Biomedical subjects
E Cameron
Publications and source records attributed to E Cameron.
Neutrophil sequestration in lungs removed at surgery. The effect of microscopic emphysema.
Neutrophils within the lungs are considered to play an important role in the pathogenesis of pulmonary emphysema. We have studied the intravascular distribution of reinjected autologous 111In-labeled neutrophils in lung specimens resected 10 min after reinjection from 10 patients undergoing surgery for peripheral bronchogenic tumors. An excess of neutrophils relative to that expected for the 99mTc-labeled erythrocyte blood volume was confirmed in all specimens (range, 3- to 136-fold). In seven specimens which were completely examined, this excess displayed a skewed distribution, with a median neutrophil sequestration of 20-fold excess, and correlated with local blood volume (r = -0.51; p < 0.001). There was also a significant correlation between alveolar wall surface area per unit volume of lung (AWUV) and neutrophil excess, when randomly selected tissue blocks from each specimen were analyzed (r = 0.34, n = 51, p = 0.012). This same trend was demonstrated when whole specimen median values were considered (r = 0.64, n = 7, p = 0.07). Thus in areas of the lungs with lower AWUV values (increasing microscopic emphysema), fewer neutrophils were present. These studies add further support to the view that emphysema per se is not associated with an increased sequestration of pulmonary intravascular neutrophils.
Conditional expression and oncogenicity of c-myc linked to a CD2 gene dominant control region.
Over-expression of the c-myc gene is widely implicated in the genesis of lymphoid neoplasia, including tumours of the T-cell lineage. To study the effects of deregulated c-myc expression on T-cell development and oncogenesis, we sought to generate a transgenic mouse model in which c-myc expression was targeted specifically to the T-cell lineage. A plasmid construct containing a dominant control region (DCR) from the human CD2 locus linked 5' to the human c-myc gene was used to generate 2 lines of transgenic mice. Both strains developed thymic lymphoma at low frequency, but thymic development and peripheral T-cell numbers were otherwise apparently normal. Low tumour penetrance was consistent with the observed lack of stable CD2-myc transgene mRNA in tissues of healthy transgenic mice. In contrast, transgene RNA was detected in all malignant tumours as well as in early lymphomatous lesions. RNase protection analyses confirmed these findings and showed that the PI human c-myc promoter was active in all neoplastic tissues but not in the thymus or other tissues of healthy transgenic mice. Despite the low spontaneous tumour incidence, the presence of the transgene markedly and uniformly accelerated the onset of tumours after neonatal infection with Moloney murine leukaemia virus. All tumours were rearranged for T-cell receptor beta-chain genes and were of T-cell origin from their surface phenotype (Thy-1+, CD3+, CD4+/-, CD8+, sIg-). Virus-accelerated tumours contained clonal integrations of Moloney murine leukaemia virus, suggesting that proviral insertional mutagenesis may have played a role in tumour development. Analysis of several candidate myc-cooperating genes failed to reveal any rearrangements apart from a low frequency involving proviral insertion at the pim-1 locus. The CD2-myc mouse should therefore be a valuable system in screening for novel myc-collaborating genes involved in T-cell lymphoma.
Low dose preoperative radiotherapy for carcinoma of the oesophagus: results of a randomized clinical trial.
One-hundred-and-seventy-six patients with potentially operable squamous cell carcinoma or adenocarcinoma of the middle or lower thirds of the oesophagus were randomly assigned to preoperative radiotherapy or surgery alone. Patients assigned to the radiotherapy arm received 20 Gy in 10 treatments over 2 weeks, using parallel opposed 4 MV beams. The preoperative radiotherapy was not associated with any significant acute morbidity or any increase in operative complications. The median survival of the overall group of 176 patients was 8 months, and the 5-year survival was 13%. There was no significant difference in the survival of the 90 patients who received preoperative radiotherapy and the 86 who were managed by surgery alone. Proportional hazards analysis identified lymph node involvement, high tumour grade and male sex as significant adverse prognostic features, but the treatment option assigned had no prognostic significance. It was concluded that low dose preoperative radiotherapy offered no advantage over surgery alone.
The minimum effective dose of lignocaine to prevent injection pain due to propofol in children.
In a single-blind study of 100 children aged 1 to 10 years, the minimum effective dose of lignocaine required to prevent injection pain due to propofol was 0.2 mg.kg-1 when veins on the dorsum of the hand were used. This is more than twice the adult value. We concluded that injection pain should not limit the use of propofol in children if an adequate amount of lignocaine is mixed immediately prior to injection.
Renal transplantation at the University of Pennsylvania Medical Center: an update of results in the cyclosporine era.
