Period, age, and cohort effects on substance use among young Americans: a decade of change, 1976-86

In an earlier article in this Journal, we reported analyses that differentiated among period, age, and cohort effects on substance use among American youth 18 to 24 years old, from the high school classes of 1976 to 1982 during the period of 1976 to 1982. The present analyses extend the classes and years to 1986, and the age range to 18-28. A cohort-sequential design is employed, based on annual surveys of nationally representative samples of high school seniors, plus annual follow-up surveys of each senior class. Twelve different classes of drugs, both licit and illicit, are examined. Several different types of period, age, and cohort effects over the last decade are identified. Alcohol use (monthly and occasions of heavy use), and the use of marijuana, cocaine, amphetamines, methaqualone, barbiturates, LSD, psychedelics other than LSD, and tranquilizers all showed period effects. Occasions of heavy drinking, cigarette smoking, monthly and daily use of alcohol, and annual prevalence of cocaine, amphetamines, barbiturates, LSD, and narcotics other than heroin showed age effects. Class effects were seen for cigarette smoking and daily marijuana use.     

HTN-APT: computer aid in hypertension management

Hypertension-aid in physician treatment (HTN-APT) is an expert computer system that assists the physician in determining the best form of treatment for the individual hypertensive patient. The HTN-APT system aids the physician in managing the hypertensive patient by keeping a record of the patient's progress, allowing easy access to drug information, and generating recommendations and critiques about treatment options. The treatment recommendations are ranked by an analogue indication-contraindication scheme whereby each drug both singly and in combination is evaluated for patient suitability on the basis of more than 30 possible patient factors. When the computer-generated recommendations were evaluated by a group of family physicians, the HTN-APT system was found to make beneficial treatment recommendations without major judgmental error.     

Relationship between circulating thyroid hormones and humoral immunity in immature male chickens

The objective of this experiment was to examine the relationship between levels of circulating T3, T4, and humoral immunity in immature male chickens. Three week old Single Comb White Leghorn male chicks were used as the experimental animals. In order to produce a wide range of circulating thyroid hormone concentrations, birds were divided into groups and received one of nine treatments including surgical thyroidectomy; 0.1% propylthiouracil (PTU) in the feed; 1 ppm T3 and 10 ppm T4 in the feed. Antibody production against sheep red blood cells (SRBC) (thymus-dependent antigen) and Brucella abortus (BA) (thymus-independent antigen) was tested at 6 weeks of age. Concentrations of T3 and T4 were measured in birds from each treatment group at 7 and 11 weeks of age. At 11 weeks of age, birds were weighed, sacrificed and lymphoid organs removed and weighed. There were positive correlations between circulating thyroid hormones and weights of bursa of Fabricius and spleens. There were no significant correlations between circulating thyroid hormones and antibody production. It was concluded that physiological levels of thyroid hormones are needed to maintain normal weights of bursa and spleen. Furthermore, we conclude that lower than physiological levels might be sufficient for normal antibody production. Finally, stimulation of antibody production using thyroid hormones may require different doses than what were utilized in this study.     

Diagnostic challenges of using CSF assay of tau and beta-amyloid42 in atypical degenerative dementias of the Alzheimer type

This report presents three cases of atypical degenerative dementias in order to illustrate challenges associated with the use of biologic markers of Alzheimer's disease (AD) for diagnosis and management. Clinical diagnostic methods followed the NINCDS-ADRDA criteria for AD. Additional diagnostic studies included serial neurocognitive testing, MRI, neuroSPECT, ApoE genotyping, and a CSF assay of tau and beta-amyloid(42). For patient 1, both the clinical and biologic markers were consistent with AD. The patient was diagnosed with AD with a high degree of confidence, even though the base rate of nonfamilial AD at this age group (<55 years) is exceedingly rare. This case argues favorably for the use of biologic markers to aid in confirming a diagnosis in an atypical dementia. Patient 2 met the NINCDS-ADRDA criteria for AD, although with less confidence. Neurocognitive data indicated a progressive right hemispheric syndrome, insight was preserved, and ApoE was 3/3, but tau concentrations and beta-amyloid(42) were highly consistent with cut-offs for AD; the differential fell on the Pick's disease/frontotemporal degeneration spectrum. Patient 3 had no clinical evidence of the disease, even when evaluated via extensive neurocognitive testing over a 2-year interval. However, ApoE was 4/4, and CSF assay of tau and beta-amyloid(42) were within the AD range. Therefore, while the CSF assay of tau and beta-amyloid(42) markers was confirmatory of AD, each case was highly atypical. Results illustrate the lack of normative data available when using biologic markers for highly atypical cases, calling into question their usefulness for such patients. These cases illustrate the interplay between neuropsychological and biological markers in establishing neurodegenerative diagnoses.     

