Search PubMed⌕ Search

Biomedical subjects

R Harrison

Publications and source records attributed to R Harrison.

At least 19 recordsLinked to original sources
PubMed2003

Pulmonary vasodilation in the rat by insulin in vitro could indicate potential hazard for inhaled insulin.

AIMS/HYPOTHESIS: Hypoxic pulmonary vasoconstriction is an essential mechanism to prevent hypoxaemia in lung diseases. Insulin is known to be a systemic vasodilator but its effect on the pulmonary circulation is not known. Inhaled particulate insulin can generate locally high concentrations in the lung which could be physiologically important. METHODS: We therefore studied the effects of insulin in vitro on isolated rat pulmonary artery in a small vessel myograph. RESULTS: We have shown that pulmonary artery vasodilatation with insulin occurs in a dose-dependent manner. Pre-constriction with PGF2alpha can be abolished (105.7+/-2.9%, mean+/-SEM) and pre-constriction with hypoxia reduced (68.9+/-6.5%) by pharmacologically relevant concentrations of insulin. The characteristic phasic vasoconstriction by pulmonary vessel to hypoxia is substantially modified, resulting in sustained vasodilatation. CONCLUSIONS/INTERPRETATION: These effects could be clinically important for patients using inhaled insulins who have acute or occult chronic lung disease.

Animals↗
PubMed2003

Virtual outreach: economic evaluation of joint teleconsultations for patients referred by their general practitioner for a specialist opinion.

OBJECTIVES: To test the hypotheses that, compared with conventional outpatient consultations, joint teleconsultation (virtual outreach) would incur no increased costs to the NHS, reduce costs to patients, and reduce absences from work by patients and their carers. DESIGN: Cost consequences study alongside randomised controlled trial. SETTING: Two hospitals in London and Shrewsbury and 29 general practices in inner London and Wales. PARTICIPANTS: 3170 patients identified; 2094 eligible for inclusion and willing to participate. 1051 randomised to virtual outreach and 1043 to standard outpatient appointments. MAIN OUTCOME MEASURES: NHS costs, patient costs, health status (SF-12), time spent attending index consultation, patient satisfaction. RESULTS: Overall six months costs were greater for the virtual outreach consultations ( pound 724 per patient) than for conventional outpatient appointments ( pound 625): difference in means pound 99 ($162; 138) (95% confidence interval pound 10 to pound 187, P=0.03). If the analysis is restricted to resource items deemed "attributable" to the index consultation, six month costs were still greater for virtual outreach: difference in means pound 108 ( pound 73 to pound 142, P < 0.0001). In both analyses the index consultation accounted for the excess cost. Savings to patients in terms of costs and time occurred in both centres: difference in mean total patient cost pound 8 ( pound 5 to pound 10, P < 0.0001). Loss of productive time was less in the virtual outreach group: difference in mean cost pound 11 ( pound 10 to pound 12, P < 0.0001). CONCLUSION: The main hypothesis that virtual outreach would be cost neutral is rejected, but the hypotheses that costs to patients and losses in productivity would be lower are supported.

Cost of Illness↗
PubMed2003

Upregulation of the oncogene c-myc in Barrett's adenocarcinoma: induction of c-myc by acidified bile acid in vitro.

BACKGROUND AND AIMS: C-myc over expression is implicated in malignancy although to date this has not been studied in Barrett's metaplasia. We sought to determine c-myc expression in the malignant progression of Barrett's metaplasia and whether it may be induced by bile acids seen in gastro-oesophageal refluxate. METHODS: C-myc protein and mRNA levels were assessed in 20 Barrett's metaplasia and 20 oesophageal adenocarcinoma samples by western blotting and real time polymerase chain reaction. Levels of c-myc and proliferation were also assessed in cell lines OE21, OE33, SW-480, and TE-7 stimulated with pulses or continuous exposure to the bile acids deoxycholic acid and chenodeoxycholic acid. RESULTS: C-myc protein was upregulated in 50% of Barrett's metaplasia and 90% of oesophageal adenocarcinoma samples compared with squamous, gastric, and duodenal controls. C-myc immunolocalisation in Barrett's metaplasia revealed discrete nuclear localisation, becoming more diffuse with progression from low to high grade dysplasia to adenocarcinoma. Both continual and pulsed bile acid induced c-myc at pH 4, with no effect at pH 7 or with acidified media alone. Pulsed bile acid treatment induced proliferation (p<0.05); in contrast, continuous exposure led to suppression of proliferation (p<0.05). CONCLUSIONS: We have shown upregulation of c-myc with malignant progression of Barrett's metaplasia and suggest that acidified bile may be a novel agent responsible for induction of this oncogene.

