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Biomedical subjects

L A Smith

Publications and source records attributed to L A Smith.

At least 109 records · Page 6Linked to original sources
PubMed1997

Vacuum pack technique of temporary abdominal closure: a four-year experience.

The purpose of this review is to present a 4-year experience with the vacuum pack technique of temporary abdominal closure. From April 1992 to December 1996, 171 vacuum packs were performed on 93 patients. Eighty-seven vacuum packs were performed on 38 general surgical patients, and 84 vacuum packs were performed on 55 trauma patients. Overall hospital mortality was 32 per cent. Methods of achieving permanent wound closure varied in 73 patients. Four patients (4.3%) developed enterocutaneous fistulae; four patients developed intra-abdominal abscesses (4.3%). There were no eviscerations. Management of the complicated intra-abdominal process is discussed: 1) the decision to manage the abdomen in an open fashion; 2) which method of temporary closure to use; 3) subsequent explorations; 4) when the abdomen should be closed; 5) which type of closure to use; and 6) when the abdominal wall should be revised (herniorrhaphy). The vacuum pack is the method of choice for open abdomen management and temporary abdominal closure at our institution. With careful subsequent management, good patient outcome can be achieved.

Abdomen↗
PubMed1996

A Drosophila calcium channel alpha1 subunit gene maps to a genetic locus associated with behavioral and visual defects.

We have cloned cDNAs that encode a complete open reading frame for a calcium channel alpha1 subunit from Drosophila melanogaster. The deduced 1851 amino acid protein belongs to the superfamily of voltage-gated sodium and calcium channels. Phylogenetic analysis shows that the sequence of this subunit is relatively distant from sodium channel alpha subunits and most similar to genes encoding the A, B, and E isoforms of calcium channel alpha1 subunits. To indicate its similarity to this subfamily of vertebrate isoforms, we name this protein Dmca1A, for Drosophila melanogaster calcium channel alpha1 subunit, type A. Northern blot analysis detected a single 10. 5 kb transcript class that is regulated developmentally, with expression peaks in the first larval instar, midpupal, and late pupal stages. In late-stage embryos, Dmca1A is expressed preferentially in the nervous system. Variant transcripts are generated by alternative splicing. In addition, single nucleotide variations between cDNAs and genomic sequence are consistent with RNA editing. Dmca1A maps to a chromosomal region implicated in, and is the likely candidate for, the gene involved in the generation of behavioral, physiological, and lethal phenotypes of the cacophony, nightblind-A, and lethal(1)L13 mutants.

Amino Acid Sequence↗
PubMed1996

Young adults' relations with grandparents following recent parental divorce.

This study employed a large survey of young adults to consider the association between recent parental divorce and intergenerational solidarity between adult grandchildren and their grandparents. The results indicate no significant association between parental divorce and young adults' reports of affective, associational, or functional solidarity in relation to either maternal or paternal grandparents. Adult grandchildren from divorced families, however, were more likely than those from intact families to initiate contacts with their grandparents on their own, and to see their paternal grandparents without their father accompanying them. We conclude that parental divorce does not influence adult grandchild-grandparent relations because, at least in part, adult grandchildren are less dependent than young children on the middle-generation parent to facilitate this relationship.

Adolescent↗
PubMed1996

Renal sensory receptor activation causes prostaglandin-dependent release of substance P.

Renal mechanoreceptor (MR) activation by increased ureteral pressure (increases UP) results in an increase in afferent renal nerve activity (ARNA) that is blocked by substance P receptor blockade and prostaglandin (PG) synthesis inhibition. To examine the interaction between substance P and PGs, the release of substance P and PGE into the renal pelvis was studied before and during renal pelvic perfusion with indomethacin. Before indomethacin, increases UP increased ARNA 43 +/- 6% and renal pelvic release of substance P from 11 +/- 3 to 29 +/- 8 pg/min and PGE from 319 +/- 71 to 880 +/- 146 pg/min. Indomethacin blocked the increases in ARNA and release of substance P and PGE produced by increases UP. Time control experiments showed reproducible increases in ARNA and release of substance P and PGE during increases UP. Mechanical stimulation of the renal pelvic wall in vitro resulted in an increase in PGE release from 110 +/- 8 to 722 +/- 152 pg/min, which was abolished by indomethacin, suggesting a de novo PGE synthesis. The data suggest that increases UP results in a renal pelvic release of PGE, which facilitates the release of substance P and activation of renal pelvic MR.

