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Biomedical subjects

M Donnelly

Publications and source records attributed to M Donnelly.

At least 19 recordsLinked to original sources

Routine nasopharyngeal biopsy in adults presenting with isolated serous otitis media: is it justified?

Nasopharyngeal malignancy accounts for less than 2 per cent of all head and neck cancers. Serous otitis media (SOM) causing deafness is a recognized indicator of nasopharyngeal obstruction and the possibility of a nasopharyngeal malignancy must be considered in all adults. Examination under anaesthesia (EUA) and biopsy of the nasopharynx is routinely undertaken in many centres to rule out nasopharyngeal malignancy in adults with SOM. The purpose of this 10-year retrospective study was to evaluate the case records of all adult cases of SOM, including their presentation, clinical findings, management and nasopharyngeal biopsy results. Eighty-five patients were included in the study. Fifty-nine presented with unilateral SOM and 26 with bilateral SOM. The primary presenting complaint in all cases was hearing loss. A nasopharyngeal mass was documented in 55 patients (69 per cent). Four nasopharyngeal masses were noted to have irregular or exophytic mucosa on flexible nasendoscopy. All patients underwent a EUA of the ears and a nasopharyngeal biopsy. The four patients with suspicious-looking masses were all found to have malignancies (two squamous cell carcinomas, one B-cell non-Hodgkin lymphoma and one adenocarcinoma). Three of these patients presented with unilateral SOM and one with bilateral SOM. All other patients with masses were found to have benign lymphoid hyperplasia. In total, 4.7 per cent of the adults with conductive hearing loss secondary to SOM were found to have a malignancy on nasopharyngeal biopsy. We would advocate a high index of suspicion of a nasopharyngeal tumour in adults presenting with SOM. If a mass is found in the nasopharynx then it should be biopsied. If no mass is found then it is not necessary to biopsy; however, close follow up, with repeat fibre-optic nasendoscopy, is advised.

Adult↗

Anatomical variation at the saphenofemoral junction.

BACKGROUND: This study was designed to document the surgical anatomy of the saphenofemoral junction (SFJ). METHODS: The anatomy of the SFJ was recorded diagrammatically in 2089 consecutive groin dissections performed to treat primary varicose veins. The number of primary tributaries, bifid systems, junctional tributaries and the relationship of the external pudendal artery (EPA) to the long saphenous vein (LSV) were recorded. RESULTS: The LSV was bifid in 18.1 per cent of legs. The number of tributaries at the SFJ varied from one to ten. In 33.4 per cent one or more (junctional) tributaries joined the LSV or common femoral vein deep to the deep fascia. The EPA crossed anterior to 16.8 per cent of LSVs. In 4.6 per cent it passed posterior to one large tributary or trunk of a bifid LSV and anterior to the second trunk, making identification of the second trunk particularly difficult. CONCLUSION: A thorough understanding of the anatomical variations of the SFJ is important in ensuring that the junction is managed safely and adequately in patients with varicose veins. Failure to appreciate these variations may account for a significant proportion of inadequate primary varicose vein surgery.

Adult↗

Changes in trauma service workload since the introduction of the penalty points system.

With the introduction of the penalty points system (PPS) has come many media reports indicating a reduction in road traffic accident (RTA) rates. We hypothesised that reduced RTAs would result in a reduction in hospital trauma workloads. To study this we examined the numbers of RTA related femoral shaft fracture presentations to the six Dublin teaching hospitals and Waterford regional hospital within the six months since the introduction of the PPS and the two previous corresponding six month periods. We also analysed all RTA related discharges from Beaumont hospital during these three time periods. Whilst a slight reduction in RTA related femoral shaft fracture numbers was observed a dramatic reduction in total RTA related discharges from Beaumont hospital was identified with 70 patients discharged in the first six months since the introduction of the PPS compared to 124 and 125 discharges in the same two preceding six month periods. This reduction was greatest for head and thoracic injuries which were halved, while total numbers of limb injuries were maintained, resulting in no reduction in orthopaedic RTA related discharges or workload.