Adenocarcinoma↗
PubMed2003

An exploratory study of language interpretation services provided by videoconferencing.

We explored the feasibility and acceptability of the remote provision of a language interpretation service during general practice consultations. Three methods were used to provide an interpretation service: a physically present interpreter (PI), a remote interpreter accessed using an ISDN videoconferencing link at 128 kbit/s (VI) and a remote interpreter accessed by telephone (TI). Thirty-six non-English-speaking patients were invited to take part and 35 agreed to do so. Twenty-nine (83%) of the patients recruited were female. The age range of the participants was 24-51 years. Fourteen consultations took place with a physically present interpreter, 11 using videoconferencing and 10 using the telephone. Mean scores on the Patient Enablement Instrument were 5.2 for the PI group, 2.3 for the VI group and 5.1 for the TI group. Mean scores on the Medical Interview Satisfaction Scale were 5.3 for the PI group, 4.9 for the VI group and 5.3 for the TI group. The visual quality and sound quality of remote interpreting were satisfactory. Both videoconferencing and hands-free telephones can deliver an acceptable interpreting service in primary care.

Adult↗
PubMed2003

Detecting mood disorders in men diagnosed with cancer who seek semen cryopreservation: a chance to improve service.

UNLABELLED: To assess the prevalence of mood disorders in patients diagnosed with cancer and who pursue fertility preservation. Prospective questionnaire. The Human Assisted Reproduction (H.A.R.I.) unit, Rotunda Hospital. Twenty nine men were recruited between August 2001 and January 2002. Patients were informed about the study and requested to sign a consent form prior to completing the Hospital Anxiety and Depression Scale (HADS). Information regarding the patients diagnosis and prognosis were obtained from a standard referral form completed by the referring oncologists. The prevalence of mood disorders and to determine if this is related to the pretreatment prognosis. Anxiety was diagnosed in 44.8% and depression in 17.2% of patients. However clinically significant anxiety and depression was diagnosed in 13.8% and 6.9% respectively. There was no significant difference in the scores for anxiety and depression in the good prognosis group compared with the guarded group. Reduced sperm count was diagnosed in 26.9% of men and decreased motility in 30.8%, but neither of these were influenced by mood. CONCLUSION: Anxiety and depression are commonly encountered in patients with cancer. Most cases are of mild to moderate severity. Knowledge of our patients' psychological status will contribute to an improved service.

Adolescent↗
PubMed2002

Joint teleconsultations (virtual outreach) versus standard outpatient appointments for patients referred by their general practitioner for a specialist opinion: a randomised trial.