Animals↗
PubMed1996

Bradykinin and protein kinase C activation fail to stimulate renal sensory neurons in hypertensive rats.

In normotensive rats, renal sensory receptor activation by increased ureteral pressure results in increased ipsilateral afferent renal nerve activity, decreased contralateral efferent renal nerve activity, and contralateral diuresis and natriuresis, a contralateral inhibitory renorenal reflex response. In spontaneously hypertensive rats (SHR), increasing ureteral pressure fails to increase afferent renal nerve activity. The nature of the inhibitory renorenal reflexes indicates that an impairment of the renorenal reflexes would contribute to the increased efferent renal nerve activity in SHR. We therefore examined whether there was a general decrease in the responsiveness of renal sensory receptors in SHR by comparing the afferent renal nerve activity responses to bradykinin in SHR and Wistar-Kyoto rats (WKY). In WKY, renal pelvic perfusion with bradykinin at 4, 19, 95, and 475 micromol/L increased afferent renal nerve activity by 1066 +/- 704, 2127 +/- 1121, 3517 +/- 1225, and 4476 +/- 1631% x second (area under the curve of afferent renal nerve activity versus time). In SHR, bradykinin at 4 to 95 micromol/L failed to increase afferent renal nerve activity. Bradykinin at 475 micromol/L increased afferent renal nerve activity in only 6 of 10 SHR. In WKY, renal pelvic perfusion with the phorbol ester 4beta-phorbol 12,13-dibutyrate, known to activate protein kinase C, resulted in a peak afferent renal nerve activity response of 24 +/- 4%. However, 4beta-phorbol 12,13-dibutyrate failed to increase afferent renal nerve activity in SHR. These findings demonstrate decreased responsiveness of renal pelvic sensory receptors to bradykinin in SHR. The impaired afferent renal nerve activity responses to bradykinin in SHR may be due to a lack of protein kinase C activation or a defect in the intracellular signaling mechanisms distal to protein kinase C activation.

Animals↗
PubMed1996

Relationships between ambient sounds and the accuracy of pharmacists' prescription-filling performance.

Associations between ambient sounds and accuracy of pharmacists' prescription-filling performance in a pharmacy was studied. Pharmacists were videotaped as they filled prescriptions each workday for 23 days. Each filled prescription was inspected by the investigator. Deviations from the physician's written order were considered errors. Videotape analysis was used to detect unpredictable, predictable, uncontrollable, and controllable sounds. A within-subjects case control study design was employed to determine whether the frequency of ambient sounds was significantly different when prescriptions with errors, compared with those without errors, were filled. Loudness, in terms of equivalent sound levels (Leq) for each half hour, was analyzed for a relationship to dispensing error rate. A mean dispensing error rate of 3.23% was found. Unpredictable sounds, controllable sounds, and noise had a significant effect on pharmacists which resulted in a decreased dispensing error rate. These results suggest that the quality of pharmacists' performance is not adversely affected by ambient sound. As equivalent sound levels increased, the error rate increased to a point, then decreased.

Case-Control Studies↗
PubMed1996

Adaptation of a foot plate for use in an isokinetic and isotonic leg press.

The use of isokinetic equipment and the leg press exercise have been major components of rehabilitation for the past several years when redeveloping muscular strength. Recently, closed kinetic chain exercises have been shown to be more beneficial and have less adverse affects on the knee when rehabilitating a patient's lower extremity. The purpose of this article is to introduce the leg press foot plate to the rehabilitative community. This foot plate is a versatile piece of equipment that has been adapted for use with various isokinetic, isometric, and isotonic devices in order to do leg press exercises. The device allows for closed kinetic chain strengthening and testing from equipment typically used only for open kinetic chain activities.

