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Biomedical subjects

M Hilton

Publications and source records attributed to M Hilton.

At least 19 recordsLinked to original sources

Persistent buccopharyngeal membrane in an adult.

Persistence of the buccopharyngeal membrane (BPM) also called the oropharyngeal membrane is a rare congenital oropharyngeal anomaly. We report a case of an adult aboriginal male patient with a membrane that closed his oropharyngeal isthmus except for a 2 cm diameter central perforation. The patient had no symptoms related to this membrane and no other congenital anomalies were found. This finding has not previously been reported in an adult. The embryology and management of this rare condition is discussed.

Adult↗

Investigating the environmental transport of human pharmaceuticals to streams in the United Kingdom.

The occurrence of 12 selected pharmaceutical compounds and pharmaceutical compound metabolites in sewage treatment works (STW) effluents and surface waters was investigated. The substances selected for the monitoring programme were identified by a risk ranking procedure to identify those substances with the greatest potential to pose a risk to the aquatic environment. STW final effluent and surface water samples were collected from Corby, Great Billing, East Hyde, Harpenden and Ryemeads STWs. Ten of the 12 pharmaceutical compounds were detected in the STW effluent samples: propranolol (100%, median = 76 ng/l), diclofenac (86%, median = 424 ng/l), ibuprofen (84%, median = 3086 ng/l), mefenamic acid (81%, median = 133 ng/l), dextropropoxyphene (74%, median = 195 ng/l), trimethoprim (65%, 70 ng/l), erythromycin (44%, < 10 ng/l), acetyl-sulfamethoxazole (33%, median =< 50 ng/l), sulfamethoxazole (9%, median =< 50 ng/l), tamoxifen (4%, median =< 10 ng/l). In the corresponding receiving streams, fewer compounds and lower concentrations were found: propranolol (87%, median = 29 ng/l), ibuprofen (69%, median = 826 ng/l), mefenamic acid (60%, median = 62 ng/l), dextropropoxyphene (53%, median = 58 ng/l), diclofenac (47%, median =< 20 ng/l), erythromycin (38%, median =< 10 ng/l), trimethoprim (38%, median =< 10 ng/l), acetyl sulfamethoxazole (38%, median =< 50 ng/l). Four human pharmaceutical compounds were detected in samples upstream of the STWs sampled: ibuprofen (57%, median = 181 ng/l), trimethoprim (36%, median < 10 ng/l), erythromycin (17%, median =< 10 ng/l), propranolol (14%, median =< 10 ng/l), suggesting that longer range stream transport of some compounds is possible. The particular STW that was sampled and the month that it was sampled significantly influenced the measured concentrations of several, but not all, substances. There was no significant relationship between usage data and the overall frequency with which different substances were detected. There was however, some evidence to suggest that usage data are positively associated with concentrations of pharmaceuticals in effluent and, particularly, with concentrations measured in surface waters below STWs. These results suggest that most sewage treatment works in England and Wales are likely to be routinely discharging small quantities of pharmaceuticals into UK rivers. None of the pharmaceuticals were found at concentrations that were high enough to cause acute toxic impacts to aquatic organisms. However, insufficient data were available to be able to comment on whether the concentrations measured have the potential to result in more subtle long-term effects on aquatic organisms (e.g. effects on growth, ability to reproduce).

