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Biomedical subjects

H Smith

Publications and source records attributed to H Smith.

At least 109 records · Page 6Linked to original sources
PubMed1999

Evaluation of 3-hour ambulation post cardiac catheterization.

There is much variation in the length of immobilization for patients post cardiac catheterization. While it is generally agreed that a period of time on bedrest is necessary to prevent post procedural complications, the optimal duration remains unknown. The purpose of this study was to evaluate the effects of 3-hour ambulation post cardiac catheterization with a 7 french (F) arterial catheter on bleeding, hematoma formation, and vascular complications. Retrospective chart data were gathered for a period of 8 months for patients who were on the traditional 5-hour ambulation protocol, and prospective data were gathered for a period of 7 months for patients who received the 3-hour protocol. A total of 880 patients were included in the study, with 472 in the 5-hour ambulation group and 408 in the 3-hour ambulation group. The overall incidence of delayed bleeding and hematoma formation for the 15 month study period was 19.1%, with no occurrence of vascular complications in either group. Patients who received the 3-hour ambulation protocol experienced a significantly lower rate of bleeding and hematoma formation (13%) than patients who received the 5-hour ambulation protocol (24.4%) (p < 0.001). Ambulating patients 3 hours post cardiac catheterization with a 7F catheter was found to be safe, and thus has the potential to decrease hospital length of stay, as well as increase patient comfort.

Adolescent↗
PubMed1999

'Bin bag' study: a survey of the research requests received by general practitioners and the primary health care team.

General practitioners receive a large and increasing number of unsolicited requests to participate in research. This study describes the volume and nature of research requests received by 18 primary care teams in a three-month period. On average, each practice receives 16 to 24 research requests each year. The most frequent request is to complete a questionnaire (32%). Only one-fifth of studies originate from academic or service general practice. Remuneration for participating in a study was only offered for 15% of studies. Although general practice teams feel swamped by research requests, this sensation may be exaggerated by invitations to participate in non-scientific surveys as well as true research projects. Practice teams would welcome help in distinguishing quality research proposals from the remainder.

Data Collection↗
PubMed1998

Lactate causes changes in gonococci including increased lipopolysaccharide synthesis during short-term incubation in media containing glucose.

Gonococci (strain BS4(agar)), emerging from lag-phase during 1-1.5 h incubation in a medium containing glucose (28 mM) and either 5 microM or 50 microM sodium lactate, show enhanced capacity for their lipopolysaccharide (LPS) to be sialylated by cytidine 5'-monophospho-N-acetyl neuraminic acid. The sialyltransferase content of the lactate-treated gonococci was not greater than that of control organisms and showed no differences in LPS components. However, the total LPS content of the lactate-treated gonococci was 10-20% higher than that of control organisms, so lactate enhancement may be due to more sialyl receptors becoming available due to an overall stimulation of LPS synthesis. The protein and pentose contents of the lactate-treated gonococci were also higher than those of controls, indicating stimulation of protein synthesis and ribosome production. Electron microscopy showed hair-like external appendages on control but not on lactate-treated gonococci. The above growth conditions are unnatural. However, when concentrations of glucose and lactate were adjusted to values akin to those occurring in vivo (glucose 5 mM alone and with either 1 mM or 10 mM lactate), and gonococcal multiplication occurred during the short incubation period (1-1.5 h), lactate again induced greater contents of LPS, protein and pentose. A high content of LPS, which will contribute to pathogenicity, should be a constant feature of gonococci growing in human urogenital tissues, where lactate is ever present with glucose.

Bacterial Proteins↗
PubMed1998

Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial. The South Wiltshire Out of Hours Project (SWOOP) Group.

OBJECTIVE: To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls. DESIGN: Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention. SETTING: One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire. SUBJECTS: All patients contacting the out of hours service or about whom contact was made during specified times over the trial year. INTERVENTION: A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software. MAIN OUTCOME MEASURES: Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial. RESULTS: 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.

Adolescent↗
PubMed1998

Employment after coronary angioplasty or coronary bypass surgery in patients employed at the time of revascularization.