Accidents, Traffic↗

Patients' recall of clinical information following laparoscopy for acute abdominal pain.

BACKGROUND: Failures in doctor-patient communication and patients' understanding continue to confound improvements in the delivery of quality healthcare. In the context of acute abdominal pain managed by means of laparoscopy, it was hypothesized that patients are either not adequately informed, or do not reliably retain simple relevant information transmitted at the time of the procedure. This study was designed to evaluate the reliability of information transfer between doctor and patient in this setting, including the diagnosis and whether or not the appendix was removed. METHODS: A retrospective study of 350 consecutive patients who had undergone laparoscopy for acute abdominal pain over 3.5 years was designed. Each patient completed a telephone questionnaire that was used to evaluate the accuracy of patients' information. RESULTS: In total, 26.9 per cent of patients did not know or were incorrect regarding the surgical procedure performed. Similarly, 20.0 per cent of all patients did not know or were incorrect regarding the status of their appendix after surgery and 30.0 per cent of patients were incorrect regarding the diagnosis. Despite all of these statistics, 91.4 per cent of patients were happy with the information they had received regarding the procedure. CONCLUSION: Some 26.9 per cent of patients who underwent laparoscopy for acute abdominal pain were incorrect or did not know about the procedure that had been performed. This could lead to a further unnecessary operation should they re-present with similar symptoms.

Abdominal Pain↗

What influences physiotherapy use by children with cerebral palsy?

AIM: To investigate factors that influence the frequency of physiotherapy currently used by a population of children with moderate to severe cerebral palsy (CP). METHODS: A survey using a postal questionnaire was sent to 212 parents of children with moderate to severe CP. The families were identified from a geographically defined case register of children with CP in Northern Ireland (the Northern Ireland Cerebral Palsy Register). Eighty-five per cent of parents responded. One-third of parent responses regarding their child's use of physiotherapy were validated with their child's physiotherapist and the level of agreement was high. RESULTS: Ninety-four per cent (169/180) of children received conventional physiotherapy from a statutory source during the school term. Of these, 61% (104/169) used 'intense' levels of physiotherapy (defined as at least twice a week). A higher proportion of intense users were children with severe CP compared with moderate CP (69% vs. 47%; P < 0.01); with moderate intellectual impairment (IQ </= 70 > 50) compared with severe (IQ </= 50) or no intellectual impairment (IQ > 70) (81% vs. 64% vs. 39% respectively; P < 0.01) and at schools for physical disability (PD) compared with severe learning disability (SLD) or mainstream (MS) schools (82% vs. 66% vs. none respectively; P < 0.001). After controlling for severity of motor impairment and the presence and severity of intellectual impairment, children with CP at MS schools used on average significantly less physiotherapy compared with children with similar levels of motor impairment at PD schools (P < 0.001). CONCLUSIONS: Children with CP in MS schools use less physiotherapy compared with children with similar levels of disability in special schools. Organizing services around special schools may limit the degree to which children with CP and other disabilities are successfully integrated into MS education.

Adolescent↗

Analysis of betamethasone in rat plasma using automated solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry. Determination of plasma concentrations in rat following oral and intravenous administration.

A method is described for the determination of betamethasone in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS-MS). The analyte was recovered from plasma by solid-phase extraction and subsequently analyzed by LC-MS-MS. A Packard Multiprobe II, an automated liquid handling system, was employed for the preparation and extraction of a 96-well plate containing unknown plasma samples, standards and quality control samples in an automated fashion. Prednisolone, a structurally related steroid, was used as an internal standard. Using the described approach, a limit of quantitation of 2 ng/ml was achieved with a 50 microl aliquot of rat plasma. The described level of sensitivity allowed the determination of betamethasone concentrations and subsequent measurement of kinetic parameters of betamethasone in rat. Combination of automated plasma extraction and the sensitivity and selectivity of LC-MS-MS offers a valuable alternative to the methodologies currently used for the quantitation of steroids in biological fluids.