BACKGROUND: The current model of general practitioner referral of patients to hospital specialists in the UK is sometimes associated with unnecessary duplication of investigations and treatments. We aimed to compare joint teleconsultations between general practitioners, specialists, and patients (virtual outreach) with standard outpatient referral. METHODS: Virtual outreach services were established in London and Shrewsbury. The general practitioners referred 3170 patients, of whom 2094 consented to participate in the study and were eligible for inclusion. 1051 patients were randomly assigned virtual outreach, and 1043 standard outpatient appointments. We followed up the patients for 6 months after their index consultation. The primary outcome measure was the offer of a follow-up outpatient appointment. Analysis was by intention to treat. FINDINGS: More patients in the virtual outreach group than the standard group were offered a follow-up appointment (502 [52%] vs 400 [41%], odds ratio 1.52 [95% CI 1.27-1.82], p<0.0001). Significant differences in effects were observed between the two sites (p=0.009) and across different specialties (p<0.0001). Virtual outreach increased the offers of follow-up appointments more in Shrewsbury than in London, and more in ear, nose, and throat surgery and orthopaedics than in the other specialties. Fewer tests and investigations were ordered in the virtual outreach group by an average of 0.79 per patient (0.37-1.21, p=0.0002). Patients' satisfaction (analysed per protocol) was greater after a virtual outreach consultation than after a standard outpatient consultation (mean difference 0.33 scale points [95% CI 0.23-0.43], p<0.0001), with no heterogeneity between specialties or sites. INTERPRETATION: The trial showed that allocation of patients to virtual outreach consultations is variably associated with increased offers of follow-up appointments according to site and specialty, but leads to significant increases in patients' satisfaction and substantial reductions in tests and investigations. Efficient operation of such services will require appropriate selection of patients, significant service reorganisation, and provision of logistical support.

Ambulatory Care Facilities↗
PubMed2002

Self-reported physical health among older surrogate parents to children orphaned and affected by HIV disease.

Around the globe, older relatives, largely grandparents, have become the surrogate parents to children and adolescents orphaned by parental death from HIV/AIDS and to those whose infected parents are too ill to serve as their primary caregivers. Largely invisible to research, programme and policy initiatives, these older surrogate parents face compounded stress and the risk of neglected and compromised health. An exploratory study of third- and fourth-generation relatives (n=20, mean of 59 years) found an average of 3.3 chronic health conditions. Fifty-five per cent rated their own health as "fair" or "poor" and 70% reported having insufficient time to attend to their own health. Supportive services are needed to address the health needs of these "hidden patients".

Adolescent↗
PubMed2002

Respiratory depression in the acute management of seizures.

The incidence of respiratory depression following treatment of prolonged seizures with benzodiazepines is variable in the literature. We retrospectively reviewed the charts of children treated for prolonged seizure over a one year period. Of the 56 seizures treated, 30 received lorazepam, 19 diazepam, and seven both drugs. Twenty two episodes (39%) of prolonged seizure were treated with multiple doses of benzodiazepines. In eight events (14%), there was documented respiratory depression following the administration of one or more doses of benzodiazepine; in six of these, multiple doses were given. The doses used were often at the low end or less than the recommended dose for treatment of status epilepticus. These data support suggestions that multiple doses of benzodiazepines increase the risk of respiratory depression.

Anticonvulsants↗
PubMed2002

Design and performance of a multicentre, randomized controlled trial of teleconsulting.

We have designed and performed a multicentre, randomized controlled trial of teleconsulting. The trial investigated the effectiveness and cost implications in rural and inner-city settings of using videoconferencing as an alternative to general practitioner referral to a hospital specialist. The participating general practitioners referred a total of 3170 patients who satisfied the entry criteria. Of these, 1040 (33%) failed to provide consent or otherwise refused to participate in the trial. Of the patients recruited to the trial, a total of 1902 (91%) completed and returned the baseline questionnaire. Although the trial was successful in recruiting sufficient patients and in obtaining high questionnaire response rates, the findings will require careful interpretation to take account of the limits which the protocol placed on the ability of general practitioners to select patients for referral.

Family Practice↗
PubMed2001

Suicide inactivation of xanthine oxidoreductase during reduction of inorganic nitrite to nitric oxide.

Xanthine oxidoreductase (XOR) is progressively inactivated while catalysing the reduction of inorganic nitrite to NO by xanthine. Inactivation results from conversion of the enzyme into its desulpho-form. The rate of inactivation increases with nitrite concentration. Similar behaviour was shown when NADH replaced xanthine as reducing substrate. A kinetic model is proposed incorporating a 'suicide' inactivation involving an enzyme-substrate (product) complex, rather than inactivation by free NO. The model provides a good fit to progress curves of the reaction of xanthine or NADH with nitrite in the presence of the oxidase or dehydrogenase forms of the enzyme. Inorganic nitrate, like nitrite, was shown to be reduced at the molybdenum site of XOR. With xanthine as reducing substrate, nitrite was produced in essentially a 1:1 stoichiometric ratio with respect to urate. Unlike the case of nitrite, the enzyme was not significantly inactivated, implying that inactivation during nitrite reduction depends on the presence of nascent NO in its enzyme complex.

