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Biomedical subjects

D Thomas

Publications and source records attributed to D Thomas.

At least 235 records · Page 13Linked to original sources

Molecular cloning of a putative cyclic nucleotide-gated ion channel cDNA from Limulus polyphemus.

Cyclic nucleotide-gated channels have been proposed to mediate the electrical response to light in the ventral photoreceptor cells of the horseshoe crab, Limulus polyphemus. However, a cyclic nucleotide-gated channel has not been identified from Limulus. We have cloned a putative full-length cyclic nucleotide-gated channel cDNA by screening cDNA libraries constructed from Limulus brain using a probe developed from Limulus ventral eye nerves. The putative full-length cDNA was derived from two overlapping partial cDNA clones. The open reading frame encodes 905 amino acids; the sequence shows 44% identity to that of the alpha subunit of the bovine rod cyclic GMP-gated channel over the region containing the transmembrane domains and the cyclic nucleotide binding domain. This Limulus channel has a novel C-terminal region of approximately 200 amino acids, containing three putative Src homology domain 3 binding motifs and a putative coiled-coil domain. The possibility that this cloned channel is the same as that detected previously in excised patches from the photoreceptive membrane of Limulus ventral photoreceptors is discussed in terms of its sequence and its expression in the ventral eye nerves.

Animals↗

Perivalvular abscesses associated with endocarditis; clinical features and prognostic factors of overall survival in a series of 233 cases. Perivalvular Abscesses French Multicentre Study.

AIMS: The purposes of this study were to determine the clinical features and to identify prognostic factors of abscesses associated with infective endocarditis. METHODS AND RESULTS: During a 5-year period from January 1989, 233 patients with perivalvular abscesses associated with infective endocarditis were enrolled in a retrospective multicentre study. Of the patients, 213 received medical surgical therapy and 20 medical therapy alone. No causative microorganism could be identified in 31% of cases. Sensitivity for the detection of abscesses was 36 and 80%, respectively using transthoracic and transoesophageal echocardiography. Surgical treatment consisted of primary suture of the abscess (38%), insertion of a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of the abscess cavity (20%). The 1 month operative mortality was 16%. Actuarial rates for overall survival at 3 and 27 months in operated patients were 75 +/- 10% and 59 +/- 11%, respectively. Increasing patient age, staphylococcal infection, and fistulization of the abscess were found to be independent risk factors in both 1 month and overall operative mortality. Renal failure was a risk factor predictive of operative mortality at 1 month, whereas uncontrolled infection and circumferential abscess were regarded as risk factors predictive of overall operative mortality. CONCLUSION: The data determined prognostic factors of abscesses associated with infective endocarditis.

Abscess↗

The Mantero flexor tendon repair in zone 1.

Mantero and colleagues have reported a modification of the Bunnell pull-out method for the repair of zone 1 flexor digitorum profundus (FDP) lacerations that allows active postoperative mobilization. We report a series of 24 FDP lesions in 20 adult patients treated with this technique. The mean duration of the rehabilitation regimen, which was followed by all patients, was 4.2 months. Functional assessment using Strickland's criteria demonstrated 23 excellent to good results and one poor due to a septic rupture. Nineteen of the 20 patients were satisfied with treatment and all but one of the patients returned to work within an average of 2.6 months after operation. In comparison to other zone 1 repair methods with active mobilization regimens, the Mantero technique gives better functional outcomes and appears to be more reliable.

Adolescent↗

The effects of posteroventral pallidotomy on the preparation and execution of voluntary hand and arm movements in Parkinson's disease.

