Biomedical subjects
E A Harris
Publications and source records attributed to E A Harris.
Cutaneous oesophagostomiasis in man.
A case is presented of infection by Oesophagostomum, a nematode worm, producing a cutaneous nodule in man. Of the 70 individual cases reported in man it is believed that this is the first in which the worm has produced a lesion outside the gastro-intestinal tract and without evidence of bowel infection. This finding suggests either that the worm is able to achieve direct skin penetration or that it can be disseminated from the bowel via the bloodstream or the lymphatics. The pathology caused by Oesophagostomum and the possible modes of infection are discussed in relation to studies in animals, particularly simians and cattle.
The Cartwright report and consent.
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Design of retrovirus vectors for transfer and expression of the human beta-globin gene.
Regulated expression of the human beta-globin gene has been demonstrated in cultured murine erythroleukemia cells and in mice after retrovirus-mediated gene transfer. However, the low titer of recombinant viruses described to date results in relatively inefficient gene transfer, which limits their usefulness for animal studies and for potential gene therapy in humans for diseases involving defective beta-globin genes. We found regions that interfered with virus production within intron 2 of the beta-globin gene and on both sides of the gene. The flanking regions could be removed, but intron 2 was required for beta-globin expression. Inclusion of beta-globin introns necessitates an antisense orientation of the gene within the retrovirus vector. However, we found no effect of the antisense beta-globin transcription on virus production. A region downstream of the beta-globin gene that stimulates expression of the gene in transgenic mice was included in the viruses without detrimental effects on virus titer. Virus titers of over 10(6) CFU/ml were obtained with the final vector design, which retained the ability to direct regulated expression of human beta-globin in murine erythroleukemia cells. The vector also allowed transfer and expression of the human beta-globin gene in hematopoietic cells (CFU-S cells) in mice.
Correction of inert gas washin or washout for gas solubility in blood.
We show that when an inert gas is washed into the lungs its retention in the blood during any one breath is approximately proportional to its solubility. This relationship makes possible the correction of washin or washout data for blood uptake or release, provided that two gases of different solubility are used simultaneously. The method automatically allows for the characteristics of an individual washin or washout and for the occurrence of recirculation within a fairly short washin or washout period. It has been tested in models with nonuniform ventilation and perfusion and closely approximates the behavior of a truly insoluble gas. In the derived ventilation distribution, gas solubility appears as ventilation to units of low turnover. In the case of N2 this effect is small but causes appreciable overestimation of lung volume. The recovered dead space and main alveolar distribution are insignificantly affected.
The alveolar carbon monoxide uptake fraction: a simple, alternative measure of carbon monoxide transfer.
The measurement and interpretation of "diffusing capacity" by either single-breath or steady-state methods are complicated by both technical and conceptual difficulties. The CO uptake fraction is less complex but, as originally described, it is unacceptably sensitive to dead-space ventilation. A modification (the "alveolar CO uptake fraction", UA) largely removes this factor. We have measured UA in thirteen healthy subjects and 100 patients with a variety of pulmonary disorders. It is reproducible and appears sensitive to clinical abnormality. Its technical and interpretative simplicity suggest its use as an alternative to other measures of CO transfer.
Measurement of dead-space volume.
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Human alveolar gas-mixing efficiency for gases of differing diffusivity in health and airflow limitation.
1. Incomplete mixing of alveolar gas may be expressed as an equivalent alveolar dead space serving a remaining alveolar space in which mixing is regarded as complete. Calculation of this dead space during multiple-breath, inert gas wash-in or wash-out leads to an estimate of 'multiple-breath alveolar mixing efficiency' (MBME). 2. We measured MBME in 25 healthy subjects and six patients with chronic airflow limitation (CAL), and in three asthmatic patients before and after bronchial provocation with histamine aerosol, from successive breaths during open-circuit, multiple-breath wash-in of a mixture containing helium (He) and sulphur hexafluoride (SF6). The simultaneous use of a light and a heavy gas helps to identify diffusive mechanisms. 3. MBME fell almost linearly with log Z, the proportion of total wash-in remaining uncompleted. For a given Z, MBME was always lower for SF6 than for He in the same subject. In health the lowest MBME (52.2%) was seen for SF6 in a man aged 21 years. The same wash-in yielded a ventilation distribution with an extreme range of specific ventilation of less than 1 decade. MBME of this order is thus consistent with estimates of ventilation distribution in health. 4. Patients with CAL showed a big increase in the volume of the conducting airways or 'series dead space' (VDS) for both gases, and VDS was always bigger for SF6 than for He. This very large VDS appears to be the main reason for wash-in delay in these patients, followed by impaired diffusive mixing in the peripheral air spaces. Ventilation maldistribution may play little part in the mixing defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Gastro-intestinal helminths of donkeys in Burkina Faso.
Thirty adult donkeys from Burkina Faso were necropsied and their gastro-intestinal worm burdens counted and determined. The strongylids were the most abundant species with a prevalence of 100% for Strongylus vulgaris. Four species of Strongylus, two of Triodontophorus and six of the Cyathostominae were recovered. All of the animals were also infested with habronematid nematodes, but oxyurid and ascaridid nematodes were found in low numbers. In addition to the nematodes, the paramphistomid trematode Gastrodiscus aegyptiacus and the anoplocephalid cestode Anoplocephala magna occurred in varying numbers. Faecal egg-counts from 131 donkeys ranged between 100 and 9,200 for strongylid eggs.
