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Biomedical subjects

I Wilkinson

Publications and source records attributed to I Wilkinson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Improved laboratory test selection and enhanced perception of test results as tools for cost-effective medicine.

Inconsistencies in the way physicians perceive and handle identical laboratory results have untoward effects on morbidity, mortality and cost of medical care. In this context, the selection of suitable tests to answer definite clinical questions, and the manner in which laboratory results are presented have great impact on the action taken by the clinician. This review addresses preferred methods to improve laboratory test selection, and examines methods that more effectively convey laboratory results to clinicians. It is anticipated that refined selection of tests, and presentation of the test results in a configuration that is easily perceived by the clinician, will facilitate interpretation of laboratory reports. Furthermore, any measures that promote the application of laboratory information in medical practice improve economics at the laboratory-clinical interface. The presently described methods to optimize test selection and interpretation are: likelihood ratios to provide estimates of the ability of a test to identify a clinical condition; consensus- and discriminant function-analysis to estimate the performance of tests in diagnosing a particular disease or condition; receiver operating characteristic (ROC) curves to assess discrimination capabilities. The methods which improve test result perception are expression of results as multiples of the upper normal limit, utilizing signal strength to provide prognostic probabilities, and presentation of results in graphic forms that display mutually interrelated functions, with a specific cluster of results being highly suggestive of a given condition. In addition, we discuss application of expert systems to provide rules based on knowledge and experience to analyze results of tests and suggest diagnosis and action, including additional tests when required. It is anticipated that judicious utilization of laboratory services by application of the reviewed methodologies will help to achieve medically justified responses at a lower cost and help to achieve a proper balance between cost of tests and their clinical usefulness.

Clinical Laboratory Techniques↗
PubMed1997

Characterization of five different proteins produced by alternatively spliced mRNAs from the human cAMP-specific phosphodiesterase PDE4D gene.

We have isolated and characterized complete cDNAs for two isoforms (HSPDE4D4 and HSPDE4A5) encoded by the human PDE4D gene, one of four genes that encode cAMP-specific rolipram-inhibited 3',5'-cyclic nucleotide phosphodiesterases (type IVPDEs; PDE4 family). The HSPDE4D4 and HSPDE4D5 cDNAs encode proteins of 810 and 746 amino acids respectively. A comparison of the nucleotide sequences of these two cDNAs with those encoding the three other human PDE4D proteins (HSPDE4D1, HSPDE4D2 and HSPDE4D3) demonstrates that each corresponding mRNA transcript has a unique region of sequence at or near its 5'-end, consistent with alternative mRNA splicing. Transient expression of the five cDNAs in monkey COS-7 cells produced proteins of apparent molecular mass under denaturing conditions of 68, 68, 95, 119 and 105 kDa for isoforms HSPDE4D1-5 respectively. Immunoblotting of human cell lines and rat brain demonstrated the presence of species that co-migrated with the proteins produced in COS-7 cells. COS-cell-expressed and native HSPDE4D1 and HSPDE4D2 were found to exist only in the cytosol, whereas HSPDE4D3, HSPDE4D4 and HSPDE4D5 were found in both cytosolic and particulate fractions. The IC50 values for the selective PDE4 inhibitor rolipram for the cytosolic forms of the five enzymes were similar (0.05-0.14 microM), whereas they were 2-7-fold higher for the particulate forms of HSPDE4D3 and HSPDE4D5 (0.32 and 0.59 microM respectively), than for the corresponding cytosolic forms. Our data indicate that the N-terminal regions of the HSPDE4D3, HSPDE4D4 and HSPDE4D5 proteins, which are derived from alternatively spliced regions of their mRNAs, are important in determining their subcellular localization, activity and differential sensitivity to inhibitors.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Neurological outcome of severe cystic periventricular leukomalacia.

OBJECTIVE: To determine the neurological outcome of a cohort of premature babies having ultrasound diagnoses of severe cystic periventricular leukomalacia. METHODOLOGY: All neonatal intensive care unit admissions born at less than 35 weeks gestation or weighing less than 1500 g underwent serial cranial ultrasounds. Those developing severe bilateral cystic periventricular leukomalacia (12 patients) were then followed clinically to a mean age of 27.3 months. RESULTS: Ten of the 12 patients fulfilling strict ultrasound criteria survived. All had a major neurological handicap, all having spastic quadriparesis and visual impairments, with most suffering global developmental delay and epilepsy. CONCLUSIONS: Severe bilateral cystic periventricular leukomalacia results in major permanent handicap. It is currently impossible to identify most patients with this condition while they are being ventilated. Non-ultrasound techniques are needed to diagnose the condition earlier, and to give guidance to management.

