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Biomedical subjects

T Lewis

Publications and source records attributed to T Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1996

The effect of white matter low attenuation on cognitive performance in dementia of the Alzheimer type.

The effect of leukoaraiosis or white matter low attenuation (WMLA) on cognitive function is not fully understood. We compared the neuropsychological performance of 37 Alzheimer's disease patients with WMLA on CT brain scans with a similar group of 31 Alzheimer's disease patients with no evidence of white matter lesions. Patients with WMLA performed significantly worse on tests of visuospatial function (Cube Analysis test, p = 0.004), and cognitive speed (Kenrick Digit Copying test, p = 0.05) compared to those with no visible white matter lesions. Patients with widespread WMLA performed generally worse in tests of cognitive function than those with frontal or a mixture of frontal and occipital WMLA. This was most significant in the areas of attention (forward digit span, p = 0.003), visual recognition (p = 0.004), and cognitive speed (p = 0.03). There is an association between impaired cognitive performance and the presence of WMLA in Alzheimer's disease patients, with WMLA probably contributing to the cognitive impairment. This is most evident in patients with widespread white matter lesions.

Aged↗
PubMed1996

Preliminary synthetic studies of methyllycaconitine, a potent nicotinic acetylcholine receptor antagonist: rapid syntheses of AE-bicyclic analogues.

A series of bicyclic analogues incorporating the homocholine motif of methyllycaconitine has been prepared to test the hypothesis that this is the essential pharmacophore of this potent, selective nicotinic receptor antagonist. A double Mannich reaction has been employed to construct the 3-azabicyclo[3.3.1]-nonane ring system, containing an N-ethylpiperidine moiety. The neopentyl-like alcohol was then esterified, using isatoic anhydride under basic conditions, to afford the corresponding anthranilate.

Aconitine↗
PubMed1996

Do agoraphobics interpret the environment in large shops and supermarkets differently?

Agoraphobics typically have difficulties in visiting supermarkets. The brief report presents results of a survey investigating the properties of supermarkets which provoke or ease anxiety-related responses in shoppers (N = 500) and two further groups: agoraphobics (N = 40) and participants responding to a local press advert (N = 54). Results showed that layout features, stairways and diminished access were rated as more anxiety provoking in the agoraphobic-type groups compared to general shoppers. The safety-signal model of agoraphobic behaviour was supported although some evidence of dysfunction of spatial orientation was found.

Activities of Daily Living↗
PubMed1996

Emergency thoracotomy for thoracic trauma in the accident and emergency department: indications and outcome.

To assess the efficacy of emergency thoracotomy performed for thoracic trauma in the accident and emergency department, a retrospective analysis of patients who underwent this procedure and were brought to hospital by the Helicopter Emergency Medical Service was carried out. Between 1991 and 1994, 16 patients had emergency thoracotomy performed in the accident department. Twelve patients had sustained blunt trauma and four patients had sustained penetrating injuries. Three patients first assessed at the scene and 11 patients on arrival at the emergency department had Glasgow Coma Scores < 3. Eight thoracotomies were performed by the cardiothoracic team and eight by the trauma team. There was one survivor in this group; he had been stabbed at multiple sites and emergency thoracotomy was required to control bleeding from an intercostal vessel. Our results demonstrate experience of one of the first phase Level One trauma centres in the United Kingdom. From our small series, we believe that selection criteria for emergency thoracotomy in trauma patients need to be revised. From this series and a review of the literature, patients with penetrating injuries, vital signs at the scene and those with a high index of suspicion for tamponade seem to benefit most from thoracotomy in the emergency setting.

Adolescent↗
PubMed1996

Affect, attachment, memory: contributions toward psychobiologic integration.

Recent decades have seen a marked expansion in knowledge regarding human neurophysiology, and psychiatry is currently challenged with the task of integrating this information with a psychodynamic understanding of emotional life. In this paper we review portions of the relevant literature regarding the basic brain functions of affect, memory, and attachment, and we consider the implications of these data for integrated psychobiologic conceptualizations of emotional dysfunction and its treatment. In particular, data from these three areas of study point to the possibility that implicit memory of the early attachment relationship, communicated via the language of affect, is an enduring neural structure that influences both emotional self-regulation and behavior related to relatedness. Finally, we consider the implications of this proposition for the nature of psychotherapy, which from a psychobiologic view might be profitably conceptualized as a directed attachment relationship whose purpose is the revision of the implicit emotional memory of attachment.

Affect↗
PubMed1995

Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines.

