Effects of L-5HTP with and without carbidopa on plasma ß-endorphin and pain perception

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxy-tryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator for pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) higher than that after L-5HTP alone. Neither subjective pain threshold and tolerance nor RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.     

All cause mortality and its determinants in middle aged men in Finland, The Netherlands, and Italy in a 25 year follow up.

STUDY OBJECTIVE--The aims were (1) to compare all cause mortality in population samples of different cultures; and (2) to cross predict fatal event by risk functions involving risk factors usually measured in cardiovascular epidemiology. DESIGN--The study was a 25 year prospective cohort study. The prediction of all cause mortality was made using the multiple logistic equation as a function of 12 risk factors; the prediction of months lived after entry examination was made by the multiple linear regression using the same factors. POPULATION SAMPLES--There were five cohorts of men aged 40-59 years, from Finland (two cohorts, 1677 men), from The Netherlands (one cohort, 878 men), and from Italy (two cohorts, 1712 men). SETTING--The Finnish cohorts came from geographically defined rural areas, the Dutch cohort from a small town in central Holland, and the Italian cohorts from rural villages in northern and central Italy. MEASUREMENTS AND MAIN RESULTS--All cause mortality was highest in Finland (557 per 1000), and lower in The Netherlands (477) and in Italy (475). The solutions of the multiple logistic function showed the significant and almost universal predictive role of certain factors, with rare exceptions. These were age, blood pressure, cigarette smoking, and arm circumference (the latter with a negative relationship). Similar results were obtained when solving a multiple linear regression equation predicting the number of months lived after entry examination as a function of the same factors. The prediction of fatal events in each country, using the risk functions of the others, produced limited errors, the smallest one being -2% and the largest +11%. When solving the logistic model in the pool of all the cohorts with the addition of dummy variables for the identification of nationality, it also appeared that only a small part of the mortality differences between countries is not explained by 12 available risk factors. CONCLUSIONS--A small set of risk factors seems to explain the intercohort differences of 25 year all cause mortality in population samples of three rather different cultures.     

Functional assessment: a holistic approach to rehabilitation of the geriatric client

Functional assessment of the elderly client provides a structured approach to the complex and multidimensional issues in rehabilitation. Rehabilitation nurses may be familiar with some of the long-standing functional assessment tools, such as Barthel's index. It is important to have a working knowledge of a variety of tools, as well as an ongoing awareness of newer ones as they are developed (e.g., the Functional Independence Measure). Functional assessment is part of comprehensive geriatric evaluation. After initial assessment by rehabilitation team members, the team considers the patient's strengths and supports and develops a problem list (NIH, 1987). The individualized plan of care is developed with the elderly client to achieve maximum rehabilitation potential. Functional assessment tools assist in measuring rehabilitation progress and in clinical decision making. They also can be used in clinical research in geriatric rehabilitation. The number of elderly persons in this country is growing rapidly. Rehabilitation nurses will need to expand their clinical skills to integrate holistic geriatric assessment.     

L-acetylcarnitine in depressed elderly subjects. A cross-over study vs placebo

An open, cross-over study was performed on a population of 24 geriatric patients hospitalized because of depressive syndrome. They were subdivided, according to Hamilton's Scale as modified for the aged, into low- and high-score subgroups. The study period covered 2 months. Half the patients received acetylcarnitine for 1 month and placebo thereafter (Group A); the other half received placebo and acetyl-carnitine thereafter (Group B). Statistical evaluation was twofold: parametrical analysis of variance was carried out on 4 subgroups (A1, A2, B1 and B2) and analysis of the score percentage modifications before and after treatment was performed on Groups A and B. The experimental results showed that acetylcarnitine treatment was highly effective and statistically significant in subgroups A1/B1, A2/B2, A1, B1 and B2. In particular, it should be noted that depressive tendencies were significantly modified in most groups, whereas general somatic symptoms as well as anxiety, asthenia and sleep disturbances proved to be little affected. Clinical evaluation, carried out by calculation of modifications in pre- and post-treatment score percentages, provided clear evidence that acetylcarnitine was particularly effective in patients showing more serious clinical symptoms. The drug caused no side-effects at the doses and regimens used.     

Diet and 20-y mortality in two rural population groups of middle-aged men in Italy

The relationships between individual diet, measured in 1965 on the two Italian rural cohorts of the Seven Countries Study on Cardiovascular Disease, and subsequent mortality from all and specific causes of death in 20 y are studied. The analysis covers 1536 men aged 45-64 y at entry to the study. By using a cluster analysis technique, individuals are aggregated into four groups so that the elements within a group have a higher degree of similarity in dietary nutrients than between groups. Impressive differences in death rates between groups are found especially at the 10- and 15-y anniversaries. The relative risk between the least and the most favored group in 15-y mortality from coronary heart disease is 4.7; in 10 y the relative risk for cancer mortality is 2.9 and for liver cirrhosis approximately 4.     

