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Biomedical subjects

M Perry

Publications and source records attributed to M Perry.

At least 19 recordsLinked to original sources
PubMed2025

The UTRs of Leishmania donovani vary in length and are enriched in potential regulatory structures.

Leishmania spp. regulate gene expression largely post-transcriptionally, yet untranslated regions (UTRs) remain poorly delineated. We generated high-quality genome and transcriptome datasets for Leishmania donovani strain 1S2D (Ld1S) by combining PacBio HiFi de novo assembly with Oxford Nanopore direct RNA sequencing of promastigotes and axenic amastigotes. The genome assembly consists of 65 scaffolds totaling ~33.3 Mb. Structural comparisons to LdBPK282A1 revealed numerous rearrangements, including some reshuffling genes among polycistronic transcription units and validated by polycistronic reads from RNA sequencing. Promastigote and amastigote RNA sequencing produced 469,010 and 46,729 monocistronic reads containing a spliced-leader and a polyA tail sequences, defining 8,479 transcripts and supporting 7,415 of the 7,969 annotated protein coding genes, as well as 604 putative long non-coding RNAs. We annotated UTRs for 4,921 genes and observed that putative RNA G-quadruplexes were markedly enriched in UTRs. We also noted that 31.9% and 11.5% were expressed into multiple isoforms in promastigotes and amastigotes, respectively. Collectively, these data provide a comprehensive annotation of L. donovani genes and their UTRs and reveal widespread and stage-specific UTR length polymorphisms, and, overall, points to an important role of 3' UTR in post-transcriptional regulation in L. donovani.

Journal Article↗
PubMed2005

Audit of intrapartum group B streptococcus prophylaxis.

Group B streptococcus is the most frequent cause of severe early onset neonatal infection. For over 3 years our department has employed a risk-factor-based protocol of intra-partum antibiotic prophylaxis. Prophylaxis has been considered adequate if women receive antibiotics more than 4 hours before delivery. This study aims (1) to establish the adequacy of intrapartum prophylaxis in routine clinical practice and (2) to determine whether changing the time interval (from commencement of prophylaxis to delivery) for adequacy from 4 to 2 hours (based on RCOG guidelines) improves the percentage of women receiving adequate prophylaxis. This was an audit against established protocol. Case notes of consecutive deliveries over a 4-week period were reviewed retrospectively. A total of 396 deliveries occurred during the study period. Some 44 women (11%) were eligible for antibiotic prophylaxis. Adequate prophylaxis was achieved in 21 cases (49%). If the time for prophylaxis to be considered adequate was reduced from 4 to 2 h, the number of women receiving adequate prophylaxis increased to 33 (76%). In conclusion, despite the protocol being well established, only half of the eligible women receive adequate intra-partum prophylaxis. Reducing the time interval from 4 to 2 h appreciably increases the number of women receiving adequate prophylaxis, which reduces the necessity of providing neonatal prophylaxis.

Anti-Bacterial Agents↗
PubMed2002

CDP840. A prototype of a novel class of orally active anti-inflammatory phosphodiesterase 4 inhibitors.

The discovery, synthesis and biological activity of a series of triarylethane phosphodiesterase 4 inhibitors is described. Structure-activity relationship studies are presented for CDP840 (29), a potent, chiral, selective inhibitor of PDE 4 (IC(50) 4nM). CDP840 is non-emetic in the ferret at 30mgkg(-1) (po), active in models of inflammation and reverses ozone-induced bronchial hyperreactivity in the guinea pig.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-kappa B). Injection of 5T2MM myeloma cells into C57BL/KaLwRij mice resulted in the development of bone disease characterized by a significant decrease in cancellous bone volume in the tibial and femoral metaphyses, an increase in osteoclast formation, and radiologic evidence of osteolytic bone lesions. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established myeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy receptor for RANKL, prevented the development of lytic bone lesions. OPG treatment was associated with preservation of cancellous bone volume and inhibition of osteoclast formation. OPG also promoted an increase in femoral, tibial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system may play a critical role in the development of osteolytic bone disease in multiple myeloma and that targeting this system may have therapeutic potential.

Animals↗
PubMed2001

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Agrobacterium tumefaciens↗
PubMed2001

The effects of lamotrigine on sleep in patients with epilepsy.

