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Biomedical subjects

J Lovell

Publications and source records attributed to J Lovell.

At least 19 recordsLinked to original sources

Magnetic versus manual guidewire manipulation in neuroradiology: in vitro results.

INTRODUCTION: Standard microguidewires used in interventional neuroradiology have a predefined shape of the tip that cannot be changed while the guidewire is in the vessel. We evaluated a novel magnetic navigation system (MNS) that generates a magnetic field to control the deflection of a microguidewire that can be used to reshape the guidewire tip in vivo without removing the wire from the body, thereby potentially facilitating navigation along tortuous paths or multiple acute curves. METHOD: The MNS consists of two permanent magnets positioned on either side of the fluoroscopy table that create a constant precisely controlled magnetic field in the defined region of interest. This field enables omnidirectional rotation of a 0.014-inch magnetic microguidewire (MG). Speed of navigation, accuracy in a tortuous vessel anatomy and the potential for navigating into in vitro aneurysms were tested by four investigators with differing experience in neurointervention and compared to navigation with a standard, manually controlled microguidewire (SG). RESULTS: Navigation using MG was faster (P=0.0056) and more accurate (0.2 mistakes per trial vs. 2.6 mistakes per trial) only in less-experienced investigators. There were no statistically significant differences between the MG and the SG in the hands of experienced investigators. One aneurysm with an acute angulation from the carrier vessel could be navigated only with the MG while the SG failed, even after multiple reshaping manoeuvres. CONCLUSION: Our findings suggest that magnetic navigation seems to be easier, more accurate and faster in the hands of less-experienced investigators. We consider that the features of the MNS may improve the efficacy and safety of challenging neurointerventional procedures.

Catheterization↗

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗

Pitfalls in homozygosity mapping.

There is much interest in use of identity-by-descent (IBD) methods to map genes, both in Mendelian and in complex disorders. Homozygosity mapping provides a rapid means of mapping autosomal recessive genes in consanguineous families by identifying chromosomal regions that show homozygous IBD segments in pooled samples. In this report, we point out some potential pitfalls that arose during the course of homozygosity mapping of the enhanced S-cone syndrome gene, resulting from (1) unexpected allelic heterogeneity, so that the region containing the disease locus was missed as a result of pooling; (2) identification of a homozygous IBD region unrelated to the disease locus; and (3) the potential for inflation of LOD scores as a result of underestimation of the extent of inbreeding, which Broman and Weber suggest may be quite common.

Alleles↗

Fusogenic domains of golgi membranes are sequestered into specialized regions of the stack that can be released by mechanical fragmentation.

A well-characterized cell-free assay that reconstitutes Golgi transport is shown to require physically fragmented Golgi fractions for maximal activity. A Golgi fraction containing large, highly stacked flattened cisternae associated with coatomer-rich components was inactive in the intra-Golgi transport assay. In contrast, more fragmented hepatic Golgi fractions of lower purity were highly active in this assay. Control experiments ruled out defects in glycosylation, the presence of excess coatomer or inhibitory factors, as well as the lack or consumption of limiting diffusible factors as responsible for the lower activity of intact Golgi fractions. Neither Brefeldin A treatment, preincubation with KCl (that completely removed associated coatomer) or preincubation with imidazole buffers that caused unstacking, activated stacked fractions for transport. Only physical fragmentation promoted recovery of Golgi fractions active for transport in vitro. Rate-zonal centrifugation partially separated smaller transport-active Golgi fragments with a unique v-SNARE pattern, away from the bulk of Golgi-derived elements identified by their morphology and content of Golgi marker enzymes (N-acetyl glucosaminyl and galactosyl transferase activities). These fragments released during activation likely represent intra-Golgi continuities involved in maintaining the dynamic redistribution of resident enzymes during rapid anterograde transport of secretory cargo through the Golgi in vivo.

Animals↗

Life-threatening pica: liver abscess from perforating foreign body.

A case is presented of a patient with a psychiatric illness and pica who developed a pyogenic liver abscess due to perforation of the duodenum by a pen. This report emphasizes the importance of ultrasound and computed tomography in making a rapid diagnosis. The relative superiority of ultrasound was revealed because an anaesthetic was not required for scanning, and in addition to the liver abscess, the precise location of the perforating foreign body was demonstrated.

