Head injuries from road accidents--a diminishing problem?
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Biomedical subjects
Publications and source records attributed to D Simpson.
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Seventy-four patients with Stage T3 N0 M0 squamous carcinoma of the glottis were treated initially by either surgery or radiotherapy between 1980 and 1985. The treatment adopted was determined by consultant preference. The long-term survival in both groups was approximately the same. Of 38 patients treated initially by radiotherapy, 25 had local recurrence. Fifteen of these underwent salvage surgery and 10 died of disease. Thirteen patients (33 per cent) retained their larynx. One of the major advantages of treating patients with stage T3 N0 M0 carcinoma of larynx by radiotherapy initially is that approximately one-third will retain their larynx. Local recurrences can usually be treated readily by salvage surgery.
The use of a drug screening service has been investigated over a nine month period during which 1500 urine samples from 765 patients were analysed. Preliminary drug screening of urine samples was performed by EMIT immunoassays adapted for use on the Cobas Bio analyser; further identification and confirmation were carried out by Toxi-Lab thin-layer chromatography and capillary gas chromatography. A large number of positive results were obtained for benzodiazepines, cannabinoids, methadone and opiates (mainly dihydrocodeine). Only a limited number of urines gave positive results for amphetamine and related stimulants; cocaine metabolite was rarely detected in samples. The service proved to be of considerable value in the management of drug misusers, and for the identification of new substances taken by the local population.
Following suggestions that spurious results occur with EMIT assays--so-called 'fliers'--many laboratories perform such assays in duplicate. In this study, using a Cobas-Bio centrifugal analyser and cost-effective assays developed in the authors' laboratory, complete EMIT assays were run, each with its own calibration curve, on three anti-epileptic drugs using plasma samples, and five drugs of abuse using urine samples. No serious spurious results were obtained. It is suggested that there is no inherent tendency for EMIT assays to produce 'fliers' and that when these occur they may be explained by factors common to many other types of assay.
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The National Health Services in Wales has adopted a strategic approach based on health gain. Five approaches to meeting this problem are considered (i) eliminating basic inefficiencies; (ii) eliminating unnecessary clinical activity; (iii) doing what is done now but differently; (iv) investing now to save later and (v) withdrawing from a particular area of activity, because it is less important than other competing claims. Each of these is briefly considered with particular reference to the Welsh situation. Three particular lines of advance are identified to achieve the above: creating new sources of information; working more effectively across organisational boundaries; and making the cultural changes to make it all possible.
Cost-effective immunoassays for the detection of amphetamines, benzodiazepines, and methadone in urine have been developed using Syva EMIT reagents and a Cobas Bio centrifugal analyser. With this method up to 2470 samples can be assayed with a single 100 test EMIT kit while maintaining acceptable precision. Mean CVs of 3.8-6.6% were obtained for concentrations around the manufacturer's recommended threshold level (300 micrograms/l). Comparison of the methods with the Abbott TDx system showed good correlation for methadone. The methods compared less well for amphetamines, and it was not possible to obtain a useful correlation for benzodiazepines. Heat treatment prior to analysis did not affect the detection of benzodiazepines and methadone; there was a mean decrease of 14% for amphetamines.
C26H28N2O10, Mr = 528.5, triclinic, P1, a = 9.524 (1), b = 11.8187 (8), c = 12.615 (1) A, alpha = 66.512 (7), beta = 83.321 (9), gamma = 88.758 (8) degrees, V = 1293.0 (4) A3, Dx = 1.357 g cm-3, Z = 2, lambda(Cu K alpha) = 1.54178 A, mu = 8.99 cm-1, F(000) = 556, T = 293 K, final R = 0.039, wR = 0.048 for 2425 reflections with I greater than 3 sigma(I). The tetra-substituted valerolactone ring has a boat conformation and the relative stereochemistries of the three pairs of adjacent substituents are cis-trans-trans.
C15H28O4Si, Mr = 300.5, monoclinic, P2(1)/a, a = 11.194 (4), b = 10.944 (3), c = 14.815 (5) A, beta = 95.01 (3) degrees, V = 1808 (2) A3, Dx = 1.104 g cm-3, Z = 4, lambda(Mo K alpha) = 0.71069 A, mu = 1.43 cm-1, F(000) = 656, T = 293 K, final R = 0.052, wR = 0.058 for 1630 reflections with I greater than 3 sigma(I). The valerolactone ring is in a boat conformation and the three ring substituents are cis.
Measurement of cutaneous vibrotactile thresholds may be useful for assessment of the functional integrity of the somatosensory system. To validate a rapid method of determining vibrotactile thresholds that uses a commercially available electromechanical device, vibrotactile thresholds were compared with standardized physical examination findings of sensory function and electrophysiological parameters in 79 patients referred to the Mount Sinai Hospital Neurophysiology Laboratory for clinical electrophysiological evaluation. A statistically significant monotonic association between graded physical examination of vibration perception and vibrotactile threshold was observed for all digits tested in the upper and lower extremities. Statistically significant associations were also observed between vibrotactile thresholds and a variety of electrophysiological measures of the median, ulnar, tibial, peroneal, and sural nerves. The strongest associations were observed between great toe vibrotactile thresholds and late response latencies measured in nerves in the lower extremities. Determination of vibrotactile thresholds may be useful in settings where quantitative measures of large fiber nerve function are desirable and electrophysiological study is not feasible.