PURPOSE: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in REM, slow-wave sleep (SWS) and sleep latency, and increased percentage of light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of lamotrigine (LTG) on sleep. METHODS: Ten adults with focal epilepsy, in whom the decision was made to add LTG to either phenytoin (PHT) or carbamazepine (CBZ) for control of seizures, were the subjects of this study. Patients underwent pre- and posttreatment polysomnography (PSG) and completed sleep questionnaires. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon sign rank test. RESULTS: Seven patients were taking CBZ, and three were treated with PHT. All subjects were titrated to an LTG dose of 400 mg/day. Treatment with LTG produced a significant decrease in SWS and an increase in stage 2 sleep percentage. No significant difference in ESS or any of the other polygraphic variables was observed. However, LTG treatment was associated with a reduction in arousals and stage shifts and an increase in REM periods. No subjects reported insomnia with treatment. CONCLUSIONS: LTG appears to be less disruptive to sleep than some of the older AEDs.

Adult↗
PubMed2001

Early detection of type 2 diabetes: the role of the community nurse.

Recent changes to the diagnostic criteria for type 2 diabetes have raised concerns that if steps are not taken to address relevant issues, the number of diagnosed sufferers will escalate in future years, with a similar increase in the prevalence of associated complications. Research suggests that for many patients, complications are evident at the time of diagnosis, and may have been present for several years before a diagnosis was made. Late presentation is the cause of considerable morbidity and mortality among these patients, largely because undiagnosed complications are often irreversible by the time the underlying diabetes is discovered. The current emphasis on public health augments the need for community nurses to recognize warning signs, particularly in patients who are at an increased risk of developing diabetes. This article aims to raise awareness of early signs and symptoms, and gives a brief insight into some of the associated health problems. If community nurses are to play a significant role in reducing the potentially devastating effects of this disease, they will need to be involved tin educating patients and implementing screening and intervention programmes.

Community Health Nursing↗
PubMed2001

TB and prisons.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMed2000

Urinary biomarkers of atrazine exposure among farm pesticide applicators.

PURPOSE: This study assessed the feasibility of three laboratory methods for the detection of atrazine, a triazine herbicide, and its related metabolites in urine collected from field applicators.METHODS: Urine samples were collected from 256 randomly sampled field applicators 8 hours post application. Of these, 99 reported atrazine use during the application prior to sample collection and these samples were subsequently analyzed for urinary biomarkers.RESULTS: 37.4% (n = 37) samples showed detectable levels (minimum = 1.0 ng/mL) of deethylatrazine using gas chromatographic mass spectrometry (GCMS) analysis (X = 14.2 ng/mL; s.d. = 13.5). Fifty samples were tested using atrazine mercapturate in urine ELISA methods and 80% (n = 40) of these samples showed detectable levels of atrazine (X = 6.4 ng/mL; s.d. = 7.5). Of 10 samples tested by triazines in water ELISA methods, a common assay used for the detection of atrazine in groundwater, 100% showed detectable levels of atrazine (X = 22.4 ng/mL; s.d. = 13.9). Of the 21 samples collected from non-applicators and tested by GCMS, none evidenced detectable atrazine levels. Using GCMS as the gold standard, analyses showed that the mercapturate in urine ELISA was 48% sensitive and 91% specific whereas the triazines in water ELISA was 69% sensitive and 100% specific.CONCLUSIONS: It is possible to detect one-time atrazine exposures through analysis of urinary biomarkers among pesticide applicators. The feasibility of triazines in water ELISA methods for use in field studies for analyzing the presence of atrazine and related metabolites in urine was supported, but these methods need further testing on larger applicator samples before they can be used for standard screening.

Journal Article↗
PubMed2000

Fine-needle aspiration of the thyroid.