We studied the effect of posteroventral pallidotomy on movement preparation and execution in 27 parkinsonian patients using various motor tasks. Patients were evaluated after overnight withdrawal of medication before and 3 months after unilateral pallidotomy. Surgery had no effect on initiation time in unwarned simple and choice reaction time tasks, whereas movement time measured during the same tasks was improved for the contralesional hand. Movement times also improved for isometric and isotonic ballistic movements. In contrast, repetitive, distal and fine movements measured in finger-tapping and pegboard tasks were not improved after pallidotomy. Preparatory processes were investigated using both behavioural and electrophysiological measures. A precued choice reaction time task suggested an enhancement of motor preparation for the contralesional hand. Similarly, movement-related cortical potentials showed an increase in the slope of the late component (NS2) when the patients performed joystick movements with the contralesional hand. However, no significant change was found for the early component (NS1) or when the patient moved the ipsilesional hand. The amplitude of the long-latency stretch reflex of the contralesional hand decreased after surgery. In summary, the data suggest that pallidotomy improved mainly the later stages of movement preparation and the execution of proximal movements with the contralesional limb. These results provide detailed quantitative data on the impact of posteroventral pallidotomy on previously described measures of upper limb akinesia in Parkinson's disease.

Electroencephalography↗

Sperm mitochondria-associated cysteine-rich protein (SMCP) is an autoantigen in Lewis rats.

A common repertoire of rat sperm antigens have previously been identified by Western blotting of sperm proteins with sera obtained after vasectomy or isoimmunization with sperm. Aside from a determination of their apparent masses, however, the biochemical characteristics of these antigens have remained unknown. In this study, a rat testis cDNA expression library was screened with polyclonal antibodies obtained from rats immunized with isologous spermatozoa to identify and sequence a full-length clone encoding rat sperm mitochondria-associated cysteine-rich protein (SMCP). The open reading frame of SMCP was expressed in the pET22b vector, and recombinant SMCP (rec-SMCP) was purified. Sera from rats that had been vasectomized or hyperimmunized with isologous sperm specifically recognized rec-SMCP whereas preimmune sera from these experimental groups did not react. Rabbit antiserum produced to rec-SMCP recognized rec-SMCP on Western blots and precisely immunolocalized SMCP to the mid-piece of rat sperm. On Western blots against sperm extracts, the rabbit antibody recognized a major protein band of approximately 22-25 kDa that co-migrated with bands of identical mass that were recognized by sera from hyperimmune or vasectomized rats. These findings demonstrate that SMCP is a sperm autoantigen, recognized following vasectomy, and an isoantigen, recognized by antibodies generated through isologous immunization with sperm.

Amino Acid Sequence↗

Visualization of AqpZ-mediated water permeability in Escherichia coli by cryoelectron microscopy.

Transport of water across the plasma membrane is a fundamental process occurring in all living organisms. In bacteria, osmotic movement of water across the cytoplasmic membrane is needed to maintain cellular turgor; however, the molecular mechanisms of this process are poorly defined. Involvement of aquaporin water channels in bacterial water permeability was suggested by the recent discovery of the aquaporin gene, aqpZ, in Escherichia coli. By employing cryoelectron microscopy to compare E. coli cells containing (AqpZ+) and lacking (AqpZ-) aquaporin, we show that the AqpZ water channel rapidly mediates large water fluxes in response to sudden changes in extracellular osmolarity. These findings (i) demonstrate for the first time functional expression of a prokaryotic water channel, (ii) evidence the bidirectional water channel feature of AqpZ, (iii) document a role for AqpZ in bacterial osmoregulation, and (iv) define a suitable model for studying the physiology of prokaryotic water transport.

Aquaporins↗

Spontaneous late improvement of myocardial viability in the chronic infarct zone is possible, depending on persistent TIMI 3 flow and a low grade stenosis of the infarct artery.

