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Biomedical subjects

J Montgomery

Publications and source records attributed to J Montgomery.

At least 19 recordsLinked to original sources
PubMed2006

Current research priorities in chronic fatigue syndrome/myalgic encephalomyelitis: disease mechanisms, a diagnostic test and specific treatments.

Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months duration, which is accompanied by various rheumatological, infectious and neuropsychiatric symptoms. A collaborative study group has been formed to deal with the current areas for development in CFS research--namely, to develop an understanding of the molecular pathogenesis of CFS, to develop a diagnostic test and to develop specific and curative treatments. Various groups have studied the gene expression in peripheral blood of patients with CFS, and from those studies that have been confirmed using polymerase chain reaction (PCR), clearly, the most predominant functional theme is that of immunity and defence. However, we do not yet know the precise gene signature and metabolic pathways involved. Currently, this is being dealt with using a microarray representing 47,000 human genes and variants, massive parallel signature sequencing and real-time PCR. It will be important to ensure that once a gene signature has been identified, it is specific to CFS and does not occur in other diseases and infections. A diagnostic test is being developed using surface-enhanced, laser-desorption and ionisation-time-of-flight mass spectrometry based on a pilot study in which putative biomarkers were identified. Finally, clinical trials are being planned; novel treatments that we believe are important to trial in patients with CFS are interferon-beta and one of the anti-tumour necrosis factor-alpha drugs.

Fatigue Syndrome, Chronic↗
PubMed2006

A placebo-controlled, double-blind, randomized controlled trial of a natural killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome.

BACKGROUND: Previous research has suggested that natural killer (NK) cell activity may be reduced in patients with chronic fatigue syndrome (CFS). AIM: To evaluate the effectiveness of a putative NK cell stimulant, BioBran MGN-3, in reducing fatigue in CFS patients. DESIGN: Randomized, double-blind, placebo-controlled trial. METHODS: We recruited 71 patients with CFS (according to the Centers for Disease Control 1994 criteria) attending an out-patient specialist CFS service. Participants were given oral BioBran MGN-3 for 8 weeks (2 g three times per day) or placebo equivalent. The primary outcome measure was the Chalder physical fatigue score. Self-reported fatigue measures, self-assessment of improvement, change in key symptoms, quality of life, anxiety and depression measures were also included. RESULTS: Data were complete in 64/71 patients. Both groups showed marked improvement over the study duration, but without significant differences. Mean improvement in the Chalder fatigue score (physical scale) was 0.3 (95%CI -2.6 to 3.2) lower in the BioBran group. DISCUSSION: The findings do not support a specific therapeutic effect for BioBran in CFS. The improvement showed by both groups over time highlights the importance of placebo controls when evaluating interventions in CFS.

Adult↗
PubMed2006

Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.

We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.

Amodiaquine↗
PubMed2006

Flexible trainees in Scotland.

INTRODUCTION: Demand for flexible training is increasing. The contribution of such trainees to the trained medical workforce is not clear. METHODS: All full time and flexible trainees in Scotland were 'tracked' at the completion of training. RESULTS: 80% of flexible trainees took up a consultant post of which 93% were in Scotland. 82% of full time trainees took up a consultant post of which 80% were in Scotland. DISCUSSION: Flexible trainees become consultants at the same rate as their full time counterparts. They are commonly geographically tied and are therefore more likely to remain in Scotland and contribute to retention of doctors in this country.

Attitude of Health Personnel↗
PubMed2004

Minimum inhibitory concentrations of some antimicrobial drugs against bacteria causing uterine infections in cattle.

The minimum inhibitory concentrations (MICs) of oxytetracycline, cephapirin, cephapirin/mecillinam, cefquinome, ceftiofur and enrofloxacin, candidate antibiotics for the principal bacteria associated with uterine infections: Escherichia coli, Arcanobacterium pyogenes and the anaerobic bacteria Fusobacterium necrophorum and Prevotella melaninogenicus, were determined by the agar dilution method. The bacteria were isolated from animals with clinical metritis and/or endometritis. For E coli, cefquinome and enrofloxacin had the lowest MIC90 and MIC50 values (< 0.06 microg/ml), and oxytetracycline and cephapirin had the highest values. For A pyogenes, oxytetracycline had the highest MIC50 value (16 microg/ml), but all the cephalosporins had values below 0.06 microg/ml. For the anaerobic bacteria, enrofloxacin and oxytetracycline had the highest MIC50 values but all the cephalosporins had values of 0.06 microg/ml or below.