BACKGROUND: Although fine-needle aspiration (FNA) of the thyroid is the key preoperative investigation of thyroid lesions, there are overlaps in the criteria for diagnosis of certain lesions, particularly important among which are those for follicular neoplasms. A proposal for a 5-category working system for thyroid FNA diagnosis is presented, devised using clearly defined diagnostic guidelines with a prospective 2-year evaluation in 1 center. METHODS: The results of FNA of 156 patients with nodular thyroid lesions are presented. All patients were observed over a 2-year period in a multidisciplinary thyroid clinic. In some cases, the aspirates were repeated before excision of the lesion. The results of the FNA are classified by worst category for each patient, according to a 5-category scheme: THY1: inadequate; THY2: benign; THY3: indeterminate; THY4: suspicious lesion; THY5: malignant. RESULTS: Seventy-five of the 156 patients (48.1%) proceeded to excision, of these 50 (67%) showed multinodular goiter or adenomatoid nodule within a goiter, 7 (9.3%) showed evidence of Hashimoto thyroiditis or lymphocytic thyroiditis alone, 1 (1.3%) showed evidence of Reidel thyroiditis, and 1 (1.3%) showed evidence of a parathyroid cyst. Eight patients (11%) showed evidence of follicular adenoma, and 5 patients (6.6%) showed papillary carcinoma; 1 (1.3%) showed follicular carcinoma, and 2 (2.7%) showed lymphoproliferative disease. There was a significant difference in the number of benign as compared with neoplastic thyroid lesions excised in the indeterminate (THY3) (2 of 13 [15%]) as compared with the suspicious categories (THY4) (10 of 24 [42%]), (P = 0.05). Although no false-negative FNAs were identified in this series, there was 1 false-positive (THY5) FNA. CONCLUSIONS: The use of an indeterminate (THY3) category is helpful because it improves the diagnostic efficacy of thyroid FNA. The indeterminate (THY3) category is clinically useful and may markedly reduce or eliminate false-negative FNA in many patients with thyroid nodules. Cancer (Cancer Cytopathol)

Biopsy, Needle↗
PubMed2000

Identifying montages that best detect electrographic seizure activity during polysomnography.

STUDY OBJECTIVES: Recognizing epileptic seizures during video polysomnography (VPSG) can be challenging, particularly when using standard, limited EEG montages and paper speed. Few sleep laboratories have PSG equipment that allows for the recording of 18 channels of EEG without compromising the ability to detect sleep apnea, periodic limb movements, and parasomnias. We studied the ability of sleep medicine- and EEG-trained polysomnographers to correctly identify epileptic seizures during PSG using 4, 7, and 18 channels of simultaneous EEG, recording at conventional PSG and EEG paper speeds. The purpose of this study was to determine the value of limited EEG montages viewed with EEG reformatting capability in the identification of seizures during PSG. DESIGN: Blinded EEG analysis of seizures and arousals during VPSG. SETTING: Tertiary care hospital with sleep laboratory and epilepsy monitoring unit. PATIENTS: Subjects with focal (partial) epilepsy that underwent video-EEG monitoring. INTERVENTIONS: We designed two 7-channel EEG montages that might facilitate the identification of seizures arising from the frontal and temporal lobes. Sleep medicine- and EEG-trained polysomnographers were asked to review tracings containing frontal or temporal lobe epileptic seizures and arousals from sleep. Utilizing the capability of our digital recording equipment to reformat EEG channels and change paper speeds, we asked the readers to classify events recorded with 4, 7, and 18 channels of simultaneous EEG, at paper speeds of 10 and 30 mm/sec. MEASUREMENTS AND RESULTS: 6 readers viewed 32 sleep-related events (13 frontal lobe seizures, 11 temporal lobe seizures, and 8 arousals). The following factors were analyzed for their influence on accuracy of event detection: 1) the type of training of the reader (EEG vs. sleep medicine); 2) the number of EEG channels (4, 7, or 18); and 3) paper speed (10 vs. 30 mm/sec). Pair-wise comparisons and generalized estimating equations were used to identify factors leading to more accurate detection of seizures and arousals. 77% of events were correctly identified: 74% of seizures and 88% of arousals. Seizure detection was better using 7 and 18 channels (sensitivity of 82% and 86%, respectively) than 4 EEG channels (sensitivity of 67%) for temporal lobe seizures only. The number of EEG channels did not affect the accuracy of frontal lobe seizure detection. For EEG-trained readers, accuracy was greater using 30 mm/sec than 10 mm/sec paper speed (85% vs. 78% correct, respectively). CONCLUSIONS: Adding EEG channels and EEG reformatting capabilities to PSG interpretation improves the detection of some types of epileptic seizures. Accuracy of temporal lobe seizure detection using an abbreviated 7-channel montage approximates that of an 18-channel EEG recording. However, the same is not true of frontal lobe seizures in which accuracy was similar regardless of the number of EEG channel available. Further studies are needed to identify specific EEG montages that would best detect epileptiform activity during VPSG.

Electrodes↗
PubMed2000

HPA-1a-mediated platelet interaction with monocytes in vitro: involvement of Fcgamma receptor (FcgammaR) classes and inhibition by humanised monoclonal anti-FcgammaRI H22.

