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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 55 records · Page 3Linked to original sources

Compliance and effectiveness of 1 year's home telemonitoring. The report of a pilot study of patients with chronic heart failure.

UNLABELLED: Patients with a diagnosis of heart failure, registered at the study practice, were recruited into the study. First, they had a cardiologist's assessment. They were then randomised into telemonitored patients who measured pulse, BP, weight and video consulted, and controls. AIM: To examine the acceptability, effectiveness and reliability of home telemonitoring. RESULTS: A high proportion of those invited took part (n=20/24). Compliance with measuring weight, pulse and BP remained high throughout the study. The data collection system and secure web-server were reliable. The telemonitoring group complied better with collecting prescriptions for their cardiac drugs. Video consulting started with enthusiasm, but became less useful. There were no significant differences in the quality of life (GHQ) and Chronic Heart Failure (Guyatt) questionnaire scores between the telemonitored group and the controls. CONCLUSIONS: Home telemonitoring is an acceptable reliable intervention. Baseline rates for compliance with self-monitoring are set out in this study. Benefit in terms of compliance with medication and self-monitoring is still seen after 1 year. Video consulting over ordinary telephone lines did not show sustained benefit, and was not complied with.

Aged↗

Early endosseous integration enhanced by dual acid etching of titanium: a torque removal study in the rabbit.

Textured implant surfaces are thought to enhance endosseous integration. Torque removal forces have been used as a biomechanical measure of anchorage, or endosseous integration, in which the greater forces required to remove implants may be interpreted as an increase in the strength of bony integration. The purpose of this study was to compare the torque resistance to removal of screw-shaped titanium implants having a dual acid-etched surface (Osseotite) with implants having either a machined surface, or a titanium plasma spray surface that exhibited a significantly more complex surface topography. Three custom screw-shaped implant types - machined, dual acid-etched (DAE), and titanium plasma sprayed (TPS) - were used in this study. Each implant surface was characterized by scanning electron microscopy and optical profilometry. One DAE implant was placed into each distal femur of eighteen adult New Zealand White rabbits along with one of the other implant types. Thus, each rabbit received two DAE implants and one each of the machined, or TPS, implants. All implants measured 3.25 mm in diameter x 4.00 mm in length without holes, grooves or slots to resist rotation. Eighteen rabbits were used for reverse torque measurements. Groups of six rabbits were sacrificed following one, two and three month healing periods. Implants were removed by reverse torque rotation with a digital torque-measuring device. Three implants with the machined surface preparation failed to achieve endosseous integration. All other implants were anchored by bone. Mean torque values for machined, DAE and TPS implants at one, two and three months were 6.00+/-0.64 N-cm, 9.07+/-0.67 N-cm and 6.73+/-0.95 N-cm; 21.86+/-1.37 N-cm, 27.63+/-3.41 N-cm and 27.40+/-3.89 N-cm; and 27.48+/-1.61 N-cm, 44.28+/-4.53 N-cm and 59.23+/-3.88 N-cm, respectively. Clearly, at the earliest time point the stability of DAE implants was comparable to that of TPS implants, while that of the machined implants was an order of magnitude lower. The TPS implants increased resistance to reverse torque removal over the three-month period. The results of this study confirm our previous results that demonstrated enhanced bony anchorage to dual acid-etched implants as compared to machined implants. Furthermore, the present results indicate that dual acid etching of titanium enhances early endosseous integration to a level which is comparable to that achieved by the topographically more complex TPS surfaces.

Analysis of Variance↗

Positron emission tomography imaging for herpes virus infection: Implications for oncolytic viral treatments of cancer.

Molecular therapy using viruses would benefit greatly from a non-invasive modality for assessing dissemination of viruses. Here we investigated whether positron emission tomography (PET) scanning using [(124)I]-5-iodo-2'-fluoro-1-beta-d-arabinofuranosyl-uracil (FIAU) could image cells infected with herpes simplex viruses (HSV). Using replication-competent HSV-1 oncolytic viruses with thymidine kinase (TK) under control of different promoters, we demonstrate that viral infection, proliferation and promoter characteristics all interact to influence FIAU accumulation and imaging. In vivo, as few as 1 x 107 viral particles injected into a 0.5-cm human colorectal tumor can be detected by [(124)I]FIAU PET imaging. PET signal intensity is significantly greater at 48 hours compared with that at 8 hours after viral injection, demonstrating that PET scanning can detect changes in TK activity resulting from local viral proliferation. We also show the ability of FIAU-PET scanning to detect differences in viral infectivity at 0.5 log increments. Non-invasive imaging might be useful in assessing biologically relevant distribution of virus in therapies using replication-competent HSV.

Antiviral Agents↗

Middle cerebral artery Doppler in severe intrauterine growth restriction.