Animals↗
PubMed2001

Reduction of organic nitrates catalysed by xanthine oxidoreductase under anaerobic conditions.

Xanthine oxidoreductase catalyses the anaerobic reduction of glyceryl trinitrate (GTN), isosorbide dinitrate and isosorbide mononitrate to inorganic nitrite using xanthine or NADH as reducing substrates. Reduction rates are much faster with xanthine as reducing substrate than with NADH. In the presence of xanthine, urate is produced in essentially 1:1 stoichiometric ratio with inorganic nitrite, further reduction of which is relatively slow. Organic nitrates were shown to interact with the FAD site of the enzyme. In the course of reduction of GTN, xanthine oxidoreductase was progressively inactivated by conversion to its desulpho form. It is proposed that xanthine oxidoreductase is one of several flavoenzymes that catalyse the conversion of organic nitrate to inorganic nitrite in vivo. Evidence for its further involvement in reduction of the resulting nitrite to nitric oxide is discussed.

Anaerobiosis↗
PubMed2001

Cloning of the mouse dysferlin gene and genomic characterization of the SJL-Dysf mutation.

The SJL mouse strain has been widely used as an animal model for experimental autoimmune encephalitis (EAE), inflammatory muscle disease and lymphomas and has also been used as a background strain for the generation of animal models for a variety of diseases including motor neurone disease, multiple sclerosis and atherosclerosis. Recently the SJL mouse was shown to have myopathy due to dysferlin deficiency, so that it can now be considered a natural animal model for limb-girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). We have cloned the mouse dysferlin cDNA and analysis of the sequence shows that the mouse dysferlin gene is characterized by six C2 domain sequences and a C-terminal anchoring domain, with the human and the mouse dysferlin genes sharing > 90% sequence homology overall. Genomic analysis of the SJL mutation confirms that the 171 bp RNA deletion has arisen by exon skipping resulting from a splice site mutation. The identification of this mutation has implications for the various groups using this widely available mouse stock.

Amino Acid Sequence↗
PubMed2001

Costs of occupational injuries and illnesses in California.

OBJECTIVES: The purpose of this study was to estimate the annual incidence, the mortality, and the direct and indirect costs associated with occupational injuries and illnesses in California in 1992. To achieve this, we performed aggregation and analysis of national and California data sets collected by the U.S. Bureau of Labor Statistics, California Workers' Compensation Insurance Rating Bureau, California Division of Industrial Relations, the National Center for Health Statistics, and the U.S. Health Care Financing Administration. METHODS: To assess incidence of and mortality from occupational injuries and illnesses, we reviewed data from state and national surveys and applied an attributable risk proportion method. To assess costs, we used the cost-of-illness, human capital, method that decomposes costs into direct categories such as medical expenses and insurance administration expenses as well as indirect categories such as lost earnings, lost home production, and lost fringe benefits. Some cost estimates were drawn from California data, whereas others were drawn from a national study but were adjusted to reflect California's differences. Cost estimates for injuries were calculated by multiplying average costs by the number of injuries. For the majority of diseases, cost estimates relied on the attributable risk proportion method. RESULTS: Approximately 660 job-related deaths from injury, 1.645 million nonfatal injuries, 7,079 deaths from diseases, and 0.133 million illnesses are estimated to occur annually in the civilian California workforce. The direct ($7.04 billion, 34%) plus indirect ($13.62 billion, 66%) costs were estimated to be $20.7 billion. Injuries cost $17.8 billion (86%) and illnesses $2.9 billion (14%). These estimates are likely to be low because: (1) they ignore costs associated with pain and suffering, (2) they ignore home care provided by family members, and (3) the numbers of occupational injuries and illnesses are likely to be undercounted. CONCLUSION: Occupational injuries and illnesses are a major contributor to the total cost of health care and lost productivity in California. These costs are on a par with those of all cancers combined and only slightly less than the cost of heart disease and stroke in California. Workers' compensation covers less than one-half of the costs of occupational injury and illness.

