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Biomedical subjects

C J Thompson

Publications and source records attributed to C J Thompson.

At least 163 records · Page 9Linked to original sources

The effect of spontaneous reperfusion on metabolic function in early human cerebral infarcts.

Twelve patients were studied within 48 hours of stroke using positron emission tomography to determine cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction, cerebral blood volume, cerebral pH (CpH), and cerebral metabolic rate for glucose (CMRGlc), the last calculated using published normal rate constants (CMRGlc[N]) and those for severe ischemia. In these studies, a cortical region of severe ischemia (I) was outlined, its metabolic and perfusion properties evaluated, and its length measured. The contralateral uninvolved cortical rim (C) in these patients and the cortical rim in 5 older normal patients were used for comparison. The length of region I correlated with the neurological deficit measured independently by a clinical scoring method. The 12 patients fell into two groups: Group I (8 patients), whose CBF in I was 9.3 +/- 2.5 ml/100 gm/min (mean +/- SEM) and was in every patient lower than that in C (33.1 +/- 2.2), and Group 2 (4 patients), whose CBF in I was 42.1 +/- 8.5 ml/100 gm/min and was in every case higher than that in C (28.2 +/- 1.5). In Group I, region I showed a CMRGlc(N)/CMRO2 ratio of 0.22 +/- 0.06 and a CpH of 6.83 +/- 0.06. In Group 2, the same ratio in the region I was 0.58 +/- 0.09 and the CpH was 7.12 +/- 0.05. The CMRGlc (N)/CMRO2 ratio for the contralateral hemisphere was comparable in the two groups. Our data suggest that, within 48 hours of the clinical onset of stroke, the ischemic cortex is already reperfused in one third of patients. Those ischemic regions with persistent hypoperfusion appear acidotic, whereas in the reperfused regions, despite evidence of an increased CMRGlc/CMRO2 ratio, acidosis is not evident. The implications of these findings for therapies proposed in acute human cerebral ischemia are discussed.

Acute Disease↗

Characterization of the herbicide-resistance gene bar from Streptomyces hygroscopicus.

A gene which confers resistance to the herbicide bialaphos (bar) has been characterized. The bar gene was originally cloned from Streptomyces hygroscopicus, an organism which produces the tripeptide bialaphos as a secondary metabolite. Bialaphos contains phosphinothricin, an analogue of glutamate which is an inhibitor of glutamine synthetase. The bar gene product was purified and shown to be a modifying enzyme which acetylates phosphinothricin or demethylphosphinothricin but not bialaphos or glutamate. The bar gene was subcloned and its nucleotide sequence was determined. Interspecific transfer of this Streptomyces gene into Escherichia coli showed that it could be used as a selectable marker in other bacteria. In the accompanying paper, bar has been used to engineer herbicide-resistant plants.

Journal Article↗

Thallium-201 single-photon emission computed tomographic estimates of left ventricular mass in patients with and without ischemic heart disease.

A new automated edge detection program has been developed to estimate left ventricular mass from single-photon emission computed tomographic (SPECT) thallium-201 images of patients. Left ventricular (LV) mass was measured from contrast angiograms in 21 patients and was compared with LV mass estimated from thallium-201 tomographic studies. A comparison of angiographic mass to mass estimated from stress studies yielded an r = 0.97 (SEE = 21.6 gm) and a comparison of angiographic mass to mass determined from the redistribution images yielded r = 0.96 (SEE = 23.0 gm). Values of mass from stress and redistribution studies varied 7.3% +/- 6.7 and 8.8% +/- 9.2, respectively, when compared with values obtained by cineangiography. LV mass derived from the stress and redistribution studies were highly correlated (r = 0.97; SEE = 21.9 gm). Linear regression analysis revealed a slope of 1.06 (stress ventricular mass = 1.06 X redistribution mass - 14.9 gm). Thirteen patients had two thallium-201 SPECT studies performed approximately 1 month apart. Estimated LV mass was highly correlated when the two studies were compared (r = 0.94; SEE = 21.7 gm comparing the two stress studies; and r = 0.93, SEE = 19.4 gm for the two redistribution studies). We conclude that SPECT thallium-201 imaging can define LV mass accurately and reproducibly in normal, ischemic, or infarcted tissue.

