Environmental radon daughters reveal pathognomonic changes in the brain proteins and lipids in patients with Alzheimer's disease and Parkinson's disease, and cigarette smokers.

This paper presents an investigation of the retention of environmental radon daughters, 210Po (alpha particle emitting radio-nuclide) and 210Bi (beta particle emitting radio-nuclide), in lipid and protein fractions of the cortical grey and subcortical white matter from the frontal and temporal brain lobes of patients who had suffered from Alzheimer's disease or Parkinson's disease, of cigarette smokers, and of control subjects. 210Po and 210Bi radioactivity increased tenfold in the cortical grey and subcortical white protein fraction in patients with Alzheimer's disease and smokers, and tenfold in the cortical grey and subcortical white lipid fraction in patients with Parkinson's disease. Free radicals generated by radon daughters may add to the severity of the radio-chemical injury to the brain astrocytes. The pathognomonic distribution of radon daughters to lipids in patients with Parkinson's disease and to proteins in patients with Alzheimer's disease was attributed to high chlorine affinity of radon daughters. The changes in the membrane protein pores, channels, and gates in patients with Alzheimer's disease and in the lipid bilayer in patients with Parkinson's disease are at the core of what the authors think are two systemic brain diseases.

Factors limiting force during slow, shortening actions of the quadriceps femoris muscle group in vivo.

Speed-torque relations of the quadriceps femors muscle group were determined using eight healthy subjects. Isometric or isovelocity, shortening muscle actions were performed at 15 speeds (0-6.28 rad s-1) and torque was measured 0.78 and 0.52 rad below horizontal. Unilateral actions were evoked by surface electrical stimulation or by maximal voluntary effort. Stimulation current evoked a torque equal to approx. 70% of maximal voluntary isometric and was held constant across speeds. For the voluntary or stimulation tests, torque decreased (P < 0.05) with increasing speed. This response in relative terms was greater (P < 0.05) for the stimulation than for the voluntary tests. The difference in the decline in relative torque for the simulation vs. voluntary tests was not influenced by the angle at which torque was measured, and thereby muscle length. Speed-torque data for the two stimulation tests fit a linearized plot of a hyperbolic relation for the higher tests speeds. When torque was measured at the greater joint angle (0.78 rad), and thereby longer muscle length, the equation was Po-P/V = Po 0.724-1.078 (P < 0.05, r2 = 0.95) for speeds greater than 0.70 rad s-1. For the shorter muscle length, the equation for data collected at speeds greater than 1.13 rad s-1 was Po-P/V = Po 0.467 + 4.61 (P < 0.05, r2 = 0.91). Inclusion of data for the next slower speed markedly compromised the 'fit' for either linear relation.(ABSTRACT TRUNCATED AT 250 WORDS)

Mapping of electrical muscle stimulation using MRI.

The purpose of this study was to map the pattern of muscle contractile activity elicited by electromyostimulation (EMS). A secondary interest was to determine whether EMS evoked a different pattern of contractile activity than voluntary (VOL) efforts. These objectives were addressed by examining the pattern and extent of contrast shift in magnetic resonance (MR) images after isometric actions of the left m. quadriceps of seven subjects had been elicited by EMS (1-s train of 500-microseconds sine wave pulses at 50 Hz) or by VOL means. For both conditions, five sets of 10 muscle actions were executed at each of the three force levels equal to 25, 50, and 75% of maximal VOL isometric torque. There were 1-s, 1.5-min, and 30-min rests between muscle actions, sets, and torque levels, respectively. Transaxial proton MR images (TR/TE = 2,000/30, 60) of m. quadriceps femoris were obtained with a 1.5-T imager at rest and after completion of the five sets of isometric actions at each force level. MR image contrast shift, as indicated by T2 values > 1 SD above the mean resting muscle T2, was calculated per pixel. Torque declined approximately 18% (P < 0.05) during each EMS set independent of the preset relative force level but recovered between sets. EMS increased T2 values above rest (29 +/- 0.2 to 36 +/- 0.5, P < 0.05) in regions of muscle dispersed throughout a given cross section. The pattern of muscle stimulation, as reflected by increased T2 values, varied markedly among subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of eccentric actions on the metabolic cost of resistance exercise.

