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Biomedical subjects

M Bennett

Publications and source records attributed to M Bennett.

At least 19 recordsLinked to original sources

Plague metapopulation dynamics in a natural reservoir: the burrow system as the unit of study.

The ecology of plague (Yersinia pestis infection) in its ancient foci in Central Asia remains poorly understood. We present field data from two sites in Kazakhstan where the great gerbil (Rhombomys opimus) is the major natural host. Family groups inhabit and defend burrow systems spaced throughout the landscape, such that the host population may be considered a metapopulation, with each occupied burrow system a subpopulation. We examine plague transmission within and between family groups and its effect on survival. Transmission of plague occurred disproportionately within family groups although not all gerbils became infected once plague entered a burrow system. There were no spatial patterns to suggest that family groups in close proximity to infected burrow systems were more at risk of infection than those far away. At one site, infection increased the chances of burrow-system extinction. Overall, it is useful to consider the burrow system as the unit of study within a much larger metapopulation.

Animals↗

Contrasting dynamics of Bartonella spp. in cyclic field vole populations: the impact of vector and host dynamics.

Many zoonotic disease agents are transmitted between hosts by arthropod vectors, including fleas, but few empirical studies of host-vector-microparasite dynamics have investigated the relative importance of hosts and vectors. This study investigates the dynamics of 4 closely related Bartonella species and their flea vectors in cyclic populations of field voles (Microtus agrestis) over 3 years. The probability of flea infestation was positively related to field vole density 12 months previously in autumn, but negatively related to more recent host densities, suggesting a dilution effect. The 4 Bartonella species exhibited contrasting dynamics. Only B. grahamii, showed a distinct seasonal pattern. Infection probability increased with field vole density for B. doshiae, B. taylorii and BGA (a previously unidentified species) and with density of coexisting wood mice for B. doshiae and B. grahamii. However, only the infection probability of BGA in spring was related to flea prevalence. B. doshiae and BGA were most common in older animals, but the other 2 were most common in non-reproductive hosts. Generally, host density rather than vector abundance appears most important for the dynamics of flea-transmitted Bartonella spp., possibly reflecting the importance of flea exchange between hosts. However, even closely related species showed quite different dynamics, emphasising that other factors such as population age structure can impact on zoonotic risk.

Animals↗

A role for vector-independent transmission in rodent trypanosome infection?

Within host-pathogen systems where vector-borne transmission is the primary route of infection, little or no attention has been paid to the relative importance of secondary or alternative routes of transmission. Here, by contrast, we report the results from a controlled longitudinal field-scale experiment in which the prevalence of fleas (Siphonaptera) was manipulated and the occurrence and distribution of a flea-borne protozoan (Trypanosoma (Herpetosoma) microti) in a natural field vole (Microtus agrestis) population was monitored over a 2-year period. A non-systemic insecticide was applied to individual voles within two treatment grids and the prevalences of fleas and of T. microti were monitored on these and on two control grids. Blood samples were taken from all voles and PCR-based methods used to determine infection status. Insecticidal treatment was highly effective at reducing overall flea prevalence and recaptured animals (treated ca. 4 weeks previously) were very rarely infested (ca. 3%, compared with 50-70+% normally). On the other hand, the probability of trypanosome infection was reduced in treated animals on experimental grids to only around one-third of that normally observed. This suggests that direct, as opposed to flea-borne, transmission may not only occur, it may also be of epidemiological importance. The possibility that the importance of such transmission routes may have been underestimated in 'vector-borne' infections more generally is discussed.

Animals↗

Power Doppler ultrasound assessment of follicular vascularity in the early follicular phase and its relationship with outcome of in vitro fertilization.