Actinomycetaceae↗
PubMed2004

Human lead exposure in England from approximately 5500 BP to the 16th century AD.

Lead concentration and isotope ratio data are presented for the tooth enamel of 77 individuals buried in England and spanning approximately 5000 years from the Neolithic until the 16th century AD. Whereas other tissues may be affected by diagenesis in the burial environment, the Pb concentration of tooth enamel is directly related to childhood exposure. This record is preserved post-mortem and over archaeological time. Tooth enamel Pb concentrations in the prehistoric period appear to be variable within the range 0.04 to approximately 0.4 ppm, with occasional higher levels. The Romano-British and medieval periods show a marked increase in Pb exposures with enamel concentrations reaching up to approximately 40 ppm. These exposures would today be associated with industrial pollution. Exposures appear to be highly variable compared with modern people, however, with many medieval individuals having very low enamel Pb concentrations comparable with prehistoric people. Lead isotope data refine this picture. We distinguish between the diverse isotopic ratios we believe to be characteristic of 'natural' exposure to Pb-from geological sources via the diet-and the much narrower isotopic range characteristic of exposure to technological Pb from ore sources. Taken together the data suggest that the maximum concentrations associated with 'non-technological' exposure at any period are approximately 0.5-1.0 ppm, similar to that reported for modern people in England.

Adult↗
PubMed2004

Microbiological and serological study of leptospirosis in horses at slaughter: first isolations.

A bacteriological survey of kidneys from 145 abattoir horses was performed, which resulted in the isolation of two Leptospira strains. The isolates were serologically typed as belonging to serogroups Australis and Pomona, and REA identified them as L. interrogans serovar Bratislava and L. kirschneri serovar Tsaratsovo, respectively. These are the first Leptospira isolates obtained from horses in Portugal and the Bratislava strain is the first serogroup Australis strain to be isolated in this country. The 145 horses were also serologically tested for leptospiral antibodies, and 37% had MAT titres #10878;1:10.

Agglutination Tests↗
PubMed2001

Immunohistochemical detection of inducible nitric oxide synthase, nitrotyrosine and manganese superoxide dismutase following hyperglycemic focal cerebral ischemia.

We have characterized the temporal changes in iNOS, MnSOD and nitrotyrosine immune reactivity in a rat model of permanent middle cerebral artery occlusion under acute hyperglycemic or normoglycemic conditions followed by either 3- or 24-h recovery. We found that the macroscopic labeling pattern for all three antibodies colocalized with the ischemic core and penumbra which was determined by cresyl violet histological evaluation in adjacent sections. Hyperglycemia induced prior to ischemia resulted in earlier infarction which correlated with increased immunoreactivity for iNOS, MnSOD and nitrotyrosine. In the penumbral region of the frontal cortex, labeling of specific cell structures was largely limited to cortical neurons near the corpus callosum and was apparent earlier in the hyperglycemic rats. Increased polymorphonuclear leukocyte adhesion in blood vessels was observed at 24 h in the hyperglycemic group. At both of the recovery times studied, we observed only minor vascular staining for nitrotyrosine and none for iNOS. Our results are consistent with hyperglycemia resulting in an early and concomitant increase in both superoxide and nitric oxide production which can lead to peroxynitrite formation that then nitrates tyrosine residues. It would appear that hyperglycemic ischemia contributes to the early induction of key enzymes involved in nitric oxide bioavailability.

Animals↗
PubMed2001

Bacteremia caused by a Helicobacter pullorum-like organism.

