Biomedical subjects
Publications and source records attributed to R Gray.
Massive hemoptysis, a rare complication of pulmonary actinomycosis, is generally treated surgically. We describe a patient with massive hemoptysis due to pulmonary actinomycosis who was treated successfully by means of selective bronchial artery embolization. The role of BAE is discussed.
The main objective of preoperative imaging studies is to define as accurately as possible the number, size, location, and relationship of tumor masses in the liver to pertinent portal and hepatic venous vasculature. Computerized tomographic portography images hepatic veins and segmental portal vein branches and identifies the anatomical location of tumor nodules with excellent sensitivity and a low false-positive rate. The intraoperative correlation of computerized tomographic portography on 30 patients in the last 20 months at this institution shows a sensitivity of 88 per cent with a low rate of false-positivity. The ability to detect metastatic lesions in the liver by computerized tomographic portography diminishes when the lesions are noted to be less than 1 cm. The authors conclude that the preoperative interpretation of the computerized tomographic portogram provides valuable information not previously available to the surgeon operating on the liver.
Cocaine abuse is now known to result in a wide variety of medical illnesses. We report our experience with one patient who had abdominal pain and was found to have near-total infarction of all abdominal viscera. The cause of this and other medical complications of cocaine abuse (i.e., extreme vasoconstriction) is discussed in detail. Physicians should maintain a high index of suspicion when dealing with complaints of abdominal pain by cocaine users.
We evaluated a new analyzer that measures lactate in undiluted whole blood by direct (or undiluted) amperometry [Nova Stat Profile 7 Analyzer (SP7); Nova Biomedical, Waltham, MA] by comparing it with two other analyzers, one for measuring lactate in whole blood by indirect (or diluted) amperometry [Model 2300; Yellow Springs Instrument Co. (YSI), Yellow Springs, OH] and another for measuring lactate in plasma by enzymatic colorimetry (aca; Du Pont Co., Wilmington, DE). All between-method comparisons of the three methods showed that the results for plasma were comparable (Sy/x = 0.24-0.33 mmol/L). Within-method comparisons by the YSI differed substantially between plasma and whole blood (Sy/x = 0.48 mmol/L), but within-method comparisons by the SP7 produced better agreement between plasma and whole blood (Sy/x = 0.18 mmol/L). The difference between whole blood and plasma by YSI is related to hematocrit, with the greatest differences noted for samples with the highest hematocrit. Serum lactate measured by SP7 had between-day imprecision (CV) ranging from 12% at 0.5 mmol/L to 4.2% at 3.7 mmol/L, showed a linear standard curve to at least 11.5 mmol/L, and was independent of hematocrit. There was a mean bias of approximately 0.4 mmol/L for results in the reference range for both plasma and whole blood by SP7 compared with plasma results by either aca or YSI.
The Medical Research Council's AML 10 Children Trial commenced in 1988. It is a multicentre collaborative study based on 4 courses of intensive chemotherapy with additional allogeneic bone marrow transplantation for children with a matched sibling donor. The remaining children are randomised either to an autologous transplant using unpurged marrow or stopping therapy. To date 156 eligible patients have been entered with a CR rate of 91%. 56% of children are still alive 2 years after trial entry and 57% are in CR 3 years after achieving CR. The treatment regimen is intensive but mortality and morbidity are acceptable. The study will need to accrue patients for a further 2 to 3 years in the hope of defining the role of allogeneic and autologous marrow transplantation.
An ancillary study (INT 0076) to the Intergroup clinical trial of node-negative breast cancer patients (INT 0011) was performed to retrospectively evaluate DNA flow cytometry measurements of ploidy (DNA content) and proliferative capacity (S-phase fraction) for their ability to predict time to recurrence. Of the 915 patients eligible for the clinical trial, 788 were registered for the ancillary flow cytometry study (INT 0076). Four hundred and three of these patients [estrogen receptor (ER)-positive, tumor size less than 3 cm] had been registered to the observation arm of the clinical trial and 385 (ER-negative and/or tumor size greater than or equal to 3 cm) had been randomly assigned to adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and prednisone for six cycles) or to observation. Paraffin blocks from 95% (748 of 788) of these patients were obtained, 712 of which had sufficient cancer tissue to be evaluable for the flow cytometric assay. DNA ploidy status (DNA diploid vs DNA aneuploid) was evaluable for 565 (79%) specimens, 64% of which were aneuploid. Proliferative capacity was estimated by the percentage of cells having an S-phase DNA content, using a trapezoidal modeling algorithm(s) as previously described. The median S-phase value for the entire group (both registered and randomly assigned patients) was 6.97%, which defined the cutoff for interpretation of high or low S-phase values. With a median follow-up time of 4.55 years, S-phase fraction, but not ploidy status, is a significant predictor for time to recurrence in both the randomly assigned and the untreated population (observed registered group and observed randomly assigned group).(ABSTRACT TRUNCATED AT 250 WORDS)