OBJECTIVE: To determine whether ovarian perifollicular blood flow (PFBF) in the early follicular phase (EFP) was associated with treatment outcome. DESIGN: Retrospective longitudinal cohort study. SETTING: Tertiary referral centre/university hospital. PATIENTS: Thirty-four women underwent 37 IVF cycles, which resulted in 35 embryo transfers. INTERVENTIONS: Serial transvaginal scans using power Doppler ultrasound during the follicular phase. Ovarian PFBF of follicles > or =5 mm was subjectively assessed using a modified grading system (grades 0-4). MAIN OUTCOME MEASURES: Ovarian PFBF and pregnancy. RESULTS: Treatment cycles were retrospectively divided into two groups: Group 1 (n=20) had cycles with at least one small (5-10 mm) or medium (11-14 mm) size follicle(s) of high grade (2-4) PFBF on cycle day 5 or 6 or 7; and Group 2 (n=17), had cycles that did not. Group 1 had a significantly higher proportion of high grade large follicles in the late follicular phase (35% vs. 21%) (OR 2.0; 95% CI 1.1-3.7) and higher clinical pregnancy rate (47% vs. 12%) (OR 6.3; CI 1.1-35.7) compared to Group 2. CONCLUSION: High grade ovarian PFBF in the EFP during IVF is associated with both high grade PFBF in the late follicular phase and a higher clinical pregnancy rate.

Adult↗

Inositol pyrophosphates: metabolism and signaling.

Inositol pyrophosphates belong to the diverse family of inositol polyphosphate species that have a range of signaling functions. Since the discovery of inositol pyrophosphates in the early 1990s, enormous progress has been achieved in characterising this class of molecules, linking their biological presence to a wide range of cellular functions, including vesicular trafficking, apoptosis, telomere maintenance and protein phosphorylation. The activity of inositol pyrophosphates appears to be related to their rapid turnover in cells and also to their pyrophosphate groups, which are considered to contain high-energy bonds. Together, these observations suggest that inositol pyrophosphates may represent a class of cellular messengers with basic and not yet fully characterised functions. This review aims at summarising the recent progress of our knowledge of this exciting class of molecules, from inositol pyrophosphate discovery to the description of their physiological functions.

Animals↗

Sympatric Ixodes trianguliceps and Ixodes ricinus ticks feeding on field voles (Microtus agrestis): potential for increased risk of Anaplasma phagocytophilum in the United Kingdom?

The importance of wild rodents as reservoirs of zoonotic tick-borne pathogens is considered low in the United Kingdom because, in studies to date, those parasitized by exophilic Ixodes ricinus ticks carry almost exclusively larvae and thus have a minor role in transmission cycles. In a cross-sectional study, 11 (6.7%) of 163 field voles (Microtus agrestis) captured at field sites in Northern England were PCR-positive for Anaplasma phagocytophilum. The voles were found to act as hosts for both larval and nymphal I. ricinus and all stages of the nidicolous tick I. trianguliceps, and eight individuals were infested with ticks of both species at the same time. Two of 158 larval and one of 13 nymphal I. ricinus, as well as one of 14 larval and one of 15 nymphal I. trianguliceps collected from the rodents were PCR-positive. These findings suggest that habitats where field voles are abundant in the United Kingdom may pose a risk of A. phagocytophilum infection because (i) field voles, the most abundant terrestrial mammal in the United Kingdom, may be a competent reservoir; (ii) the field voles are hosts for both nymphal and larval ixodid ticks so they could support endemic cycles of A. phagocytophilum; and (iii) they are hosts for nidicolous I. trianguliceps, which may alone maintain endemic cycles, and exophilic I. ricinus ticks, which could act as a bridge vector and transmit infections to humans and domesticated animals.

Anaplasma phagocytophilum↗

Hyperbaric oxygen therapy for delayed onset muscle soreness and closed soft tissue injury.

