Long-term retention of implicit learning in Huntington''s disease

Implicit learning was examined in 15 Huntington's disease (HD) patients and 15 control subjects (NC) using a semantic decision-making task. HD patients demonstrated only slightly reduced priming; like NC subjects, their decision times decreased over repeated presentations, though to a somewhat lesser degree. On explicit recognition testing, the HD group made significantly more false positive errors than did the control group, suggesting an impairment of effortful retrieval. The groups displayed equivalent retention of implicitly learned material after 6 months. The striatal neuronal loss of early Huntington's disease does not markedly affect priming or retention of primed stimuli, but may alter explicit memory judgements.     

Phase II trial of Didemnin B in patients with advanced renal cell carcinoma

Summary Twenty-three patients with advanced renal cell cancer were treated with Didemnin B. One partial response was achieved (5%) in 21 evaluable patients. An allergic reaction was noted in four patients including one patient with anaphylaxis. Didemnin B is not recommended in the treatment of renal cell carcinoma.     

Effects of baclofen and phaclofen on receptive field properties of rat whisker barrel neurons

Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. lontophoretically-applied (−)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABA_A and GABA_B mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution.     

Neurotensin injected into the nucleus accumbens blocks the psychostimulant effects of cocaine but does not attenuate cocaine self-administration in the rat

The neuropeptide neurotensin (NT) has been shown to modulate mesolimbic dopaminergic activity. Neurotensin injected into the VTA produces motor stimulation and release of dopamine in the nucleus accumbens. In contrast, when neurotensin is administered into the nucleus accumbens, it produces neuroleptic-like effects such as attenuation of the locomotor activity elicited by psychostimulants. In the present study, the hypothesis that neurotensin injected into the nucleus accumbens might modulate the psychostimulant and reinforcing actions of cocaine was tested. In experiment one, rats were trained to self-administer cocaine intravenously on an FR5 schedule of reinforcement. Following the establishment of baseline responding, rats were implanted with bilateral cannulae in the nucleus accumbens. One week later, rats were injected into the nucleus accumbens with various doses of neurotensin (4.2, 8.4 and 16.7 μg, total doses bilaterally) immediately prior to the self-administration session. No significant effects were found with any of the doses of neurotensin tested on the self-administration of cocaine. However, in experiment 2, neurotensin at doses of 4.2 and 16.7 μg injected into the nucleus accumbens significantly reduced the locomotor activation induced by an acute injection of cocaine (15 mg/kg i.p.) and a dose of 16.7 μg attenuated the locomotor activation induced by amphetamine (0.75 mg/kg i.p.). Thus, neurotensin in the nucleus accumbens appears to specifically modulate the acute locomotor activating properties of cocaine but not cocaine self-administration. Different mechanisms by which NT interacts with dopamine in the nucleus accumbens may provide a means of selectively altering psychostimulant motor actions without affecting psychostimulant reinforcement.     

Comparison of the Permeability Characteristics of a Human Colonic Epithelial (Caco-2) Cell Line to Colon of Rabbit,Monkey, and Dog Intestine and Human Drug Absorption

The in vitro permeabilities of Caco-2 monolayers and permeabilities in tissue sections from colon of monkey, rabbit, and dog were compared using a series of compounds. The selected compounds differed in their physicochemical properties, such as octanol/water partition coefficient, water solubility, and molecular weight. Their structure included steroids, carboxylic acids, xanthins, alcohols, and polyethylene glycols. A linear permeability relationship was established between Caco-2 and colon tissue from both rabbit and monkey. The results suggest that Caco-2 is twice as permeable as rabbit and five times as permeable as monkey colon. However, no clear relationship could be established between Caco-2 monolayers and dog colon permeability. A relationship between permeability in Caco-2 monolayers and human absorption was found. The results suggest that within certain limits, permeability of Caco-2 monolayers may be used as a predictive tool to estimate human drug absorption.     

Improving immunization coverage

A study was made on the causes of unsatisfactory progress in immunization coverage in an area of Tamil Nadu, southern India. The findings led to the appointment of additional community health workers (CHW), improvement in supervision, the enhancement of accessibility to services through an increase in the number of peripheral clinics and the organizing of temporary clinics, and the concentration of effort on underprivileged groups. As a result, immunization coverage was more than doubled. The Community Health and Development Project, a primary health care program serving 68 villages since 1981 with a population of about 80,000 was the site of the study which was conducted by discussions with staff and various members of the community. Issues explored were nonacceptance or dropout reasons, and specific factors affecting immunization coverage. A special effort was made to obtain the views of staff working at the periphery, particularly CHWS. The service area was divided into 4 sectors and the CHWS, auxiliary nurse midwives, community health nurses and other development staff in each were brought together for discussions. Views were also solicited from mothers' clubs and youth groups and in meetings with village leaders. Issues raised were further considered by supervisory staff. Statistical studies and other studies were done to clarify doubtful issues and test hypotheses emerging from the discussion. Poor immunization coverage was linked to inadequate supervision of CHWs, scattered communities (village with houses clustered together had better acceptance rates), difficulty of access to health services (distance factors), and low economic and educational status. In light of the study findings, community health workers were increased from 42 in 1984 to 57 in 1987 to cover all the villages, with modifications in selection method to make the worker acceptable to all sections of the villages; abolishment of the auxiliary nurse midwife and addition of a new category, health aide, to link the CHW and the community health nurse, increase of peripheral clinics from 37 to 75 and holding of more temporary clinics, more efforts to reach all socioeconomic groups and increased health education through film shows, drama, and work with village groups.