OBJECTIVE: To examine longitudinal changes in middle cerebral artery blood flow assessed by Doppler in severely growth restricted fetuses. METHODS: Eighteen structurally normal singleton pregnancies complicated by suspected intrauterine growth restriction were monitored by serial measurement of the pulsatility index of the middle cerebral artery over 7 to 72 days. Outcome measures included indication for delivery, umbilical venous pH and admission to and length of stay in neonatal intensive care. RESULTS: Thirteen fetuses demonstrated severe intrauterine growth restriction based on subsequent birth weights being below the 2.5th centile, two had intrauterine growth restriction (birth weights between the 2.5th and 5th centiles), and three had birth weights between the 5th and 50th centiles. The middle cerebral artery pulsatility index showed rapid and sharp changes between examinations in those severely growth restricted fetuses which required delivery before 34 weeks. This pattern was not obvious in severely growth restricted fetuses delivered after 34 weeks, or in those less severely growth restricted, regardless of the gestation at delivery. Changes in middle cerebral artery pulsatility index contributed to the decision to deliver in three cases. The middle cerebral artery pulsatility index demonstrated greater variation in those fetuses with cord pHs of less than 7.25. The length of stay in neonatal intensive care decreased with increasing gestational age and birth weight. CONCLUSIONS: The difference in the pattern of change in middle cerebral artery pulsatility index in intrauterine growth restricted fetuses may be a reflection of maturity in addition to the degree of fetal compromise. The decision to deliver was multifactorial. The middle cerebral artery pulsatility index only influenced the decision to deliver when changes in other parameters were evident.

Amniotic Fluid↗

The use of a bioactive skin substitute decreases length of stay for pediatric burn patients.

BACKGROUND: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA). This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children. METHODS: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n = 20). These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy. Standard therapy consisted of application of antimicrobial ointments and hydrodebridement. The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS. Data were analyzed using the student's t test. RESULTS: Data for age, percent TBSA burn and LOS are reported as means +/- SEM. The children who received standard therapy were 2.99 +/- 0.7 years compared with those receiving TransCyte were 3.1 +/- 0.8 years. There was no difference between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 +/- 1.4% TBSA versus TransCyte, 12.7 +/- 1.3% TBSA. There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group. Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%). Children treated with TransCyte had a statistically 6 significant decreaed LOS compared with those receiving standard therapy, 5.9 +/- 0.9 days versus 13.8 +/- 2.2 days, respectively (P =.002). CONCLUSIONS: This is the first study using TransCyte in children. The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS. This new approach to pediatric burn care is effective and improves the quality of care for children with burns.

Burn Units↗

Caregivers of ICU patients discharged home: what burden do they face?

Reforms in healthcare aimed at cost-cutting have led to early hospital discharge for many patients, including those who have sustained critical illness or injury requiring admission to an intensive care unit (ICU). Many former ICU patients experience ongoing health-related problems following discharge from hospital, and need ongoing support and care from their family once discharged. However, family members who take on a caregiving role often experience an enormous burden. The literature has demonstrated the impact of economic, social, physical and psychological factors on those who care for the critically ill following discharge. It is therefore essential that all nurses involved in the ongoing management of ICU patients have an understanding of the caregiving role, and consider both the patient and his/her carer in the discharge planning process. This paper reviews the literature on caregiving, and examines research studies which describe and measure the factors involved in the caregiving role. Although only a small number of studies specifically focus on caregivers of former ICU patients, findings suggest that these caregivers experience a substantial burden which is associated with the complexity of the patient's physical and psychological impairment, and complex technology. To enable nurses to incorporate planning strategies and interventions aimed at minimizing the impact on the caregiver, further research is needed to more fully explore, examine and measure the factors involved in caring for ICU patients post-discharge. Furthermore, ongoing research and evaluation of interventions will build an evidence-base to inform future practice.

Caregivers↗

Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux.

OBJECTIVE: To describe the occurrence of relative proton pump inhibitor (PPI) drug resistance in the treatment of laryngopharyngeal reflux (LPR). STUDY DESIGN AND SETTING: A retrospective review was performed for 1053 consecutive adults undergoing double-probe (simultaneous esophageal and pharyngeal) pH testing in our laboratory. Two hundred five patients who had pH studies performed while taking at least a daily dose of PPI therapy were identified; 167 qualified for further analysis. The pH data was reviewed for the presence of abnormalities in either esophageal or pharyngeal acid exposure to evaluate drug efficacy. RESULTS: Forty-four percent (74/167) of the study patients demonstrated abnormal levels of acid exposure. Results were further analyzed to compare failure rates based on different dosage regimens. Patients on once daily doses of PPI failed at a rate of 56%, with lower failure rates for higher-dose regimens. CONCLUSIONS: A significant number of LPR patients on PPI therapy demonstrate relative drug resistance.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Interleukin 12 secretion enhances antitumor efficacy of oncolytic herpes simplex viral therapy for colorectal cancer.