Environmental Monitoring↗

The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a syndrome characterised by short-lived episodes of vertigo in association with rapid changes in head position. It is a common cause of vertigo presenting to primary care and specialist otolaryngology clinics. Current treatment approaches include rehabilitative exercises and physical manoeuvres including the Epley manoeuvre. OBJECTIVES: To assess the effectiveness of the Epley manoeuvre compared to other treatments available for posterior canal benign paroxysmal positional vertigo, or no treatment. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 1, 2004), MEDLINE (1966 to 2004), EMBASE (1974 to 2004) and reference lists of identified publications. Date of the most recent search was January 2004. SELECTION CRITERIA: Randomised trials of adults diagnosed with posterior canal BPPV (including a positive Dix-Hallpike test). Comparisons sought: Epley manoeuvre versus placebo Epley manoeuvre versus untreated controls Epley manoeuvre versus other active treatment Outcome measures that were considered include: frequency and severity of attacks of vertigo; proportion of patients improved by each intervention; and conversion of a "positive" Dix-Hallpike test to a "negative" Dix-Hallpike test DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trials for quality. MAIN RESULTS: Fifteen trials were identified but twelve studies were excluded because of a high risk of bias, leaving three trials in the review. Trials were mainly excluded because of inadequate concealment during randomisation, or failure to blind outcome assessors. The studies included in the review (Lynn 1995; Froehling 2000; Yimtae 2003) addressed the efficacy of the Epley manoeuvre against a sham manoeuvre or control group by comparing the proportion of subjects in each group who had complete resolution of their symptoms, and who converted from a positive to negative Dix-Hallpike test. Individual and pooled data showed a statistically significant effect in favour of the Epley manoeuvre over controls. There were no serious adverse effects of treatment. REVIEWERS' CONCLUSIONS: There is some evidence that the Epley manoeuvre is a safe effective treatment for posterior canal BPPV, although this is based on the results of only three small randomised controlled trials with relatively short follow up. There is no good evidence that the Epley manoeuvre provides a long term resolution of symptoms. There is no good evidence comparing the Epley manoeuvre with other physical, medical or surgical therapy for posterior canal BPPV.

Humans↗

Ginkgo biloba for tinnitus.

BACKGROUND: Tinnitus can be described as the perception of sound in the absence of external acoustic stimulation. At present no specific therapy for tinnitus is acknowledged to be satisfactory in all patients. There are a number of reports in the literature suggesting that Ginkgo biloba may be effective in the management of tinnitus. However, there also appears to be a strong placebo effect in tinnitus management. OBJECTIVES: To assess the effect of Ginkgo biloba in patients who are troubled by tinnitus. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 4 2003), MEDLINE (1966 - 2003), EMBASE (1974 - 2003), and reference lists of identified publications. Date of the most recent search was December 2003. SELECTION CRITERIA: Adults (18 years and over) complaining of tinnitus. Adults with a primary complaint of cerebral insufficiency where tinnitus forms part of the syndrome. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trials for quality. MAIN RESULTS: Twelve trials were identified from the search as being relevant to the review. Ten trials were excluded on methodological grounds. No trials of tinnitus in cerebral insufficiency reached a satisfactory standard for inclusion in the review. There was no evidence that Ginkgo biloba was effective for the primary complaint of tinnitus. The incidence of side effects was small. REVIEWERS' CONCLUSIONS: The limited evidence did not demonstrate that Ginkgo biloba was effective for tinnitus which is a primary complaint. There was no reliable evidence to address the question of Ginkgo biloba for tinnitus associated with cerebral insufficiency.

Adult↗

The Epley (canalith repositioning) manoeuvre for benign paroxysmal positional vertigo.

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a syndrome characterised by short-lived episodes of vertigo in association with rapid changes in head position. It is a common cause of vertigo presenting to primary care and specialist otolaryngology clinics. Current treatment approaches include rehabilitative exercises and physical manoeuvres including the Epley manoeuvre. OBJECTIVES: To assess the effectiveness of the Epley manoeuvre compared to other treatments available for posterior canal benign paroxysmal positional vertigo, or no treatment. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library, Issue 2 2001), MEDLINE (1966 onwards), EMBASE (1974 onwards), and reference lists of identified publications. Date of the most recent search was June 2001. SELECTION CRITERIA: Randomised trials of adults diagnosed with posterior canal BPPV (including a positive Dix-Hallpike test). Comparisons sought: - Epley manoeuvre versus placebo. - Epley manoeuvre versus untreated controls. Epley manoeuvre versus other active treatment. Outcome measures that were considered include: frequency and severity of attacks of vertigo; proportion of patients improved by each intervention; and conversion of a "positive" Dix-Hallpike test to a "negative" Dix-Hallpike test DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trials for quality. MAIN RESULTS: Eleven trials were identified but nine studies were excluded because of a high risk of bias, leaving two trials in the review. Trials were mainly excluded because of inadequate concealment during randomisation, or failure to blind outcome assessors. Both studies included in the review (Lynn 1995, Froehling 2000) addressed the efficacy of the Epley manoeuvre against a sham manoeuvre by comparing the proportion of subjects in each group who had complete resolution of their symptoms, and who converted from a positive to negative Dix-Hallpike test. Individual and pooled data showed a statistically significant effect in favour of the Epley manoeuvre over controls. There were no serious adverse effects of treatment. REVIEWER'S CONCLUSIONS: ~bullet~There is some evidence that the Epley manoeuvre is a safe effective treatment for posterior canal BPPV, although this is based on the results of only two small randomised controlled trials with relatively short follow up. ~bullet~There is no good evidence that the Epley manoeuvre provides a long term resolution of symptoms. ~bullet~There is no good evidence comparing the Epley manoeuvre with other physical, medical or surgical therapy for posterior canal BPPV.

