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Biomedical subjects

B Armstrong

Publications and source records attributed to B Armstrong.

At least 19 recordsLinked to original sources

Decreased plasma atriopeptin response to volume-overloading maneuvers and exercise after atriopulmonary anastomosis of Fontan.

Atriopulmonary anastomosis results in a chronic right atrial pressure-volume overload. Water and salt retention is a frequent clinical observation in patients after atriopulmonary anastomosis. The purpose of this study was to examine if this could be related to an inability to increase already elevated circulating atriopeptin (ANP) in response to central volume-overloading conditions. Eighteen patients (mean age 16 +/- 6 years) with an atriopulmonary anastomosis underwent routine cardiac catheterization during which a 5-minute head-down 10 degrees tilt was performed. Peripheral venous and right atrial blood samples were obtained under basal conditions, and after tilting and angiography for determination of ANP concentrations. At a different time, circulating ANP levels were measured during a maximal graded exercise protocol. Increased circulating ANP concentrations were found under basal conditions (114 +/- 10 pg/ml). Tilting and cardioangiography resulted in significant increases in mean atrial pressure (basal: 12 +/- 0.7 mm Hg; tilt: 13.4 +/- 0.63 mm Hg; after angiography: 15.8 +/- 0.8 mm Hg), but not in atrial or peripheral ANP. Compared with the expected threefold increase in plasma ANP induced by maximal exercise in healthy control subjects, only a slight (0.25-fold) increase was found in patients. These observations suggest a reduced stimulus-release response after atriopulmonary anastomosis, which could be related to a loss of atrial stretch receptor sensitivity, achievement of the limit for maximal right atrial secretion, or an alteration in right atrial compliance, or a combination.

Adolescent

Frequent activation of the Ki-ras oncogene at codon 12 in N-methyl-N-nitrosourea-induced rat prostate adenocarcinomas and neurogenic sarcomas.

Rat neoplasms induced by methylating carcinogens frequently contain ras genes activated by a single point mutation. Rat prostatic tumors induced by a combination of a single injection of N-methyl-N-nitrosourea (MNU) and long-term treatment with testosterone were examined for the presence of such activating point mutations in ras genes. These tumors, which arose exclusively in the dorsolateral prostate, included both adenocarcinomas and sarcomas. Activating mutations in codon 12 of the Ki-ras gene were found in 7 of 10 carcinomas and 4 of 5 sarcomas, using selective oligonucleotide hybridization analysis of DNA amplified by the polymerase chain reaction (PCR). However, no mutated Ha-ras oncogenes were detected. The presence of PCR-engineered Hphl restriction sites created by the existence of a G35----A mutation in the rat Ki-ras oncogene identified the mutation as a GC----AT transition at the second position of codon 12. Production of O6-methylguanine adducts in the Ki-ras codon 12 followed by base mispairing during replicative DNA synthesis is thus the likely molecular mechanism of initiation of prostatic carcinogenesis by MNU in the rat. Three of the four sarcomas positive for the Ki-ras G35----A mutation were immunohistochemically defined as of Schwann cell origin, indicating that involvement of the ras gene family is possible in tumorigenesis of this cell lineage. Loss of the wild-type Ki-ras allele was also observed in all four of these sarcomas.

Adenocarcinoma

Acute lymphoblastic leukaemia among Spanish children and mothers' occupation: a case-control study.

STUDY OBJECTIVE: The aim was to investigate the association between mothers' occupational exposure during pregnancy and the incidence of acute lymphoblastic leukaemia in children. DESIGN: The study was a case-control investigation. A face to face interview was used to assess exposures at work and relevant confounding variables. SETTING: The study was community based and was carried out in five provinces of Spain. SUBJECTS: 128 cases less than 15 years of age were interviewed (91% of those eligible). Controls (one for each case) were chosen from the census lists and were matched on year of birth, sex and municipality. MEASUREMENTS AND MAIN RESULTS: Children of mothers working at home had a relative risk (RR) of 7.0 (95% CI = 1.59-30.79) of developing acute lymphoblastic leukaemia. Exposure to organic dust was associated with a RR of 5.5 (95% CI = 1.21-24.8). There was a statistically significant interaction between exposure to organic dust and working at home. The majority of women working at home were hired by local industries to sew different types of tissues (cotton, wool, synthetic fibres) on a machine. CONCLUSION: A similar association has not been reported before: if confirmed, this finding may suggest a new health concern.

Adolescent

Use of radiofrequency current to ablate accessory connections in children.