Maintenance of a low energy expenditure during exercise in space is important because of the confined environment of the space craft. Resistance exercise is receiving increased attention as an exercise countermeasure, and we have shown that training with concentric (con) and eccentric (ecc) muscle actions induces greater increases in strength than training with only con actions. This study determined if performance of both actions markedly increased the metabolic cost of resistance exercise. Seventeen middle-age males performed each repetition of a "warm-up" and four sets of the leg press exercise with only con (Group CON, n = 8) or with con and ecc (Group CON/ECC, n = 9) actions. Sets were separated by 3 min of rest and each was performed to failure by selecting a resistance that allowed performance of the prescribed number of repetitions (7 to 10). The net energy cost of exercise was estimated from oxygen consumption data that were obtained at rest before exercise, during exercise, and for 20 min of recovery. The total work performed during the con actions was about 290 J.kg-1 body weight for both groups. The energy cost for this work was about 3 x 10(-3) cal.J-1. The requirement for the CON/ECC group to also lower the load increased (p less than 0.05) the energy cost 14%. These results indicate that con actions are mainly responsible for the metabolic cost of resistance exercise. Because ecc actions enhance the resistance training-induced increases in strength that are evident with only con actions with minimal additional energy cost, we suggest that they be considered in exercise prescriptions for use in space.

Effect of voluntary vs. artificial activation on the relationship of muscle torque to speed.

The speed-torque relationship of the right knee extensor muscle group was investigated in eight untrained subjects (28 +/- 2 yr old). Torque was measured at a specific knee angle during isokinetic concentric or eccentric actions at nine angular velocities (0.17-3.66 rad/s) and during isometric actions. Activation was by "maximal" voluntary effort or by transcutaneous tetanic electrical stimulation that induced an isometric torque equal to 60% (STIM 1) or 45% (STIM 2) of the voluntary isometric value. Torque increased (P less than 0.05) to 1.4 times isometric as the speed of eccentric actions increased to 1.57 rad/s for STIM 1 and STIM 2. Thereafter, increases in eccentric speed did not further increase torque. Torque did not increase (P greater than 0.05) above isometric for voluntary eccentric actions. As the speed of concentric actions increased from 0.00 to 3.66 rad/s, torque decreased (P less than 0.05) more (P less than 0.05) for both STIM 1 and STIM 2 (two-thirds) than for voluntary activation (one-half). As a result of these responses, torque changed three times as much (P less than 0.05) across speeds of concentric and eccentric actions with artificial (3.4-fold) than voluntary (1.1-fold) activation. The results indicate that with artificial activation the normalized speed-torque relationship of the knee extensors in situ is remarkably similar to that of isolated muscle. The relationship for voluntary activation, in contrast, suggests that the ability of the central nervous system to activate the knee extensors during maximal efforts depends on the speed and type of muscle action performed.

Force and EMG signal patterns during repeated bouts of concentric or eccentric muscle actions.

Healthy males (n = 14) performed three bouts of 32 unilateral, maximal voluntary concentric (CON) or eccentric (ECC) quadriceps muscle actions on separate days. Surface electromyography (EMG) of the m. vastus lateralis (VL) and m. rectus femoris (RF) and torque were measured. Integrated EMG (IEMG), mean (MPF) and median power frequencies and torque were averaged for seven separate blocks of four consecutive muscle actions. Torque was greater (P less than 0.05) for ECC than for CON muscle actions at the start of exercise. It did not decline throughout ECC exercise, but decreased (P less than 0.05) markedly for each bout and over bouts of CON exercise. Thus, torque overall was substantially greater (P less than 0.05) for ECC than for CON exercise. At the start of exercise IEMG of VL or RF was greater (P less than 0.05) for CON than for ECC muscle actions. This was also true for overall IEMG activity during exercise. The IEMG increased (P less than 0.05) modestly for both muscles during each bout of CON or ECC muscle actions, but did not change for the VL over bouts. The IEMG of RF decreased (P less than 0.05) modestly over CON but not ECC exercise bouts. At the beginning of the first bout of exercise the IEMG/torque ratio was twofold greater (P less than 0.05) for CON than ECC muscle actions. The ratio of IEMG/torque increased (P less than 0.05) markedly during CON but did not change during ECC exercise. Thus, by the end of the third bout there was a fivefold difference (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The half-life of 218Po.

Direct observation of the 218Po alpha-peak decay with a microcomputer-controlled alpha-spectrometer yielded a mean half-life value of 3.040 +/- 0.008 min, where the error quoted represents twice the standard deviation of the means from 38 separate decay measurements. The 1912 and 1924 218Po half-life measurements, which provided the 3.05-min value listed in nuclear tables for the past 60 y, are critically reviewed. Two more recent experiments, which yielded longer values of 3.11 min (Van Hise et al. 1982) and 3.093 min (Potapov and Soloshenkov 1986), are also discussed.

