Ionizing radiations and chromosomes.
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Biomedical subjects
Publications and source records attributed to R Moore.
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A link between irritable bowel syndrome (IBS) and psychiatric illness is well recognized. The authors set out to establish whether a group with a risk of poor outcome IBS could be identified at presentation to a general hospital clinic in a prospective series of 70 subjects. Potential risk factors showed no correlation with IBS outcome at 6-9 months. There was a high rate of persistent mental illness. Clinicians offering specialist care for IBS should consult with psychiatric services to provide assessment irrespective of IBS outcome if major psychopathology is not to be neglected.
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The precision and accuracy of a prompt-gamma neutron activation facility developed to assess total body protein in rats is estimated. The coefficient of variation of nitrogen measurement, as estimated by repeated measurements on 15 rats, was 5.5% for an equivalent dose of 60 mSv (Q = 20). Good agreement was observed in comparing the results of in vivo neutron activation analysis and chemical carcass analysis performed by the Kjeldahl method. The application of the technique in comparing the effect of a low-fat and a high-fat diet on body protein in rats is demonstrated.
OBJECTIVE: To quantify longitudinal increases in fetal, fetal liver, and fetal brain volume using echo-planar magnetic resonance imaging and to quantify the results using appropriate statistical modeling. METHODS: Fifty-six singleton fetuses were studied using echo-planar (snap-shot) magnetic resonance imaging, between 19 weeks and term. They were assessed at a variety of different gestations and on a different number of occasions, thereby requiring multilevel statistical modeling to analyze the pattern of fetal growth. RESULTS: Fetal volume varied according to the following equation: square root (radical) [fetal volume]=-37.71+2.17 x gestational age (GA)-0.004 x GA(2). The equation for fetal liver volume was radical[fetal liver volume]=9.47+0.56 x GA-0.02 x GA(2), for fetal brain volume was radical[fetal brain volume]=15.50+0.69 x GA-0.014 x GA(2), and for placental volume radical[placental volume]=28.54+0.95 x GA-0.039 x GA(2), where GA is the gestational age in weeks -30. CONCLUSION: The assessment of fetal, fetal organ, and placental volume was feasible using echo-planar magnetic resonance imaging from 20 weeks to term. Multilevel statistical modeling can be applied to analyze sets of data with different measurements on different occasions. This information is useful clinically to assess abnormal fetal growth.
Ionizing radiation has been used to treat cancers for a century. However, radioresistance remains a major problem in the clinic. Recent advances in the understanding of the molecular events that occur following ionizing radiation leading to DNA damage and repair, apoptosis, and cell cycle arrests suggest new ways in which the radiation response might be manipulated. Seventy-eight cases of carcinoma of the cervix of the same stage (II A and B) were analyzed retrospectively. All patients were treated with radiotherapy (RT) with a dose varying from 35 Gy to 50 Gy with 200 cGy per fraction. Subsequent to the completion of radiotherapy, all patients underwent surgery 4-6 weeks later. On histological examination of the surgical specimens, 51% of the cases (40) showed a complete response to therapy with no viable tumor cells. 49% of cases (38) had residual tumors ranging from a small focus to lesions extending through more than half the thickness of the cervical wall. p53 (mutant), bcl-2, p21 and bax proteins were studied on the paraffin sections of the biopsies (pretreatment) of those patients who failed to respond to RT and compared to similar studies on biopsies of patients who had a complete response to RT. In addition, the minichromosome maintenance (MCM) 2 proliferative marker was also done on all cases. Expression of all proteins was done using immunohistochemsitry. In the radioresistant cases, 15% (six cases) showed positivity for bcl-2 and p21, respectively, and 34% (13 cases) showed mutant p53. None of the radiosensitive tumors were positive for the above proteins. 75% of the radiosensitive tumors (30 cases) were positive for the bax antibody, whereas 81% of the radioresistant tumors (31 cases) were negative for bax. The MCM2 proliferative marker was positive in > 80% of cells in 81.5% of radioresistant tumors (31 cases) as compared to < 40% of cells that were positive in 70% of radiosensitive tumors (28 cases). The P-value for the biological markers was calculated using the chi-squared test, and was highly significant (P < 0.01) for all the parameters tested. However, there was no statistical significance by univariate analysis when the dose of radiation was analyzed with respect to the markers and the histological response. There was also no correlation between the radiation response and timing of surgery. The above data strongly suggest that bax, along with proliferative markers, could play a role in determining which tumors are likely to respond to radiation therapy. The presence of bcl-2, p21 and p53 could also be related to radioresistance of the tumors.