BACKGROUND: Several investigators have recently ablated electrophysiologically mapped accessory connections in the adult human myocardium by using radiofrequency current. To examine the effectiveness and safety of radiofrequency current for ablation of accessory connections in children, 20 consecutive patients (age, 3-18 years) with preexcitation and/or supraventricular tachycardia were evaluated by electrophysiological study. METHODS AND RESULTS: Nineteen of the 20 patients were completely studied and demonstrated accessory connections. After identification of the earliest retrograde atrial activation site, a steerable 7F catheter (with a 4-mm-long electrode at the distal tip) was placed within the ventricular cavity ipsilateral to the accessory connection and positioned at the atrioventricular valve annulus directly opposite the earliest point of retrograde atrial activation. Radiofrequency current was delivered at 50-65 volts for 10-60 seconds at a frequency of 500 kHz. Radiofrequency pulses were delivered for two to 26 trials. Upon completion of radiofrequency trials, repeat electrophysiological testing was performed. Thirteen of 19 subjects (68%) experienced definite successful ablation of their accessory pathway; an additional patient had probable successful ablation, yielding an overall success rate of 74%. Eighty-seven percent of individuals with a left-sided pathway had permanent ablation and 100% with a manifest left-sided pathway experienced successful ablation. Only 29% of the first seven patients had a successful result; in contrast, 92% of the next 12 patients had successful interruption of their accessory pathways. After ablation, 4-day continuous electrocardiographic telemetry disclosed no significant arrhythmias. CPK enzyme rises peaked at 12-24 hours. The rise was excessive and associated with general anesthesia in five patients. The isoenzyme MB fraction rose mildly in five other patients and returned to normal within 72 hours. No clinical or electrocardiographic evidence of myocardial ischemia was detected. Follow-up for 4-12 months indicates no return of preexcitation or tachycardia in any patient whose accessory connection was successfully ablated. CONCLUSIONS: This experience indicates that radiofrequency current is an effective and safe technique for ablation of accessory connections in children.

Adolescent

Descriptive study of prognostic factors influencing survival of compensated silicotic patients.

The objective of this study was to assess survival and the prognostic influencing survival of compensated silicotic patients. All workers compensated for silicosis in the Province of Quebec from 1938 to 1985 (n = 1,165) were included. Clinical data were those collected during the exam that led to a compensation decision. Due to missing data, a subcohort of 961 patients was used for multivariate analysis of clinical prognostic factors with the Cox proportional hazards model. The following factors made an independent contribution to survival: age at compensation, smoking, dyspnea, expectoration, abnormal breath sounds, radiographic appearance, and vital capacity. On the basis of the model, patients with small opacities alone on their chest radiograph and who did not have dyspnea, expectoration, or abnormal breath sounds had a survival similar to the average Quebec man; other patients had a poorer survival. We conclude that it is possible to identify at the time of compensation, silicotic patients who are likely to have a life expectancy similar to that of the general population. Symptoms and physical signs as well as radiographic and lung function abnormalities appear to be useful prognostic indicators in compensated silicotic patients.

Dyspnea

The relationship between respiratory impairment and asbestos-related pleural abnormality in an active work force.

With the general improvement in environmental controls in workplaces where asbestos is used, an increasing number of workers are seen who exhibit isolated pleural plaques. The question as to whether these are associated with respiratory impairment independently of parenchymal disease remains unresolved. The question was reinvestigated using quantitative gallium-67 lung scanning to take into account early parenchymal change not evident on the chest radiograph. We carried out a cross-sectional study of 110 construction insulators all currently at work. Overall, 58.2% had pleural abnormality, 52.5% pleural plaques only, and 5.5% diffuse pleural thickening as assessed from the PA chest radiograph. Compared with those without, those with any pleural abnormality had a decrease in FEV1 and FVC on average of 222 and 402 ml (p less than 0.05), and those with isolated pleural plaques, a decrease on average of 200 and 350 ml (p less than 0.05), after taking into account age, height, smoking status, and the presence of parenchymal abnormality as assessed by chest radiography and gallium uptake. The complaint of dyspnea with strenuous activities was also significantly related to the width and extent of chest wall pleural thickening (p less than 0.05), independently of parenchymal disease. This study suggests that the most common radiographic findings in asbestos-exposed, isolated pleural plaques are associated with a significant reduction in FEV1 and FVC, which cannot be attributed to the presence of radiographic and subradiographic pulmonary fibrosis.

Adult

Stochastic development of invasive potential in rat mammary tumors induced by N-methyl-N-nitrosourea.