This chapter presents a summary of living-related, living-unrelated, and cadaver renal transplantation performed at the University of Pennsylvania Medical Center between January 1984 and October 1992. Over the past 9 years, 895 patients (557 males, 338 females, mean age 42 yrs) received 942 renal transplants; 599 patients received kidneys from cadaver donors (n = 627) and 296 patients received kidneys (n = 315) from living donors of all types. During this period, 151 patients were retransplanted, sometimes more than once (159 total retransplants, 124 secondary grafts, and 35 third or more transplants). An analysis of patient ant graft survival rates (calculated by actuarial methods) for different categories of transplant recipients was performed. Black recipients, as a racial subcategory, had the poorest graft outcome, especially when followed over the long term. Graft survival rates for Black recipients who were retransplanted with cadaver grafts were even worse and were noted to be similar to the diabetic population that received cadaver retransplants (66% vs 62% at 1 yr and 32% vs 25% at 5 yrs). Diabetic recipients of living-donor transplants had excellent graft survival results, similar to nondiabetic, living-donor recipients (patient survival rates 98% and 92% vs 97% and 92% at 1 and 5 yrs; graft survival rates 92% and 82% vs 92% and 82% at 1 and 5 yrs). HLA-identical recipients of first cadaver grafts demonstrated the best outcome in the entire cadaver series (graft survival rates 91% and 83% at 1 and 5 yrs, respectively). HLA-identical recipients of second or more cadaver grafts had poorer results than expected (50% graft survival at 1 yr) despite a 100% patient survival rate. HLA-identical recipients of living-related grafts had the best graft survival rates (96% at 1 yr and 94% at 5 yrs) and superior graft survival rates for retransplanted grafts as well (100% at 1 and 5 yrs). We conclude that in the last decade, patient and graft survival rates for cadaveric and living-donor renal transplants have improved dramatically relative to the results obtained in the pre-CsA era. Long-term graft survival in Black recipients remains lower than in other races, suggesting the need to analyze other factors to explain poorer graft survival in this recipient population. Results in diabetic recipients continue to be excellent at our center, encouraging the continuation of our aggressive approach to try to transplant diabetics as early as possible, particularly when a living donor is available.
Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump.
To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time.
Innovation vs. quality control: an 'unpublishable' clinical trial of supplemental ascorbate in incurable cancer.
A computerized data bank was created recording the details of all cancer patients attending three district general hospitals in West Central Scotland over a 4.5 year period 1978-1982. At the conclusion of the trial, the records of 2804 individual patients were available for study, of whom 1826 had reached an incurable stage. 294 of these incurable cancer patients had received supplemental ascorbate at some stage in their illness, whereas 1532 had not, and served as controls. Analysis showed that the ascorbate-supplemented patients had a median overall survival time (343 days) almost double that of the controls (180 days). Our difficulties in having this simple, but important, observation published are briefly recounted in the introduction.
Protocol for the use of vitamin C in the treatment of cancer.
A protocol for the use of vitamin C in the treatment of cancer, developed over a number of years in Vale of Leven Hospital, Scotland, is presented. Clinical experience has shown this protocol to be both safe and efficient. It need not be followed 'to the letter', but provides general guidance to physicians unfamiliar with this therapeutic approach. It recommends that all cancer patients treated in this fashion be given an initial course of intravenous ascorbate followed by a maintenance oral dose to be continued indefinitely thereafter. The importance of continuous as opposed to intermittent administration is emphasized.
Reticulum cell sarcoma: two complete 'spontaneous' regressions, in response to high-dose ascorbic acid therapy. A report on subsequent progress.
In 1975, we reported the remarkable case of a 42-year-old man with histologically proven widely disseminated reticulum cell sarcoma who, in a remarkably short time, appeared to enjoy not one, but two, complete spontaneous regressions of his fatal illness. Both these regressions coincided exactly in time with intravenous high-dose ascorbate administration, and it seemed reasonable to conclude that this unconventional therapy must have been responsible for his excellent responses. For those interested in spontaneous regressions of cancer and the possible mechanisms, we now report his subsequent progress some 17 years later.
Mitral prosthetic replacement in small left atria.
A modified transseptal approach for exposure of the difficult mitral valve is described. This allows the surgeon to visualize the valve, especially during prosthetic replacement, in the presence of a small, friable, or noncompliant left atrium.
Paediatric acquired immunodeficiency syndrome (PAIDS) in Trinidad and Tobago.
The first twenty-one cases of Paediatric Acquired Immunodeficiency Syndrome (PAIDS) in Trinidad and Tobago were studied. An overwhelming majority of patients were of African descent. Most of the children presented within the first year of life, the average time between presentation and death was 4 1/2 months, and the majority presented with either diarrhoea or pneumonia or failure to thrive, common conditions in the West Indies. Fever lasting longer than two weeks as well as hepatomegaly were clues which led to a definitive diagnosis.
Therapeutic monitoring of cyclosporine: impact of a change in standards on 125I-monoclonal RIA performance in comparison with liquid chromatography.
This study examines the measurement of cyclosporine (CsA) by 125I-monoclonal RIA, and describes the impact of the recent change in the standard curve provided. CsA concentrations in serum and whole-blood control samples measured by 125I-RIA were initially 8-18% higher than those by HPLC. During the first two months of 1989, a significant and sustained deviation in the 125I-RIA produced results that exceeded the HPLC results by 21-28% (P less than 0.001). Introduction of the new standard curve in March 1989 returned the concentration of the whole-blood controls to the previous range (11-12% above HPLC, P less than 0.001). Measurement of clinical samples from heart, liver, and bone-marrow graft recipients by 125I-RIA by both old and new kit standards produced a close linear correlation (y = 0.89 x - 19.02; r = 0.99; n = 75, range = 40-850 micrograms/L), with use of the new standards yielding results 82 (SD 8)% of those with the preceding assay. However, even with the new standard curve, CsA concentrations by 125I-RIA in the clinical samples exceeded those by HPLC by a factor of 1.37 (SD 0.18) to 1.52 (SD 0.19). Segregation for transplant type did not affect the RIA/HPLC ratio. The results suggest cross-reactivity of the 125I-RIA with material present in vivo.
A good way forward.
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