Four thousand eighty inbred rats were maintained from weaning on various different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA). The principal aim was to characterize the dose-response relationship for the effects of these agents on esophageal cancer (NDEA) or on various types of liver cancer (NDEA and NDMA), although NDEA also caused a few tumors of the nasopharynx and NDMA also caused a few tumors of the lung. The numbers of tumors of mesenchymal and Kupffer cells in the liver were too few to allow easy characterization of the dose-response relationships, and although NDMA induced large numbers of bile duct neoplasms, NDEA did not. Thus, the four principal dose-response relationships studied were of NDEA on esophageal or liver cells and of NDMA on bile duct or liver cells. At doses sufficiently high for the median time to death from the disease of interest to be estimated, relationships were observed of the general form (Dose rate) x (median)n = constant where n was about 2.3 for the first three relationships and about 1 for the last one (NDMA on liver cell tumors). By contrast, at doses sufficiently low for longevity to be nearly normal (median survival about 2.5 years), there remained no material dependence on the dose rate of the age distribution of the induced neoplasms. At these low dose rates, the number of liver (but not of esophageal) neoplasms induced by treatment was simply proportional to the dose rate. This finding is not surprising, since the background incidence of liver (but not of esophageal) neoplasms was appreciable. The linear relationship observed at low dose rates (below 1 ppm) suggests that under these experimental conditions, among rats allowed to liver their natural life span, a dose of 1 ppm of NDEA or NDMA in the drinking water will cause about 25% to develop a liver neoplasm, a dose of 0.1 ppm will cause about 2.5% to do so, and a dose of 0.01 ppm will cause about 0.25% to do so, etc., with no indication of any "threshold." (At these low dose rates, the incidence of liver neoplasms appears likely to exceed greatly that of esophageal neoplasms.) In addition, even quite low dose rates of the test agents caused a variety of nonneoplastic liver abnormalities (e.g., hyperplastic nodules, or shrinkage of hepatocytes) at a frequency roughly proportional to the dose rate.
A Weibull analysis is presented of the dose and time relationships for the effects on 4080 inbred rats of chronic ingestion in the drinking water of 16 different doses of N-nitrosodimethylamine (NDMA) or N-nitrosodiethylamine (NDEA). The sites chiefly affected were the liver (by both agents) and the esophagus (by NDEA only). Since the experiment continued on into extreme old age, effects became measurable at doses of only 0.01 to 0.02 mg/kg/day, which is an order of magnitude lower than previously achieved. (After only 2 years of treatment, however, the TD50 doses needed to halve the proportion of tumorless survivors would have been about 0.06 mg/kg/day of NDEA, or about 0.12 mg/kg/day of NDMA.) The general pattern of response was that the natural logarithm of the probability of remaining tumorless was given by the product of two terms, the first (the "Weibull b value") depending on the dose rate but not on the duration of exposure and the second depending not on dose at all but only on duration. For all types of tumor the dependence on duration was fairly similar (and for each the second term was taken to be -t7, where t = years of treatment), but for different types of tumor the dependence on dose rate was quite different. For esophageal tumors, the "Weibull b value" was approximately proportional to the cube of the dose rate of NDEA (males 21 d3, females 11 d3, where d = dose rate in mg/kg adult body weight/day), and the background incidence was unmeasurably low. For liver tumors induced by NDEA, the b value was approximately proportional to the fourth power of dose rate + 0.04 mg/kg/day [males, 19 (d + 0.04)4; females, 32 (d + 0.04)4], although the relationships were somewhat different for the different cell types of liver tumor. This one formula implies both approximate linearity at low doses and an approximately cubic relationship within the higher range of doses that was studied. For liver tumors induced by NDMA, the Weibull b value was approximately proportional to the sixth power of dose rate + 0.1 mg/kg/day [males, 37 (d + 0.1)6; females, 51 (d + 0.1)6], again with some variation between liver cell types, and again implying approximate linearity at low doses. These algebraic formulae should, of course, be trusted only in the range of doses where they were derived, and particularly not above it.(ABSTRACT TRUNCATED AT 400 WORDS)
In parallel with a larger experiment on 4080 rats fed 16 different concentrations of N-nitrosodiethylamine (NDEA) or N-nitrosodimethylamine (NDMA) from 6 weeks of age, a variety of smaller experiments on a total of 1040 rodents were undertaken and are the subject of the present report. Three separate subjects were addressed. Studies of 16 different concentrations of N-nitrosopyrrolidine and N-nitrosopiperidine given from age 6 weeks onwards to small groups of rats yielded dose-response relationships for the effects of N-nitrosopyrrolidine on liver tumors and for those of N-nitrosopiperidine on tumors of the liver and upper gastrointestinal tract that resembled those seen for NDMA and NDEA, respectively, except that N-nitrosopyrrolidine and N-nitrosopiperidine were less potent [the respective dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment being approximately 0.4 (males) and 0.6 (females) mg/kg adult body weight/day for each agent]. Alternatively, it