The aim of this study was to evaluate whether, in the treatment of active non-cholesteatomatous chronic otitis media, the effectiveness of gentamicin with hydrocortisone ear-drops is due solely to the contained steroid or to the combination of antibiotic and steroid. Sixty-four patients presenting to the Ear, Nose and Throat outpatient department with active non-cholesteatomatous chronic otitis media were randomly allocated to receive either gentamicin with hydrocortisone ear-drops, or betamethasone ear-drops, for up to 4 weeks. Activity in the ear was assessed at 2 and 4 weeks. Gentamicin with hydrocortisone combination drops were significantly more effective than betamethasone drops (P less than 0.001) in producing inactivity of chronic otitis media, being effective in 80% as opposed to 29% of cases. The effectiveness of gentamicin with hydrocortisone ear-drops appears to be due to the combination of antibiotic and steroid.
Using Syva EMIT reagents and a Cobas Bio centrifugal analyser we have developed a cost-effective assay for the detection of cannabinoids in urine. With this method, up to 1500 samples can be assayed with a single 100 test kit while maintaining acceptable precision. A mean CV of 6.1% was obtained for the concentration range 80-130 micrograms/l. The method is suitable for high-risk urines since heart treatment may be performed prior to analysis. There was no significant change in the measured concentration of cannabinoids in urine samples on storage in plastic containers, refrigerated or frozen, for up to seven weeks.
The frequency of hprt mutants in peripheral blood T-lymphocytes of two putative Lesch-Nyhan individuals and their parents was determined by a cell cloning assay to quantify the frequency of thioguanine-resistant mutants. The results confirmed the Lesch-Nyhan diagnosis and demonstrated that the mother has an elevated mutant frequency consistent with being heterozygous for an hprt mutation. Mass cultures of T-lymphocytes from both the children and their mother, as well as cultures of hprt mutant clones from the mother, were employed as sources of mRNA for cDNA sequence analysis. These hprt mutants show a single base substitution (T----C transition) at position 170 (exon 3). The predicted amino acid change is the substitution of threonine for methionine56. We have designated this new Lesch-Nyhan mutation hprtMontreal. The use of T-lymphocyte cultures allows rapid sequence analyses of hprt mutations, as well as family studies to define the origin of a particular mutation.
The mutagenic epoxide metabolite of acrylonitrile, 2-cyanoethylene oxide (ANO), was used to treat human TK6 lymphoblasts (150 microM x 2 h ANO). A collection of hypoxanthine-phosphoribosyltransferase (hprt) mutants was isolated and characterized by dideoxy sequencing of cloned hprt cDNA. Base-pair substitution mutations in the hprt coding region were observed in 19/39 of hprt mutants: 11 occurred at AT base pairs and 8 at GC base pairs. Two -1 frameshift mutations involving GC bases were also observed. Approximately half (17/39) of the hprt mutants displayed the complete loss of single and multiple exons from hprt cDNA, as well as small deletions, some extending from exon/exon junctions. Southern blot analysis of 5 mutants with single exon losses revealed no visible alterations. Analysis of 1 mutant missing exons 3-6 in its hprt mRNA revealed a visible deletion in the corresponding region in its genomic DNA. The missing exon regions of 4 mutants (one each with exons 6, 7 and 8 loss and one mutant with a 17-base deletion of the 5' region of exon 9) were PCR amplified from genomic DNA and analyzed by Southern blot using exon-specific probes. The exons missing from the hprt mRNA were present in the genomic hprt sequence. DNA sequencing of the appropriate intron/exon regions of hprt genomic DNA from a mutant with exon 8 loss and a mutant exhibiting aberrant splicing in exon 9 revealed point mutations in the splice acceptor site of exon 8 (T----A) and exon 9 (A----G), respectively.
We have determined the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (hprt) mutations that arose in vivo in the T lymphocytes of a normal male subject. In previous studies approximately 16% (23/141) of the mutants from this individual analyzed by Southern blot displayed large structural alterations in hprt. Thirty-two mutants without these large hprt structural alterations produced sufficient hprt cDNA for polymerase chain reaction amplification and DNA sequence analysis. Base substitutions in hprt cDNA resulting in missense mutations and one mRNA splicing aberration (inclusion of intron sequences) were observed in 18/32 of these these mutants; substitutions occurred at both AT and GC base pairs. Small deletions (3/32), a tandem change and a single base insertion were also observed among the hprt cDNAs. Exon skipping and inclusion of hprt intron sequences in the hprt cDNA were observed in an additional 9/32 of the mutants. Analysis of T cell receptor (TCR) gene rearrangements revealed that six of eight mutants with an identical hprt T----A transversion displayed the same TCR rearrangement pattern, indicating that they were clonally related and arose from a single in vivo mutational event.