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Biomedical subjects

P M Kemp

Publications and source records attributed to P M Kemp.

35 records · Page 2Linked to original sources

Whole blood levels of dodecanoic acid, a routinely detectable forensic marker for a genetic disease often misdiagnosed as sudden infant death syndrome (SIDS): MCAD deficiency.

We investigated whether or not elevated whole blood dodecanoic acid concentration was due to a beta-oxidation defect in fatty acid metabolism previously reported. We prospectively analyzed blood from 55 consecutive sudden infant death syndrome (SIDS) cases for fatty acid concentrations by gas chromatograph. Three of 55 cases had elevated dodecanoic acid concentrations (> or = 18.4 mg/L). The three SIDS cases with elevated blood dodecanoic acid were confirmed to have medium chain acyl-CoA dehydrogenase (MCAD) deficiency by outside laboratories, indicating that elevated dodecanoic acid is highly specific and sensitive for predicting MCAD deficiency in SIDS victims. Dodecanoic acid was easily detected in routine toxicology for acid and neutral drugs done at autopsy. MCAD deficiency is an autosomal recessive genetic disease, carrying a 25% recurrence risk. Families should be notified that siblings, both presently living and yet to be born, should be screened for this deficiency because MCAD deficiency can be treated, and sudden, unexplained infant deaths of living and subsequent offspring can be prevented.

Acyl-CoA Dehydrogenase↗

Pulmonary embolism. Is the clinical history a useful adjunct to aid the interpretation of the equivocal lung scan?

Pulmonary embolism is commonly fatal, yet notoriously difficult to detect. Diagnosis often relies on the ventilation-perfusion radionuclide scan, which itself is frequently equivocal. It has been suggested that if the equivocal ventilation-perfusion scan is interpreted in the light of clinical information, diagnostic accuracy can be improved. However, which features in the history should be considered? In this study of 197 patients undergoing ventilation-perfusion scanning, the clinical data of the 98 patients with either high-probability or normal scans were compared to the scan findings. The presence of a deep vein thrombosis was significantly associated with a high probability scan, whereas the presence of constant chest pain was significantly associated with a negative scan. Classical symptoms for pulmonary embolism, namely pleuritic chest pain and hemoptysis, were poor predictors of high-probability scans. Consequently, the authors advise considerable caution when using the clinical data to aid the interpretation of the equivocal lung scan in the individual case.

Confidence Intervals↗

A voxel-by-voxel multivariate analysis of cerebral perfusion defects in divers with 'bends'.

Past analysis of dysbaric-induced cerebral perfusion defects, demonstrated by 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography in divers using quantitative and/or univariate techniques, has resulted i considerable controversy regarding the significance of these lesions compared to those seen in control subjects, correlations with clinical findings and the role of 99Tcm-HMPAO as a prognostic indicator in decompression sickness. We tried to address these problems by using a multivariate approach to a voxel-by-voxel analysis, involving the use of principal components, to determine ranges of normality in 50 reference controls. In subsequent images, abnormality was defined as 10 spatially connected voxels at an appropriate significance level of three standard deviations. The images of 50 divers with clinically diagnosed 'bends' were compared with those of a further 40 normal population controls with no previous history of loss of consciousness, head injury or dysbarism. The results showed that 19 of 50 divers with 'bends' and 3 of 40 population controls had significant perfusion defects, representing a significant difference between divers with dysbarism and population controls at the level P < 0.002. It is concluded that dysbarism causes significant cerebral cortical perfusion defects in affected divers both in 'silent' and symptomatic (clinically correlated) areas.

Adolescent↗

Cannabinoids in humans. I. Analysis of delta 9-tetrahydrocannabinol and six metabolites in plasma and urine using GC-MS.

This report describes a method for the quantitative analysis of delta 9-tetrahydrocannabinol and six of its metabolites, 8 alpha-hydroxy-delta 9-tetrahydrocannabinol, 8 beta-hydroxy-delta 9-tetrahydrocannabinol, 11-hydroxy-delta 9-tetrahydrocannabinol, 8 alpha,11-dihydroxy-delta 9-tetrahydrocannabinol, 8 beta,11-dihydroxy-delta 9-tetrahydrocannabinol, and 11-nor-9-carboxy-delta 9-tetrahydrocannabinol. In addition, the method was designed to detect cannabidiol and cannabinol, two naturally occurring cannabinoids. Plasma and urine samples were hydrolyzed with bacterial (Escherichia coli) beta-glucuronidase and extracted with hexane-ethyl acetate (7:1). Analysis and quantitation were performed by gas chromatography-mass spectrometry in the electron ionization mode coupled with selected ion monitoring. The cannabinoids were detected as their trimethylsilyl derivatives to enhance their chromatographic separation and mass spectral characteristics. The linearity of the procedure was excellent for all of the compounds within the range tested (0-100 ng/mL). Limits of detection ranged from 0.5 to 1.5 ng/mL in urine and from 0.6 to 2.1 ng/mL in plasma depending on the analyte.