was estimated that the risks to rats from lifelong exposure to 1 microgram/kg adult body weight/day of each agent might be about 0.1%, and that the risks to rats from lower doses would be proportionately less. Studies of 16 different concentrations of NDEA on small groups of female mice and female hamsters yielded the types of dose response that would be expected for upper gastrointestinal tumors, liver cell tumors, and Kupffer cell tumors in mice (no other types of liver tumor being produced, in contrast with previous reports) and for tracheal and liver cell tumors in hamsters (no clear effect on upper gastrointestinal tumors being apparent in hamsters). The dose rates needed to halve the proportion of tumorless survivors after 2 years of treatment were approximately 0.3 mg/kg adult body weight/day, i.e., 5 times that for the same agent in rats. In part, however, this may be because treatment started at an older age in these species. Studies were undertaken of the effects on esophageal and liver tumorigenesis of starting the treatment of rats with NDEA at 3 or at 20 weeks of age instead of at 6 weeks of age (as in the main experiment). Earlier treatment resulted in slightly greater dosage rates, if dosage was measured in mg/kg/day, and hence in a correspondingly more rapid yield of esophageal tumors, but the effect was not large. By contrast, an earlier start to treatment resulted, after a fixed duration of treatment, in animals having a 3-fold higher incidence rate of liver tumors, while a later start resulted in a 2-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)
Tetanic stimulation of the Schaffer collateral inputs into area CA1 of the hippocampus causes N-methyl-D-aspartate (NMDA) receptor activation, an effect that contributes to the induction of long-term potentiation (LTP) in this region. The present studies demonstrate that LTP-inducing tetanic stimulation in rat hippocampal area CA1 elicited increased levels of cAMP. The elevation of cAMP was blocked by the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). Bath application of NMDA also resulted in an increase in cAMP in CA1, an effect that was blocked by both APV and removal of extracellular Ca2+. These findings suggest that activation of NMDA receptors elicits a Ca(2+)-dependent increase in cAMP, and taken together with the data from tetanic stimulation, suggest that NMDA-receptor-mediated increases in cAMP could play a role in the induction of LTP in area CA1. One role for cAMP may be to increase Ca2+ influx through voltage-gated Ca2+ channels, as it was observed that application of either 8-bromo-cAMP or NMDA increased the fractional open time of high-threshold Ca2+ channels in CA1 pyramidal cells. Our results raise the possibility that a positive-feedback loop for Ca2+ influx in area CA1 exists. In this model, NMDA receptor-mediated Ca2+ influx leads to an enhancement of further Ca2+ influx via intermediate steps of increased cAMP and subsequent increased voltage-gated Ca2+ channel activity.
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A prospective study with 4 years of follow-up involving 127 consecutive symptomatic patients (60.6% with claudication, 39.4% with critical ischemia) who underwent aortobifemoral bypass surgery is described. A new grading system for the classification of arterial outflow was applied to determine its usefulness in predicting the outcome of surgery. Preoperative angiograms were numerically scored according to the arterial outflow status at the level of main segmental involvement. Higher scores corresponded to worse outflows. Outflow scores ranged between 1 and 10 with a mean of 3.6 +/- 0.24. The main comparison was between patients with scores of less than 5 (group A, n = 80) and patients with scores of 5 or more (group B, n = 47). Better outflow was associated with higher postoperative mean increases in the ankle-brachial index (ABI) (group A, 0.35 +/- 0.03; group B, 0.17 +/- 0.04; P less than .001) and transcutaneous oximetry (PtcO2) (group A, 15.4 mm Hg +/- 1.8; group B, 8.4 mm Hg +/- 3.0; P = .01). At 4-year follow-up, group A had higher cumulative rates of patency (98.3% vs 78.0%, P less than .001), symptomatic relief (84.0% vs 23.3%, P less than .001), and palliation (67.0% vs 19.9%, P less than .001). In conclusion, angiographic outflow, as evaluated with the system described, successfully helped predict postoperative increases in ABI and PtcO2 and the cumulative rates of graft patency, symptomatic relief, and palliation.
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Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML.
A new approach to the management of acute epistaxis is described using suction with the operating microscope to define the bleeding point prior to the application of hot wire cautery. This technique was shown to be completely successful in stopping haemorrhage in 82% of acute referrals in a prospective series of 33 patients. It resulted in a significant reduction both in the use of nasal packing and in the length of hospital stay compared with a group of controls treated by traditional means. It is proposed that in most cases of acute epistaxis the bleeding point is accessible to cautery and nasal packing should be reserved for a minority of refractory cases. This avoids unnecessary patient discomfort and the complications of prolonged nasal packing and hospitalization.
Wound excision with delayed closure after 4-5 days remains the essential principle for successful war surgery. When there are mass casualties the planning of effective triage before the event is the single most important element in achieving the best for the most.