In vitro susceptibility of various genotypic strains of Toxoplasma gondii to pyrimethamine, sulfadiazine, and atovaquone

Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC50s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth kinetics were determined in THP-1 cell cultures using real-time PCR. IC50s were determined in MRC-5 cell cultures using a T. gondii-specific enzyme-linked immunosorbent assay performed on cultures. Mutations in dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and cytochrome b genes were determined by sequencing. Pyrimethamine IC50s ranged between 0.07 and 0.39 mg/liter, with no correlation with the strain genotype but a significant correlation with growth kinetics. Several mutations found on the DHFR gene were not linked to lower susceptibility. Atovaquone IC50s were in a narrow range of concentrations (mean, 0.06 +/- 0.02 mg/liter); no mutation was found on the cytochrome b gene. IC50s for sulfadiazine ranged between 3 and 18.9 mg/liter for 13 strains and were >50 mg/liter for three strains. High IC50s were not correlated to strain genotypes or growth kinetics. A new mutation of the DHPS gene was demonstrated in one of these strains. In conclusion, we found variability in the susceptibilities of T. gondii strains to pyrimethamine and atovaquone, with no evidence of drug resistance. A higher variability was found for sulfadiazine, with a possible resistance of three strains. No relationship was found between drug susceptibility and strain genotype.     

Artificial neural networks versus proportional hazards Cox models to predict 45-year all-cause mortality in the Italian Rural areas of the Seven Countries Study

ABSTRACT: BACKGROUND: Projection pursuit regression, multilayer feed-forward networks, multivariate adaptive regression splines and trees (including survival trees) have challenged classic multivariable models such as the multiple logistic function, the proportional hazards life table Cox model (Cox), the Poisson's model, and the Weibull's life table model to perform multivariable predictions. However, only artificial neural networks (NN) have become popular in medical applications. RESULTS: We compared several Cox versus NN models in predicting 45-year all-cause mortality (45- ACM) by 18 risk factors selected a priori: age; father life status; mother life status; family history of cardiovascular diseases; job-related physical activity; cigarette smoking; body mass index (linear and quadratic terms); arm circumference; mean blood pressure; heart rate; forced expiratory volume; serum cholesterol; corneal arcus; diagnoses of cardiovascular diseases, cancer and diabetes; minor ECG abnormalities at rest. Two Italian rural cohorts of the Seven Countries Study, made up of men aged 40 to 59 years, enrolled and first examined in 1960 in Italy. Cox models were estimated by: a) forcing all factors; b) a forward-; and c) a backward-stepwise procedure. Observed cases of deaths and of survivors were computed in decile classes of estimated risk. Forced and stepwise NN were run and compared by Cstatistics (ROC analysis) with the Cox models. Out of 1591 men, 1447 died. Model global accuracies were extremely high by all methods (ROCs > 0.810) but there was no clear-cut superiority of any model to predict 45-ACM. The highest ROCs (> 0.838) were observed by NN. There were inter-model variations to select predictive covariates: whereas all models concurred to define the role of 10 covariates (mainly cardiovascular risk factors), family history, heart rate and minor ECG abnormalities were not contributors by Cox models but were so by forced NN. Forced expiratory volume and arm circumference (two protectors), were not selected by stepwise NN but were so by the Cox models. CONCLUSIONS: There were similar global accuracies of NN versus Cox models to predict 45-ACM. NN detected specific predictive covariates having a common thread with physical fitness as related to job physical activity such as arm circumference and forced expiratory volume. Future attention should be concentrated on why NN versus Cox models detect different predictors.     

Determinants of all causes of death in samples of Italian middle-aged men followed up for 25 years.

A total of 1712 men aged 40 to 59 years in two rural cohorts of northern and central Italy have been followed up for 25 years after an entry examination in 1960. Forty one individual characteristics have been considered as possible predictors of death in the next 25 years. After exclusion of 55 men with life threatening diseases (cardiovascular and cancer) and of 161 men because of missing measurements, 1495 men have been analysed for relation between entry factors and subsequent death (n = 670). Twelve factors eventually emerged as powerful predictors of future death: in hierarchical order, age, blood pressure, forced expiratory volume, cigarette smoking, xanthelasma, mother life-status, arm circumference, father life-status, shoulder-pelvis ratio, vital capacity, arcus senilis, and serum cholesterol. Discrimination as provided by logistic modelling placed 19.6% of all cases in the upper decile of the estimated risk, 36.8% in the upper quintile, 2.5% in the lowest decile, and 7.1% in the lowest quintile. Out of those located in the lowest decile of risk, 11.4% died within 25 years while the corresponding percentage in the upper decile was 87.3%. Use of the Cox model yielded slightly better coefficients than logistic function.