Developmental Disabilities↗
PubMed1996

Laser therapy for breast cancer: MR imaging and histopathologic correlation.

PURPOSE: To investigate magnetic resonance (MR) imaging guidance of interstitial laser photocoagulation to treat primary breast cancer. MATERIALS AND METHODS: Twenty female patients with symptomatic breast cancers diagnosed at cytologic examination underwent interstitial laser photocoagulation by means of a single fiber prior to surgical excision. Gadolinium-enhanced T1-weighted three-dimensional fast low-angle shot (FLASH) MR imaging was performed before and after laser therapy (median, 48 hours; range, 24-96 hours). Following resection, tumors were mapped in detail histopathologically. The extent of disease, size of laser burn, and extent of residual tumor were correlated with MR findings. RESULTS: Twenty-seven tumors were detected at histopathologic examination in the 20 patients. Five patients had more than one invasive mass. Twenty-five of the 27 tumors were identified as discrete enhancing masses at MR. The two missed invasive foci were obscured on MR images by diffuse patchy enhancement that correlated with the presence of an associated extensive intraductal component. Early (4-hour) follow-up images failed to depict the laser effect. Later (24-96 hours) follow-up images depicted the laser-induced necrosis as a zone of nonenhancement within the residual enhancing tumor. The correlation coefficients (MR vs histopathologic analysis) for the laser-burn diameter and residual tumor were 0.80 and 0.86, respectively. CONCLUSION: Delayed gadolinium-enhanced MR images can help define the extent of laser-induced necrosis and residual tumor after interstitial laser photocoagulation therapy in breast cancer.

Adult↗
PubMed1995

Economics 101: exploring the land of costs.

The word "cost" is a slippery, chameleon-like beast that changes its meaning to suit the occasion. The author's "economish" dictionary will help you survive the purchasing jungle.

Accounting↗
PubMed1992

Investigation of the tendency to wheeze in pollen sensitive patients.

We have undertaken a double blind placebo controlled study of the effect of nasal beclomethasone on the tendency to wheeze in 20 unselected hay fever sufferers, half with a history of previous seasonal wheezing. We found no difference between either bronchial hyperresponsiveness, as measured by methacholine challenge, home-monitored PEFR, nor recorded wheeze nor cough between treated and placebo groups although the numbers were small. All were allowed the antihistamine cetirizine hydrochloride 10 mg daily. Eighteen out of the 19 patients had either bronchial hyperresponsiveness (PD20 methacholine < 8 mumol or a > 2 doubling dose change in their PD20 during the pollen season). We have shown a significant positive correlation between a hay fever score (HFS) (created by taking the sum of the home scored; nasal discharge, nasal blockage, eye irritation, sneeze and antihistamine use) and peak seasonal specific IgE to mixed grass pollen (Spearman correlation coefficient 0.5 P < 0.02). There was also a positive correlation between the rise in specific IgE from pre to peak season and the HFS, correlation coefficient 0.6 P = 0.03).

Administration, Intranasal↗
PubMed1991

An audit of the clinical use of magnetic resonance imaging of the head and spine.

An audit was undertaken of the use of magnetic resonance imaging for clinical problems of the head and spine. Using a form of simulation, two consultant clinicians were asked to assess a sequential series of 200 patients referred for magnetic resonance. The clinicians considered that 200 magnetic resonance studies could replace about 330 other imaging and neurophysiology investigations; the cost of the alternative tests approximated the cost of magnetic resonance. However, there was considerable variation between cases in the costs of investigations potentially replaced by the procedure under audit, and this variation suggests ways in which magnetic resonance might be used more cost-effectively in the future.

Brain↗
PubMed1990

Comparative evaluation of nonradiometric BACTEC and improved oxoid signal blood culture systems in a clinical laboratory.