Journal Article↗
PubMed1995

Short- and long-term changes in striatal and extrastriatal dopamine uptake sites in the MPTP-treated common marmoset.

The 'short-term' (15-30 days) and 'long-term' (18-42 months) effects of the systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on [3H]mazindol binding to dopamine uptake sites was investigated in the common marmoset. In the 'short-term' MPTP-treated group, [3H]mazindol binding was reduced in the caudate-putamen (by -82 to -98% with respect to controls), substantia nigra pars compacta (-71 to -84%), ventral tegmental area (-72%) and nucleus accumbens (-54%). [3H]Mazindol binding in the globus pallidus, frontal cortex and substantia nigra pars reticulata was much lower and was unaffected by MPTP treatment. In the 'long-term' MPTP-treated group [3H]mazindol binding was still greatly reduced in the substantia nigra pars compacta (by -76 to -89%), ventral tegmental area (-71%) and most of the caudate-putamen (-69 to -98%), although the reduction in [3H]mazindol binding in the nucleus accumbens (-27%) and rostroventral caudate nucleus (-69%) was less than in the 'short-term' MPTP-treated group. The motor deficits induced by MPTP treatment in the common marmoset are largely reversible with increasing survival times (Ueki et al., 1989, Neuropharmacology 28, 1089). In the present study, the apparent 'recovery' in [3H]mazindol binding in the rostroventral caudate nucleus and nucleus accumbens may indicate regeneration of dopamine neurone terminals in these regions and this may contribute to the behavioural recovery seen in this primate model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Short and long-term changes in cerebral [14C]-2-deoxyglucose uptake in the MPTP-treated marmoset: relationship to locomotor activity.

The "short-term" (0.7 +/- 0.1 months post-MPTP) and "long-term" effects (36.7 +/- 4.4 months) of MPTP treatment on motor behaviour and [14C]-2DG uptake were investigated in the common marmoset. The subcutaneous administration of MPTP greatly reduced locomotor activity (-94% with respect to controls) and induced motor disability in the "short-term" MPTP-treated marmoset group. In the "long-term" MPTP group, MPTP treatment did not significantly affect locomotor activity (-27% with respect to controls) and there was partial recovery of motor disability. In the "short-term" MPTP group, there were increases in [14C]-2DG uptake in the GPl (+31 to +37%), SNc (+34 to +42%), VTA (+35%), LC (+23%), PPN (+19%) and in the VA (+19%), VL (+20%) and AM (+17%) thalamic nuclei. [14C]-2DG uptake was decreased in the STN (-15%). In the "long-term" MPTP group, [14C]-2DG uptake was increased in the GPl (+18%), SNc (+27%), VTA (+25%), PPN (+19%), ventral caudate nucleus (+18 to +23%), NAc (+22%), F.Ctx (+18%) and in the VA (+34%), VL (+28%), AV (+33%) and AM (+24%) thalamic nuclei. [14C]-2DG uptake was unchanged in the STN. The increase in metabolic activity of the surviving DA neurones and/or the reactive gliosis may account for the initial increase in [14C]-2DG uptake in the SNc and VTA. On the other hand, in the "long-term" MPTP-treated animals the increase in [14C]-2DG uptake in the SNc (though less than in the "short-term" MPTP group), ventral caudate and NAc may reflect the regenerative changes in the dopaminergic system in these areas. Despite the behavioural recovery, [14C]-2DG uptake remained elevated in the target areas for medial pallidal output (the thalamic nuclei and PPN). However, the attenuation of the changes in [14C]-2DG uptake in the GPl and STN of "long-term" MPTP-treated marmosets suggest that the striato-GPl and GPl-STN outputs closely reflect motor function in this primate model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Differential anti-parkinsonian effects of benzazepine D1 dopamine agonists with varying efficacies in the MPTP-treated common marmoset.