Adult↗

Effects of methylglyoxal on rat pancreatic beta-cells.

The addition of the alpha-ketoaldehyde methylglyoxal (0.5 or 1 mmol/L) to single isolated rat pancreatic beta-cells caused a rapid, marked depolarization resulting in electrical activity. This effect of methylglyoxal on beta-cell was reversible upon removal of the alpha-ketoaldehyde, and could be inhibited by the anion channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). Methylglyoxal also resulted in elevated cytosolic [Ca2+] and an intracellular acidification in intact rat islets. In perifused islets, methylglyoxal provoked a modest, transient stimulation of secretion but inhibited glucose-induced insulin release. Incubation of islets with methylglyoxal resulted in the formation of large quantities of D-lactate, indicating metabolism of the alpha-ketoaldehyde via the glyoxalase pathway. The effects of methylglyoxal on beta-cell membrane potential, cytosolic [Ca2+] and intracellular pH were also observed in response to phenylglyoxal which is also effectively metabolized via the glyoxalase pathway. However, t-butylglyoxal which is poorly metabolized via the glyoxalase pathway, caused neither depolarization of the membrane potential nor intracellular acidification, but did inhibit glucose-induced insulin release. These findings suggests that the depolarization and acidification evoked by methyl- and phenylglyoxal are dependent upon their metabolism via the glyoxalase pathway. The possible mechanisms coupling alpha-ketoaldehyde metabolism via the glyoxalase pathway with membrane depolarization are discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

HIV/AIDS patients' perspectives on adhering to regimens containing protease inhibitors.

OBJECTIVE: To gather qualitative data regarding HIV/AIDS patients' perspectives about HIV-1 protease inhibitors (PIs), and about their experiences taking and adhering to regimens containing PIs. DESIGN: Six focus groups of persons under care for HIV were conducted between September and November 1996 regarding participants' knowledge, awareness, experiences when taking, and adherence to antiretroviral regimens containing PIs. An identical discussion guide was used to facilitate all six groups. Focus group proceedings were audiotaped, transcribed, coded for themes, and analyzed qualitatively. SETTING: HIV/AIDS practices of three teaching hospitals and two community health centers. PATIENTS/PARTICIPANTS: Fifty-six patients with HIV disease: 28 men and 28 women. MEASUREMENTS AND MAIN RESULTS: Knowledge and positive impressions of PIs were prevalent among this diverse group of persons with HIV, and did not differ by race/ethnicity or gender. Most knew that these were new, potent medications for treating HIV/AIDS. Networks of persons with HIV and medical providers were the most important information sources. Those taking PIs were aware that adherence to the regimen is important, and most were using special strategies to maximize their own adherence, but expressed considerable frustration about the central role these medication regimens had assumed in their life. A subset who did not believe they would adhere to these regimens had declined treatment with them. Motivating factors for taking and adhering to these complex regimens were improving CD4 counts and viral loads and the patient-provider relationship. CONCLUSIONS: Among those with HIV/AIDS, awareness of PIs and their effectiveness is substantial, owing to the impact of informal networks and medical providers. This early positive "reputation" of PIs may enhance motivation for adherence. Those who are taking PIs invest substantial effort adhering to these complex regimens, but resent the need to make medications the focus of their lives.

Adult↗

Alcohol and the nervous system.

Alcoholism is regarded as a multifactorial disorder, but the causes of alcoholism are poorly understood. The most important part of dealing with this widespread health and social problem is a prevention and early identification and treatment of those at risk. Therapeutic intervention should take place before development of cognitive impairment and physical dependence, otherwise treatment of developed alcoholism is notoriously unsatisfactory.

Alcohol Withdrawal Delirium↗

Common bond.

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Breast Neoplasms↗

Carbamazepine and sciatica.

Carbamazepine is useful in the management of various painful conditions. The mechanism of its action is not known. Whatever its mechanism, Carbamazepine appears to have a good chance of relieving painful disorders with episodic, flashing pain. Two cases of sciatica responding favourably to carbamazepine are presented in detail.

Carbamazepine↗