Coronary Disease↗

Estimation of cerebral oxygen utilization rate by single-bolus 15O2 inhalation and dynamic positron emission tomography.

This study shows that regional CMRO2 can be estimated by means of nonlinear regression using dynamic positron emission tomographic data acquired during 1 min following single-bolus inhalation of 15O2. The feasibility of simultaneous estimation of CBF, cerebral blood volume (CBV), oxygen extraction ratio (OER), and CMRO2 was assessed by simulations using the model of Mintun et al. Four oxygen metabolic measurements, each consisting of a CBF, CBV, and 15O2 bolus study, were carried out on three volunteers. Regional values for CBF, CBV, OER, and CMRO2 were derived in two ways: from the fits of the time-activity curves of the dynamic 15O2 bolus study alone [CMRO2(fit)] and from the three separate studies [CMRO2 (control)]. For the 56 regions of interest analyzed, using a fit interval of 60 s, CMRO2(fit) was 93.4 +/- 7.8% of CMRO2(control) (mean +/- SD) with a correlation coefficient of r = 0.95. CMRO2(control) ranged from 87 to 290 mumol/min/100 g. Individual simultaneous estimates of CBF, CBV, and OER were not reliable. Finally, we found that the validity of the model was limited in practice to the first minute after tracer inhalation.

Administration, Inhalation↗

Transcriptional regulation of bialaphos biosynthesis in Streptomyces hygroscopicus.

A DNA sequence (brpA) which regulates the expression of the genes of the bialaphos biosynthesis pathway (bap) in Streptomyces hygroscopicus was identified and characterized. A newly isolated nonproducing mutant (NP57) had a pleiotropic defect involving at least 6 of the 13 known bap genes; only the step 6 conversion could be detected. NP57 was more sensitive to bialaphos than its parent and had depressed levels of the demethylphosphinothricin acetyltransferase activity (step 10 in the pathway) which confers bialaphos resistance. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of extracts of this mutant showed that it lacked proteins corresponding to steps 5 and 10. NP57 lacked mRNAs for steps 5, 10, and 13. Bialaphos productivity of NP57 was restored by transformation with a plasmid containing a 5.9-kilobase DNA fragment which was adjacent to the structural gene cluster. Subcloning experiments showed that a 1.3-kilobase fragment from this primary clone restored all the defects of NP57. We conclude that brpA can activate the transcription of the bialaphos resistance gene as well as at least six other bap structural genes.

Cloning, Molecular↗

New method of serotyping Escherichia coli: mathematical development.

A mathematical analysis of serological data has provided the basis for a new serotyping routine. This paper describes the process whereby the results of agglutination reactions between the standard O antigens of Escherichia coli and rabbit antisera raised against them were used to produce a much simpler, faster, and cheaper method of serotyping. This new method for serotyping E. coli requires on average only one-fifth of the serum used in the previous method and requires less than half the laboratory time. By using this method, an efficient serotyping routine can be established for any set of comparable data regardless of the bacterial group.

Agglutination Tests↗

New method of serotyping Escherichia coli: implementation and verification.

This paper describes the implementation and verification of a new method of serotyping Escherichia coli based on a mathematical analysis of the results of agglutination reactions between standard O antigens of E. coli and rabbit antisera raised against them. Details of the new method, which uses on average one-fifth of the serum used for the old method and is now in routine use in New Zealand, are given.

Agglutination Tests↗

Hypernatraemia due to a reset osmostat for vasopressin release and thirst, complicated by nephrogenic diabetes insipidus.

We describe a patient with chronic hypernatraemia (plasma sodium 148-155 mmol/l) and partial nephrogenic diabetes insipidus who had received prolonged lithium treatment. Despite stopping the drug for one year the abnormalities remained. Infusion of hypertonic saline (NaCl 855 mmol/l) allowed the characterization of osmoregulation of thirst and vasopressin secretion. Linear regression analysis of plasma vasopressin and osmolality defined the function, pAVP = 0.27 (pOsm - 301), and analysis of thirst measured by a visual analogue scale and plasma osmolality, the function, thirst = 0.16 (pOsm - 302) where pAVP and pOsm represent plasma arginine vasopressin and osmolality respectively. The slopes of the regression lines which describe the sensitivity of the osmoreceptors were within the normal range, but both abscissal intercepts, which define the thresholds for vasopressin release and thirst, were markedly elevated in comparison to normal (upper limit less than 290 mOsm/kg). Other investigations of electrolytes, anterior pituitary function and high definition computed tomographic scanning of hypothalamo-pituitary region were all normal. We conclude that this patient's chronic hypernatraemia was due to resetting of the osmostats for both vasopressin release and thirst, a rarely described mechanism to account for hypernatraemia. Although it is probable that the partial nephrogenic diabetes insipidus was related to prolonged lithium therapy, the cause of the reset osmostats remains unclear.