Recovery of ventilation distributions by gas wash-out of a mechanical pump.
A method for deriving virtually continuous distributions of ventilation in the lungs from multiple-breath wash-out of inert, insoluble gases has been tested using a mechanical pump in which two parallel compartments, simulating lung regions, could be differentially ventilated to any desired, and known, extent. With more than moderate non-uniformity, bimodal distributions were always recovered from wash-out data, and with high reproducibility. In a substantial proportion of wash-out experiments ventilation was recovered in regions of very low and very high turnover in addition to the expected modes. These spurious modes may be abolished by various computational devices, none entirely satisfactory. Simultaneous wash-out and wash-in of two or three gases of similar diffusivity give essentially identical solutions. When the pump is operated with the two cylinders out of phase, emptying patterns derived from gas wash-out correspond quite well with those expected from the pump setting. These results help to identify and clarify some of the errors which affect physiological wash-out studies.
Second-look laparotomy in ovarian cancer: evaluation of pathologic variables.
From 1977 through 1982, 135 patients with ovarian cancer, having a mean age of 53.7 years and no clinical evidence of disease after approximately 1 year of treatment, underwent a "second-look" laparotomy. Of the 135 patients, 58 (43%) had histologic confirmation of disease at the second-look procedure. Persistent disease was positively correlated with the original stage and negatively correlated with the extent of the original reductive surgery. The original histologic grade or cellular subtype did not significantly influence the findings at reexploration. Patient survival, as judged by percentage of patients alive 3 years after the second-look laparotomy, was dependent on the following surgical/pathologic parameters: tumor size at reexploration, peritoneal cytologic features, residual tumor after reexploration, and histologic grade.
Sulphonylurea therapy doubles B-cell response to glucose in type 2 diabetic patients.
The effect of sulphonylurea therapy for 3 weeks on glucose-stimulated insulin secretion and insulin resistance was studied in Type 2 diabetic patients. The fasting plasma insulin and C-peptide concentrations on diet alone were compared with each subject's fasting concentrations on sulphonylurea treatment at a lower fasting plasma glucose and at the original diet-alone glycaemic level obtained by the hyperglycaemic clamp technique. At this isoglycaemic level (mean 11 mmol/l), plasma insulin levels increased from 6.9 mU/l on diet alone to 12.1 mU/l on sulphonylurea treatment (p less than 0.01). The subjects were also studied by the hyperglycaemic clamp technique at mean glycaemic levels of 13 mmol/l before and after sulphonylurea treatment; the incremental insulin response was similarly enhanced from 7.6 +/- 3.5 to 13.7 +/- 6.9 mU/l (p less than 0.02) respectively. Sulphonylureas appear to reduce glycaemia by enhancing B-cell function two-fold. In the patients studied this was from approximately 21% to 37% of a normal response. Insulin resistance assessed by the same hyperglycaemic clamps as endogenous plasma insulin concentrations divided by glucose infusion rates was unchanged by sulphonylurea therapy (mean 4.37 compared to 4.40 mU X 1(-1) X mg-1 X kg X min on diet alone).
Taylor laminar dispersion in human airways.
Healthy subjects took breaths of approximately 200 ml or approximately 600 ml, from functional residual capacity, of a mixture of He, Ar, SF6 (approximately 7% each), 21% O2, balance N2. Without breath-holding they expired steadily to residual volume. Concentrations of He, Ar and SF6 were measured continuously near the lips and expressed in each case as a fraction of the inspired concentration. After the bigger breaths the order in phase 2 was SF6 greater than Ar greater than He and at the end of phase 3 He greater than SF6, in agreement with other workers. After small breaths, and especially with low inspiratory flows, the early part of phase 2 showed, in a highly significant number of experiments, the order He greater than Ar greater than SF6; in these cases phase 3 still showed He greater than SF6. These results are fully consistent with the occurrence, during inspiration, of Taylor laminar dispersion (TLD) in airways situated within about 200 ml from the lips. They show that the end of phase 3 cannot be used to infer the presence or absence of TLD, and that correction for the response of the mass spectrometer is of crucial importance in the interpretation of phase 2.
First record of Trichostrongylus axei infection of man in the Caribbean region.
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Data acquisition from a multiplex, quadrupole mass spectrometer.
Although various methods have been used to correct the output of a respiratory mass spectrometer for the delay and rise time in its response, thereby reducing the error in measured gas concentrations, there are additional considerations in the case of a multiplex mass spectrometer. The measured signal from the detector is a series of discrete samples of the concentration of several different gases rather than a continuous monitor of a single gas concentration as generated by other types of mass spectrometer. If the time constant of the mass spectrometer is of the same order as the interval between samples of a gas in the multiplex mode, correction techniques based on continuous-time analysis would not be as valid as those based on discrete-time analysis. Such correction techniques were compared to the use of a simple time shift. For multibreath gas washout analysis with simulated worst-case 'square wave breathing' it was found that, because of the complex nature of the response of the mass spectrometer, a simple time shift provided a reduction in error nearly equal to that of an additional first order response correction, and that such further corrections may be unnecessary or even invalid under some circumstances.
Hospital admissions for asthma.
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Response characteristics of a mass spectrometer.
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