To gain insight into mechanisms of platelet destruction and its possible inhibition during fetal/neonatal alloimmune thrombocytopenia (FAIT/NAIT) the binding to monocytes (Mo) of anti-HPA-1a-sensitised platelets, the initial step in IgG-mediated destruction by effector cells, was evaluated in an in vitro assay. Neonatal Mo were compared with adult Mo as effectors in the assay. Moreover, the potential involvement of Fcgamma receptor (FcgammaR) classes during platelet destruction in the disease was tested by using FcgammaR class-specific reagents as inhibitors of the binding reaction. Neonatal Mo were 37% less active than adult Mo in their interaction with anti-HPA-1a-sensitised platelets (p < 0.05). The FcgammaRI-specific reagents human monomeric IgG and humanised anti-FcgammaRI monoclonal H22 caused virtually complete inhibition of platelet binding to Mo. When compared to an intravenous immunoglobulin preparation the inhibitory activity of H22 was 10-100 x greater than that of the latter compound. Monoclonal anti-FcgammaRII IV.3 and anti-FcgammaRIII 3G8 decreased platelet binding by 70% and 64%, respectively, but only the anti-FcgammaRII inhibition was statistically significant (p < 0.001). Finally, anti-HPA-1a-sensitised platelets bound to 131H- but not to 131R- FcgammaRIIa transfected 3T6 mouse fibroblasts (p < 0.01), in an anti-HPA-1a-concentration-dependent manner. The results suggest that FcgammaRI and FcgammaRIIa may be involved in anti-HPA-1a-mediated platelet destruction by mononuclear phagocytes during FAIT/NAIT. Moreover, the much greater potency ofmonoclonal H22 than of intravenous immunoglobulin as an inhibitor of anti-HPA-1a-mediated Mo-platelet interaction, might render it superior to the latter agent in the maternal therapy of the disorder.

Adult↗
PubMed2000

The bicoronal flap (craniofacial access): an audit of morbidity and a proposed surgical modification in male pattern baldness.

Maxillofacial surgeons have used the bicoronal flap for nearly three decades to gain access to the craniofacial skeleton. A retrospective analysis of 68 bicoronal flaps done over a five-year period showed that our incidence of permanent morbidity was low. Although 24 patients (35%) experienced some form of sensory abnormality immediately after the operation, this persisted for longer than two years in only one. Complete motor recovery occurred by one year in all 15 patients (22%) who developed postoperative frontalis weakness. Three patients developed male pattern baldness postoperatively, which resulted in exposure of the scar and poor cosmesis. This prompted a cadaveric study in which we assessed the feasibility of modifying the position of the standard bicoronal incision in people who are prone to hair loss. The pivotal point of the bicoronal flap was found to lie at its most inferior aspect. By extending the incision into the skin crease in front of the lobe of the ear it was possible to adjust the anteroposterior position of the bicoronal incision without limiting access to the facial skeleton. We therefore advocate occipitally placed incisions with preauricular extensions in patients who are prone to male pattern baldness.

Adolescent↗
PubMed2000

Academic general practice in Manchester under the early National Health Service: a failed experiment in social medicine.

During the Second World War, medical academics hoped to reform medical practice and education in Great Britain, increasing doctors' sensitivity to the social and environmental causes of ill health and orientating them towards prevention. At the start of the National Health Service (NHS), central planning aimed to raise the status of isolated urban general practitioners (GPs) by grouping them in an experimental health centre. This offered a locus for social medicine, encouraging cooperation and research with local authority staff (nurses, midwives, and social workers). The Manchester case study confirms that health centre working could not be disseminated while conditions for teamwork were absent elsewhere. The failure of academic planning can be attributed to a top-down approach upon demoralized urban practice. While the participants did not form an autonomous group, economic incentives drove the growth of group practice elsewhere and made health centres superfluous to government. The College of General Practitioners developed in parallel, offering an alternative path towards an academic discipline. The case study also suggests a relationship between the emergence of groups and a psychological orientation in practice. A patient-centred model became important within teaching and gave identity to the displine, but it probably had little impact on everyday practice.

Family Practice↗
PubMed2000

Admixture with whole blood does not explain false-negative urease tests.

Rapid urease test sensitivity for Helicobacter pylori is reduced in the presence of active upper gastrointestinal bleeding. The aim of this study was to evaluate the in vitro effect of whole blood on rapid urease testing. Urease solution was added to normal saline, and heparinized whole blood both positive and negative for H. pylori antibody. The mixtures were then serially diluted in saline, and/or whole blood and added to three different rapid urease kits. The admixture of urease in H. pylori-seropositive whole blood diluted in either saline or whole blood enhanced performance in both kits fourfold compared with saline alone. No false-negative results were observed in either kit. Seronegative whole blood produced similar results. Undiluted saline or whole blood produced no positive rapid urease tests. Whole blood accelerates the urease reaction in vitro. Neither H. pylori antibody-positive nor -negative whole blood adversely impacted the rapid urease test. False-negative rapid urease test results in upper gastrointestinal bleeding cannot be explained by admixture with whole blood.