Humans↗

The Epley manoeuvre for benign paroxysmal positional vertigo--a systematic review.

Benign paroxysmal positional vertigo (BPPV) is a syndrome characterized by short-lived episodes of vertigo in association with rapid changes in head position. Current treatment approaches include rehabilitative exercises and physical manoeuvres including the Epley manouevre. Randomized clinical trials of the Epley manoeuvre were identified. Outcome measures that were considered include: frequency and severity of attacks of vertigo; proportion of patients improved by each intervention; and conversion of a 'positive' Dix-Hallpike test to a 'negative' Dix-Hallpike test. Patients who received the Epley manoeuvre were more likely to have complete resolution of their symptoms [odds ratio 4.92 (95% C.I. 1.84-13.16)], and more likely to convert from a positive to negative Dix-Hallpike test [odds ratio 5.67 (95% C.I. 2.21-14.56)]. There were no serious adverse effects of treatment. There is some evidence that the Epley manouevre is a safe effective treatment for posterior canal BPPV.

Humans↗

Middle ear instillation of gentamicin and streptomycin in chinchillas: electrophysiological appraisal of selective ototoxicity.

The purpose of this study was to investigate selective vestibular ototoxicity of gentamicin and streptomycin in the chinchilla model. In total, 10 chinchillas underwent left middle ear instillation of one of three agents: gentamicin, streptomycin and saline. Electrophysiological data (otoacoustic emissions (OAEs), auditory brainstem evoked response (ABRs), and ice-water electronystagmography were recorded before and after instillation. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphological changes in the cochlear and vestibular neuroepithelia were correlated with electrophysiological changes. Widespread ipsilateral cochlear and vestibular neuroepithelial injuries were observed and correlated with loss of OAEs, ABRs and ice-water caloric response. This study provides no evidence of selective vestibular ototoxicity of gentamicin or streptomycin. Morphological damage correlates with, but precedes loss of electrophysiological parameters. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

Animals↗

Dissection versus diathermy for tonsillectomy.

BACKGROUND: Tonsillectomy is a commonly performed surgical procedure. There are several operative methods currently in use, but the superiority of one over another has not been clearly demonstrated. OBJECTIVES: To compare the morbidity associated with tonsillectomy by two different techniques - dissection and diathermy. SEARCH STRATEGY: Cochrane Controlled Trials Register, Medline (1966-2000), Embase (1974-2000). Reference lists were scanned for additional material. SELECTION CRITERIA: Randomised controlled trials of children and adults undergoing tonsillectomy or adenotonsillectomy by dissection or diathermy techniques. Trials were assessed for methodological quality according to the method outlined in the Cochrane Reviewers Handbook. DATA COLLECTION AND ANALYSIS: The reviewers assessed each trial and extracted data independently. MAIN RESULTS: Twenty-two potential studies were identified for further assessment. Twenty trials were not included because they did not meet the inclusion criteria for randomisation methods, controls or outcome criteria. Two trials met the inclusion criteria, one comparing monopolar dissection diathermy with conventional cold dissection in children, and the other comparing microscopic bipolar dissection with cold dissection in children and adults. These studies demonstrate reduced intraoperative bleeding, but increased pain in the diathermy group. There was no difference in the rate of secondary bleeding overall, although the power of both studies to detect a small difference was insufficient. REVIEWER'S CONCLUSIONS: There are insufficient data to show that one method of tonsillectomy is superior. There is evidence that pain may be greater after monopolar dissection. Large, well designed randomised controlled trials are necessary to determine the optimum method for tonsillectomy.

Adult↗

Cooperation between HGF and CNTF in promoting the survival and growth of sensory and parasympathetic neurons.