Exercise alters the distribution of ammonia and lactate in blood.

Six subjects (3 males, 3 females) worked for 4 min on a cycle ergometer at 115% of peak O2 uptake (VO2). Venous samples drawn before, directly after, and 15 min after exercise were analyzed for ammonia (NH3) and lactate concentrations of plasma, whole blood, and erythrocytes (RBCs) to examine the effect of exercise on blood NH3 and lactate distribution. Exercise increased (P less than 0.05) the [NH3] of plasma and RBCs, with the larger (P less than 0.05) change in plasma (1.8- vs. 0.7-fold). This reduced (P less than 0.05) the RBC-to-plasma [NH3] ratio of 2.4 at rest to 1.3. The plasma-to-RBC [lactate] gradient (P less than 0.05) at rest (0.5 mmol/l) increased (P less than 0.05) 16-fold immediately after exercise (8.7 mmol/l), reflecting the greater increase (P less than 0.05) in plasma than RBCs [lactate] (15.5 vs. 7.5 mmol/l). [Lactate] and [NH3] did not decrease (P greater than 0.05) immediately after to 15 min after exercise. Plasma and whole blood [NH3] or [lactate] were correlated (r greater than 0.93, P less than 0.01) at all sample times, but the slopes of the relations for [NH3] (immediately after vs. 15 min after exercise) or for [lactate] (before and immediately after vs. 15 min after exercise) differed (P less than 0.05). The results indicate that supramaximal exercise alters the distribution of NH3 and lactate between plasma and RBC, thus changing the relations between plasma and whole-blood concentrations of these metabolites. The alteration of NH3 distribution may reflect changes in the pH gradient between plasma and RBCs.

Need for insulin therapy in type II diabetes mellitus. A randomized trial.

To identify patients with type II diabetes mellitus for whom insulin therapy is most beneficial, we conducted a randomized controlled trial in the general medicine clinic of a university hospital. Asymptomatic, obese, insulin-treated patients were given diet and diabetes education and, in half of these patients, insulin therapy was withdrawn. Over six months, patients developing hyperglycemic symptoms or acetonemia were counted as study failures. Failure criteria developed in 13 of 25 insulin-withdrawal patients, at a median of four weeks after withdrawal, compared with two of 24 control subjects. Elevated stimulated glucose levels predicted the need for insulin therapy. Hyperglycemia worsened in insulin-withdrawal patients who did not meet study failure criteria, but it improved in control patients. Study patients were insulin deficient as shown by low baseline C peptide values (0.43 +/- 0.05 nmol/L). The prompt metabolic decompensation precipitated by insulin withdrawal suggests that insulin-deficient patients may benefit from insulin therapy and may need it to prevent symptomatic hyperglycemia.

Eating disorders: diagnosis and management by the internist.

Anorexia nervosa and bulimia are two of the four eating disorders that appear to be increasingly prevalent. Each has its own diagnostic criteria and medical hazards, though certain features are shared. It is important for internists to be aware of these disorders, since their management is best accomplished by a team consisting of an internist, a psychotherapist, and a nutritionist. The internist's key role in anorexia nervosa is in encouraging and coordinating treatment; in bulimia it is in making a diagnosis. In both, the internist is called upon to recognize and treat medical complications and to collaborate in the management and follow-up of these patients.

Propranolol and depression: a reevaluation based on a pilot clinical trial.

A wide range of neuropsychiatric side effects are attributed to propranolol including visual hallucinations, somnulence, memory impairment, decrease in response time, dizziness, confusional states, insomnia, nightmares, fatigue, sedation and depression. Benson et al., in a summary review of several clinical studies of 5,846 patients being treated with a variety of beta adrenergic blocking agents, listed depression as a rare side effect of propranolol that was usually reported only after long term treatment at high doses. Despite the widely circulated attribution that depression is a side effect of propranolol, there is a paucity of evidence to directly link this drug with clinically significant mood disturbance. For example, the most widely quoted reference attributing propranolol as a depressogenic agent was a "letter to the editor" which was a retrospective, uncontrolled, unblinded study that did not use a standardized depression rating scale. Most of the evidence linking propranolol to depressive symptoms have derived from scattered case reports in which the onset of depressive symptoms were attributed to this agent. Given the well known cyclic onset and remissions of affective disorders, and the prevalence of depression in the general medical population as a whole, the role of propranolol in these cases is debatable.