OBJECTIVE: To assess the strategy of combining oncolytic herpes simplex virus (HSV) therapy with immunomodulatory therapy as treatment for experimental colon cancer. The oncolytic HSV recombinant NV1023 and the interleukin 12 (IL-12)-secreting oncolytic NV1042 virus were evaluated in vitro and in vivo with respect to antitumor efficacy. SUMMARY BACKGROUND DATA: Genetically engineered, replication-conditional, attenuated HSVs have shown oncolytic activity against a wide variety of solid malignancies. Other strategies for treating cancer have involved immunomodulation and cytokine gene transfer using viral vectors. This study has combined both of these strategies by inserting the murine IL-12 gene into a replication-competent HSV. This approach allows oncolytic therapy to replicate selectively within and lyse tumor cells while providing the host immune system with the cytokine stimulus necessary to recruit and activate inflammatory cells needed to enhance the antitumor effect. METHODS: NV1023 is a multimutant HSV based on the wild-type HSV-1 F strain. NV1042 was created by insertion of the mIL-12 gene into NV1023. Cytotoxicity and viral proliferation of both NV1023 and NV1042 within murine CT26 colorectal cancer cells were first shown. Cells infected with NV1042 were then shown to produce significant levels of IL-12. Using an experimental flank model of colon cancer, mice were treated with both high and low doses of NV1023 or NV1042 and were followed up for both cure and reduction in tumor burden. RESULTS: Both viruses could replicate within and kill CT26 cells in vitro, with 100% cytotoxicity achieved after infection by either virus. Only NV1042 could produce mIL-12. Therapy using high viral doses to treat animals in vivo showed equal efficacy between NV1023 and NV1042, with five of seven cures for each virus. When viral doses were lowered, only the cytokine-producing NV1042 virus could reduce tumor burden and cure animals of their disease. CONCLUSIONS: Both NV1023 and NV1042 have the oncolytic potential to kill colon cancer cells at higher doses. Cytokine production by NV1042 may allow lower doses of viral therapy to be used without losing antitumor efficacy. The combination of oncolytic viral therapy and immunomodulatory strategies should be further investigated as treatment for colon cancer.

Animals↗

Application of three-dimensional resonant acoustic spectroscopy method to rock and building materials.

This paper presents the experimental and theoretical results of applying resonant acoustic spectroscopy (RAS) to determine elastic parameters and losses in such consolidated granular materials as rock and building bricks. First, the theoretical aspects of the RAS method are outlined. A computer code for the rectangular and cylindrical samples was developed and tested. The results of experiments on specimens of rock and ceramic brick are then described. Finally, a modification of the previously published RUS algorithm is presented which permits a significant reduction in computing time for elongated samples.

Journal Article↗

The use of a new continuous wireless cardiorespiratory telemonitoring system by elderly patients at home.

The diagnosis and management of increasing numbers of patients with chronic diseases in the community require new technologies and strategies of care. We have used a new wireless cardiorespiratory telemonitoring system to monitor 14 elderly patients with a variety of chronic diseases at home. The electrocardiogram (ECG), heart rate and variability, and breathing were recorded on two separate occasions for 24 h. There was no difference in the data recorded when a research nurse applied the monitoring system and when the patients applied it themselves. The ECG and heart rate were recorded for 98% of the monitored time, and the frequency and periodicities of breathing were recorded for 74% and 61% of sleep and rest time by visual and automatic analysis, respectively. The results show that 24 h activity and cardiorespiratory telemonitoring can be performed by elderly patients at home. Significant unsuspected abnormalities of breathing and heart rhythm, amenable to treatment, were also detected.

Aged↗

Cross-cultural validation of the McGill Quality of Life questionnaire in Hong Kong Chinese.

The main focus of palliative care services is to improve patients' quality of life (QOL). The potential value of assessment of QOL in palliative care is being increasingly recognized. The McGill Quality of Life questionnaire (MQOL) is designed specifically for palliative care patients, but its cross-cultural validity needs to be determined before it can be applied in populations of different cultures and ethnic groups. The cross-cultural validity of MQOL was investigated using a translated and modified version in Chinese--the MQOL-HK--in 462 palliative care patients in Hong Kong. Results show that the MQOL-HK is acceptable, valid and reliable. There is good acceptability, construct validity, convergent and divergent validity, test-retest and inter-rater reliability. Our study confirms that QOL does have cross-culturally robust constructs. Principal components analysis shows that the domains of physical, psychological, existential and support are all relevant and applicable in Chinese culture. Multiple regression analysis reveals that existential domain is the most important domain in predicting overall QOL. 'Face', eating and sex are additional facets of QOL that also need to be considered. The worst physical symptom on admission is the item of QOL with the lowest score, which need more care and attention by palliative care workers. A cross-culturally validated QOL instrument cannot just help ensure an accurate evaluation of profile, determinants, and changes of QOL, but is also a valuable asset for future comparison and evaluation of palliative care services and interventions across the world.