California↗
PubMed2001

The inner ear of dogs with X-linked nephritis provides clues to the pathogenesis of hearing loss in X-linked Alport syndrome.

Alport syndrome is an inherited disorder of type IV collagen with progressive nephropathy, ocular abnormalities, and high-tone sensorineural deafness. In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha5 chain of type IV collagen lead to loss of the alpha3/alpha4/alpha5 network and increased susceptibility of the glomerular basement membrane to long-term damage. The molecular defects that underlie the otopathology in this disease remain poorly understood. We used a canine model of X-linked Alport syndrome to determine the expression of type IV collagen alpha-chains in the inner ear. By 1 month in normal adult dogs, the alpha3, alpha4, and alpha5 chains were co-expressed in a thin continuous line extending along the basilar membrane and the internal and external sulci, with the strongest expression along the lateral aspect of the spiral ligament in the basal turn of the cochlea. Affected dogs showed complete absence of the alpha3/alpha4/alpha5 network. The lateral aspect of the spiral ligament is populated by tension fibroblasts that express alpha-smooth muscle actin and nonmuscle myosin and are postulated to generate radial tension on the basilar membrane via the extracellular matrix for reception of high frequency sound. We propose that in Alport syndrome, the loss of the alpha3/alpha4/alpha5 network eventually weakens the interaction of these cells with their extracellular matrix, resulting in reduced tension on the basilar membrane and the inability to respond to high frequency sounds.

Animals↗
PubMed2001

Metal binding affinity and structural properties of an isolated EF-loop in a scaffold protein.

To establish an approach to obtain the site-specific calcium binding affinity of EF-hand proteins, we have successfully designed a series of model proteins, each containing the EF-hand calcium-binding loop 3 of calmodulin, but with increasing numbers of Gly residues linking the loop to domain 1 of CD2. Structural analyses, using different spectroscopic methods, have shown that the host protein is able to retain its native structure after insertion of the 12-residue calcium-binding loop and retains a native thermal stability and thermal unfolding behavior. In addition, calcium binding to the engineered CD2 variants does not result in a significant change from native CD2 conformation. The CD2 variant with two Gly linkers has been shown to have the strongest metal binding affinity to Ca(II) and La(III). These experimental results are consistent with our molecular modeling studies, which suggest that this protein with the engineered EF-loop has a calmodulin-like calcium binding geometry and backbone conformation. The addition of two Gly linkers increases the flexibility of the inserted EF-loop 3 from calmodulin, which is essential for the proper binding of metal ions.

Amino Acid Motifs↗
PubMed2001

Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir.

BACKGROUND: Strategies for prevention of liver graft reinfection by hepatitis B virus (HBV) have been developed during recent years. Initially, passive immunoprophylaxis with high titre HBV immunoglobulin (HBIg), followed by lamivudine prophylaxis, and then the combination of lamivudine and HBIg have been employed. However, suboptimal use of the combination may be associated with failure of prophylaxis reflected by the emergence of HBV species with genetic changes that confer resistance to lamivudine and HBIg. Reinfection of the graft by HBV can be associated with rapid development of liver failure. CASE REPORT: A 43 year old HBV infected man received lamivudine before transplantation, and lamivudine and HBIg after transplantation. Despite prophylaxis, graft reinfection and severe hepatitis were observed. The observed serological evolution and genetic sequencing of the emergent HBV species suggested selection of lamivudine resistant and surface antigen escape mutants consecutively. Adefovir treatment began after the development of graft failure. OUTCOME: A rapid exponential decline in serum HBV titre was observed. Liver function tests normalised and signs of liver failure resolved. CONCLUSION: The use of HBIg and lamivudine permits prevention of graft reinfection by HBV for the majority of patients. Adefovir, a potent inhibitor of lamivudine resistant HBV, should be used when failure of prophylaxis is associated with graft hepatitis.

Acute Disease↗