blackman-type curve and the distributions of irradiance on the elements were derived by computer simulation, based on a model of shoot geometry. The parameters (initial slope and maximum rate) of the Blackman-curve of an element were estimated iteratively by the method of least squares, i.e., by minimizing the residual sum of squares of simulated and measured rates of shoot photosynthesis. The parameter estimation was done separately for direct and diffuse radiation, and the models were evaluated based on the notion that, for the "ideal" model, the estimated parameter values should be the same in direct and diffuse radiation. Both models produced shoot photosynthesis curves that agreed well with measurements, but there was a discrepancy in the estimated parameter values, indicating that differences in the photosynthetic response of shoots in direct and diffuse radiation could not be explained solely on the basis of the simulated irradiance distributions. The agreement was, however, much better for the volume element model, which accounts for penetration of radiation into the needles.

A summary index for the assessment of quality of life in angina pectoris.

When exploring the effects of anti-anginal therapy on quality of life (QL), it is essential to use concise, reliable, outcome measures which focus on those aspects of the disease which are affected by the anginal pain, and which are expected to be responsive to medical intervention. Analysis based on a single comprehensive index is preferable to the use of several indexes as it avoids the potential for conflicting inferences from multiple comparisons. In this paper, we describe the development of a QL index which summarizes the three questionnaires used in the North Karelian Quality of Life (KarQuol) study. The summary index (SI) will be used to compare transdermal and oral nitrate therapy in patients with angina pectoris, and represents the first stage in the construction of a disease-specific evaluative index for future trials.

Anti-anginal therapy and quality of life. A comparison of the effects of transdermal nitroglycerin and long-acting oral nitrates.

A total of 112 male patients with severe effort-induced angina pectoris (New York Heart Association functional classes II and III) participated in a randomized open trial consisting of a 6 month phase with 3 month treatment cross-overs. The aim of the study was to compare the effect of transdermal nitroglycerin (TN) patches and long-acting oral nitrates (LAON) on quality of life (QL). During the cross-over period 30 patients (20 on TN and 10 on LAON) withdrew from the study, over half of them within the first month. Although the results should be interpreted with some caution, they showed that improvement in QL was present for both treatments but greater during the transdermal therapy (unadjusted p = 0.07, adjusted p = 0.03). Anginal attacks were associated with improved QL scores, and fewer attacks occurred on TN (p = 0.06). Improvement in QL was most pronounced in patients whose recorded duration of angina was less than 8 years.

Fatal poisonings with antidepressants in Finland 1985-1987.

In Finland the majority of the users of antidepressants are women and old age people. In the 80's the number of fatal poisonings has increased. During the years 1985-1987 58% of these poisonings were women who belonged to the younger age group of the users. The older tricyclic drugs are known to be more toxic, at least in overdose, than the newer antidepressants especially when they are compared to mianserin. Of the latter, however, lately more serious side effects have been reported. For this reason the use of the different kinds of antidepressants in Finland had changed: the sales of doxepin and amitriptyline have increased and those of maprotiline and mianserin have decreased. To study the role of antidepressants in sudden and unexpected deaths the fatality ratio (defined as fatalities divided by defined daily doses per 1000 inhabitants/day) was calculated for four most prescribed antidepressants. As to the sales, amitriptyline has to be considered to be the leading antidepressant followed by doxepin, mianserin and maprotiline. As a detection in the forensic toxicological screening the sales related ratios showed that maprotiline was most commonly found followed by doxepin, amitriptyline and mianserin. When an antidepressant was the cause of death the fatality ratio was highest for doxepin (6.4) followed by maprotiline (4.3), amitriptyline (4.0) and mianserin (1). In cases of established suicides the order was the same again.(ABSTRACT TRUNCATED AT 250 WORDS)

Leisure-time physical activity is inversely related to risk factors for coronary heart disease in middle-aged Finnish men.

Coronary risk factors and levels of physical activity at leisure were measured in a random sample of 3975 men 25-64 years of age residing in four areas of Finland. An index of leisure-time physical activity (LTPA) as the product of weekly exercise sessions times their usual intensity (expressed as metabolic equivalents) was computed. It showed a graded, inverse association with mean arterial blood pressure, smoking and serum thiocyanate, coronary heart disease risk estimate (combining blood pressure, total cholesterol and smoking), and a nonlinear favorable association with serum lipoproteins. In multiple regression analysis, LTPA contributed significantly and independently to the variation in mean arterial pressure; the standardized regression coefficients were -0.06 for LTPA, 0.09 for weekly alcohol consumption, 0.25 for body mass index, 0.25 for age. In the regression of coronary risk estimate, the standardized regression coefficients were -0.19 for LTPA, 0.22 for weekly alcohol consumption, 0.09 for body mass index, 0.15 for age. There was no evidence that LTPA above 2000 kcal of weekly energy expenditure was associated with further reduced coronary risk factor levels. These findings thus support the inverse direction of the association between exercise and coronary risk factors but they also point towards an independent, but modest, role of leisure-time physical activity as a determinant of coronary risk estimate and blood pressure.