BACKGROUND: Soft tissue injuries (including muscle damage after unaccustomed exercise) are common and are often associated with athletic activity. Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen at environmental pressures greater than one atmosphere. OBJECTIVES: To assess the benefits and harms of HBOT for treating soft tissue injury, including delayed onset muscle soreness (DOMS). SEARCH STRATEGY: We searched the following in July 2004: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM and reference lists from relevant articles. Relevant journals were handsearched and researchers in the field contacted. SELECTION CRITERIA: Randomised trials comparing the effect on closed soft tissue injury (including DOMS) of therapeutic regimens which include HBOT with those that exclude HBOT (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Four reviewers independently evaluated study quality and extracted data. Most of the data presented in the review were extracted from graphs in the trial reports. MAIN RESULTS: Nine small trials involving 219 participants were included. Two trials compared HBOT versus sham therapy on acute closed soft tissue injuries (ankle sprain and medial collateral knee ligament injury respectively). The other seven trials examined the effect of HBOT on DOMS following eccentric exercise in unconditioned volunteers. All 32 participants of the ankle sprain trial returned to their normal activities. There were no significant differences between the two groups in time to recovery, functional outcomes, pain, or swelling. There was no difference between the two groups in knee function scores in the second acute injury trial; however, intention-to-treat analysis was not possible for this trial. Pooling of data from the seven DOMS trials showed significantly and consistently higher pain at 48 and 72 hours in the HBOT group (mean difference in pain score at 48 hours [0 to 10 worst pain] 0.88, 95% CI 0.09 to 1.67, P = 0.03) in trials where HBOT was started immediately. There were no differences between the two groups in longer-term pain scores or in any measures of swelling or muscle strength. No trial reported complications of HBOT but careful selection of participants was evident in most trials. AUTHORS' CONCLUSIONS: There was insufficient evidence from comparisons tested within randomised controlled trials to establish the effects of HBOT on ankle sprain or acute knee ligament injury, or on experimentally induced DOMS. There was some evidence that HBOT may increase interim pain in DOMS. Any future use of HBOT for these injuries would need to have been preceded by carefully conducted randomised controlled trials which have demonstrated effectiveness.

Athletic Injuries↗

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is common and radiotherapy is one well-established treatment for some solid tumours. HBO may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing HBO may result in a reduction in mortality and tumour recurrence. OBJECTIVES: To assess the benefits and harms of radiotherapy while breathing HBO. SEARCH STRATEGY: In November 2004 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library Issue 3), MEDLINE, EMBASE , CINAHL, DORCTHIM and reference lists of articles. Relevant journals were handsearched. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air (with or without sham therapy). DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the method of Schulz (Schulz 1995) and extracted the data from the included trials. MAIN RESULTS: Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBO and 1153 control). With HBO, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (Relative risk (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11 and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBO varied with different fractionation schemes. Local tumour recurrence was less likely with HBO at one year (head and neck, RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix RR 0.60, P = 0.04, NNT = 5) and five years (head and neck (RR 0.77, P = 0.01). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH 22) with HBO. AUTHORS' CONCLUSIONS: There is some evidence that HBO improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBO is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the primary studies included in this review demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.

Combined Modality Therapy↗

Hyperbaric oxygen therapy for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) includes acute myocardial infarction and unstable angina. ACS is common and may prove fatal. Hyperbaric oxygen therapy (HBOT) will improve oxygen supply to the threatened heart and may reduce the volume of heart muscle that will perish. The addition of HBOT to the standard treatment may reduce death rate and other major adverse outcomes. OBJECTIVES: To assess the benefits and harms of adjunctive HBOT for treating ACS. SEARCH STRATEGY: We searched the following from inception to November 2004: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTHIM, and references from selected articles. Relevant journals were handsearched and researchers in the field contacted. SELECTION CRITERIA: Randomised studies comparing the effect on ACS of regimens that include HBOT with those that exclude HBOT. DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Handbook and extracted data from included trials. MAIN RESULTS: Four trials with 462 participants contributed to this review. There was a trend towards, but no significant decrease in, the risk of death with HBOT (relative risk (RR) 0.64, 95% CI 0.38 to 1.06, P=0.08). There was evidence from individual trials of reductions in the risk of major adverse coronary events [MACE] (RR 0.12, 95% CI 0.02 to 0.85, P=0.03; NNT 4, 95% CI 3 to 10) and some dysrhythmias following HBOT (RR 0.59, 95% CI 0.39 to 0.89, P=0.01; NNT 6, 95% CI 3 to 24), particularly complete heart block (RR 0.32, 95%CI 0.12 to 0.84, P=0.02), and that the time to relief of pain was reduced with HBOT (Weighted Mean Difference [WMD] 353 minutes shorter, 95% CI 219 to 488, P<0.0001). One trial suggested a significant incidence of claustrophobia in single occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, 95%CI 1.92 to 521, P=0.02). AUTHORS' CONCLUSIONS: For people with ACS, individual small trials suggest the addition of HBOT reduced the risk of Major Adverse Cardiac Events, some dysrrhythmias, and reduced the time to relief from ischaemic pain, but did not reduce mortality. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT. The routine application of HBOT to these patients cannot be justified from this review.

