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Biomedical subjects

R Douglas

Publications and source records attributed to R Douglas.

At least 19 recordsLinked to original sources

Effect of amygdaloid kindling on [3H]dopamine and [14C]acetylcholine release from rat prefrontal cortex and striatal slices.

The involvement of the dopaminergic (DA) systems in the control of limbic kindled seizures is ill defined. The effects of kindling on DA activity may have been overlooked in the past, because of its subtle unilateral occurrence and/or the variance of the endogenous imbalance of DA activity in normal animals. In the present study rats were screened for their endogenous DA imbalance using amphetamine-induced rotational behaviour. Electrical or sham kindling was applied in the hemisphere with the higher endogenous DA activity. Sections of the bilateral prefrontal cortex and dorsal and ventral striatum were dissected either 2 hours or 21 days after the final seizure and the electrically stimulated release of [3H]DA and [14C]acetylcholine (ACh) determined. Release was also measured in the presence of quinpirole or sulpiride to assess the activity of pre- and postsynaptic DA D2-receptors. Long-term effects of kindling consisted of facilitation of ACh release in the ventral striatum contralateral to the kindled amygdala and bilateral depression of DA release in the prefrontal cortex. Kindling therefore produced area specific changes in neurotransmitter systems giving rise to increased pro-convulsive cholinergic activity in the ventral striatum and decreased anti-convulsive dopaminergic activity in the prefrontal cortex.

Acetylcholine

Ambulation using the reciprocating gait orthosis and functional electrical stimulation.

Until recently, rehabilitation engineering offered 2 different methods to improve daily living independence for spinal cord paralyzed subjects. One, the use of various orthotics and the other, the application of functional electrical stimulation. In the present work we chose to combine reciprocating gait orthosis (RGO) with functional electrical stimulation (FES) into one hybrid system. A detailed biomechanical and clinical instruction for the use of this system is given. Results obtained from application of the hybrid system on a complete T4 paraplegic patient demonstrate that the most significant contribution was the reduced invested energy cost required for stand-up and for ambulation.

Adult

Visibility of synaptically induced conductance changes: theory and simulations of anatomically characterized cortical pyramidal cells.

A recent report has provided evidence that there are no significant increases in the neuronal input conductance during the response of cortical cells in cat visual cortex to non-preferred visual stimuli (Douglas et al., 1988). A criticism of experiments of this kind is that changes in the membrane conductance occurring in the dendritic tree may not be visible from electrodes that impale the soma. Our paper describes theoretical and numerical results concerning the visibility of synaptically induced conductance changes from intracellular electrodes, in both ideal and anatomically well-characterized cortical neurons. Based on earlier work by Rall (1967), we here derive theoretical expressions for the change in input conductance at any location in a passive dendritic tree resulting from activation of a single synapse and obtain bounds for the effects of multiple synapses. We find that the conductance change measured at the cell body is always less than the sum of the synaptic conductance changes and that this observed conductance change does not depend on the synaptic reversal potential. For the case of an infinite dendritic cylinder, the change in input resistance due to a single synaptic input decays exponentially with distance of the synapse from the recording site. Numerical simulations of synaptic inputs that change approximately as fast as the membrane time-constant produce an increase in input conductance that is only slightly less visible than that of a constant input. We also compute the changes in somatic input conductance of 2 morphologically identified pyramidal cells from cat visual cortex during activity of a single inhibitory basket cell with known synaptic input locations. We find that the increase in conductance due to the activity of the inhibitory basket cells is clearly visible from the cell body of the pyramidal cells and that a 70% reduction in the amplitude of excitation is associated with at least a 30% increase in somatic input conductance, which would be visible in intracellular recordings. Taken together with the negative experimental evidence of Douglas et al. (1988), our results cast doubt on a large class of models of direction selectivity that rely on synaptically mediated inhibitory conductance increases to veto or block excitatory conductances increases.

Animals

Conservative treatment of traumatic closed hepatic haematoma.