BACKGROUND: Mitogen-activated protein (MAP) kinase is central to a signal transduction pathway that triggers cell proliferation or differentiation. Activation of the p42mapk isoform requires its phosphorylation at two residues, Thr 183 and Tyr 185, and this phosphorylation is catalysed by MAP kinase kinase (MAPKK). Relatively little is known, however, about the enzymes that dephosphorylate these residues, thereby inactivating the pathway. Recently, the CL100 phosphatase has been shown to inactivate p42mapk in vitro by dephosphorylating Thr 183 and Tyr 185 at similar rates. CL100, the product of an immediate early gene, is synthesized within one hour of stimulating cells with growth factors or exposure to oxidative stress or heat shock. Incubation of NIH 3T3 fibroblasts with cycloheximide prevents both synthesis of CL100 and inactivation of p42mapk after stimulation with serum. RESULTS: Depleting cells of CL100 and preventing its induction using cycloheximide stopped the inactivation of p42mapk in Swiss 3T3 fibroblasts following stimulation with epidermal growth factor (EGF), but had no effect on the rapid inactivation of p42mapk in response to EGF in adipose (3T3-L1) or chromaffin (PC12) cells or in response to platelet-derived growth factor (PDGF) in endothelial (PAE) cells. Moreover, maximal induction of CL100 mRNA and a CL100-like activity did not trigger inactivation of p42mapk, which was sustained at a high level after stimulation of PC12 cells with nerve growth factor, PAE cells with serum, or Swiss 3T3 cells with PDGF. Dephosphorylation of Tyr 185 but not Thr 183 of p42mapk was suppressed by vanadate in EGF-stimulated PC12 cells; dephosphorylation of Thr 183, by contrast, was elicited by a vanadate-insensitive activity. Protein phosphatase-2A was the only vanadate-insensitive phosphatase acting on Thr 183 of p42mapk or on MAPKK to be detected in PC12 cell extracts. Phosphorylation of Thr 183 also inhibited the dephosphorylation of Tyr 185 in vitro by the major vanadate-sensitive Tyr 185-specific phosphatase, explaining why dephosphorylation of Thr 183 is rate-limiting for p42mapk inactivation in PC12 cells after stimulation with EGF. CONCLUSIONS: The rapid inactivation of p42mapk initiated five minutes after stimulation of endothelial, adipose and chromaffin cells with growth factor is not catalysed by CL100, but rather by protein phosphatase 2A and by a protein tyrosine phosphatase distinct from CL100. Induction of CL100 is not accompanied by the inactivation of p42mapk in a number of situations.

3T3 Cells↗
PubMed1995

An HPLC assay for the norditerpenoid alkaloid methyllycaconitine, a potent nicotinic acetylcholine receptor antagonist.

The extremely potent and selective nicotinic acetylcholine receptor antagonist methyllycaconitine, MLA, and related norditerpene alkaloids are finding increasing use as neurochemical probes and as targets for structure-activity relationship studies. In this work, an assay procedure for MLA which utilises ion suppression reverse-phase HPLC with UV absorbance detection at 270 nm is described. The method detected 280 ng MLA on column.

Aconitine↗
PubMed1995

Surgical delays and outcomes in patients treated with pneumatic antishock garments: a population-based study.

Until mid-1991, our emergency medical services (EMS) system required the routine application of pneumatic antishock garments (PASGs) in all trauma cases, and inflation of the garment if the patient was hypotensive (systolic blood pressure < 90 mm Hg). The findings in 398 trauma patients who underwent emergency surgery when PASG was still being routinely applied were compared with the findings in 590 trauma patients who underwent emergency surgery after routine PASG application had been discontinued. Since the discontinuation of routine PASG application, scene time intervals for "intermediate" blunt and penetrating trauma activations have not changed, but scene times for "full-activation" blunt trauma have actually increased (6.4 minutes with PASG and 9.5 minutes without PASG, P = .0004). Transport times were found to be a function of the type of trauma; patients with penetrating injuries were transported more rapidly (P < .0001) than patients with blunt trauma, even after controlling for injury severity and point of origin. Total time elapsed from EMS activation to the start of surgery for "full" activations, both blunt and penetrating, was unchanged (52.8 minutes with PASG and 53.8 minutes without PASG for penetrating trauma, 117.9 minutes with PASG and 105.1 minutes without PASG for blunt trauma). Times for "intermediate" activations did not change significantly. Length of intensive care unit (ICU) stay did not change. Within the subgroup of patients with femoral but not pelvic fractures, time spent at the scene of injury was shorter for patients treated with PASG than for those treated without (9.5 minutes v 14.5 minutes, P = .0066). Predicted and actual mortality rates were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohort Studies↗
PubMed1995

The relationship between white matter low attenuation on brain CT and vascular risk factors: a memory clinic study.