In common marmosets systemically treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), the behavioural effects of benzazepine D1 dopamine (DA) agonists with full/supramaximal (SKF 80723 and SKF 82958), partial (SKF 38393, SKF 75670 and SKF 83565) and no efficacies (SKF 83959) in stimulating adenylate cyclase (AC) activity were investigated. The benzazepine derivatives, with the exception of SKF 82958 (8 fold D1 DA receptor selectivity), demonstrated high D1 DA receptor affinity and selectivity (approximately 100 fold or more) in rat striatal homogenates. Administration of MPTP in marmosets induced locomotor hypoactivity, rigidity and motor disability. SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine) and SKF 75670 (3-CH3 analogue) further reduced locomotor activity (by -70 to -80%) and increased motor disability (by +22 to +67%) in these animals. SKF 83565 (6-Cl, 3-CH3, 3'-Cl analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue) had only a slight effect on locomotor activity but decreased motor disability at high doses (-46 to -60%). In contrast, SKF 83959 (6-Cl, 3-CH3, 3'-CH3 analogue) and SKF 80723 (6-Br analogue) produced pronounced increases in locomotion (6-10 fold) and a reversal in motor disability (by -64 to -77%). Oral activity, consisting largely of abnormal, 'dyskinetic' tongue protrusions and vacuous chews, was increased in animals treated with SKF 38393, SKF 83565, SKF 82958 and more especially with SKF 80723 and SKF 83959. Grooming was increased with SKF 82958 and more especially with SKF 80723 and SKF 83959. In contrast, quinpirole (D2 DA agonist), reversed the MPTP-induced motor deficits in the marmoset, with no effect on grooming and oral activity. The present findings further demonstrate the antiparkinsonian actions of some D1 DA agonists in MPTP-treated primates. However, in general the behavioural effects of benzazepines failed to correlate with either their D1 DA receptor affinity/selectivity or their efficacy in stimulating adenylate cyclase (AC) activity. These observations further implicate a behavioural role for D1 DA receptors uncoupled to AC and/or a role for extrastriatal D1 DA receptors in mediating the behavioural response to D1 DA agonists.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

A study on the cause of death due to waglerin-I, a toxin from Trimeresurus wagleri.

Waglerin-I, a lethal toxin isolated from the venom of Trimeresurus wagleri, consists of 22 amino acid residues with a proline-rich sequence. In the present study, we investigated the cause of death and the possible site of action of this toxin. In anesthetized mice, i.v. administration of waglerin-I at 0.5 microgram/g produced respiratory failure within 5 min. The blood pressure could be maintained by the application of artificial respiration immediately after respiratory arrest. Waglerin-I at 4 microM reversibly blocked the indirect twitch of the mouse phrenic nerve-hemidiaphragm preparation, but had no effect on the direct twitch. It is concluded that respiratory failure, resulting from neuromuscular block, is the primary cause of death due to waglerin-I in mice. In contrast to the results obtained in mice, in anesthetized rats no toxic effects on respiration and blood pressure were observed except for a transient hypotension up to 10 micrograms/g (i.v.). In accordance with the in vivo experiments, waglerin-I at concentrations up to 40 microM did not block the indirect twitch of the rat diaphragm. It thus appears that rats are resistant to the toxic effects of waglerin-I.

Animals↗
PubMed1995

Effects of waglerin-I on neuromuscular transmission of mouse nerve-muscle preparations.

The effects of waglerin-I, a toxin from Trimeresurus wagleri, on neuromuscular (NM) transmission were studied on the phrenic nerve-diaphragm preparation and triangularis sterni nerve-muscle preparation of mice. The toxin (1.2-4.0 microM) reversibly inhibited the indirectly elicited twitch tension of the diaphragm and decreased the ACh-elicited muscle contracture of chronically denervated diaphragm, while the directly elicited twitch tension was not affected. The toxin reversibly decreased the amplitude of miniature endplate potential (MEPP) at 0.52 microM and endplate potential (EPP) at 1.2-4 nM. The toxin (120 nM-0.4 microM) also decreased the quantal content of EPP. The perineural waveforms were recorded with an extracellular electrode placed into the perineural sheaths of motor nerves of M. triangularis sterni. The toxin (4 microM) did not alter the amplitudes of waveforms related to sodium and potassium currents of the nerve terminal action potential, while the waveform related to calcium current was decreased. It is concluded that the toxin acts on both presynaptic and postsynaptic sites of the mouse motor endplate, and that the presynaptic effect is apparently more potent than the postsynaptic effect.