Bulimarexia and related serious eating disorders with medical complications.

Bulimarexia, an eating disorder that is characterized by binge eating followed by self-induced vomiting or abuse of cathartic or diuretic drugs, has been defined as both a sequela of anorexia nervosa and a distinct eating disorder. In this review the presentation, prevalence, and complications of the various eating disorders--anorexia nervosa, pica, rumination disorder of infancy, and bulimia/bulimarexia--are discussed. Detailed attention is given to the potential medical hazards of bulimarexia. These hazards may be categorized according to the organ system affected or the individual behavioral components of bulimarexia. Because bulimarexia is commonly practiced in secrecy, its presentation may be in the form of one of its medical complications. Therefore, physicians must know the behavioral components of bulimarexia and its potential medical hazards. Optimal care of these patients requires collaborative efforts from a physician and behavioral therapist.

Suppression of the cardiac conditioned response by delta-9-tetrahydrocannabinol: a comparison with other drugs.

Using classical conditioning procedures, the cardiac conditioned response (CCR) was established by pairing one of two tones with the delivery of a peripheral electric shock in Rhesus monkeys. The other tone had no terminal consequence. Such a procedure results in an anticipatory 'anxiety' or 'fear' response to the impending shock signalled by the reinforced tone. The heart rate before the tone in two of the animals was characterized by tachycardia and by bradycardia in the other animal. The effect of intravenous Delta-9-tetrahydrocannabinol (THC) was compared to various doses of diazepam, chlorpromazine, and morphine. The results indicate that THC blocks the CCR in a does-related manner. The effects of THC were similar to diazepam, an anti-anxiety drug. Chlorpromazine and morphine affected the conditioned response in an unreliable manner, and both drugs would attenuate the response in some cases and potentiate it in other instances.

Isolation of substances from human vaginal secretions previously shown to be sex attractant pheromones in higher primates.

Fractionation of vaginal secretions from sexually human females by partitioning and chromatographic procedures demonstrates the presence of short-chain fatty acids seen as crucial pheromonal components in previous higher primate studies. In addition, the appearance of these short-chain fatty acids suggests a possible correlation of the rise and fall of hormone levels during the female menstrual cycle.

Double-blind placebo-controlled efficacy study of ketazolam (U-28,774).

The safety and efficacy of ketazolam (15 mg capsules) was compared to placebo in seventy-nine out-patients suffering from psychoneurotic anxiety, moderate or worse in severity. A flexible dosage range of 15-75 mg was used in this double-blind study lasting twenty-eight days. The average optimum therapeutic dose of ketazolam was 46-9 mg administered as a once-day dose at bedtime. Ketazolam was found to be significantly better than placebo in alleviating anxiety and its concomitant symptomatology as measured by the Hamilton Anxiety Rating Scale, three Physician's Global Impressions, two Patient's Global Impressions, and three Target Symptoms. Fifteen patients dropped from the placebo group before completion of the study, and two withdrew from the ketazolam group. The patients receiving ketazolam experienced a greater reduction in symptomatology throughout the study when compared to the placebo group. Side-effects experienced by the ketazolam patients were less than, or equal to, the placebo patients. No deleterious side-effects occurred. No differences between the two groups were found for vital signs, EKG's, laboratory tests, or physical examinations.

Preference studies of triazolam with standard hypnotics in out-patients with insomnia.

One hundred and four patients suffering from insomnia took part in four different two-night double-blind crossover trials of triazolam. In three separate studies, triazolam 0-5 mg was compared to placebo, flurazepam 30 mg and chloral hydrate 500 mg. Triazolam 0-5 mg was found to be preferred and to be superior to placebo, flurazepam and chloral hydrate in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to the other treatments on the following: How much did the medication help you sleep, onset of sleep, duration of sleep and number of awakenings. Additionally, triazolam was superior to chloral hydrate on the feeling in the morning parameter. In another comparison of triazolam 0-25 mg to flurazepan 15 mg, triazolam was not significantly better than flurazepam on any of the efficacy parameters except that the patients felt more alert the morning following triazolam that following flurazepam. On all efficacy endpoints, trends for all parameters favoured triazolam 0-25 mg over flurazepam 15 mg. Untoward side-effects in these four studies were minimal.