Biomarkers↗

Cannabinoids in humans. II. The influence of three methods of hydrolysis on the concentration of THC and two metabolites in urine.

Glucuronide conjugates of cannabinoids were previously identified in humans. For gas chromatographic-mass spectrometric (GC-MS) analysis of the unconjugated compounds in human urine, it is necessary to cleave the glucuronide moiety. Base hydrolysis and two forms of enzymatic hydrolysis were compared in this study to examine any quantitative differences between the hydrolysis methods. Human volunteers (n = 8) each smoked one marijuana cigarette containing 3.58% delta 9-tetrahydrocannabinol (THC) and submitted urine samples prior to smoking, 5 min after smoking, and hourly for 8 h thereafter. Urine (1 mL) was buffered to the optimum pH for each form of enzyme tested. beta-Glucuronidase from Escherichia coli (bacteria) or Helix pomatia (mollusk) was added to the specimens, followed by overnight incubation at 37 degrees C. Following hydrolysis, the samples were extracted using hexane-ethyl acetate (7:1) and derivatized with N,O-bis(trimethylsilyl)-trifluoroacetamide plus 1% trimethylchlorosilane, which converted the cannabinoids to their trimethylsilyl derivatives. GC-MS analysis revealed striking differences between the hydrolysis methods. Concentrations of unconjugated THC and 11-hydroxy-THC (11-OH-THC) using E. coli were significantly increased over all other methods tested (p < .05). These results demonstrate the species-dependent nature of glucuronidase activity in hydrolyzing THC and 11-OH-THC glucuronides and the ineffectiveness of base hydrolysis on these hydroxylated compounds. The need for further study to find the optimum conditions necessary for the complete hydrolysis of cannabinoid conjugates is suggested.

Dronabinol↗

Cerebral perfusion and psychometric testing in military amateur boxers and controls.

The objective was to compare two neurophysiological variables in active amateur boxers with non-boxing sportsmen. 41 boxers and 27 controls were given psychometric tests: 34 boxers and 34 controls underwent technetium-99m hexamethylpropyleneamineoxime single photon emission computerised tomography (Tc-99m HMPAO SPECT) cerebral perfusion scans. The controls performed better at most aspects of the psychometric tests. Boxers who had fought fewer bouts had a tendency to perform better at psychometric tests than those boxers who had fought more bouts. Tc-99m HMPAO SPECT cerebral perfusion scanning showed that controls had less aberrations in cerebral perfusion than the boxers. In conclusion, significant differences were shown in two neurophysiological variables between young amateur sportsmen who box and those who do not. The long term effects of these findings remain unknown.

Adolescent↗

An estimation of noise levels in HMPAO RCBF SPECT images using simulation and phantom data; comparison with results obtained from repeated normal controls.

The purpose of this work was to determine noise levels in HMPAO RCBF SPECT images. Eight simulated images of a uniform sphere of activity were made at each of three different count levels. Three images of the Amersham brain phantom were obtained at each of three count levels, roughly corresponding to the simulation levels. Image reconstruction involved a modified Shepp-Logan filter with and without attenuation correction. The scaling constant in the Budinger equation was shown to vary little over the count range used with a mean value of 23 for uncorrected phantom data and 27 for corrected phantom data, corresponding to RMS noise levels of 7%-15%. The variance due to noise was calculated as a percentage of the variance obtained for 53 normal control studies following image registration and normalization. Values of 54% for uncorrected images and 67% for corrected images were obtained. For 10 normal controls a repeated study was performed. The ratio of within-subject to (single sample) between-subject variance was determined as 73% for uncorrected images and 78% for corrected images.

Algorithms↗

A method for assessing the significance of abnormalities in HMPO brain SPECT images.

METHODS: A normal atlas for HMPAO rCBF SPECT images was obtained from images of 53 normal controls. Following image registration and normalization, a mean image was extracted, while images representing correlated normal deviants were identified using principal component analysis. These images formed the "building blocks" of the atlas. For subsequent images, the atlas was used to create a "nearest normal equivalent" image, which was compared to a residual standard deviation image to determine the significance of deviations in the new image. RESULTS: Images from 30 patients (10 with Alzheimer's disease; 12 with single or multiple infarcts; and 8 normals) were analyzed. CONCLUSION: Using an optimal decision level, 10/10 patients with Alzheimer's disease and 11/12 patients with infarcts were correctly identified, with only one false-positive resulting. We utilized a database of images obtained from normal controls to create a normal atlas.

Alzheimer Disease↗

Paediatric resuscitation in adverse circumstances: a comparison of three routes of systemic access.