Administration, Oral↗

Use of physiotherapy and alternatives by children with cerebral palsy: a population study.

OBJECTIVES: To describe the use of physiotherapy services and alternative therapies by a population of children with moderate to severe cerebral palsy (CP). DESIGN: Descriptive cross-sectional survey. SUBJECTS: A total of 212 parents of children aged 4-14 years with moderate to severe CP were identified from the Northern Ireland Cerebral Palsy Register (NICPR) and a random subsample of their paediatric physiotherapists. MAIN MEASURES: A standardized description of motor impairment or assessment form; a postal questionnaire to parents and paediatric physiotherapists (to validate parents' reports of service use). RESPONSE RATES: In total, 85% of parent questionnaires were returned and 100% of paediatric physiotherapists responded. RESULTS: Service use among families was high; on average the families had contact with approximately seven services in a 6-month time interval. The overwhelming majority of children (96%) received physiotherapy during the school term and most (59%) received treatment at least twice a week for 30 min; 43% of children had their physiotherapy discontinued over the summer holidays. Over one-quarter (28%) of families had opted out of the NHS and bought alternatives like conductive education (21%) or private forms of conventional physiotherapy (16%). Children with more severe forms of CP, in special education, particularly at schools for physical disability, were high-intensity users of the physiotherapy service. Despite this, 74% of parents wanted more physiotherapy for their child. CONCLUSIONS AND IMPLICATIONS: The demand for physiotherapy services is likely to continue given the relatively stable prevalence rate of CP, the proportion of children with disabling CP and the level of parent interest in the service. A number of quality aspects and gaps in the service have been identified.

Adolescent↗

The impact of indoor residual spraying with malathion on malaria in refugee camps in eastern Sudan.

An exploratory trial of the efficacy of indoor spraying with malathion on morbidity and mortality in refugee camps in eastern Sudan was conducted during the rainy season of 1997. The interior walls of houses from a randomly selected group of five camps were sprayed with malathion in mid-September and morbidity and mortality rates in the camps for the months October to December compared with rates in five controls. Pyrethrum spray collection and human landing catches were performed in two collection rounds. An exophagic but endophilic population of Anopheles arabiensis was the most common mosquito collected. The mean human blood index of 242 mosquitoes from eight camps was 0.51. Only two of 1040 mosquitoes examined harboured sporozoites. Blood samples of 83 putative malaria patients were examined for parasites by PCR. Mortality rates in the 3 months following spraying were significantly lower in sprayed camps although differences in clinical malaria incidence between sprayed and non-sprayed camps were not significant.

Animals↗

Computational analysis of the autocatalytic posttranslational cyclization observed in histidine ammonia-lyase. A comparison with green fluorescent protein.

Density functional calculations using hybrid functionals (B3LYP) have been performed to study the mechanism of the autocatalytic posttranslational cyclization observed in histidine ammonia-lyase. Two mechanisms were analyzed, the commonly accepted mechanism in which cyclization precedes dehydrogenation (reduced mechanism) and a mechanism in which dehydrogenation precedes cyclization (oxidized mechanism). The reduced pathway is not supported by the calculations, while the alternative oxidized mechanism where a dehydration occurs prior to the formation of the ring yields reasonable energetics for the system. Database searches showed that the oxidative mechanism in which the formation of the dehydro amino acids in residue i + 1 precedes the cyclization is also structurally advantageous as it results in shorter distances between the carbonyl carbon of residue i and the amide nitrogen of residue i + 2 and, therefore, preorganizes the protein for cyclization. Conformational searches showed that these distances were also unusually short and exhibited very little variation in the Delta-Ala143 HAL tetramer, indicating that like GFP the tetrameric form of HAL is rigidly preorganized for cyclization. The monomeric form of HAL is less preorganized than the tetrameric form of HAL. Dehydro amino acids aid in the preorganization, but the main driving force in the rigid tight turn formation is the influence of the surrounding protein.

Amino Acids↗

Nurse endoscopists in United Kingdom health care: a survey of prevalence, skills and attitudes.