In order to discover the prevalence of white matter low attenuation (WMLA) in the brain and its relationship to vascular risk factors in our Memory Disorders Clinic patients we assessed brain CT scans of 202 patients referred to our clinic between January 1991 and December 1992. One hundred patients (49.5%) had WMLA, and the prevalence increased with increasing severity of cognitive impairment. It was 12% in patients with no evidence of dementia, 32% in those with isolated memory loss, and 59%) in patients with possible or probable dementia. There was a correlation between WMLA and systolic blood pressure, heart disease, peripheral vascular disease, focal neurological signs on examination and central atrophy on CT. No correlation was found between WMLA and low blood pressure, blood glucose or cholesterol level. Our findings indicate that WMLA probably plays an important role in cognitive impairment, and that thromboembolic rather than haemodynamic factors are probably more important in its pathogenesis.

Aged↗
PubMed1995

Traumatic carotid and vertebral artery dissection in a professional jockey: a cautionary tale.

Jockeys accept bony fractures and soft tissue injuries as occupational hazards. An average National Hunt jockey falls once in ten races with an injury rate of 4.25%. Head injury is a common cause of morbidity and the benefit of helmets is well recognized. Neck injuries are also common and usually musculoskeletal. Although rare, trauma to the neck arteries may go unnoticed yet have catastrophic consequences. Internal tears can allow arterial blood to dissect the layers of the arterial wall and obstruct the lumen. Severe obstruction may lead to cerebral ischaemia and infarction. An appreciation of the early clinical signs caused by this process may allow effective intervention. We report a case which illustrates these points.

Adult↗
PubMed1995

XCL100, an inducible nuclear MAP kinase phosphatase from Xenopus laevis: its role in MAP kinase inactivation in differentiated cells and its expression during early development.

We have cloned the Xenopus laevis homologue (XCL100) of the human CL100 (Thr/Tyr) MAP kinase phosphatase. Expression of the XCL100 mRNA and protein is inducible by serum stimulation and oxidative/heat stress in a X. laevis kidney cell line. In contrast, XCL100 is constitutively expressed in growing Xenopus oocytes. Recombinant XCL100 protein is able to dephosphorylate both tyrosine and threonine residues of activated p42 MAP kinase in vitro and both the Xenopus and human CL100 proteins were localised predominantly in the nucleus in transfected COS-1 cells. As nuclear translocation of activated MAP kinase is necessary for some of its essential functions in proliferation and cell differentiation our results indicate a role for CL100 in the regulation of these nuclear signalling events. In Xenopus kidney cells both heat shock and serum stimulation lead to transient activation of MAP kinase. However, in contrast to results previously reported from studies on mammalian fibroblasts the inactivation of MAP kinase in these epitheloid cells is rapid and is not dependent on synthesis of new protein. These results indicate that the induction of CL100 (or CL100-like enzymes) may not be required for MAP kinase inactivation in all cell types. Finally, during early embryogenesis, levels of XCL100 mRNA are greatly increased at the mid-blastula transition, suggesting that this enzyme may be involved in the regulation of MAP kinase activity during early development.

Amino Acid Sequence↗
PubMed1994

Photoaffinity labeling of the ryanodine receptor/Ca2+ release channel with an azido derivative of ryanodine.

Ryanodine receptors/Ca2+ release channels play an important role in regulating the intracellular free calcium concentrations in both muscle and nonmuscle cells. Ryanodine, a neutral plant alkaloid, specifically binds to and modulates these Ca2+ release channels. In the work described here, we characterize the interaction of a tritium-labeled, photoactivable derivative of ryanodine (3H-labeled 10-O-[3-(4-azidobenzamido)propionyl]ryanodine ([3H]ABRy)) with the ryanodine receptor of skeletal, cardiac, and brain membranes. Scatchard analysis demonstrates that this ligand binds to a single class of high affinity sites in skeletal muscle triads. Furthermore, competition binding assays of [3H]ryanodine with skeletal, cardiac, and brain membranes in the presence of increasing concentrations of unlabeled ABRy illustrate that this azido derivative of ryanodine is able to specifically displace [3H]ryanodine from its binding site(s). Analysis of the effects of Ca2+, ATP, and KCl on [3H]ABRy binding in triad membranes shows a similar modulation of binding to that seen in these membranes with [3H]ryanodine. Photoaffinity labeling of triads with [3H]ABRy resulted in specific and covalent incorporation of [3H]ABRy into a 565-kDa protein that was shown to be the skeletal muscle ryanodine receptor. Digestion of the labeled ryanodine receptor revealed a [3H]ABRy-labeled 76-kDa tryptic fragment that was identified with an antibody directed against the COOH-terminal of the receptor. These results demonstrate that the 76-kDa COOH-terminal tryptic fragment contains the high affinity binding site for ryanodine.