Angina, Unstable↗

Hyperbaric oxygen for carbon monoxide poisoning.

BACKGROUND: Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning. OBJECTIVES: To examine randomized trials of the effectiveness of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning. SEARCH STRATEGY: We searched MEDLINE (1966-present), EMBASE (1980-present), and the Controlled Trials Register of the Cochrane Collaboration, supplemented by a manual review of bibliographies of identified articles and discussion with recognized content experts. SELECTION CRITERIA: All randomized controlled trials involving non-pregnant adults acutely poisoned with carbon monoxide (regardless of severity), with adequate or unclear allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted from each trial information on: the number of randomized patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up. MAIN RESULTS: Seven randomized controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials, two represent incomplete publications (one interim analysis, one abstract). Of these six trials, four found no benefit of HBO for the reduction of neurologic sequelae, while two others did. Although pooled analysis does not suggest a benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12, p=0.18), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by apparent changes in the primary outcome during the course of the trial. AUTHORS' CONCLUSIONS: Existing randomized trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomized controlled trial.

Carbon Monoxide Poisoning↗

Systematic review of hyperbaric oxygen in the management of chronic wounds.

BACKGROUND: Many therapeutic options exist for chronic wounds. Hyperbaric oxygen therapy (HBOT) is one such option. It may be used for diabetic, venous, arterial and pressure ulcers. METHODS: Following a systematic search of the literature, pooled analyses of predetermined clinical outcomes of randomized controlled trials involving the use of HBOT for chronic wounds were performed. Relative risks (RR) and number needed to treat (NNT) with 95 per cent confidence intervals (c.i.) were calculated. RESULTS: Six studies met the inclusion criteria. No appropriate trials were located for arterial and pressure ulcers. Pooled data from five trials on diabetic ulcers (118 patients) suggested a significant reduction in the risk of major amputation with HBOT (RR: 0.31; c.i. 0.13 to 0.71) with a NNT of 4 (c.i. 3 to 11). Sensitivity analyses did not alter the results. Ulcer healing and the rate of minor amputation were not influenced by HBOT. Data from one trial on venous ulcers suggested significant wound size reduction at the end of the treatment, but not at follow-up. CONCLUSIONS: There is evidence that HBOT reduces the risk of major amputation in diabetic patients. For venous, arterial or pressure ulcers there is a lack of data. Further trials may be warranted.

Amputation, Surgical↗

Trypanosomes, fleas and field voles: ecological dynamics of a host-vector--parasite interaction.

To investigate the prevalence of a flea-borne protozoan (Trypanosoma (Herpetosoma) microti) in its field vole (Microtus agrestis) host, we monitored over a 2-year period a range of intrinsic and extrinsic parameters pertaining to host demographics, infection status and vector (flea) prevalence. Generalized Linear Mixed Modelling was used to analyse patterns of both flea and trypanosome occurrence. Overall, males of all sizes and ages were more likely to be infested with fleas than their female counterparts. Flea prevalence also showed direct density dependence during the winter, but patterns of density dependence varied amongst body mass (age) classes during the summer. Trypanosome prevalence did not vary between the sexes but was positively related to past flea prevalence with a lag of 3 months, with the highest levels occurring during the autumn season. A convex age-prevalence distribution was observed, suggesting that individuals develop a degree of immunity to trypanosome infection with age and exposure. An interaction between age and whether the individual was new or recaptured suggested that infected animals are less likely to become territory holders than their uninfected counterparts.

