'Clock' and 'motor' components in absolute coordination of rhythmic movements

Human subjects swung, through motions at the two wrists, hand-held pendulums of variable mass and length. Within a pair, the two pendulums could be of the same or different magnitude. The subjects were required to produce a coordinated state in which the two rhythmic units oscillated at a single common period. Fifty-four conditions of absolute coordination, that is, 54 different pairs of wrist-pendulum systems, were investigated for each of three subjects in the course of six sessions. Each condition of absolute coordination was conducted in the out of phase mode and at the single most comfortable period. The period variances of the right and left systems in the 162 instances of absolute coordination were analysed according to a method that assumes that a timekeeper function and a motor implementation function contribute independently to the variance in the periodic timing of a rhythmic movement. The major findings were that in absolute coordination: (a) a system's 'motor' variance, but not its 'clock' variance, depended on the deviation of the period of absolute coordination tau from the system's characteristic period; (b) right and left 'clock' variances were related and (c) neither the 'motor' variances nor the 'clock' variances were affected by deviations in the mean phase relation from 180 degrees. The results were discussed in terms of their implications for interpreting von Holst's notions of maintenance tendency and magnetic effect and, more generally, the neural and dynamical basis of absolute coordination.     

Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer

Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t_1/2 of 11.1±4 min and a t_1/2 of 246±78 min at the dose of 1 g/m², while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m² dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (V_d) was 14.5±1. at the 1 g/m² dose and increased to 73 1. at the 33 g/m² dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m² dose and decreased to 1% at the 33 g/m² dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m². However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity.     

Infratemporal fossa and lateral skull base dissection: long-term results

In 1981, we described a new surgical technique featuring en bloc removal of infratemporal fossa malignancies. This approach offered a systematic resection of cancers in this region and was designated "stylohamular dissection" because the medial boundary of the bloc is surgical plane between the styloid process and the hamulus of the pterygoid. All structures lateral to this plane are removed, sparing the internal carotid artery. Since 1977, twenty infratemporal fossa and lateral skull base dissections have been performed for palliation of metastatic or recurrent disease in the infratemporal fossa. Most patients obtained palliation of trismus, facial pain, or relief from an unmanageable ulcerating lesion. This technique offers improved average disease-free intervals, as well as enhanced survival rates compared to non-en bloc resections. A summary of the case presentations, survival statistics, and surgical technique with detailed cadaver dissections are presented.     

Plant sterols in vegetables and fruits commonly consumed in Sweden

Summary Plant sterols are known to have serum cholesterol lowering effects. A high dietary intake might therefore have a positive impact on health. All food items of vegetable origin contain some amount of plant sterols. The aim of this study was to analyse the plant sterol content of vegetables and fruits commonly consumed in Sweden, and to compare fresh and cooked samples of the same items. Altogether 20 different vegetables and 14 fruits were analysed. All vegetables and fruits were purchased in two shops in the city of Gothenburg, Sweden. Lyophilization was performed within one month of the items being purchased. The samples were frozen at −20 (C and analysed within six months, with a GLC method after acid hydrolysis, alkaline hydrolysis and silylation with tri-methylsilylether. The acid hydrolysis was done in order to detect the fraction of glycosylated plant sterols, which are split during boiling with HCl. The median plant sterol content of vegetables was 14 (3.8–50) mg/100 g edible portion. The highest concentrations were found in broccoli, Brussels sprouts, cauliflower and olives. The median plant sterol content of fruits was 16 (3–44) mg/100 g edible portion. The highest concentrations were found in oranges and passion fruits. The plant sterol concentrations were thus low in vegetables and fruits commonly consumed in Sweden. A serum cholesterol lowering effect attributed to the plant sterols in vegetables and fruits would therefore be of limited significance. Received: 25 September 1998, Accepted: 10 February 1999     

Paroxysmal tremor and orofacial dyskinesia secondary to a biopterin synthesis defect

We report a child with a systemic biopterin synthesis defect due to an absence of 6-pyruvoyl-tetrahydropterin synthase who had an unusual presentation, with three episodes of coarse "rubral-like" tremor in arms and legs orofacial dyskinesia between the ages of 3 and 6 months. Response to levodopa therapy and CSF neurotransmitter metabolite concentrations before and after therapy suggests that his clinical syndrome resulted from a secondary dopamine deficiency.     

Pharmacokinetics and metabolism of β-2′-deoxythioguanosine and 6-thioguanine in man

Summary Resistance to the antileukemic agent 6-thioguanine (TG) inevitably develops in animal tumors. However, a new agent, -2-deoxythioguanosine (-TGdR) can overcome TG resistance in animal tumor models and is therefore of potential clinical use. The pharmacokinetics of radiolabeled TG were compared with those of -TGdR in patients with cancer after intravenous administration. [³⁵S]--TGdR (5.4 mg/kg, 200 mg/m², 200 Ci total) was administered to five patients; the radiolabel in the plasma declined with an initial half-life (t_1/2) of 14 min and a terminal t_1/2 of 19.3 h. Within 24 h, 65% of the radiolabel was excreted in the urine. In contrast, after administration of [³⁵S]-6-TG (3.4 mg/kg, 125 mg/m², 200 Ci total) the average initial t_1/2 was 40 min while the terminal phase t_1/2 was 28.9 h. Urinary excretion of the radiolabel was 75% of the dose 24 h after administration. Both thiopurines were rapidly and extensively degraded and excreted as 6-thioxanthine, inorganic sulfate, S-methyl-6 thioxanthine, and 6-thiouric acid in addition to other products. Small amounts of unchanged drug were also excreted. These studies suggest that -TGdR is merely a latent form of TG.Deceased, to whose memory this paper is dedicated     

Lewy bodies in the presence of Alzheimer's disease.

Large numbers of Lewy bodies in the substantia nigra were found in a case of Alzheimer's disease. Parkinsonian symptoms were not recognized. The patient appears to be an example of an association recognized by Woodard but not yet understood. The case is discussed in the context of reported relationships between Parkinson's disease or "Lewy body disease" and dementia, on the one hand, and reports linking various forms of psychoses with an unusually high incidence of Lewy bodies, on the other.     

The Effect of 12-Step-Based Fellowship Participation on Abstinence Among Dually Diagnosed Persons: A Two-Year Longitudinal Study

Abstract

A large percentage of individuals are dually-diagnosed with a psychiatric disorder and a substance use disorder. Such persons typically face more difficulties and have poorer outcomes than do single disorder substance users. Among noncomorbid substance users, treatment and participation in 12-Step groups have been shown to enhance the likelihood of abstinence from substance misuse. Specialized 12-Step based fellowships have recently emerged to address the recovery needs of dually-diagnosed persons. The present study is a longitudinal investigation of the effect of such 12-Step based groups on abstinence among dually-diagnosed persons. Participants were members of Double Trouble in Recovery (DTR) who were recruited at community-based meetings in New York City and reinterviewed twice at yearly intervals. Generalized estimating equation analysis indicated that, over the two-year study period, ongoing DTR attendance was significantly associated with a greater likelihood of abstinence after controlling for other pertinent variables, such as mental health symptoms. For clinicians, these findings underline the importance of fostering stable affiliation with specialized 12-Step based groups among their clients.