BACKGROUND: Patients who undergo coronary angioplasty have a shorter convalescence than those who undergo coronary bypass surgery. This may improve subsequent employment. OBJECTIVE: To compare employment patterns after coronary angioplasty or surgery. DESIGN: Multicenter, randomized clinical trial. SETTING: Seven tertiary care hospitals. PATIENTS: 409 employed patients with multivessel coronary artery disease. INTERVENTION: Coronary bypass surgery or balloon angioplasty. MEASUREMENTS: Time to return to work and time spent working during 4 years of follow-up. RESULTS: Patients who underwent angioplasty returned to work 6 weeks sooner than patients who underwent coronary bypass surgery (P < 0.001), but long-term employment did not differ significantly (P > 0.2). Long-term employment was significantly lower among patients who were 60 to 64 years of age (P < 0.001), those who worked less than full-time at study entry (P < 0.001), and those who had less formal education (P = 0.005). Patients with only one source of health insurance were more likely to continue working (P = 0.005). CONCLUSIONS: Faster recovery after angioplasty speeds return to work but does not improve long-term employment, which is primarily associated with nonmedical factors.

Age Factors↗
PubMed1998

Sequence comparisons and functional studies of the proximal promoter of the carbonic anhydrase 3 (CA3) gene.

Carbonic anhydrase 3 (CA3) is a member of a gene family encoding proteins which catalyse the hydration of CO2 to generate protons and bicarbonate ions for cellular ion transport and pH homeostasis. In mouse embryos CA3 is expressed at high levels in notochord and skeletal muscle and here we demonstrate that this pattern of expression is the same in the developing human embryo. To investigate mechanisms controlling CA3 transcription, we have isolated and compared 2.8kb of sequence flanking exon 1 from the mouse and human genes. Several segments of high sequence identity >80% have been identified, the longest segments of which represent a proximal promoter region and a putative enhancer element. We have shown previously that in cultured cells the human 2.8kb promoter region imposes high level myogenic specific transcription of a reporter gene. However, we now show that while this promoter region directed muscle-specific expression in transgenic mouse embryos this was subject to position effects.

Animals↗
PubMed1998

Stepwise in vitro affinity maturation of Vitaxin, an alphav beta3-specific humanized mAb.

A protein engineering strategy based on efficient and focused mutagenesis implemented by codon-based mutagenesis was developed. Vitaxin, a humanized version of the antiangiogenic antibody LM609 directed against a conformational epitope of the alphav beta3 integrin complex, was used as a model system. Specifically, focused mutagenesis was used in a stepwise fashion to rapidly improve the affinity of the antigen binding fragment by greater than 90-fold. In the complete absence of structural information about the Vitaxin-alphav beta3 interaction, phage-expressed antibody libraries for all six Ig heavy and light chain complementarity-determining regions were expressed and screened by a quantitative assay to identify variants with improved binding to alphav beta3. The Vitaxin variants in these libraries each contained a single mutation, and all 20 amino acids were introduced at each complementarity-determining region residue, resulting in the expression of 2,336 unique clones. Multiple clones displaying 2- to 13-fold improved affinity were identified. Subsequent expression and screening of a library of 256 combinatorial variants of the optimal mutations identified from the primary libraries resulted in the identification of multiple clones displaying greater than 50-fold enhanced affinity. These variants inhibited ligand binding to receptor more potently as demonstrated by inhibition of cell adhesion and ligand competition assays. Because of the limited mutagenesis and combinatorial approach, Vitaxin variants with enhanced affinity were identified rapidly and required the synthesis of only 2,592 unique variants. The use of such small focused libraries obviates the need for phage affinity selection approaches typically used, permitting the use of functional assays and the engineering of proteins expressed in mammalian cell culture.

Antibodies, Monoclonal↗
PubMed1998

General practitioner's perceptions of the route to evidence based medicine: a questionnaire survey.

OBJECTIVES: To determine the attitude of general practitioners towards evidence based medicine and their related educational needs. DESIGN: A questionnaire study of general practitioners. SETTING: General practice in the former Wessex region, England. SUBJECTS: Randomly selected sample of 25% of all general practitioners (452), of whom 302 replied. MAIN OUTCOME MEASURES: Respondents' attitude towards evidence based medicine, ability to access and interpret evidence, perceived barriers to practising evidence based medicine, and best method of moving from opinion based to evidence based medicine. RESULTS: Respondents mainly welcomed evidence based medicine and agreed that its practice improves patient care. They had a low level of awareness of extracting journals, review publications, and databases (only 40% knew of the Cochrane Database of Systematic Reviews), and, even if aware, many did not use them. In their surgeries 20% had access to bibliographic databases and 17% to the world wide web. Most had some understanding of the technical terms used. The major perceived barrier to practising evidence based medicine was lack of personal time. Respondents thought the most appropriate way to move towards evidence based general practice was by using evidence based guidelines or proposals developed by colleagues. CONCLUSION: Promoting and improving access to summaries of evidence, rather than teaching all general practitioners literature searching and critical appraisal, would be the more appropriate method of encouraging evidence based general practice. General practitioners who are skilled in accessing and interpreting evidence should be encouraged to develop local evidence based guidelines and advice.

