THIORIDAZINE (MELLARIL?) IN PSYCHIATRIC PATIENTS

Thioridazine (Mellaril®) was given to 104 psychiatric patients with a variety of illnesses, chiefly schizophrenic reactions. Of 14 patients treated in a double-blind study with successive one-month courses of drug or placebo, nine improved most on the drug and only one on placebo. These results, although limited, confirm a definite therapeutic action for this compound.Nine of 24 patients were significantly improved after treatment with thioridazine for an average of four months following previous treatwith other phenothiazine tranquilizers. Of ten patients treated intensively with thioridazine after they had not responded to other phenothiazine drugs, two were definitely improved and three were slightly improved. Twenty-eight of 56 patients treated from the outset with thioridazine were significantly improved after an average of six months. Most patients received from 100 to 400 mg. daily. These results were comparable to those obtained from other potent phenothiazine tranquilizers. The drug is particularly advantageous for a group of schizophrenic patients who are sometimes made worse by other phenothiazine derivatives or rauwolfia alkaloids. It should also be suitable for treating patients with psychoneuroses and chronic brain syndromes.Only minimal side reactions were observed, chiefly drowsiness, dizziness and nasal stuffiness. Weight gain occurred frequently during treatment.     

Response to a Respiratory Survey

Respondents to a respiratory survey of Berlin, New Hampshire, residents in 1961 have been studied to assess the relationship between co-operation and respiratory disease prevalence. Two hundred and forty-three unco-operative subjects, interviewed at home, had significantly more morning phlegm and a lower vital capacity than carefully matched subjects who attended the central clinic. Fifty-one volunteers had the same prevalence of respiratory disease symptoms and physiological abnormalities as carefully matched subjects drawn from a probability sample of the city.It is concluded that respiratory disease prevalence will be underestimated if calculated from studies of co-operative subjects who attend a clinic. Case-finding by respiratory disease screening clinics will also miss many persons who suffer from chronic bronchitis.     

Purification and Characterization of Cytosolic NADP Specific Isocitrate Dehydrogenase from Pisum sativum

Cytosolic NADP-specific isocitrate dehydrogenase was isolated from leaves of Pisum sativum. The purified enzyme was obtained by ammonium sulfate fractionation, ion exchange, affinity, and gel filtration chromatography. The purification procedure yields greater than 50% of the total enzyme activity originally present in the crude extract. The enzyme has a native molecular weight of 90 kilodaltons and is resolved into two catalytically active bands by isoelectric focusing. Purified NADP-isocitrate dehydrogenase exhibited K_m values of 23 micromolar for dl-isocitrate and 10 micromolar for NADP, and displayed optimum activity at pH 8.5 with both Mg²⁺ and Mn²⁺.     

Use of an ungulate‐specific feed structure as a potential tool for controlling feral goats in Australian forest ecosystems

The feral Goat (Capra hircus) has successfully exploited a range of landscapes around the world with occurrences of overabundance resulting in significant damage to ecological values. In forested ecosystems in Australia, there are currently limited means to control the species when compared to the range of management techniques available for other pest animals. To redress this deficiency, we designed a feed structure combined with commercially available salt blocks to attract goats to set locations in a forested study area. Structures that exploited differences in the pedal morphology (foot size and shape) of native herbivores (kangaroos and wallabies) and ungulates (feral goats and deer) were found to be highly target‐specific, with feral goats freely able to access salt blocks, whilst nontarget native species were effectively excluded. Other introduced ungulate species, Fallow Deer (Dama dama) and Red Deer (Cervus elaphus), successfully accessed salt blocks in feed structures but at a considerably lower rate than feral goats. The capacity to present a range of bait types within a target‐specific feed structure, once matched with a humane toxicant, could provide land managers with an additional cost‐effective lethal control tool for future management of feral ungulates, particularly goats.     