Clinical Enzyme Tests↗
PubMed2000

Seroprevalence of Helicobacter pylori infection in cystic fibrosis and its cross-reactivity with anti-pseudomonas antibodies.

BACKGROUND: The prevalence of Helicobacter pylori infection and its role in gastroduodenal disease in cystic fibrosis (CF) are controversial. Additionally, serologic determination of infection in this population may be inaccurate because of cross-reactivity with other bacterial species. The seroprevalence of H. pylori in a cohort of patients with CF and its cross-reactivity with Pseudomonas antibodies were investigated. METHODS: A research enzyme-linked immunosorbent assay (ELISA), and three commercial serologic assays (PyloriStat; BioWhittaker, Walkersville, MD, U.S.A.; Flexsure; SmithKline Diagnostics, Inc., San Jose, CA, U.S.A.; and HM-CAP; EPI, Stony Brook, NY, U.S.A.) at three independent laboratories determined the seroprevalence of anti-H. pylori IgG antibodies in 70 patients with CF. Cross-reactivity between solid-phase H. pylori antigens and Pseudomonas antibodies was ascertained by a competitive inhibition assay, preadsorbing sera of patients with CF with whole cell proteins from different Pseudomonas species, and serum reanalysis by each assay. Western blot analysis before and after adsorption was performed to identify potential cross-reactive antigens. RESULTS: The research ELISA, Flexsure, Pyloristat, and HM-CAP initially showed H. pylori seropositivity of 47%, 28%, 24%, and 37%, respectively. Postadsorption seropositivity declined to 8%, 0%, 0%, and 15%, respectively. All patients with research ELISA true-positive results were confirmed endoscopically to have H. pylori infection. Western blot analysis showed a 31-kDa H. pylori protein with antigenic epitopes common to both bacterial species. CONCLUSIONS: Cross-reactivity between solid-phase H. pylori antigens and anti-Pseudomonas antibodies occurs in patients with CF. A high index of suspicion should be assumed in evaluating results of serologic H. pylori tests in this population. Preadsorption of CF sera with Pseudomonas proteins should be used in serologic testing.

Adolescent↗
PubMed2000

Phase variation in H type I and Lewis a epitopes of Helicobacter pylori lipopolysaccharide.

Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigens Lewis x (Le(x)), Le(y), and H type I. In this report, we demonstrate that the H type I epitope displays high-frequency phase variation. One variant expressed Le(x) and Le(y) and no H type I as determined by serology; this switch was reversible. Insertional mutagenesis in NCTC 11637 of JHP563 (a poly(C) tract containing an open reading frame homologous to glycosyltransferases) yielded a transformant with a serotype similar to the phase variant. Structural analysis of the NCTC 11637 LPS confirmed the loss of the H type I epitope. Sequencing of JHP563 in strains NCTC 11637, an H type I-negative variant, and an H type I-positive switchback variant showed a C14 (gene on), C13 (gene off), and C14 tract, respectively. Inactivation of strain G27, which expresses Le(x), Le(y), H type I, and Le(a), yielded a transformant that expressed Le(x) and Le(y). We conclude that JHP563 encodes a beta3-galactosyltransferase involved in the biosynthesis of H type I and Le(a) and that phase variation in H type I is due to C-tract changes in this gene. A second H type I-negative variant (variant 3a) expressed Le(x) and Le(a) and had lost both H type I and Le(y) expression. Inactivation of HP093-HP094 resulted in a transformant expressing Le(x) and lacking Le(y) and H type I. Structural analysis of a mutant LPS confirmed the serological data. We conclude that the HP093-HP094 alpha2-fucosyltransferase (alpha2-FucT) gene product is involved in the biosynthesis of both Le(y) and Le(x). Finally, we inactivated HP0379 in strain 3a. The transformant had lost both Le(x) and Le(a) expression, which demonstrates that the HP0379 gene product is both an alpha3- and an alpha4-FucT. Our data provide understanding at the molecular level of how H. pylori is able to diversify in the host, a requirement likely essential for successful colonization and transmission.

Antibodies, Monoclonal↗