Action Potentials↗
PubMed1995

Cloning and expression of mamba toxins.

Mamba venoms contain pharmacologically active proteins that interfere with neuromuscular transmission by binding to and altering the normal functioning of neuronal proteins involved, directly or indirectly, with regulating nerve transmission. Of the mamba toxins studied to date, many act on voltage-sensitive K+ channels, nicotinic or muscarinic acetylcholine receptors, or acetylcholinesterase. In an attempt to clone, characterize, and express the genes encoding these toxins, as well as other genes specifying activities not completely elucidated as yet, a cDNA library was constructed from mRNA isolated from the glands of the black mamba. Clones from the library harboring sequences encoding 14 different mamba toxins were isolated and characterized by nucleotide sequence analysis. Genes coding for three proteins, dendrotoxins (DTX) K, I, and E, were expressed as maltose-binding (MBP) fusion proteins in the periplasmic space of Escherichia coli. The DTXK-MBP fusion protein was affinity purified, cleaved from its chaperon, and the recombinant DTXK purified from MBP. Recombinant DTXK was shown to be identical to native DTXK in its N-terminal sequence, chromatographic behavior, convulsion-inducing activity, and binding to voltage-activated K+ channels in bovine synaptic membranes. Computer modeling was employed to create three-dimensional structures of DTXK and DTX1 from the X-ray crystal structure of alpha-DTX utilizing both structural and sequence homologies. Comparisons were made between the three toxins, providing a framework for site-directed mutagenesis.

Amino Acid Sequence↗
PubMed1995

Essential fatty acid deficiency impairs the responsiveness of renal pelvic sensory receptors.

The role of prostaglandins in renal sensory receptor activation was examined in rats fed an essential fatty acid-deficient (EFAD) diet to cause tissue arachidonate depletion. Littermates fed a standard diet were used as controls. In anesthetized rats, the increases in afferent renal nerve activity due to increasing ureteral pressure 2.5, 5, 7.5, 10, 12.5, and 15 mmHg were significantly reduced by the EFAD diet (P < 0.02): 3 +/- 5, 3 +/- 5, 11 +/- 5, 9 +/- 5, 19 +/- 3, and 17 +/- 5%, respectively, in EFAD rats and 23 +/- 11, 36 +/- 15, 50 +/- 15, 52 +/- 8, 72 +/- 17, and 90 +/- 19%, respectively, in control rats. In EFAD rats, addition of prostaglandin E2 (PGE2) to the renal pelvic perfusate restored the afferent renal nerve activity response to increased ureteral pressure toward that in control rats. PGE2 had no effect in control rats. Also the afferent renal nerve activity responses to renal pelvic perfusion with bradykinin at 4, 20, 100, and 500 micrograms/ml were significantly suppressed by the EFAD diet (P < 0.01): 13 +/- 15, 5 +/- 7, 60 +/- 19, and 63 +/- 20%, respectively, in EFAD rats and 122 +/- 23, 142 +/- 31, 172 +/- 19, and 190 +/- 39%, respectively, in control rats. These results demonstrate an important role for arachidonate metabolites, particularly PGE2, in renal sensory receptor activation. Together with our previous studies showing that indomethacin blocks the afferent renal nerve activity responses to increased ureteral pressure or bradykinin, the present studies provide strong evidence for an essential role of prostaglandins in renal sensory receptor activation.

Afferent Pathways↗
PubMed1995

A role for protein kinase C in bradykinin-mediated activation of renal pelvic sensory receptors.