A retrospective review was performed of nine patients with closed hepatic haematoma admitted to the Department of Surgery, Auckland Hospital, between 1980 and 1985. All resulted from blunt abdominal trauma due to motor vehicle accidents. Four haematomas were diagnosed at the time of laparotomy and were left undisturbed; four haematomas were diagnosed radiologically were also treated conservatively. One patient underwent partial right hepatic lobectomy, required a significant blood transfusion and developed a subphrenic abscess postoperatively. A further patient died from associated head injuries. The peri-operative mortality for urgent hepatic resection in multiply-traumatized patients is greater than 50%, even in experienced trauma units, and this review suggests that in haemodynamically stable patients with closed hepatic haematomas where the diagnosis can be radiologically ascertained, conservative treatment is a safe and reasonable option.

Adult

Clinical performance of Hickman and Portacath atrial catheters.

A recent advance in semipermanent vascular access has been the development of the totally implanted Portacath atrial catheter. The outcome of 100 sequential insertions of atrial catheters, 61 of which were Hickman catheters and 39 Portacaths, has been retrospectively reviewed in order to determine differences in clinical performance between these two types. The majority (90%) of the patients were from haematology or oncology wards. The incidence of complications was 66% for Hickman catheters and 46% for Portacaths. Local sepsis developed in 34% of the Hickman catheters and line-related septicaemia in 21%. The frequency of local sepsis and septicaemia following Portacath insertion was 31% and 3% respectively. Complications necessitated the removal of 33% of the Hickman catheters and 15% of Portacaths. The mean duration of insertion was 10 weeks for Hickman catheters and 24 weeks for Portacaths. It is concluded that the Portacath is less frequently complicated by sepsis and offers significant advantages for those patients in whom it is used.

Adolescent

Surrogate testing for non-A, non-B hepatitis in Queensland, Australia: an ALT microtitre tray method for screening blood donors.

The estimation of plasma alanine aminotransferase (ALT) has been proposed as a surrogate test to identify potential non-A, non-B hepatitis carriers in blood donor populations. This report describes an ALT screening procedure which uses wells of microtitration trays as reactant vessels. The method utilizes a rate reading photometer, is economical and conveniently fits into the routine workflow. Within-batch and between-batch precision was 4.1% and 6.3% at enzyme concentrations of 49 IU/I. Results of testing 29,675 healthy blood donors gave values which ranged between 1.0 IU/I and 214 IU/I. A study of 762 donations showed a significant difference in mean ALT values between males and females (p less than 0.01). When a cut-off value of 46 IU/I was used, 2.5 percent of donations were considered unsuitable for transfusion. The medico-legal implications that may arise from the introduction of this screening test into the routine work flow are discussed.

Alanine Transaminase

The crossed nigrostriatal projection decussates in the ventral tegmental decussation.

Horseradish peroxidase (HRP) tract-tracing techniques were used in 44 rats in order to establish the site of decussation of the crossed nigrostriatal projection. Somata in both the ipsilateral and the contralateral ventromedial mesencephalon were labelled after injection of HRP into the caudate nucleus. In agreement with previous studies, contralateral labelling constituted about 3% of the ipsilateral labelling. Midsagittal transection of the mesodiencephalic junction did not prevent the contralateral labelling. However, mid-sagittal transection of the ventral mesencephalon, or selective 6-hydroxydopamine (6-OHDA) lesions of the ventral tegmental decussation did prevent the contralateral labelling. Moreover, 6-OHDA lesions of the substantia nigra ipsilateral to the horseradish peroxidase injection also prevented contralateral labelling. We conclude that the crossed nigrostriatal projection decussates in the ventral tegmental decussation, and that this projection is susceptible to damage by standard 6-OHDA lesions located on the opposite side to the origin of the crossed pathway.

Animals

Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis.

The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. We identified a frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer.

Chromosomes, Human, Pair 7

Plasminogen activator inhibitor type-1: reactive center and amino-terminal heterogeneity determined by protein and cDNA sequencing.