Previous studies have shown that hepatocyte growth factor (HGF) enhances the survival and growth of neurons that depend on NGF for survival. To determine if HGF cooperates with other neurotrophic factors in the developing peripheral nervous system, we studied the effect of HGF on parasympathetic ciliary ganglion neurons and proprioceptive trigeminal mesencephalic nucleus (TMN) neurons, both of which survive with CNTF. HGF did not promote the survival of these neurons on its own but did enhance the number that survived with CNTF and increased the length and branching of their neurite arbors. HGF did not, however, enhance the survival and growth of TMN neurons incubated with BDNF, which promoted their survival as effectively as CNTF. These results show that HGF cooperates with CNTF in promoting the survival and growth of parasympathetic and proprioceptive neurons and that within the same neurons, the effects of HGF on survival and growth are selectively dependent on which other signaling pathways are concurrently activated.

Animals↗

Herpes simplex type 1 induction of persistent NF-kappa B nuclear translocation increases the efficiency of virus replication.

The latent form of the dimeric transcription factor NF-kappa B is sequestered in the cytoplasm by proteins containing ankyrin repeats, such as 1 kappa B alpha and beta, or by the p105 precursor form of the NF-kappa B p50 subunit. Tumor necrosis factor alpha or virus infection can cause targeted destruction of 1 kappa B and nuclear translocation of NF-kappa B. Following translocation, NF-kappa B mediates immune, inflammatory, or anti-apoptotic responses. Here we present evidence that beginning at around 6 h postinfection, herpes simplex virus (HSV) induces a persistent translocation of NF-kappa B into the nucleus of C33 cells, coincident with loss of both 1 kappa B alpha and 1 kappa B beta. Translocation failed to occur when infecting virus was preincubated with neutralizing antibody to viral envelope glycoproteins gD or gH, thus preventing entry, or when cells infected with viruses expressing mutated forms of immediate-early regulatory proteins lCP4 or lCP27. Surprisingly, no increase in the trans-activation function of NF-kappa B, as assayed by transient expression of CAT, was detected following HSV infection. The significance of NF-kappa B nuclear translocation for virus replication was demonstrated by an 80-90% reduction in virus yield following infection of C33 cells expressing a constitutive repressor form of 1 kappa B alpha. Models that reconcile nuclear translocation of NF-kappa B with the inability to detect NF-kappa B-dependent gene expression are discussed.

Biological Transport↗

Bcl-2 influences axonal growth rate in embryonic sensory neurons.

Bcl-2 plays a key role in regulating cell survival in the immune and nervous systems. Mice lacking the bcl-2 gene have markedly reduced numbers of B and T cells as a result of increased apoptosis, whereas mice with a transgene causing high levels of Bcl-2 expression in the immune system show extended survival of B and T cells. Overexpression of Bcl-2 in cultured neurons prevents their death following neurotrophin deprivation, and mice with a bcl-2 transgene under the control of a neuron-specific enolase promoter have increased numbers of neurons in several regions. Cultured neurons expressing antisense bcl-2 RNA have an attenuated survival response to neurotrophins, and neurons of postnatal bcl-2-deficient mice die more rapidly following NGF deprivation in vitro and are present in reduced numbers in vivo. Here, we show that Bcl-2 also plays a role in regulating axonal growth rates in embryonic neurons. Sensory neurons from the trigeminal ganglia of bcl-2-deficient mouse embryos, removed from the embryo on embryonic day 11 or 12, extend axons more slowly in vitro than do neurons from wild-type embryos of the same age. Serial measurements of axonal length in the same neurons revealed that there were marked differences in axonal growth rate between bcl-2-deficient and wild-type neurons, irrespective of whether the neurons were grown with nerve growth factor, brain-derived neurotrophic factor or neurotrophin-3. Because there was no significant difference in the numbers of wild-type and bcl-2-deficient neurons surviving with each neurotrophin at this early stage of development, the effect of Bcl-2 on axonal growth rate is not a consequence of its well documented role in preventing apoptosis.

Animals↗

RU486 inhibits synthesis of an endogenous inhibitor of cell arachidonate release from choriodecidua tissue.