Attitude of Health Personnel↗
PubMed1998

Circulating CD34+ counts and apheresis planning.

The success of peripheral blood progenitor cell (PBPC) transplantation depends upon harvesting adequate numbers of cells and accurate prediction of when to commence apheresis. Although peripheral white cell count (WBC) is commonly used to identify when to initiate apheresis it does not uniformly predict the CD34+ content of the apheresis product nor the number of exchange procedures required. We investigated whether the peripheral blood CD34+ count would not only predict harvest yield but whether it would also predict the number of apheresis procedures needed to generate at least 2 x 10(6)/kg CD34+ cells. CD34+ counts were performed over an 8-month period on the peripheral blood and PBPC harvests of all patients undergoing leucopheresis. Regression analysis showed a highly significant correlation between peripheral blood CD34+ count and yield of CD34+ cells in the apheresis product. The regression plot with WBC was weaker. We have shown that a peripheral CD34+ count > or = 62 x 10(6)/l is required to confidently achieve an adequate harvest in one apheresis, two aphereses are needed if the initial count is > or = 40 x 10(6)/l. Therefore peripheral blood CD34+ counts not only are able to determine the threshold at which to commence apheresis but are useful in predicting apheresis requirements and planning demands on the apheresis service.

Adult↗
PubMed1998

Characterization of a sialyltransferase-deficient mutant of Neisseria gonorrhoeae strain F62: instability of transposon Tn1545 delta3 in gonococci and evidence that multiple genetic loci are essential for lipooligosaccharide sialylation.

Neisseria gonorrhoeae strain JB1 was previously shown to be defective in the sialylation of lipoologosaccharide (LOS) by exogenous CMP-NANA. The LOS components synthesized by the mutant now have been shown by mass spectrometry to be similar to those in the parental strain, F62, and to include the 4.5 kDa widely conserved lacto-N-neotetraose component that can be sialylated. The same two LOS components could be sialylated on the surface of the mutant and parental strains. One major component was sialylatable after chemical extraction of the LOS from either strain. These data confirm that the mutant, JB1, retains the ability to synthesize the LOS target required for the conversion by sialylation of serum-sensitive gonococci to serum resistance. A single base frame-shift mutation was found in the lst gene from the mutant, resulting in the replacement of the final 61 amino acids at the C-terminus of the sialyltransferase by four residues. Seventeen independent clones of the lst gene were isolated from the parental strain, but none of them complemented the sialyltransferase defect of the mutant and no sialyltransferase activity expressed from the clones could be detected in Escherichia coli. Although the data suggest that the mutant might be defective in genes at more than one chromosomal locus and that multiple loci are essential for sialyltransferase synthesis and activity, the alternative possibility, that DNA adjacent to the lst gene encodes a product which is toxic to E. coli, cannot be excluded. The site of insertion of the transposon Tn1545-Delta3 in strain JB1 was cloned and sequenced. The transposon is located in an intergenic region adjacent to genes for a putative ATP-dependent transport protein, but encoding no recognizable function relevant to LOS sialylation. Evidence that transposon Tn1545-Delta3 is unstable in gonococci is presented.

Blotting, Southern↗
PubMed1998

Reply.

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Journal Article↗
PubMed1998

Comparative study of five different techniques for epidemiological typing of Escherichia coli O157.

A set of 47 Austrian human, food, and veterinary Escherichia coli O157:H7 isolates was used to evaluate five different epidemiological typing methods. Ribotyping using an automated microbial characterization system (RiboPrinter) was not suitable for detection of epidemiological relatedness. All but one E. Coli strain were typeable by phage typing. Random amplified polymorphic DNA-PCR fingerprinting was performed using primer M13 containing the sequence 5'-GAG GGT GGC GGT TCT-3' and primer 1247 (5'-AAGAGCCCGT-3'). Although both methods recognized only two clusters, both dendrograms grouped most of the EHEC O157 isolates into epidemiologically related subgroups. Pulsed-field gel electrophoresis of XbaI digested total DNA was a valuable subtyping system. We found that major differences can exist between results of multiple subtyping methods. E. coli O157 isolates should not be classified as epidemiologically related or nonrelated on the basis of a single typing method alone.