Adolescent↗

Achieving reuse of computable guideline systems.

We describe an architecture for reusing computable guidelines and the programs used to interpret them across varied legacy clinical systems. Developed for the PRODIGY 3 project, our architecture aims to support interactive, point of care use of guidelines in primary care. Legacy medical record systems in UK primary care are diverse, using different terminologies, different data models, and varying user-interface philosophies. However, our goal is to provide common guideline knowledge bases and system components, while achieving full integration with the host medical record system, and a user interface tailored to that system. In conjunction with system suppliers, we identified areas of standardization required to achieve this goal. Firstly, standardized interfaces were created for mediation with the legacy system medical record and for act management. Secondly, a standard interface was developed for communication with the User Interface for guideline interaction. Thirdly, a terminology mapping knowledge base and system component was provided. Lastly, we developed a numeric unit conversion knowledge base and system component. The standardization of this architecture was achieved by close collaboration with existing vendors of Primary Care computing systems in the UK. The work has been verified by two suppliers successfully building and deploying systems with User Interfaces which mirror their normal look and feel, communicating fully with existing medical records, while using identical Guideline Interpreter components and knowledge bases. Encouragingly further experiments in other areas of clinical decision support have not required extension of our interfaces.

Artificial Intelligence↗

Does ethanol metabolism affect erythrocyte hemolysis?

The effects of ethanol and acetaldehyde on the hemolytic stability of rabbit erythrocytes have been compared. Incubation of normal erythrocytes with ethanol facilitated both acidic and oxidative hemolysis and increased the percentages of cells that were hemolyzed at maximal rate. Acetaldehyde exerted a similar destabilizing effect on erythrocytes only in the case of oxidative hemolysis. The destabilizing effect of ethanol was observed in catalase-inactivated erythrocytes under acidic, but not oxidative, hemolysis conditions. It is concluded that the destabilizing effect of unmetabolized ethanol occurs under conditions of acidic hemolysis, whereas the destabilizing effect of the oxidation of ethanol to acetaldehyde takes place only under the conditions of oxidative hemolysis.

Acetaldehyde↗

Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy.

Herpes simplex viruses (HSV) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. They are natural human pathogens and the majority of adults have anti-HSV immunity. The current study examined the effect of preexisting immunity on the response to herpes-based oncolytic viral treatment of hepatic metastatic cancer in a murine model designed to simulate a clinical approach likely to be utilized for nonneurological tumors. Specifically, the anticancer effects of NV1020 or G207, two multimutated HSV-1 oncolytic viruses, were tested in immunocompetent mice previously immunized with a wild-type herpes simplex type 1 virus. Mice were documented to have humoral as well as cell-mediated immunity to HSV-1. Tumor response to oncolytic therapy was not measurably abrogated by immunity to HSV at the doses tested. The influence of route of viral administration was also tested in models of regional hepatic arterial and intravenous therapy. Route of viral administration influenced efficacy, as virus delivered intravenously produced some detectable attenuation while hepatic arterial therapy remained unaffected. These results demonstrate that when given at appropriate doses and in reasonable proximity to tumor targets, HSV-based oncolytic therapy can still be expected to be effective treatment for patients with hepatic malignancies.

Animals↗

Atropisomeric amides as chiral ligands: using (-)-sparteine-directed enantioselective silylation to control the conformation of a stereogenic axis

An enantiomerically pure (1-trimethylsilyl)ethyl group, constructed by a (-)-sparteine-directed enantioselective quench of a laterally lithiated tertiary aromatic amide, exerts powerful thermodynamic control over the conformation of the adjacent tertiary amide substituent. Ortholithiation and functionalization of the amide in the 6-position allows the single amide conformer to be trapped as an enantiomerically and diastereoisomerically pure amide atropisomer. Protodesilylation of the amide gives functionalized atropisomeric amides with a stereogenic axis of single absolute configuration, whose barriers to racemization have been determined by polarimetry. Enantiomerically pure amides bearing phosphine substituents are effective ligands in a Pd-catalyzed allylic substitution reaction-the first use of a nonbiaryl atropisomer as a chiral ligand-and give products with 90% ee. The rate of racemization of the phosphine-substituted amide is powerfully influenced by the presence of palladium.

Journal Article↗