Carbohydrate intake improves cognitive performance of stress-prone individuals under controllable laboratory stress

Cognitive performance has been found to decline after exposure to stress, particularly in stress-prone subjects. The present study investigated whether a carbohydrate-rich, protein-poor (CR/PP) diet, which may enhance cerebral serotonin function in stress-prone subjects due to increases in the available tryptophan, improves the performance of stress-prone subjects after exposure to acute laboratory stress. Twenty-two high-stress-prone (HS) subjects and twenty-one low-stress-prone (LS) subjects aged between 19 and 26 years performed a memory scanning task after controllable and uncontrollable stress, following either a CR/PP diet or a protein-rich, carbohydrate-poor (PR/CP) isoenergetic diet. Uncontrollable stress reduced feelings of control (F(1,38) 9.30; P = 0.004), whereas pulse rate and skin conductance increased after both stress tasks (F(1,38) 78.34; P = 0.0005 and F(1,37) 83.16; P = 0.0004). Diet, stress-proneness and stress-controllability interacted (F(1,36) 9.46; P = 0.004) in such a way that performance in HS subjects was better with the CR/PP diet than with the PR/CP diet, but only after controllable stress. As the CR/PP diet has been found to increase the plasma tryptophan:large neutral amino acids ratio, indicating an increased availability of cerebral tryptophan and, thus, higher serotonin levels, it appears that there may be an increased availability of brain serotonin in HS subjects after controllable laboratory stress.     

HMO physicians' use of referrals

Clinical uncertainty is a source of variation in medical decision-making as well as a source of work-related stress. Increasing enrollment in organized health care systems has intensified interest in understanding referral utilization as well as issues such as physician dissatisfaction and burnout. We examined whether primary care physicians' affective reactions to uncertainty and their job characteristics were associated with use of referrals and burnout. Data came from mail surveys of primary care physicians practicing in two large group model health maintenance organizations (HMOs) in the USA. Consistent with past research, we found that younger physicians had higher referral rates than older physicians, and that general internists had higher rates than either family practitioners or pediatricians. Greater stress from uncertainty increased referrals and referrals were negatively correlated with heavier work demands (patient visits per hour). Greater stress from uncertainty, perceived workload (too high) and a sense of loss of control over the practice environment were associated with higher levels of burnout.     

Joint task force "forward care" multicomponent health service support for an Army Reserve separate infantry brigade (mechanized)--Part III.

At the conclusion of 4 years' careful study of the health services support of a separate infantry brigade (mechanized) during the unit's annual training periods, the authors report on the effectiveness of a support team consisting of Army Reserve medical elements, an Active Army field unit, and a Public Health Service Clearing/Staging unit joining forces in a field environment to provide real world medical care to the same unit in a follow-on annual training period. The emphasis of the team created was on validating the forward care concept of field medical support. The result of this effort was "state of the art" medical service to the troops in the most forward areas, and a savings of 0.66 training days per soldier out of 10 days possible field training time. The cross-training of joint elements was enhanced by providing hands-on treatment of soldiers in a tactical environment, training that cannot be adequately replaced by simulated training.     

Dissociation of autonomic and cognitive effects of THC in man

Intravenous THC, 30–44.8 g/kg, was administered to four subjects. Each received THC on four occasions preceded by either i.v. saline, 0.04 mg/kg atropine sulfate, 0.2 mg/kg propranolol, or both drugs together. Heart rates, subjective intoxication and symptom ratings, time productions, and EEG activity were measured. In the absence of autonomic blocking drugs, THC produced characteristic tachycardia, subjective intoxication, and EEG effects. After combined autonomic blockade, THC had no effect on heart rate, while subjective and EEG changes remained as intense. These findings argue against the hypothesis that the subjective and EEG effects of THC are mediated by autonomic receptors or by interoception of peripheral autonomic actions of THC.To whom offprint requests should be sent     

Pulmonary metastases from benign-appearing smooth muscle tumors of the uterus.

A 42-year-old woman was found to have multiple pulmonary nodules 7 years after hysterectomy for leiomyoma. Thoracotomy revealed multiple well differentiated smooth muscle masses containing epithelial inclusions. This patient is similar to others previously reported as examples of "multiple pulmonary fibroleiomyomatous hamartoma" on the basis of slow-growth, benign-appearing histology, and the presence of epithelial elements. Evidence is presented which suggests that these cases represent metastasis from well differentiated leiomyosarcomas. There is a frequent association with uterine smooth-muscle tumor, cases with equally benign-appearing histology have shown lymph node metastasis, the nonmesenchymal elements have been shown to represent engulphed bits of adjacent pulmonary tissue, and the histologic di-ferentiation of benign from malignant mesenchymal tumors is known to be unreliable in some cases. Unlike more anaplastic leiomyosarcomas, this condition may be associated with few symptoms and prolonged survival despite widespread disease.     

Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth

One of the hallmarks of cancer is metabolic deregulation. Many tumors display increased glucose uptake and breakdown through the process of aerobic glycolysis, also known as the Warburg effect. Less studied in cancer development and progression is the importance of the glutamine (Gln) pathway, which provides cells with a variety of essential products to sustain cell proliferation, such as ATP and macromolecules for biosynthesis. To this end Gln dependency was assessed in a panel of non-small cell lung cancer lines (NSCLC). Gln was found to be essential for the growth of cells with high rates of glutaminolysis, and after exploring multiple genes in the Gln pathway, GLS1 was found to be the key enzyme associated with this dependence. This dependence was confirmed by observing the rescue of decreased growth by exogenous addition of downstream metabolites of glutaminolysis. Expression of the GLS1 splice variant KGA was found to be decreased in tumors compared with normal lung tissue. Transient knock down of GLS1 splice variants indicated that loss of GAC had the most detrimental effect on cancer cell growth. In conclusion, NSCLC cell lines depend on Gln for glutaminolysis to a varying degree, in which the GLS1 splice variant GAC plays an essential role and is a potential target for cancer metabolism-directed therapy.