Gravidin is a potent phospholipase A2 inhibitor that may contribute to the maintenance of human pregnancy. The aims of this study were to determine firstly, the site of gravidin synthesis within placental membranes and secondly, whether the antiprogestin compound, RU486, regulates synthesis. Membrane explants were taken from placentae, dissected and cultured in the presence of RU486, progesterone or inhibitors of DNA or protein synthesis and gravidin production was measured by a specific enzyme-linked immunosorbent assay. Production of gravidin was consistently greatest from choriodecidua compared with amnion and decidua. The antibiotics, cycloheximide and actinomycin D inhibited production of gravidin. The progesterone receptor antagonist RU486 at 10(-8) and 10(-7) M reduced gravidin production to 55 and 39% of the control value in membranes cultured after and before the onset of labour respectively. Progesterone at 10(-6) M stimulated gravidin production by 47% after the onset of labour. The increase in gravidin production was correlated with progesterone concentration (r = 0.47, F = 6.38, P = 0.019) in labour tissue. We conclude that the data are consistent with the hypothesis that gravidin production may be partially regulated by progesterone.

Adult↗

Cervical spine imaging in trauma patients: a simple scheme of rationalising arm traction using zonal divisions of the vertebral bodies.

OBJECTIVE: To evaluate the effectiveness of arm traction for cervical spine imaging in trauma patients and devise a scheme to predict the probability of visualising the C7/T1 level in trauma patients. METHODS: 98 trauma patients were studied. Each vertebral body was divided into three equal horizontal zones, the disc space between vertebral bodies being equivalent to one zone. The fifth cervical vertebra was used as the starting level (zone 1). Zones obtained pre and post arm traction on the lateral cervical spine radiographs were recorded. Results were analysed to show the probability of imaging the lower cervical spine, including the cervico-thoracic junction. RESULTS: If the initial film showed less than zone 10 (mid-C7 vertebra), the probability of showing zone 13 (upper body of T1) with arm traction was only 7.7%, that is, one success in every 13 pulls; or conversely, 12 failures in every 13 pulls. CONCLUSIONS: Unless an initial cervical spine radiograph includes the upper one third of the body of the C7 vertebra, the probability of attaining the C7/T1 level with arm traction is < 15%. It is suggested that all initial radiographs of the lateral cervical spine in major trauma patients be done with arm traction, and where the upper one third of the body of C7 vertebra is not seen, then computerised tomography, swimmer's, or oblique views be considered.

Arm↗

Characterisation of the copper uptake mechanism and isolation of the ceruloplasmin receptor/copper transporter in human placental vesicles.

In this paper we have studied copper (Cu) uptake by microvillar vesicles isolated from human term placenta. We have characterised Cu uptake from CuHis2 complexes and shown that ceruloplasmin (Cp) inhibits uptake. Inhibition is complex and variable; in one series of experiments, the Vmax for uptake drops from 31.3 +/- 1.2 nmol/min per mg vesicle protein without added Cp to 11.3 +/- 1 nmol/min per mg vesicle protein at 91 micrograms/ml Cp. Similarly, the K0.5 increases from 0.35 +/- 0.08 microM to 1.35 +/- 0.25 microM, while the n value (the Hill coefficient) falls from 1.9 +/- 0.23 in the absence of Cp to 1.1 +/- 0.13 In another series, Cp had no effect below concentrations of about 100 micrograms/ml and in a third series only increased K0.5. The variability in effect seems to be related to the specific activity of the ceruloplasmin, which in turn is related to the copper complexes of the protein. The effect is specific for Cp; apotransferrin and a2-macroglobulin have no effect. 67Cu-labelled ceruloplasmin binds specifically to vesicles of term placenta with an affinity of 2.8 microU/mg vesicle protein and a Bmax of 79 microU/mg vesicle protein. CuHis2, but not histidine alone, can block the uptake. The data can be reconciled by proposing that the binding site of the transporter is relatively small and recognises a Cu-dihistidine structure common to the low-molecular-weight complex and to the Type I and Type II coppers of ceruloplasmin. We have used these observations to develop an isolation method for the transporter and have identified it as a protein of M(r) 90,000 which is closely associated with alkaline phosphatase. There are also two proteins of M(r) 45,000 and 40,000 which may be breakdown products of the larger complex. Antibodies to the 45,000 protein block Cu binding and uptake from CuHis2 complexes, strongly implicating it as the copper transporter/ceruloplasmin receptor of human term placenta.

Carrier Proteins↗