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Biomedical subjects

K McGregor

Publications and source records attributed to K McGregor.

10 recordsLinked to original sources
PubMed1998

Moraxella catarrhalis: clinical significance, antimicrobial susceptibility and BRO beta-lactamases.

Moraxella catarrhalis is an important pathogen of humans. It is a common cause of respiratory infections, particularly otitis media in children and lower respiratory tract infections in the elderly. Colonisation of the upper respiratory tract appears to be associated with infection in many cases, although this association is not well understood. Nosocomial transmission is being increasingly documented and the emergence of this organism as a cause of bacteremia is of concern. The widespread production of a beta-lactamase enzyme renders Moraxella catarrhalis resistant to the penicillins. Cephalosporins and beta-lactamase inhibitor combinations are effective for treatment of beta-lactamase producers, and the organism remains nearly universally susceptible to the macrolides, fluoroquinolones, tetracyclines and the combination of trimethoprim and sulfamethoxazole. Two major beta-lactamase forms, BRO-1 and BRO-2, have been described on the basis of their isoelectric focusing patterns. The BRO-1 enzyme is found in the majority of beta-lactamase-producing isolates and confers a higher level of resistance to strains than BRO-2. The BRO enzymes are membrane associated and their production appears to be mediated by chromosomal determinants which are transmissible by an unknown mechanism. The origin of these novel proteins is unknown.

Anti-Bacterial Agents↗
PubMed1997

Head injury rehabilitation in the U.K.: an economic perspective.

The human and societal costs as a result of traumatic brain injury (TBI) are extensive with approximately 200-300/100,000 of the population requiring hospitalisation each year in the U.K. Advances in neurosurgical management have meant that more people sustaining head injuries are surviving. The need for rehabilitation programmes for these individuals is therefore ever increasing. While in the U.S.A. rehabilitation programmes for TBI patients are well established, in the U.K. the provision of such services is patchy and varies widely in different localities. The belated response to the rehabilitation needs of this group of individuals in the U.K. has coincided with an increased awareness of the economic efficiency of health care provision. This paper critically reviews published studies looking at the economics of rehabilitation services for brain injured patients. No studies in the U.K. were identified and all the sources discussed are from the U.S.A. The methodological guidelines underlying economic appraisal of health care are summarised and the studies assessed to determine the extent to which they fulfil these guidelines. The paper concludes that most studies purporting to provide evidence of cost-effectiveness did not include appropriate data, nor followed the methodological guidelines allowing such claims to be made. Some recommendations for future research are presented.

Brain Injuries↗
PubMed1997

What does a GP consultation cost?

BACKGROUND: Demand for information regarding the cost-effectiveness of health care treatment options is growing. It is necessary to derive unit costs for services, such as general practice (GP) consultations, in order to inform the economic evaluation. AIM: To review the literature, provide a description of the three key steps that should be followed in the costing process and to provide a method for updating costs calculated in previous years. METHOD: A literature search was carried out to identify references that specifically describe the cost of a consultation in general practice. A total of 20 references were extracted, categorized and reviewed. A cost-price index for health care goods was obtained from the British Medical Association and used to construct a table to allow rapid reference and updating of cost results. The costs reported in the literature were updated and compared. RESULTS: Twenty published studies referring to the unit cost of a GP consultation were located in the searches. Half of these did not describe the methodology used to derive the costs; of those that did, less than half covered the necessary steps to derive unit costs. The cost of an average 10-minute consultation in 1995/96 figures was estimated to be 6.90 +/- 2.73 pounds. CONCLUSION: Great variation exists regarding the methodology for costing a GP consultation. If the methods used are stated explicitly and incorporate the three steps described, then results obtained in previous years may be updated using the cost-price index as shown (Table 1). Interpretation in this area must be made with caution.

Cost-Benefit Analysis↗
PubMed1996

A pilot study of combination therapy with interferon-alpha-2a and 5-fluorouracil in metastatic carcinoid and malignant endocrine pancreatic tumours.

BACKGROUND: In view of the encouraging single agent response rates to interferon and 5-fluorouracil (5-FU) in malignant carcinoid and endocrine pancreatic tumours and the theoretical benefits of combination therapy with 5-FU and interferon in other tumours a study was designed to look at the feasibility of this combination, given for 12 months, in these tumours. PATIENTS AND METHODS: Patients were treated with 5-FU 750 mg/m2 by intravenous bolus every week and 3 Mega Units of recombinant interferon-alpha-2a subcutaneously 3 times per week increasing, as tolerated, to 6 then 9 MU. Fifteen patients were entered into the study. RESULTS: One patient died suddenly of an unrelated illness and is not assessed. None of the remaining 14 patients had radiological evidence of response to treatment, although 6 had stable disease lasting for 7 to 64 weeks (median 40 weeks). Two patients did have biochemical evidence of a response, i.e., a 50% reduction in baseline urinary 5HIAA for 26 and 52 weeks. Treatment toxicity was significant. Six patients stopped treatment prematurely because of either nausea and/or diarrhoea. Overall treatment duration ranged from 4 to 64 weeks (median 7.5 weeks). CONCLUSION: Overall we found the treatment to be disappointing in terms of tolerance and response rate and do not recommend its use in malignant carcinoid or endocrine pancreatic tumours.

Adult↗
PubMed1994

A nonconsensus octamer-recognition sequence (TAATGARAT-motif) identifies a novel DNA binding protein in human Merkel cell carcinoma cell lines.