Adenosine Triphosphate↗
PubMed1994

Radioimmunoassay for the calcium release channel agonist ryanodine.

A novel photo-activatable derivative of ryanodine, 9-hydroxy-21-(4-azidobenzoyloxy)-9-epiryanodine, has been synthesized and conjugated to keyhole limpet hemocyanin for the production of antibodies with high affinity and specificity to ryanodine. The anti-ryanodine antibodies reacted specifically on immunoblots with the azido-ryanodine compound covalently conjugated to bovine serum albumin. A radioimmunoassay specific for ryanodine was developed using the anti-ryanodine antibodies, and a dissociation constant for ryanodine of 1 nM was determined. Half-maximal inhibition constants (IC50) for various ryanodine derivatives were found to range between 3.2 and 200 nM. These IC50 values correlated very well with the IC50 values obtained for the compounds binding to the skeletal muscle membrane receptor. These antibodies should be useful for the characterization of the ryanodine binding site on the sarcoplasmic reticulum Ca2+ release channel.

Animals↗
PubMed1994

Flow cytometry for monitoring contaminant exposure in black-crowned night-herons.

The flow cytometry methods (FCM) was employed to determine cellular DNA content of black-crowned night-heron (Nycticorax nycticorax) embryos and 10-day-old chicks collected at sites differing in types of chemical contamination. The coefficient of variation of DNA content (CV) in blood collected from embryos suggested cytogenetic damage at a side in Louisiana known to be contaminated with petroleum. Blood CV from chicks suggested genetic damage at a site in Texas also known to be contaminated with petroleum. Spleen CVs in chicks were significantly lower than respective means from the reference site. The CVs of chick blood and liver and spleen negatively correlated, suggesting recovery of spleen and liver cells after exposure to a clastogenic compound. Thus, the lower CVs may also have been indicative of genetic damage. Based on the findings of this study, FCM is a potential indicator of certain environmental contaminants in black-crowned night-herons.

Animals↗
PubMed1993

Analysis of a measles epidemic.

In January, February and March of 1989 an epidemic of rubeola occurred on the campus of Texas Tech University. A vaccination programme was initiated as soon as the epidemic was confirmed. Extensive case histories of all confirmed cases were collected by the Lubbock City Health Department and given an exhaustive statistical analysis by a group from the Department of Mathematics at Texas Tech University. The data and statistical analysis were used to formulate stochastic and deterministic models of the measles epidemic based on the standard SEIR model. The analysis and the simulations indicate that in order to prevent a measles outbreak on a university campus a high rate of immunity may be required (> 98 per cent). The assumptions in the models raise some interesting questions regarding social contacts which require further investigation.

Antibody Formation↗
PubMed1993

Clinical utilization and complications of sural nerve biopsy.

Surgeons frequently perform sural nerve biopsy as part of the work-up of patients with peripheral neuropathy. The indications for the procedure, therapeutic value, and complications associated with the procedure have received little attention in the surgical literature. A retrospective chart review of 60 patients with the suspected diagnosis of peripheral neuropathy undergoing sural nerve biopsy was performed. Vasculitis was suspected in 29 (48%) patients undergoing biopsy. This diagnosis was confirmed in 6 of the 29 patients and resulted in the alteration of therapy in 31% of patients with this suspected diagnosis. In 27 (45%) patients, the etiology of their peripheral neuropathy was unknown. Twelve (44%) patients in this group had sural nerve pathology; however, no change in therapy was required. Ten patients in our series had associated malignant tumors; some of these patients were diagnosed after referral for sural nerve biopsy. Twenty-five (42%) patients remained undiagnosed after biopsy. Nerve conduction studies were performed in 14 (22%) patients. Thirteen patients with abnormal lower extremity nerve conduction studies had 6 normal and 7 abnormal biopsy results. The one patient with a normal study had a normal nerve biopsy result. There were six (10%) patients with wound infections, seven (12%) patients with delayed wound healing, and three (5%) patients with new onset of chronic pain in the distribution of the sural nerve, for an overall complication rate of 27%. There was no correlation between the preoperative use of antibiotics, type of local anesthetic used, or length of nerve excised and complication rate. We conclude that the complication rate after sural nerve biopsy is significant. Strict criteria should be employed in selecting patients for sural nerve biopsy including a careful neurologic history and physical examination, nerve conduction studies, appropriate work-up for vasculitis if suspected, and implementation of a search for malignancy if this is not apparent. If the diagnosis is still in question, then sural nerve biopsy would seem appropriate, especially in patients with suspected vasculitis.

Adult↗