The BACTEC NR660 blood culture system, which uses infrared spectroscopy to detect carbon dioxide generated by bacterial growth, was compared with the new medium formulation of the Oxoid Signal system. Two trials were conducted: a comparative study of 88 organisms in simulated blood cultures and a clinical trial of 3,321 paired patient blood culture samples. Both trials showed that overall the BACTEC system performed better in the recovery of organisms. The Oxoid system was unable to detect by signal the growth of the majority of yeasts, nonfermentative gram-negative bacilli, Neisseria meningitidis, Nocardia spp., and Corynebacterium jeikeium. There were no significant differences in the yield of Staphylococcus spp., members of the family Enterobacteriaceae, Streptococcus spp., or anaerobic organisms. BACTEC detected growth more quickly than did the Oxoid system; 61% of the isolates were detected by BACTEC at 24 h, while 49% of the isolates were detected by Oxoid. The Oxoid system had a high proportion (58.5%) of false-positives, compared with 7.7% for the BACTEC system. Despite the new medium formulation of the Oxoid system, its performance is still not equivalent to that of the BACTEC system.

Bacteria↗
PubMed1989

A summary of 7q interstitial deletions and exclusion mapping of the gene for beta-glucuronidase.

Three patients are described with different phenotypes and differing de novo interstitial deletions of the long arm of a chromosome 7. The first patient has a deletion with loss of the proximal 7q11.23 band. Only three other cases have been reported with this particular deletion. Our second case shows mild dysmorphism similar to the other four patients reported with deletion of bands 7q21.12----21.3. Our third patient has a deletion of the 7q22.1----32.2 segment and has many of the phenotypic features of the other reported cases of del 7q22----32. GUSB, the gene for beta-glucuronidase, has been localised to the 7cen----q22 region. Analysis of beta-glucuronidase levels in blood leucocytes of our patients has helped more precisely to assign this gene locus to 7q21.11 or 7q22.1.

Abnormalities, Multiple↗
PubMed1988

The coagulation factor VII regulator is located on 8p23.1.

Cytogenetic and coagulation studies have been performed on two patients with different abnormalities of chromosome 8, i.e. del(8p23.1----pter) and dup(8q23.1----qter). Results confirm the existence of a regulatory mechanism for clotting factor VII on chromosome 8 and define its location to the p23.1----p23.2 region.

Blood Coagulation↗
PubMed1987

Tolerance induction in mice by conjugates of monoclonal immunoglobulins and monomethoxypolyethylene glycol. Transfer of tolerance by T cells and by T cell extracts.

The specific tolerance induced in mice by conjugates of human monoclonal IgG (HIgG) with monomethoxypolyethylene glycol (mPEG) was transferred to normal mice by spleen cells or a surface immunoglobulin negative (sIg-) Lyt-2+ subpopulation of these cells. Although transferable tolerance was demonstrable 6 to 14 days after treatment of the cell donors with tolerogen, the state of tolerance persisted in the treated mice for at least 43 days. Moreover, an extract prepared by freezing and thawing of the sIg- spleen cells obtained from mice 6 days after treatment with HIgG(mPEG)20 was capable of reducing (greater than 85%) the immune response of normal mice to heat aggregated HIgG. On the basis of these results, it is suggested that similar tolerogenic mPEG derivatives of xenogeneic monoclonal immunoglobulins (XIg) may prove to be useful therapeutic agents in man when administered before treatment with the unmodified XIg.

Animals↗
PubMed1987

Tolerogenic polyethylene glycol derivatives of xenogeneic monoclonal immunoglobulins.

It is becoming apparent that the effectiveness of xenogeneic monoclonal antibodies (XIg), which are increasingly used for diverse therapeutic purposes in man, may be counteracted by their inherent immunogenicity. Since conjugates of proteins with monomethoxypolyethylene glycol (mPEG) have proved to be effective tolerogens in other systems, we have used an experimental model in mice to explore the tolerogenicity of mPEG conjugates of a human monoclonal IgG (HIgG), i.e. a myeloma protein. Administration of these conjugates prior to immunization with heat aggregated HIgG (ha-HIgG) resulted in specific tolerance, as manifested by a marked reduction in the level of antibodies to HIgG, which was related to the degree of conjugation and the dose of conjugate administered. Thus, administration of HIgG(mPEG)20 6 to 43 days prior to immunization with ha-HIgG resulted in an inhibition of anti-HIgG antibody formation of the order of 85-90%, in relation to the titres of mice receiving PBS in lieu of HIgG(mPEG)20; these results hold the promise that mPEG conjugates of XIg may prove therapeutically useful in man in relation to organ transplantation, localization of tumours by immuno-imaging and tumour destruction by immunotoxins.

Animals↗