We report a case of bacteremia caused by a Helicobacter pullorum-like organism in a 35-year-old man with pyrexia of unknown origin. Culture of blood samples obtained at admission yielded a motile, spiral-shaped gram-negative rod, and 16S rRNA gene sequencing identified this organism as Helicobacter pullorum-like, showing 23 base differences compared with the recently described "Helicobacter canadensis" (a recently proposed group that had previously been classified within H. pullorum). We believe that this is the first report of bacteremia caused by this organism.

Adult↗
PubMed2001

Molecular and immunological characterisation of the glucose regulated protein 78 of Leishmania donovani(1).

To identify novel potential Leishmania vaccine antigens, antibodies from patients with visceral leishmaniasis (VL) were used to isolate clones from a cDNA expression library of L. donovani amastigotes. Glucose Regulated Protein (GRP78), a member of the 70 kDa heat-shock protein family was identified and characterised. The GRP78 gene was localised to chromosome 15 in L. donovani, L. major, and L. mexicana by pulse-field gel electrophoresis. The Leishmania GRP78 protein contain a carboxy-terminal endoplasmic reticulum retention signal sequence (MDDL) as does the Trypanosoma cruzi GRP78. Immunofluorescence using antibodies to the recombinant DNA-derived GRP78 protein showed staining localised to reticular material throughout the cytoplasm and in the perinuclear region of promastigotes, suggesting that the protein is localised in the endoplasmic reticulum. The protective efficacy of GRP78 was assessed in mice vaccine experiments. A GRP78 DNA vaccine primed for an immune response that protected C57Bl/6 and C3H/He mice against infection with L. major. Similarly vaccination with a recombinant form of GRP78 purified from Escherichia coli and administered with Freund's as adjuvant induced protective immunity in C57Bl/6 mice.

Amino Acid Sequence↗
PubMed2001

Recurrent transfusion-related acute lung injury.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a rare condition that is commonly associated with the transfusion of donor plasma containing WBC antibodies. Biologically active lipids that accumulate during storage of RBCs and platelets may also cause TRALI. There has been only one previously reported case of recurrent TRALI. CASE REPORT: A patient received a transfusion 2 days after undergoing hysterectomy; she developed TRALI after receiving the transfusion. The patient recovered after being on ventilation for 6 days but received an additional transfusion and had a second episode of TRALI, which required further ventilation. RESULTS: Laboratory investigation of the first episode of TRALI suggested the presence of HLA-A2 (N = 1) and granulocyte-specific IgM antibodies (N = 2) in the sera from three of the donors. All three sera reacted in crossmatch studies with the patient's granulocytes and lymphocytes. Lymphocyte-specific IgG antibodies were detected in the patient's serum. There was no evidence to suggest the involvement of WBC antibodies in the second episode of TRALI. Antibody screening of the donors' samples and both forward and reverse crossmatch studies were negative. CONCLUSION: The first episode of TRALI seems to be due to the action of HLA-A2 and granulocyte-specific IgM antibodies. The second episode may have been due to the action of lipid neutrophil-priming agents in the donors' units in association with the patient's underlying pulmonary condition (i.e., recovering from lung injury). TRALI can recur if a patient requires further transfusion support shortly after an initial episode of TRALI.

Acute Disease↗
PubMed2001

The safety and efficacy of peripheral intravenous catheters in ill neonates.

This article describes the use of a quality improvement clinical audit approach to identify insertion practices, duration of therapy, and complications related to peripheral intravenous catheters. These data provide evidence for adherence to practice standards and benchmarks for evaluation of new interventions to improve the safety and efficacy of intravenous access practices. Implications for quality improvement and clinical research related to intravenous-device practices within the neonatal intensive care unit are discussed.

Catheterization, Peripheral↗
PubMed2001

Do patient assessments of primary care differ by patient ethnicity?