We have studied the progression of breast tumors induced by N-methyl-N-nitrosourea in Wistar/Furst rats during serial passages through isogeneic animals, using characteristic markers previously defined. The tumors contained various types of structure, which evolve from intraductal nodes to duct-like structures and then to invasive strands or cells. Most primary tumors were not invasive but became so in subsequent transfers. The distribution of invasive and noninvasive tumors in the various lineages was not random, implying that the tumors differed from their inception in the propensity toward invasion. In different lineages invasive structures appeared repeatedly and independently but with different frequencies, suggesting that they were produced by a stochastic mechanism with different probability of occurrence. The possible nature of this mechanism is discussed. This experimental system is useful for further studies of tumor invasion; the results obtained are relevant for understanding and evaluating the evolution of human breast cancer.

Animals

Reversion toward an earlier stage of differentiation and loss of polarity during progression of N-methyl-N-nitrosourea-induced rat mammary tumours.

To work toward an understanding of the mechanisms of cancer progression, we have followed the changes in expression of several genes in rat mammary carcinomas during the development of invasion. Tumors were induced by N-methyl-N-nitrosourea and serially transplanted to isogeneic rats. Gene expression in individual cells was followed by immunofluorescence microscopy. We show that invading cells do not express the same genes as the primary tumor or normal adult mammary gland but are similar to the primitive mammary duct cells present in late embryos. In the most advanced tumors, the most fundamental epithelial characteristic, polarity, is lost. Relative to the mechanism of invasion, we observe that the basal lamina, often thinner than normal, always coats the strands of invading cells and may be entirely absent from single invasive cells only. These observations suggest that the basal lamina ultimately disappears because of reduced expression of the genes or the failure to assemble the components. In these tumors it is the progressive alteration in gene expression rather than the enzymatic breakdown of the basal lamina that leads to invasion. These results show that the most important aspect of cancer progression is the progressive alteration of gene expression. They also raise questions about the mechanism that causes tumor cells to retrace the steps in their differentiation.

Animals

Distribution of developmental markers in rat mammary tumors induced by N-nitrosomethylurea.

We have examined the distribution of immunological markers in 55 intraductal carcinomas induced in rats by N-nitrosomethylurea using several different regimens of carcinogen treatment. The goal was to determine the possible relationship of the marker distribution to those existing at various stages of development of the mammary gland. We have also examined two passage lines in syngeneic rats derived from two of the tumors. The distribution of markers was not affected by the regimen of administration. The primary tumors were found to maintain the general topography of mammary ducts but with infoldings of the basal layer without accompanying stroma. We attribute this to an abnormal expression of the tendency of basal cells to migrate towards the lumen to generate luminal cells. The distribution of markers in the tumors was evaluated by identifying 13 special features of distribution that are common in tumors, using all-or-none criteria. The distribution of these features bears out the high heterogeneity of tumors in which the various features vary in a seemingly independent way. There is also heterogeneity within tumors, adjacent nodes often having different marker distributions. The distribution of the markers is related to that found in the early stages of mammary development. Because of this characteristic and of the fact that the tumors contain both basal and luminal cells, they must originate from multipotent cells, probably the stem cells present in end buds and ducts as already proposed by other work. As they develop, the tumors can both differentiate towards the adult type and dedifferentiate towards a fetal type. Of the two transplanted lines one retained the same general features of primary tumors in several passages, whereas the other evolved into a fusiform cell type with a marker distribution not seen at any stage of mammary development. Foci of similar cells were already present in the primary tumor, suggesting that the tendency to progress was already determined at an early stage. The fusiform cells are similar and probably equivalent to the fusiform cells that arise in vitro in cultures of rat mammary cancers.

Animals

Urinary sodium and blood pressure in vegetarians.

Urinary sodium, potassium urea, creatinine, uric acid, plasma urea, creatinine, cholesterol, blood pressures, height, weight, and skinfold thickness were measured in some or all of 106 matched pairs of vegetarians (mainly Seventh-Day Adventists) and nonvegetarians. Mean blood pressures were lower in vegetarians (141.9/88.9 mm) than nonvegeterians (148.0/90.9 mm) but the urinary excretion of sodium was higher, although not significantly, in the vegetarians (mean of 169.7 compared with 161.2 mmole/day). The vegetarians also had a higher urinary potassium excretion (62.9 mmole/day) than the nonvegetarians (54.8 mmole/day) thus giving them a lower mean sodium to potassium ratio (3.0 compared with 3.3). Both systolic and diastolic blood pressures correlated positively with plasma cholesterol levels which were less in vegetarians (6.0 mmole/liter) than nonvegetarians (6.6 mmole/liter). They also correlated positively with the urinary sodium to potassium ratio, but only in nonvegetarians. It was concluded that dietary sodium does not explain the blood pressure differences between vegetarians and nonvegetarians.

Adolescent