OBJECTIVES: To assess the prevalence and potential benefits of attitudes towards nurse endoscopy in the United Kingdom (UK). DESIGN: Postal questionnaire. SUBJECTS: All hospitals in the UK with accident and emergency, general medical and general surgical services in October 2000. MAIN OUTCOME MEASURES: Number of teaching or district general hospitals employing nurse endoscopists, range of diagnostic and therapeutic endoscopic skills and potential benefits to the endoscopy unit and patients. RESULTS: Seventy-six hospitals employed 102 nurse endoscopists. Forty-four nurse endoscopists performed both oesophago-gastroduodenoscopy (OGD) and flexible sigmoidoscopy with solitary OGD and flexible sigmoidoscopy performed by 17 and 31, respectively. Three performed full colonoscopy while seven could perform all three procedures. Nurse endoscopists were found to provide good patient care in the majority of endoscopy units with no compromise in safety. Lead clinicians were keen to restrict nurse endoscopy to diagnostic OGD and flexible sigmoidoscopy only in the majority of units. CONCLUSIONS: Nurse endoscopy is widely practised in the UK and is not limited to one procedure or solely for diagnostic purposes. Benefits include good patient acceptability, improved care and safety. Most clinicians predict an important but restricted role for nurse endoscopy in contributing to endoscopic services.

Attitude to Health↗

Nuclear localization and shuttling of herpes simplex virus tegument protein VP13/14.

The herpes simplex virus type 1 gene UL47 encodes the tegument proteins referred to collectively as VP13/14, which are believed to be differentially modified forms of the same protein. Here we show that the major product of the UL47 gene during transient expression is VP14, suggesting that some feature of virus infection is required to produce VP13. We have tagged VP13/14 with green fluorescent protein and have demonstrated that the protein is targeted efficiently to the nucleus, where it often localizes in numerous punctate domains. Furthermore, we show that removal of the N-terminal 127 residues of the protein abrogates nuclear accumulation, and we have identified a 14-amino-acid peptide from this region that is sufficient to function as a nuclear targeting signal and transport a heterologous protein to the nucleus. This short peptide contains two runs of four arginine residues, suggesting that the VP13/14 nuclear localization signal may behave in a manner similar to that of the arginine-rich nuclear localization signals of the retrovirus transactivator proteins Tat, Rev, and Rex. In addition, by using heterokaryon assays, we show that VP13/14 is capable of shuttling between the nucleus and cytoplasm of the cell, a property that may be attributed to three leucine-rich stretches in the C-terminal half of the protein that again bear similarity to the nuclear export signals of Rev and Rex. This is the first demonstration of a tegument protein that is specifically targeted to the nucleus, a feature which may be relevant both during virus entry, when VP13/14 enters the cell as a component of the tegument, and at later times, when large amounts of newly synthesized VP13/14 are present within the cell.

3T3 Cells↗

Fluorescent tagging of herpes simplex virus tegument protein VP13/14 in virus infection.

The cellular site of herpesvirus tegument assembly has yet to be defined. We have previously used a recombinant herpes simplex virus type 1 expressing a green fluorescent protein (GFP)-tagged tegument protein, namely VP22, to show that VP22 is localized exclusively to the cytoplasm during infection. Here we have constructed a similar virus expressing another fluorescent tegument protein, YFP-VP13/14, and have visualized the intracellular localization of this second tegument protein in live infected cells. In contrast to VP22, VP13/14 is targeted predominantly to the nuclei of infected cells at both early and late times in infection. More specifically, YFP-13/14 localizes initially to the nuclear replication compartments and then progresses into intense punctate domains that appear at around 12 h postinfection. At even later times this intranuclear punctate fluorescence is gradually replaced by perinuclear micropunctate and membranous fluorescence. While the vast majority of YFP-13/14 seems to be targeted to the nucleus, a minor subpopulation also appears in a vesicular pattern in the cytoplasm that closely resembles the pattern previously observed for GFP-22. Moreover, at late times weak fluorescence appears at the cell periphery and in extracellular virus particles, confirming that YFP-13/14 is assembled into virions. This predominantly nuclear targeting of YFP-13/14 together with the cytoplasmic targeting of VP22 may imply that there are multiple sites of tegument protein incorporation along the virus maturation pathway. Thus, our YFP-13/14-expressing virus has revealed the complexity of the intracellular targeting of VP13/14 and provides a novel insight into the mechanism of tegument, and hence virus, assembly.