Presynaptic Localization of Smn and hnRNP R in Axon Terminals of Embryonic and Postnatal Mouse Motoneurons

Spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motoneuron (SMN) protein. SMN is crucial component of a complex for the assembly of spliceosomal small nuclear ribonucleoprotein (snRNP) particles. Other cellular functions of SMN are less characterized so far. SMA predominantly affects lower motoneurons, but the cellular basis for this relative specificity is still unknown. In contrast to nonneuronal cells where the protein is mainly localized in perinuclear regions and the nucleus, Smn is also present in dendrites, axons and axonal growth cones of isolated motoneurons in vitro. However, this distribution has not been shown in vivo and it is not clear whether Smn and hnRNP R are also present in presynaptic axon terminals of motoneurons in postnatal mice. Smn also associates with components not included in the classical SMN complex like RNA-binding proteins FUS, TDP43, HuD and hnRNP R which are involved in RNA processing, subcellular localization and translation. We show here that Smn and hnRNP R are present in presynaptic compartments at neuromuscular endplates of embryonic and postnatal mice. Smn and hnRNP R are localized in close proximity to each other in axons and axon terminals both in vitro and in vivo. We also provide new evidence for a direct interaction of Smn and hnRNP R in vitro and in vivo, particularly in the cytosol of motoneurons. These data point to functions of SMN beyond snRNP assembly which could be crucial for recruitment and transport of RNA particles into axons and axon terminals, a mechanism which may contribute to SMA pathogenesis.     

Implications of Using Different Methods to Characterise Anticoagulant Control in Patients with Second Generation Mechanical Heart Valve Prostheses

Objective

Characterisation of anticoagulant control is fundamental to investigations of its association with clinical outcome. Anticoagulant control depends on several factors. This paper aims to illustrate the implications of different methods for measuring and analysing anticoagulant control in patients with second generation mechanical heart valve prostheses.

Methods

International normalised ratio (INR) data collected during the 10-year follow-up of a randomised controlled trial were analysed. We considered the influence of: 3 different target INR ranges; anticoagulant control expressed as the proportion of INR readings (PoR) vs. anticoagulant control follow-up time (PoT); 3 ways of describing the profile of anticoagulant control over time.

Results

Different target INR ranges dramatically influenced derived measures of anticoagulant control; the PoT within the target range varied from 88% for the widest to 28% for narrowest range. Overall distributions of PoR and PoT observations were similar but differed by up to ±20% for individuals; PoT exceeded PoR when control was good but was less than PoR when control was poor. Classifying PoT outside the target range showed that widely varying combinations of PoT too high and too low are possible across individuals.

Conclusions

Researchers'' choices about methods for measuring and quantifying anticoagulant control markedly influence the values derived from INR readings. The use of different methods across studies makes it difficult or impossible to compare findings and to establish an evidence base for clinical practice. Methods for quantifying anticoagulant control should be standardised.     

Estimating Initial Epidemic Growth Rates

The initial exponential growth rate of an epidemic is an important measure of disease spread, and is commonly used to infer the basic reproduction number $\mathcal{R}_{0}$ . While modern techniques (e.g., MCMC and particle filtering) for parameter estimation of mechanistic models have gained popularity, maximum likelihood fitting of phenomenological models remains important due to its simplicity, to the difficulty of using modern methods in the context of limited data, and to the fact that there is not always enough information available to choose an appropriate mechanistic model. However, it is often not clear which phenomenological model is appropriate for a given dataset. We compare the performance of four commonly used phenomenological models (exponential, Richards, logistic, and delayed logistic) in estimating initial epidemic growth rates by maximum likelihood, by fitting them to simulated epidemics with known parameters. For incidence data, both the logistic model and the Richards model yield accurate point estimates for fitting windows up to the epidemic peak. When observation errors are small, the Richards model yields confidence intervals with better coverage. For mortality data, the Richards model and the delayed logistic model yield the best growth rate estimates. We also investigate the width and coverage of the confidence intervals corresponding to these fits.