Nine Kurdish children were admitted to a British Surgical Support Team facility in Northern Iraq, requiring resuscitation for dehydration estimated to be of 10% loss of body weight. Systemic access was by intravenous (IV, 6 patients), intraosseous (IO, 6 patients) and/or intraperitoneal cannulation (IP, 4 patients) and resuscitation was according to a defined protocol. Insertion times, maximum initial flow rates and complications were assessed. The mean insertion times were 78, 112 and 26 seconds and the mean maximum initial flow rates of crystalloid were 240, 60 and 400 mls/hour for IV, IO and IP routes respectively. One IV lasted more than 24 hours and three tissued. One IO cannula blocked, and one IP was removed because of saline extravasation. IO bolus injections were painful. Total volumes infused and time to adequate hydration varied widely and there were no correlations. The mortality was 33%, compared with 11% for 18 less severely dehydrated children. It is concluded that the IP and IO routes allow severely dehydrated children to be resuscitated without significant complications when IV access is difficult to establish.

Child↗

The Anagen system for automated fluorometric immunoassay.

We describe a new discrete microprocessor-controlled analyzer, the AN2000, which fully automates fluorometric immunoassays by using a magnetic separation of the solid phase and an alkaline phosphatase label. It can operate in random-access or batch mode with a dwell time typically less than 20 min. The analysis rate is 75 samples per hour and the system can hold refrigerated reagents for as many as 20 different analytes. The substrate and wash buffer are common to all analytes. The system can hold as many as 80 samples at once. The operator can select from the menu-driven operator interface any combination of the available analytes to be run for each sample, using either the touch screen or the keyboard. Results are calculated from a stored calibration curve that is stable for greater than or equal to 1 month. The AN2000 is capable of automating most assay formats because the available timings, volumes, incubations, and wash cycles can be used in any combination.

Alkaline Phosphatase↗

A possible association between fluoxetine use and suicide.

Fluoxetine has been available for use as an antidepressant since early 1988. Numerous reports have indicated that it is at least as good as some of the tricyclic antidepressants and that it does not produce as serious toxicity as the tricyclics. Recently, however, case reports have suggested that it may produce suicidal tendencies in some patients. The present report provides data from a medical examiner's office regarding the number of cases in which fluoxetine has been detected and the proportion certified as suicides.

Adult↗

Collection and handling of clinical blood samples to assure the accurate measurement of cocaine concentration.

The measurement of serum cocaine concentration is difficult because it is rapidly metabolized in vivo and in vitro. Previous investigators have used sodium fluoride (0.5-3.0%) in an attempt to stabilize its concentration in samples of whole blood, but these concentrations of sodium fluoride are not readily available outside the analytical laboratory. This study was performed to assess the stability of cocaine in whole blood when stabilized in a commonly available concentration of sodium fluoride (0.25%), with or without concomitant refrigeration. Whole blood was enriched with cocaine to a final concentration of 900 ng/mL and added to flasks containing sodium fluoride (0, 0.25, 0.5, and 1.0%) or 0.25% sodium fluoride plus potassium oxalate (gray-top Vacutainer tubes), after which it was stored at 4 degrees C or at room temperature. Whole blood cocaine concentrations were measured at 0, 24, and 48 h by gas chromatography. Sodium fluoride at all concentrations, with or without refrigeration and potassium oxalate, effectively inhibited cocaine degradation, with 86-91% of the drug present after 48 h. In contrast, substantial degradation of cocaine occurred in the samples stored without sodium fluoride, regardless of temperature. Thus, the use of commercial gray-top Vacutainer tubes effectively stabilizes cocaine in blood during procurement, transport, and short-term storage.

Chromatography, Gas↗

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems.

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.

Administration, Cutaneous↗

CA549 and TPS patterns in the diagnosis and staging of patients with breast carcinoma.

This study compares the clinical value of the breast cancer tumour makers CA549 and TPS, and their tandem use when one or both markers indicate abnormality. For 144 patients presenting with active disease, 33 were classified as Stage I, 37 as Stage II, 40 as Stage III and 34 as Stage IV. For these patients the sensitivity of CA549 using a cut-off of 10 U/ml was 27%, 32%, 42% and 79%, respectively. The sensitivity of TPS for each stage using a cut-off of 100 U/l was 12%, 22%, 28% and 73%, respectively. At these cut-off levels, 36%, 46%, 63% and 91% of patients, respectively, have either CA549 or TPS or both markers raised. For 161 patients with diagnosed benign breast disease, the specificity of marker levels was 96% for CA549, 88% for TPS and 84% for tandem use. CA549 is shown to be superior to TPS and this was confirmed by Receiver Operating Characteristic (ROC) analysis using variable threshold levels, with the areas under the curves for all stages combined being 0.74 +/- 0.03 (ISD) and 0.66 +/- 0.03, respectively. The corresponding area under the curve for tandem use (0.75 +/- 0.03) is marginally greater than for either individual marker, although the difference with respect to CA549 is statistically insignificant.

Adult↗