In anesthetized rats, activation of renal pelvic sensory receptors by bradykinin results in an increase in afferent renal nerve activity (ARNA) that is dependent on intact renal prostaglandin synthesis. Since bradykinin is a known activator of the phosphoinositide system, we examined whether the increase in ARNA produced by bradykinin involved activation of protein kinase C (PKC). Renal pelvic perfusion with the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDBu, 1 microM) increased ARNA (31 +/- 3%, P < 0.01) in rats fed a normal diet but not in rats fed an essential fatty acid-deficient (EFAD) diet. Renal pelvic perfusion with the PKC inhibitors calphostin C (1 microM), staurosporine (20 nM), and H-7 (40 microM) reduced the ARNA responses to bradykinin (20 microM) by 69 +/- 10, 76 +/- 10, and 77 +/- 10%, respectively (all P < 0.01). Pretreatment with PDBu (1 microM), known to cause a feedback inhibition of bradykinin-mediated activation of the phosphoinositide system, reduced the ARNA response to bradykinin by 73 +/- 6% (P < 0.01). Pretreatment with 4 alpha-phorbol 12,13-didecanoate was without effect. These findings suggest that activation of PKC contributes importantly to the activation of renal pelvic sensory receptors by bradykinin, likely via release of arachidonic acid.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Genomic sequences encoding the acidic and basic subunits of Mojave toxin: unusually high sequence identity of non-coding regions.

Mojave toxin (Mtx) is a heterodimeric, neurotoxic phospholipase A2 (PLA2) found in the venom of the Mojave rattlesnake, Crotalus scutulatus scutulatus, and is characteristic of all rattlesnake presynaptic neurotoxins. This paper describes the isolation and nucleotide (nt) sequence of the genomic clones encoding both the non-neurotoxic, non-enzymatic acidic subunit (Mtx-a) and the toxic, PLA2-active basic subunit (Mtx-b), and compares their structures. Both cloned genes shared virtually identical overall organization, with four exons separated by three introns, which were inserted in the same relative positions of the genes' coding regions. The exon/intron structure was similar to that reported for mammalian PLA2 genes. Most remarkable was the high degree of nt sequence identity between Mtx-a and Mtx-b. While the exons shared about 70% identity, the introns were greater than 90% identical and the 5' and 3' untranslated and flanking regions were greater than 95% identical. These findings support our earlier suggestion [Aird et al., Biochemistry 24 (1985) 7054-7058] that the genes coding for the two subunits arose from a common ancestor. There has clearly been a strong selection on the nt sequence of the non-coding regions during this evolutionary process. This is the first report of genomic sequences of PLA2-like proteins from snakes.

Amino Acid Sequence↗
PubMed1994

Na(+)-K(+)-ATPase inhibition sensitizes renal mechanoreceptors activated by increases in renal pelvic pressure.

In anesthetized rats, the activation threshold of renal pelvic mechanoreceptors was determined by graded increases in renal pelvic pressure. Ipsilateral afferent renal nerve activity increased 9 +/- 4 (NS), 34 +/- 12, 47 +/- 8, 58 +/- 13, 68 +/- 14, and 91 +/- 17% (all P < 0.01) by the increase in renal pelvic pressure from 2.5 to 15 mmHg in 2.5-mmHg steps. Contralateral diuresis and natriuresis were elicited by renal pelvic pressures > 2.5 mmHg. Renal pelvic perfusion with 1.4 mM ouabain, an inhibitor of Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase), increased basal afferent renal nerve activity transiently, lowered the activation threshold of renal mechanoreceptors to < 2.5 mmHg, and enhanced the afferent renal nerve activity, responses to increasing renal pelvic pressures by 8 and 30 mmHg. The afferent renal nerve activity response to increased renal pelvic pressure was also enhanced by renal pelvic perfusion with 900 mM NaCl but was unaltered by NaCl concentrations ranging from 10 to 600 mM. These findings show that renal pelvic mechanoreceptors are activated by increases in renal pelvic pressure within the physiological range. Although renal Na(+)-K(+)-ATPase contributes to the maintenance of the resting membrane potential of renal pelvic mechanoreceptors, the renal pelvic mechanoreceptor discharge is not influenced by physiological renal pelvic Na+ concentrations.

Afferent Pathways↗