Alcoholic ketoacidosis mimicking diabetic ketoacidosis.
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Biomedical subjects
Publications and source records attributed to D Simpson.
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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.
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Sixty-one consecutive patients who presented following an episode of deliberate self-harm (DSH) were assessed on a number of variables, including measures of hopelessness and hostility. Attempts were made to follow all of the patients. Those who were known to have had a further episode of DSH had significantly higher levels of hopelessness and intropunitive hostility after the index episode than those who did not repeat. The question of vulnerability to DSH is discussed as well as the possibility of using measures of hopelessness and intropunitive hostility to identify those at greater risk of repetition.
It is widely accepted that Sir James Young Simpson discovered the anaesthetic properties of chloroform and pioneered its application in surgery and midwifery. The name of Simpson is not infrequently also associated with the discovery of chloroform and of anaesthesia. Simpson certainly did not discover the substance chloroform or anaesthesia, there is doubt as to whether he discovered the anaesthetic properties of chloroform, and he may not have been the first person to administer chloroform anaesthesia to a patient. He did, however, play an important role in the introduction of chloroform anaesthesia particularly in midwifery and obstetrics.
We have developed simple and rapid screening tests for methanol and ethylene glycol in plasma of poisoned patients, based on the Toxi-Lab alcohol screening test. The compounds are first converted to formaldehyde, which diffuses from the patient's sample into a glass-fiber test sheet impregnated with Schiff's formaldehyde detection reagent. Subsequent exposure of the test sheet to acid and heat distinguishes formaldehyde from acetaldehyde. We recommend that samples giving positive results be analyzed by another technique to confirm the identity and concentration of the poison for use in prognosis and treatment.
Using Syva EMIT reagents and a Cobas-Bio centrifugal analyser we have developed a cost-effective assay for the detection in urine of benzoylecgonine, one of the main metabolites of cocaine. With this method up to 2470 samples can be assayed with a single 100-test EMIT Kit while maintaining acceptable precision. A mean CV of 7.0% was obtained for the concentration range 240-620 micrograms/l. Comparison of the method with the Abbott TDx system showed good correlation. The Cobas-Bio method is suitable for high-risk urines since heat treatment may be performed prior to analysis.
We have used immuno-gold labeling and electron microscopy to study the topography of thylakoid membrane polypeptides. Thylakoid vesicles formed by passage through a French press were adsorbed onto a plastic film supported by an electron microscope grid and processed for single or double immuno-gold labeling. After shadowing with platinum, the inside-out and right-side-out vesicles were identified by their distinctive morphologies. Right-side-out vesicles were labeled by a monoclonal antibody recognizing an epitope located in the trypsin-cleaved, N-terminal portion of the LHC II apoprotein, and by an antibody to CF1. A monoclonal antibody to the alpha-subunit of cytochrome b-559 reacted with a synthetic tridecapeptide corresponding to the C-terminal portion of the polypeptide. Both this antibody and a polyclonal antibody to the synthetic peptide labeled inside-out vesicles exclusively, indicating that the polypeptide C-terminus was exposed on the lumenal (exoplasmic) surface of the membrane.