Animals↗

Assessing the impact of national anti-HIV sexual health campaigns: trends in the transmission of HIV and other sexually transmitted infections in England.

OBJECTIVE: To assess the impact of the sexual component of AIDS and HIV campaigns on transmission of HIV and other sexually transmitted infections (STIs). DESIGN: Comparison of time series data. SETTING: England, 1971-1999. OUTCOME MEASURES: HIV transmission and diagnoses among men who have sex with men (MSMs), rates of attendances and specific STI diagnoses (per 100 000 total population) at genitourinary medicine (GUM) clinics. RESULTS: Awareness of AIDS and campaigns in 1983-4 among homosexual men coincided with substantial declines in transmission of HIV and diagnoses of syphilis among MSMs. During general population campaigns in 1986-7 new GUM clinic attendances requiring treatment fell by 117/10(5) in men and 42/10(5) in women. Rates for gonorrhoea fell by 81/10(5) and 43/10(5) and genital herpes by 6/10(5) and 4/10(5), respectively. Previous rises in genital wart rates were interrupted, while rates of attendances not requiring treatment (the "worried well") increased by 47/10(5) and 58/10(5) for men and women, respectively. Since 1987 diagnoses of HIV among MSMs have not declined, averaging 1300-1400 annually. Following a period of unchanging rates there have been substantial increases in GUM attendances requiring treatment, notably for gonorrhoea, syphilis, and viral STIs since 1995. CONCLUSIONS: Self help initiatives and awareness among homosexual men in 1983-4 contributed significantly to a fall in HIV transmission among MSMs, and the general campaigns of 1986-7 were associated with similar effects on all STI transmission. Both effects seem to have occurred through changing sexual behaviour, and probably contributed to the UK's low national HIV prevalence. Bacterial STI incidence has increased significantly since 1995 and there is no evidence that recent prevention initiatives have reduced HIV transmission among MSMs, hence sexual health initiatives need to be comprehensively reinvigorated in England.

Condylomata Acuminata↗

T/NK cell non-Hodgkin's lymphoma of the sinonasal tract.

Non-Hodgkin's lymphoma of the sinonasal tract is now recognized as an important cause of destructive midfacial lesions formally designated as idiopathic inflammatory processes, and commonly treated with local radiotherapy in a bid to halt the destructive process. However, left untreated, the natural history of this disease remains largely unknown. We report a case which demonstrates the slow and apparently indolent natural course that these lymphomas, if left untreated, may display, before finally evolving into overwhelming and fatal disease. We also take the opportunity to present a brief synopsis of the evolution of our understanding of this condition and to review the modern literature on it.

Disease Progression↗

Clinical features of newly presenting cases of chronic otitis media.

The clinical features of 58 consecutive patients presenting with a new case of chronic otitis media were prospectively collected over a 15-month period. Twenty-three ears had a keratin filled marginal or attic defect (14 with cholesteatoma), 20 had a self-clearing marginal or attic defect, and 21 had a central tympanic membrane perforation (including one cholesteatoma). Twenty patients (35 per cent) had an abnormal finding in the opposite ear. The patients' ages were dispersed over a wide range of age groups with a mean age of 34 years. Hearing loss was the most common presenting symptom (78 per cent), followed by otorrhoea (64 per cent). A significant proportion of patients denied any history of otorrhoea. Our findings should alert the clinician to suspecting a new case of COM in patients with hearing loss of any age, with, or without, a history of otorrhoea, regardless of their background ear history or the duration of their symptoms.

Adolescent↗