Animals↗

Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss and tinnitus: a systematic review of randomized controlled trials.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSHL) and tinnitus are common. Hyperbaric oxygen therapy (HBOT) may improve hearing loss and/or reduce the intensity of tinnitus. METHODS: We performed a systematic search of the literature for randomized controlled trials, and made pooled analyses of pre-determined clinical outcomes where possible. RESULTS: Six trials contributed to this review (304 subjects). Pooled analysis suggested a significantly increased chance of a 25 per cent improvement in hearing threshold on pure tone average with HBOT (relative risk (RR) 1.39, 95 per cent confidence interval (CI) 1.05-1.84, p = 0.02; number-needed-to-treat 5, 95 per cent CI 3-20), but not a 50 per cent increase (RR 1.53, 95 per cent CI 0.85-2.78, p = 0.16). The significance of any improvement in tinnitus following HBOT could not be assessed due to poor reporting. CONCLUSIONS: HBOT improved hearing, but the clinical significance of the level of improvement is not clear. Routine application of HBOT to patients with ISSHL is not justified by this review. More research is needed.

Hearing Loss, Sensorineural↗

The mystery of the wooden leg: vitamin C deficiency in East African prisons.

Vitamin C deficiency (scurvy) is an uncommon disease in modern times, and therefore easily misdiagnosed when it appears. While visiting prisoners in East Africa, health delegates of the International Committee of the Red Cross (ICRC) encountered prisoners suffering from a hitherto undiagnosed 'mysterious' illness, consisting mainly of swollen and hard legs, that had not responded to various treatments given by the local health centre or hospital. The ICRC set out to investigate the nature of this disease and examined 133 prisoners with the suspected clinical symptoms described as 'wooden leg' syndrome in 10 different prisons. Serum ascorbic acid levels were measured and a food basket analysis done. The diagnosis of scurvy was confirmed. All patients responded to standard treatment with oral ascorbic acid. The clinical presentation of scurvy in these East African prisons seems to be somewhat different from the classic descriptions, but is in line with historic records of the disease. Treatment is easy and cheap, and response to treatment is quick. Scurvy remains a problem in prisons in Africa and clinicians working in prisons need to be aware of its presence and its presentations.

Adolescent↗

Hyperbaric oxygen therapy for multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic, recurrent and progressive illness with no cure. On the basis of speculative pathophysiology, it has been suggested that Hyperbaric Oxygen Therapy (HBOT) may slow or reverse the progress of the disease. OBJECTIVES: The object of this review was to evaluate the efficacy and safety of HBOT in the treatment of MS. SEARCH STRATEGY: We searched the Cochrane MS Group trials register (July 2002), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2002), MEDLINE (January 1966 to October 2002) and the National Library of Medicine (NLM) database (July 2002), along with specialised hyperbaric resources and handsearching of relevant journals and proceedings. SELECTION CRITERIA: All randomised, controlled trials involving a comparison between HBOT and a sham therapy in MS were evaluated. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised all comparative trials identified, extracted data and scored them for methodological quality. MAIN RESULTS: We identified ten reports of nine trials that satisfied selection criteria (504 participants in total). Two trials produced generally positive results, while the remaining seven reported generally no evidence of a treatment effect. None of our three a priori subgroup analyses placed these two trials in the same group and were therefore unable to account for this difference. Three analyses (of 21) did indicate some benefit. For example, the mean Expanded Disability Status Scale (EDSS) at 12 months was improved in the HBOT group (group mean reduction in EDSS compared to sham -0.85 of a point, 95% confidence interval -1.28 to -0.42, P = 0.0001). Only the two generally positive trials reported on this outcome at this time (16% of the total participants in this review). REVIEWER'S CONCLUSIONS: We found no consistent evidence to confirm a beneficial effect of hyperbaric oxygen therapy for the treatment of multiple sclerosis and do not believe routine use is justified. The small number of analyses suggestive of benefit are isolated, difficult to ascribe with biological plausibility and would need to be confirmed in future well-designed trials. Such trials are not, in our view, justified by this review.

Humans↗