Aged↗

Acute suppression of plasma vasopressin and thirst after drinking in hypernatremic humans.

Drinking rapidly abolishes thirst and vasopressin secretion in dehydrated humans before major changes in plasma osmolality are observed. We studied the effects of drinking on plasma vasopressin and thirst in seven healthy volunteers rendered hypernatremic by the infusion of hypertonic (855 mmol/l) sodium chloride solution. Thirst was measured on a visual analogue scale (0-10 cm). Infusion of hypertonic saline caused linear increases in plasma osmolality (289 +/- 1 to 306 +/- 1 mosmol/kg, mean +/- SE, P less than 0.001), plasma vasopressin (0.6 +/- 0.2 to 6.4 +/- 1.9 pmol/l, P less than 0.001), and thirst (1.4 +/- 0.4 to 7.4 +/- 0.5 cm, P less than 0.001). Water was allowed 15 min after cessation of the infusion, and within 5 min of drinking both plasma vasopressin and thirst were significantly lower than postinfusion. After 20 min of drinking, plasma vasopressin had fallen from 6.5 +/- 0.9 to 1.3 +/- 0.3 pmol/l (P less than 0.001) and thirst from 7.7 +/- 0.5 to 1.0 +/- 0.2 cm (P less than 0.001) despite no significant change in plasma osmolality (306 +/- 0.9 to 304 +/- 0.8 mosmol/kg, P = 0.17), and the drinking of 1,200 +/- 60 ml of water, over 85% of the mean cumulative water intake in the 30-min drinking period. Control studies in the same subjects showed comparable rises in plasma vasopressin, plasma osmolality, and thirst during hypertonic saline infusion but no fall in any of these parameters during an equivalent 30-min period after the infusions, during which water was withheld.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thirst in diabetes insipidus: clinical relevance of quantitative assessment.

Patients with cranial diabetes insipidus are unable to concentrate urine, and depend on thirst and water intake to prevent hypertonic dehydration. Using a visual analogue scale (0-10 cm) we studied osmotically stimulated thirst induced by hypertonic saline infusion in 15 patients with diabetes insipidus and 15 healthy controls. Plasma osmolality in the patients rose from 292 +/- 1 to 316 +/- 1 mOsm/kg (p less than 0.001), and 13 patients showed a progressive rise in thirst ratings (1.4 +/- 0.4 to 8.1 +/- 0.3 cm, p less than 0.001) with abolition of thirst by drinking, in a similar fashion to controls. Water intake following infusion was greater in patients than controls (p less than 0.001). Linear regression analysis of thirst and plasma osmolality showed no difference in the osmotic threshold for thirst onset, or the sensitivity of thirst osmoreceptors, between 13 of the patients and the control group. One patient was shown to be hypodipsic and compulsive water drinking was demonstrated in another: abnormal thirst perception caused abnormalities of salt and water balance in these two patients. Most patients with cranial diabetes insipidus have normal thirst mechanisms, though clinically significant hypodipsia or hyperdipsia may co-exist with vasopressin deficiency.

Adult↗

Estimation of left ventricular mass in normal and infarcted canine hearts using thallium-201 SPECT.