Both the urokinase-type and tissue-type plasminogen activator can convert their approximately 54 kDa type-1 inhibitor (PAI-1) to an inactive form with a lower apparent molecular mass. We have determined the amino-terminal amino acid sequences of human native and converted PAI-1, and isolated PAI-1 cDNA and determined the nucleotide sequence in regions corresponding to the amino-terminus and the cleavage site. The data show that the conversion of the inhibitor consists of cleavage of an Arg-Met bond 33 residues from the carboxy-terminus, thus localizing the reactive center of the inhibitor to that position. In addition, a heterogeneity was found at the amino-terminus, with a Ser-Ala-Val-His-His form and a two-residue shorter form (Val-His-His-) occurring in approximately equal quantities.

Amino Acid Sequence

Hemispheric disconnection and rotational behaviour.

Several studies have demonstrated the existence of crossed pathways interconnecting the bilateral extrapyramidal system. The present study has evaluated the role of the thalamus in the interhemispheric control of nigrostriatal function by observing the effect of midsagittal thalamic transection on amphetamine-induced rotation in rats. The effect of thalamic transection on net rotational asymmetry did not differ from the effects of sham operations. Also, the transection did not affect the rotational asymmetry induced by subsequent lesioning of the dominant hemisphere substantia nigra. The failure to affect the rotation asymmetry by the transection suggests either that the inter-hemispheric pathway does not control extrapyramidal asymmetry or that the crossing takes place outside the thalamus. In an additional group of rats, thalamic transection did not interrupt retrograde labeling of somata in the substantia nigra and ventral tegmental area by horseradish peroxidase injected in the contralateral caudate. Thus, the crossed nigrostriatal projection does not decussate via the thalamus. It is suggested that this pathway decussates in the ventral mesencephalon.

Amphetamine

Transfer factor and hepatitis B: a double blind study.

A prospective, double blind placebo-controlled trial was carried out on twenty-nine patients with hepatitis B. Thirteen received transfer factor and sixteen placebo. There were no significant differences between the two groups in any clinical or laboratory measurements made, although a rapid early reduction of serum aspartate transaminase levels by transfer factor is possible. Similarly, no significant changes were delineated by the in vitro measurements of lymphocyte function. Transfer factor did not alter the natural course of hepatitis B.

Adult

Transfer factor therapy: clinical experience and the role of the E rosette assay.

Transfer factor has been administered to 17 patients, most with infectious diseases of various kinds. In 12 patients the therapy was followed by a definite clinical improvement although in most cases conventional chemotherapy was given concomitantly. In all cases where clinical improvement followed the sheep red cell or E rosette assay showed low values initially, with an improvement following therapy. This test of T lymphocyte function may be useful both in predicting patients likely to respond to transfer factor, and in monitoring response to treatment. As no specific assay of transfer factor activity is available, an in vivo rise in E rosette formation following transfer factor administration serves as a crude indicator that the injected material has some biological activity.

Abscess

The distribution of HLA in a Polynesian population-Western Samoans.

HLA and gene frequencies are presented for a Polynesian population-the Western Samoans. Within the HLA-A locus A2, A9 and A11 have the highest frequencies and account for 55% of the alleles in this locus. The alleles BW22 and BW40 had the highest frequencies in the HLA-B locus and accounted for 51% of the alleles. The blank gene frequencies for the HLA-A and B loci are .382 and .373 respectively. Significant linkage disequilibrium was found with the haplotypes A1,B7; A3,B7;A2, BW40; A9, BW40 A9, BW22. The most frequent haplotype was A2,BW40. Comparatively low values within this population and between this and other Polynesian populations are discussed in terms of selection, migration and drift.

Alleles

HL-A antigens in Europeans and Maoris with rheumatic fever and rheumatic heart disease.

Using a standard microtoxicity technique of tissue typing, the distribution of tissue antigens in 75 Maoris and 514 European disease-free blood donors was determined. Fifty Maori and 50 Europeans with rheumatic fever or rheumatic heart disease were compared with each control group. Normal Maoris had HL-A3 less frequently than Europeans (P less than .0005). HL-A28 was reduced (P less than .005) and HL-A17 increased in European patients (P less than .0005). In Maori patients there were minor differences in the frequency of HL-A3 and 8, which were increased, and HL-A10, which was diminished.

Europe