We have established a number of cell lines from Merkel cell carcinoma (MCC) of the skin. In many respects these cell lines resemble those established from small cell lung cancer (SCLC) and it is difficult to differentiate between metastatic MCC and SCLC on morphological or histochemical criteria. Both are thought to be neuroendocrine tumours and may express a number of neuroendocrine markers. SCLC cell lines express the octamer-DNA binding transcription factor brn-2 gene products N-Oct3 and N-Oct5, which are restricted to the neuroectodermal cell lineage. In DNA binding studies using a consensus octamer recognition site we have found that 4 of 8 MCC cell lines examined expressed brn-2 in at least trace amounts compared with 3 SCLC cell lines which all expressed brn-2 proteins at high levels. Moreover, these DNA binding studies were extended by using a high-affinity brn-2 recognition site related to the degenerate octamer TAATGARAT-motif. This identified a novel DNA binding protein in a subset of MCC cell lines. The protein was absent from the three SCLC cell lines, melanoma cells and brain tissue. This binding activity, which we term Merkel cell DNA nuclear (MNF), was shown to be specific by competitive inhibition with oligonucleotide binding sites and was not inhibited by polyclonal antisera against the Oct-1, Oct-2 or Brn-2 proteins. This protein may serve as a unique marker for MCC compared with SCLC cells and may be involved in regulating the Merkel cell phenotype.

Base Sequence↗
PubMed1994

Transcriptional regulation of differentiation, selective toxicity and ATGCAAAT binding of bisbenzimidazole derivatives in human melanoma cells.

To study the relationship between the structure of minor groove ligands and their affinity for specific DNA sequences that regulate gene transcription, three analogues of the A-T-specific DNA minor groove ligands Hoechst 33258 and Hoechst 33342 were synthesized with 5, 8 or 12 carbons in an aliphatic chain attached to the phenolic oxygen of the molecule. There was a striking bimodal relationship between toxicity to HeLa cells and the lipophilicity of the five analogues, toxicity being low for the compounds with a free hydroxyl (Hoechst 33258) or a 12-carbon substituent, yet high for the 5-carbon analogue. Selective killing of human melanoma cells compared with normal fibroblasts was observed for the Hoechst analogue with a 12-carbon chain attached. Hoechst 33258 itself was selectively toxic for the MM96E melanoma cell line compared with other cell lines, induced a highly dendritic morphology, increased tyrosinase activity and tyrosinase mRNA but decreased the level of gp75 (TRP-1) mRNA; message for a third pigment gene, Pmel-17, was unchanged. Tyrosinase activity was decreased in the resistant A2058 melanoma cell line and transcription was affected to a lesser extent than in MM96E. Expression of gp75 protein and two intermediate filament proteins was inhibited by Hoechst 33258 in MM96E cells. There was no major difference in the amount of 125I-Hoechst 33258 taken up by sensitive and resistant cells. Of the five derivatives studied, the parent drug Hoechst 33258 and the 2-carbon analogue (Hoechst 33342) were found to have the most inhibitory effect on affinity of octamer binding proteins for the ATGCAAAT consensus sequence found in the promoter region of certain genes associated with proliferation and differentiation. In contrast to Distamycin A (also an A-T-specific minor groove ligand), Hoechst 33258 displaced proteins already bound to the octamer motif. The G-C ligand chromomycin A3 exhibited a different spectrum of cell toxicity and tyrosinase stimulation compared with Hoechst 33258. Chromomycin A3 but not Hoechst 33258, strongly inhibited the zinc-dependent transcriptional activity of the sheep metallothionein-Ia promoter in reporter gene assays of transfected cells. Since the six metal-responsive elements of the promoter are GC-rich, this provides independent evidence for the sequence-specificity of transcriptional inactivation by one of these drugs in melanoma cells. Overall, the results suggest that Hoechst 33258 acts by inhibiting the transcription of specific genes, cell lines evidently differing in the accessibility to drugs of certain A-T-rich sequences.

Base Sequence↗
PubMed1994

A pilot study of the economic cost and clinical outcome of day patient vs inpatient management of active rheumatoid arthritis.

The aims of this pilot study, which compares day patient with inpatient care for management of active RA were (i) to test the feasibility of a trial protocol design including the method of randomization and the practicality of data collection, and (ii) to obtain preliminary information on economic cost and clinical outcome of these two methods of management. Twenty consecutive patients requiring admission for management of active RA were randomized to receive either day patient or inpatient care. All hospital, transport, community and indirect costs incurred over a 6-month period from recruitment were collected for each patient. Disease activity and clinical outcome were assessed using the Ritchie articular index, ESR, Health Assessment Questionnaire, Functional Independence Measure and Hospital Anxiety and Depression Scale. The trial protocol was found to be feasible and no patient allocated to the day patient group requested or required to be transferred to inpatient care. Day care was significantly cheaper than inpatient care despite higher transport costs; the total cost of treating 10 day patients was UK 10,272 pounds compared with 14,528 pounds for 10 inpatients. Clinical outcome was comparable in both groups for all parameters studied and there was no obvious detrimental effect on patients receiving day care. This pilot study demonstrates that day care is feasible and acceptable to patients with active RA. The preliminary data suggest that day care is substantially cheaper than inpatient care and does not apparently compromise clinical outcome.

Ambulatory Care↗