OBJECTIVE: In the chronic phase of myocardial infarction, the relation between myocardial recovery and infarct related artery status remains unclear. The spontaneous changes in rest-redistribution thallium defect size were prospectively studied over six months in 52 patients with chronic Q wave myocardial infarction. DESIGN: Changes in rest thallium defect size, thallium uptake in the infarct area, and radionuclide left ventricular ejection fraction were compared to the quantitative coronary angiogram data. Two groups of patients were considered: patients with a percentage of stenosis below 100% (group 1, n = 31); and patients with an occluded artery (group 2, n = 21). RESULTS: In the overall population, the mean (SD) defect size decreased from 28.2 (17.2)% to 24.9 (19.3)% of the whole myocardium (p = 0.01), while, in this area, the thallium uptake increased from 62.9 (13.7)% to 66. 9 (15.6)% (p < 0.001). At the time of inclusion, the defect size, thallium uptake, and ejection fraction were similar in both groups. In group 1 patients only, the reduction in defect size correlated with the improvement in ejection fraction (r = 0.41, p = 0.02) and was related to the percentage of coronary artery stenosis. TIMI 3 patients reduced the defect size while other patients increased this defect (-5.1 (7.0)% v +11.0 (14.4)%, p < 0.001). In contrast, no significant relations were found in group 2 patients. CONCLUSION: Late spontaneous recovery in thallium defect can occur in patients with a patent infarct related artery, depending on the TIMI flow grade and a low grade stenosis of the infarct related artery, and is associated with functional improvement.

Aged↗

Cardiovascular, autonomic, and plasma catecholamine responses in unilateral and bilateral carotid artery stenosis.

OBJECTIVE: To determine impairment of baroreceptor afferent activity, which may affect cardiovascular autonomic function in patients with unilateral and bilateral carotid artery stenosis. Comparison was made with normal subjects and hypertensive patients. METHODS: A series of cardiovascular autonomic function tests along with plasma noradrenaline (norepinephrine) measurements were performed in 46 patients with carotid artery stenosis (CAS); 23 had unilateral and 23 had bilateral stenosis. Comparison was made with 21 hypertensive patients (with a similar degree of raised blood pressure), and 27 normal subjects. RESULTS: Over a third of patients with unilateral and bilateral CAS had postural hypotension. Heart rate did not rise appropriately in CAS despite the postural fall in blood pressure. Pressor responses in CAS were preserved. Heart rate responses to respiratory stimuli were attenuated. Plasma noradrenaline concentrations rose normally during head up tilt. CONCLUSION: A substantial proportion with CAS had postural hypotension and attenuated heart rate responses. This was not due to sympathetic vasoconstrictor or cardiac parasympathetic failure, thus suggesting impaired afferent baroreceptor activity, probably secondary to involvement of the carotid sinus. Cardiovascular autonomic testing and assessment of postural hypotension and factors enhancing it may be of clinical relevance in such patients, especially as the symptoms of postural hypotension overlap with those due to thromboembolism.

Aged↗

Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis.

PURPOSE: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days. PATIENTS AND METHODS: Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle. RESULTS: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trend in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P >.05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P =.041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease. CONCLUSION: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.

Adult↗

Image-guided neurosurgery.

Accurate localization of lesions and minimization of trauma to the surrounding brain are of paramount importance in intracranial surgery. Stereotactic frame systems provide highly accurate methods of localization, which has been further enhanced by the introduction of sophisticated imaging modalities, and recently by the development of interactive image-guided neurosurgical technology.

Humans↗

The prognostic significance of p16INK4a/p14ARF and p15INK4b deletions in adult acute lymphoblastic leukemia.

Cytogenetic/molecular abnormalities significantly influence the prognosis of patients with acute leukemia. Recently, two genes, p16INK4a and p15INK4b, encoding two cyclin-dependent kinase inhibitor proteins of the INK4 family of Mr 15,000 and 16,000, respectively, have been localized to 9p21. Remarkably, the p16INK4a locus has been found to encode a second protein, p14ARF, known as p19ARF in mice, with a distinct reading frame. Like p16INK4a, p14ARF is involved in cell cycle regulation, blocking cells at the G1 restriction point through the activity of MDM-2 and p53. We studied bone marrow samples of 42 newly diagnosed and untreated patients with acute lymphoblastic leukemia for the incidence of deletions of p16INK4a/p14ARF and p15INK4b using Southern blot analysis and determined the clinical outcome with regard to complete remission (CR) duration, event-free survival, and overall survival. We found deletions of p16INK4a/p14ARF in 17 of 42 patients (40%), with homozygous deletions in 11 of 42 patients (26%) and hemizygous deletions in 6 of 42 patients (14%). The gene for p15INK4b was codeleted in most, but not all, cases and was never deleted without deletion of p16INK4a/ p14ARF. No correlation was observed between molecular studies and karyotype abnormalities as determined by conventional cytogenetics. Furthermore, no difference was found in the CR rate, CR duration, event-free survival, and overall survival in patients with homozygous gene deletions compared to patients with no deletions or loss of only one allele.