A new automated edge detection program has been developed to estimate left ventricular mass from single photon emission computed tomographic (SPECT) 201Tl images and 14 dogs were studied. Six of the 14 dogs underwent imaging before and 5 hr after coronary artery occlusion with a closed-chest technique. True left ventricular mass was determined at time of killing within 1 hr of the last 201Tl study. Left ventricular mass determined by tomography correlated well with autopsy left ventricular mass (r = 0.94; p less than 0.001, s.e.e. = 5.9 g) over a range of 62-156 g. The intraobserver variation between repeated measurements of the same SPECT study yielded an r = 0.99; p less than 0.0001; s.e.e. = 2.3 g. The reproducibility of the mass determination was assessed in four animals with two studies performed 10-14 days apart. The estimate of left ventricular mass from the two studies were highly correlated (r = 0.98; p less than 0.001) with a mean absolute difference of 4 g (3.3%). In the six dogs with a control and postinfarct study the mean total left ventricular mass by 201Tl tomography varied by less than 3.8% (r = 0.89; p less than 0.001). In conclusion, tomographic imaging with 201Tl can define left ventricular mass accurately and reproducibly in the dog model. The ability of this 201Tl tomographic left ventricular mass program to measure both normal and infarcted tissue accurately suggests the possibility of documenting interventions designed to alter left ventricular mass and of sizing acute infarcts and assessing interventions that may alter acute infarct size.

Animals↗

How well do physicians recognize melanoma and other problem lesions?

The alarming increase in the incidence of cutaneous malignant melanoma in the United States emphasizes the importance of its early detection and treatment. Early detection requires accurate clinical recognition of both malignant and precancerous skin lesions (dysplastic nevi). This study presents data on dermatologists' and nondermatologists' ability to diagnose skin lesions. A total of 105 nondermatologist physicians, from first-year residents to practicing physicians, and forty-eight dermatologists were asked to identify color slides or photographs of eleven cutaneous lesions, including malignant melanomas, dysplastic nevi, and innocuous lesions such as seborrheic keratoses and common moles. Diagnosis of cutaneous lesions was generally inaccurate among nondermatologists. Only 38% correctly identified four or more of the six melanomas as melanoma of any type, and 58% were unable to diagnose dysplastic nevi. Only 17% categorized their relevant training as excellent or good. Improved training in the diagnosis of skin lesions for practicing physicians and house staff is required if mortality from malignant melanoma is to be decreased in the United States.

Adult↗

The osmotic thresholds for thirst and vasopressin release are similar in healthy man.

The relationship between thirst perception and plasma osmolality was studied during hypertonic and physiological saline infusion in ten healthy volunteers. Thirst perception was quantified using a linear visual analogue scale which volunteers marked at intervals during the infusion periods. Infusion of hypertonic saline caused a steady rise in plasma osmolality together with a progressive linear increase in thirst perception and also plasma arginine vasopressin. No significant changes in thirst, plasma osmolality or plasma arginine vasopressin occurred during infusion of physiological saline. Linear regression analysis of the results defined the functions. Thirst (cm) = 0.3 (plasma osmolality-281) (r = +0.92, P less than 0.001) and plasma arginine vasopressin (pmol/l) = 0.4 (plasma osmolality-285) (r = +0.96, P less than 0.001). The osmolar threshold for thirst onset thus defined (281 mosmol/kg) was much lower than in previous studies and similar to the theoretical osmolar threshold for vasopressin release (285 mosmol/kg). We conclude that thirst perception rises in a progressive fashion throughout a wide range of plasma osmolality and that the osmolar threshold for thirst onset is similar to the theoretical osmolar threshold for vasopressin release. The results are compatible with the concept of either a single osmoreceptor subserving both thirst and vasopressin release, or two osmoreceptors sharing similar functional characteristics.

Adult↗

Dependence of the coincidence aperture function of narrow BGO crystals on crystal shape and light encoding schemes.

Although the spatial resolution in positron emission tomography is improved by reducing the crystal width, the resolution becomes increasingly non-uniform towards the edges of the field of view. This is mainly due to penetration of the gamma rays through one or more crystals before detection and the inability of current systems to resolve the depth of interaction within the crystal. This paper compares crystals with straight and pointed tips with and without tungsten septa to determine the effects of pointed tips and septa on spatial resolution and efficiency. Monte Carlo calculations are compared with extensive experimental results obtained from 16 coincidence lines between two four-BGO crystal/dual PMT detector assemblies. The spectral efficiencies for the different combinations are compared. A modest improvement in signal-to-noise ratio at the maximum resolvable frequency is demonstrated when using tungsten septa and pointed crystals. The effects of the optical coding scheme used are discussed and it is shown that most coding schemes cause diminishment of spatial resolution even at the centre of the field of view, resulting from Compton scattering to adjacent crystals.

Electrons↗