OBJECTIVE: To determine if patient assessments (reports and ratings) of primary care differ by patient ethnicity. DATA SOURCES/STUDY DESIGN: A self-administered patient survey of 6,092 Massachusetts employees measured seven defining characteristics of primary care: (1) access (financial, organizational); (2) continuity (longitudinal, visit based); (3) comprehensiveness (knowledge of patient, preventive counseling); (4) integration; (5) clinical interaction (communication, thoroughness of physical examinations); (6) interpersonal treatment; and (7) trust. The study employed a cross-sectional observational design. PRINCIPAL FINDINGS: Asians had the lowest primary care performance assessments of any ethnic group after adjustment for socioeconomic and other factors. For example, compared to whites, Asians had lower scores for communication (69 vs. 79, p = .001) and comprehensive knowledge of patient (56 vs. 48, p = .002), African Americans and Latinos had less access to care, and African Americans had less longitudinal continuity than whites. CONCLUSIONS: We do not know what accounts for the observed differences in patient assessments of primary care. The fact that patient reports as well as the more subjective ratings of care differed by ethnicity suggests that quality differences might exist that need to be addressed.

Adult↗
PubMed2000

Human tooth enamel as a record of the comparative lead exposure of prehistoric and modern people.

There is a considerable body of evidence to support the contention that the atmospheric Pb burden is now considerably greater than it was in the remote past. However, as there are a diversity of potential environmental pathways leading to Pb ingestion, it is not clear how atmospheric Pb levels relate to human exposure. It is necessary to establish a baseline for human exposure to Pb from natural sources in the pre-metallurgical past, with which contemporary exposure can be compared. This paper addresses this issue by comparing the Pb content of human dental enamel--an established proxy for Pb exposure--from modern and archaeological, pre-metallurgical individuals using thermal and plasma ionisation mass spectrometry. It is shown that mean Neolithic enamel Pb contents are approximately 0.31 +/- 0.04 ppm. These values are only one order of magnitude lower than previously reported data for the same tissues for modern juveniles, despite an established 400-fold increase in the atmospheric Pb burden. The results suggest that 'natural' exposure to Pb in food and water may have been higher than previously thought, and that the link between atmospheric Pb and human exposure warrants further investigation.

Dental Enamel↗
PubMed2000

Sensory processing of water currents by fishes.

Water currents are extremely important in the aquatic environment and play a very significant role in the lives of fishes. Sensory processing of water currents involves a number of sensory modalities including the inner ear, vision, tactile sense and the mechanosensory lateral line. The inner ear will detect whole-body accelerations generated by changes in flow, or by turbulence, whereas visual and tactile inputs will signal translational movement with respect to an external visual or tactile reference frame. The superficial neuromasts of the mechanosensory lateral line detect flow over the surface of the body and have the appropriate anatomical distribution and physiological properties to signal the strength and the direction of flow and, hence, contribute to the detection of regional differences in flow over different parts of the body.

Animals↗
PubMed2000

Presynaptic protein kinase activity supports long-term potentiation at synapses between individual hippocampal neurons.

Simultaneous microelectrode recording from two individual synaptically connected neurons enables the direct analysis of synaptic transmission and plasticity at a minimal synaptic connection. We have recorded from pairs of CA3 pyramidal neurons in organotypic hippocampal slices to examine the properties of long-term potentiation (LTP) at such minimal connections. LTP in minimal connections was found to be identical to the NMDA-dependent LTP expressed by CA3-CA1 synapses, demonstrating this system provides a good model for the study of the mechanisms of LTP expression. The LTP at minimal synaptic connections does not behave as a simple increase in transmitter release probability, because the amplitude of unitary EPSCs can increase several-fold, unlike what is observed when release probability is increased by raising extracellular calcium. Taking advantage of the relatively short axon connecting neighboring CA3 neurons, we found it feasible to introduce pharmacological agents to the interior of presynaptic terminals by injection into the presynaptic soma and have used this technique to investigate presynaptic effects on basal transmission and LTP. Presynaptic injection of nicotinamide reduced basal transmission, but LTP in these pairs was essentially normal. In contrast, presynaptic injection of H-7 significantly depressed LTP but not basal transmission, indicating a specific role of presynaptic protein kinases in LTP. These results demonstrate that pharmacological agents can be directly introduced into the presynaptic cell and that a purely presynaptic perturbation can alter this plasticity.

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