Adolescent↗

[Silent Q fever endocarditis. Report of a case].

A murmur of aortic regurgitation was discovered in an asymptomatic patient who had suffered from an acute Coxiella Burnetti infection several months before hand. Transoesophageal echocardiography, serology and direct immunofluorescence of the aortic valve confirmed the diagnosis of Q fever endocarditis. Treatment with Vibramycin and Plaquenil was instituted after aortic valve replacement. Cardiac complications of Q fever should be recognised as they may remain asymptomatic for long periods of time. Transthoracic and transoesophageal echocardiography should be widely used in acute forms of Q fever and systematic in chronic infections with Coxiella Burnetti.

Adult↗

Statistical methods for epidemiologic studies of the health effects of air pollution.

We describe two statistical designs that can provide efficient estimates of the health effects of exposure to air pollutants in epidemiologic studies. We also evaluate the effects of measurement error in exposure assessment on the accuracy of estimated health effects. The bidirectional case-crossover design is a variant of a method proposed by Maclure (1991). Our version of the method takes advantage of the fact that in epidemiologic studies involving environmental exposure, accurate information about past exposure is more readily available, and that levels of exposure are generally unaffected by the response of the subject. It differs from other case-crossover methods in that control information is assessed both before and after failure, thus avoiding confounding due to time trends in exposure. The multilevel analytic design provides a method of combining estimates of health effects made on the individual level with those made at the group level. It has great potential value in situations where variations in exposure within groups may not be great enough to provide adequate power to detect health effects, as is often the case in air pollution studies where exposure levels are similar within a geographic community. Measurement errors in exposure assessment can have substantial impact on the accuracy of estimated health effects. When the microenvironmental approach is used to estimate exposure, a standard error of 30% in estimating indoor/outdoor ratios can increase the standard error of a relative risk estimate by 50%, and introduce bias as well. Similar results hold when exposure is estimated with personal samplers. When the microenvironmental approach is used, errors in estimating indoor/outdoor ratios have more influence on the accuracy of risk estimation than do errors in estimating the time spent in microenvironments.

Absenteeism↗

Pre-operative planning and intra-operative guidance in modern neurosurgery: a review of 300 cases.

Operative neurosurgery has recently entered an exciting era of image guided surgery or neuronavigation and application of this novel technology is beginning to have a significant impact in many ways in a variety of intracranial procedures. In order to fully assess the advantages of image guided techniques over conventional planning and surgery in selected cases, detailed prospective evaluation has been carried out during the advanced development of an optically tracked neuronavigation system. Over a 2-year period, 300 operative neurosurgical procedures have been performed with the assistance of interactive image guidance, as well as the development of new software applications and hardware tools. A broad range of intracranial neurosurgical procedures were seen to benefit from image guidance, including 163 craniotomies, 53 interactive stereotactic biopsies, 7 tracked neuroendoscopies and 37 complex skull base procedures. The most common pathological diagnoses were cerebral glioma in 98 cases, meningioma in 64 and metastasis in 23. Detailed analysis of a battery of postoperative questions revealed benefits in operative planning, appreciation of anatomy, lesion location, safety of surgery and greatly enhanced surgical confidence. The authors believe that image guided surgical technology, with new developments such as those described, has a significant role to play in contemporary neurosurgery and its widespread adoption in practice will be realised in the near future.

Adolescent↗