Adolescent↗
PubMed1998

What happens to bacterial pathogens in vivo?

Most of our current knowledge about the molecular determinants of bacterial pathogenicity comes from studies with cultures in vitro. However, interest is increasing in bacterial behaviour in the complex and ever-changing environment of the infected host. New methods are revealing how bacteria behave in their hosts, providing many surprises and indicating how much of the subject remains unexplored.

Animals↗
PubMed1998

Symptom control in patients with hay fever in UK general practice: how well are we doing and is there a need for allergen immunotherapy?

BACKGROUND: Seasonal allergic rhinitis is often regarded as a trivial condition which patients should treat themselves. However, a significant proportion of sufferers are not fully controlled on standard hay fever medication, either because they do not use it properly or because their symptoms are resistant to standard therapy. The latter group may be suitable for allergen immunotherapy, which was once widely available in UK general practice but is now only available through specialist centres. AIMS: To describe the symptom control of patients with hay fever, to assess concordance with prescribed medication, and to estimate the number of patients who may benefit from referral for allergen immunotherapy. SETTING: General practices in Hampshire and Dorset, UK. METHOD: Survey of adult hay fever sufferers prescribed a non-sedating antihistamine and nasal steroid spray by their general practitioner. A postal questionnaire was sent to all eligible patients aged 16-64 registered with 16 general practices. Self-assessment of symptom control and reported compliance with medication were used to identify those patients who were suboptimally controlled and might therefore benefit from immunotherapy. RESULTS: Eight hundred and forty-six out of 62500 registered patients aged 16-64 (1.4%) were receiving both drugs, and responses were received from 627 (74.1%); 526 of these met the full entry criteria. One hundred and forty-two patients (27.0%) were using both types of drug regularly. Of the 142 patients using optimum pharmacotherapy, 54 (38.0%) reported good control of their hay fever symptoms. The remaining 62.0% experienced troublesome residual symptoms and described symptom control as partial or poor. Among those using suboptimal pharmacotherapy, 181/376 (48.1%) reported good control. CONCLUSION: Many patients are using treatment inappropriately. Current guidelines need to be applied better but there is also a significant burden of residual symptoms, even among those receiving current optimal therapy. This indicates a need for patients with severe summer hay fever to receive specialist assessment.

Adolescent↗
PubMed1998

A randomized, double-blind comparison of two dosage levels of recombinant factor VIIa in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B, with and without inhibitors. rFVIIa Study Group.

Recombinant factor VIIa (rFVIIa) was developed to provide an improved procoagulant component capable of 'by-passing' inhibitor antibodies in the treatment of haemophilic patients. The primary objective of this study was to compare the efficacy of two dosage regimens of rFVIIa (given intravenously at periodic intervals) in the treatment of joint, muscle and mucocutaneous haemorrhages in persons with haemophilia A and B with and without inhibitors. The study was designed as a randomized, double-blind, parallel group, international multicenter trial. Patients were randomly allocated to treatment A: 35 mu kg-1 or B: 70 mu kg-1, in blocks of 2. Within each block, one patient was assigned to the 35 mu kg-1 dosing regimen and the other to 70 mu kg-1 dose. One hundred and fifty subjects from 20 sites were screened for this study and 116 had baseline assessments. Of these, 84 were treated on the protocol and 32 were not treated in the study, in most cases because they did not return to the clinic with an eligible bleeding episode. One hundred and seventy-nine bleeding episodes were treated, of which 145 (81%) were acute haemarthroses. Both treatments were efficacious, with 71% having an excellent (59% and 60%) or effective (12% and 11%) response. Overall, the mean and median number of doses given per episode of joint bleeding were 3.1 and 2, respectively. The mean number of doses was 3.1 for the 70 mu kg-1 group and 2.7 for the 35 mu kg-1 group (P value = 0.142). The study concluded that rFVIIa in a dosage of 35 mu kg-1 or 70 mu kg-1 is both safe and reasonably effective in the treatment of joint or muscle haemorrhages in haemophilic patients with inhibitor antibodies to factor VIII or factor IX. It is concluded that the appropriate dose for the treatment of joint and peripheral muscle bleeding in haemophilic patients with inhibitors is 35-70 mu kg-1 given at 2-3 h intervals until haemostasis is achieved.

Adult↗