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The interpretation of plasma norepinephrine (NE) levels is not straightforward because such levels represent a complex of synaptic discharge, metabolism, uptake, and regional blood flow. Some investigators have argued that peripheral NE levels bear little semblance to sympathetic nervous system activity affecting the cardiovascular system. This study examines this question in further detail. Eleven men (average age = 29) were studied. Plasma NE levels were obtained through continuous blood withdrawal from an antecubital vein, and simultaneous blood pressures were also monitored. Each subject was studied during four 4-min intervals of rest and during four 4-min intervals of a psychiatric stress interview. The interview was a friendly, intense discussion about upsetting situations the subject faced. The interview was a powerful and consistent tool for evoking physiologic responses. It led to an 83% increase in NE levels across all time intervals (p less than 0.001). During these same intervals, systolic pressure increased by 16 mm (p less than 0.0003) and diastolic by 13 mm (p less than 0.0001); furthermore, systolic and diastolic pressures were correlated with peripheral NE levels. This implies that the increased peripheral NE level was not merely a local phenomenon but reflected a signal affecting the entire vascular system.
A sample consisting of 54 patients and 31 dentists of Chinese, Anglo-American, and Scandinavian ethnic origin were interviewed about their ways of coping with pain. Instruments designed to assess pain coping were constructed from the descriptions elicited by the interviews. The interview data thus served as the basis for cross-cultural quantitative indices. Content analysis of the interviews revealed significant differences between patients and dentists and an East-West ethnic difference between patient groups. Anglo-American patients and all dentists preferred internally applied medicines (pills, injections etc.). Chinese patients preferred external agents (salves, oils, massage, etc.) significantly more than Chinese dentists or Western subjects. Swedish and Chinese patients preferred not to use local anesthesia for dental treatment. These results were corroborated by nonparametric and multidimensional scaling analyses of the cross-cultural quantitative data. Professional socialization had a stronger influence on pain remedy description than did ethnicity, while patient descriptions of remedies appeared to be more ethnospecific, especially showing East-West differences. These anthropologic methods appeared to be valid and reliable in revealing cognitive processes involved in the pain coping preferences of these subjects.
PURPOSE: This study determined the in vitro antitumor activity of a rebeccamycin analog (NSC# 655649) using tetrazolium/formazan (MTT) and clonogenic assays against established pediatric cell lines and solid tumor specimens obtained from children. MATERIALS AND METHODS: Tumor cells from 14 established cell lines and 20 patient specimens were exposed in vitro for 1 hour to NSC# 655649 at concentrations ranging from 0.015 to 15.0 microM. The cytotoxicity (IC50) of this agent against established cell lines was determined using both the MTT (cytotoxic) and clonogenic/soft agar cloning (cytostatic) assays. Tumor specimens from children undergoing biopsy or surgical resection were also evaluated in vitro against NSC# 655649 using the clonogenic assay. For studies using patient specimens, antitumor activity was measured by comparing the number of tumor colonies from NSC# 655649-treated cells with those from solvent-treated controls. RESULTS: These studies showed that the mean IC50S using the MTT and clonogenic assays using established solid tumor cell lines were 0.94 and 0.51 microM, respectively. In general, for cell lines tested using both types of assays, the clonogenic assay resulted in a smaller IC50. The overall in vitro responses (< or = 50% survival compared to controls) using patient tumor specimens and the clonogenic assay were 35% (1.5 microM), 60% (7.5 microM), and 80% (15.0 microM). Of the 9 patients with neuroblastoma, responses to NSC# 655649 were seen in 33% (1.5 microM), 58% (7.5 microM), and 92% (15.0 microM) of the specimens. Prior chemotherapy did not appear to adversely affect in vitro responses. CONCLUSIONS: NSC# 655649 appears to have broad antitumor activity in vitro against pediatric malignancies at drug concentrations achieved during adult phase I clinical trials. These studies support the further development of NSC# 655649 for solid tumors in children.
PURPOSE: 6-Hydroxymethylacylfulvene (HMAF; MGI 114; Irofulven) is a semisynthetic analogue of the mushroom toxin illudin S that has been shown to be a potent cytotoxic agent with an improved therapeutic index compared with its parent compound. The studies were conducted to evaluate the antitumor activity of MGI 114 as a single agent and in combination with topotecan against pediatric solid tumor cell lines and xenograft models. MATERIALS AND METHODS: In vitro studies were designed to determine the cytotoxic potential of MGI 114 using the MTT assay and 13 pediatric tumor cell lines. In addition, combination in vitro studies were performed with MGI 114 and topotecan to generate isoeffect plots. Single agent and combination in vivo studies were also performed using MGI 114 against rhabdomyosarcoma and neuroblastoma xenograft models. RESULTS: After a 1-hour exposure to MGI 114, the mean IC50 (+/-standard error of mean) for medulloblastoma, neuroblastoma, Ewing sarcoma/primitive neuroectodermal tumor, and rhabdomyosarcoma cell lines were 1.58+/-0.51, 1.60+/-0.82, 1.18+/-0.08, and 3.99+/-1.69 microg/mL, respectively. When tumor cells were exposed concurrently to MGI 114 and topotecan, evidence of synergy was observed in 10 of 12 (83%) cell lines. Single agent and combination in vivo studies with MGI 114 showed that this agent had substantial, and at times curative, antitumor activity against rhabdomyosarcoma and neuroblastoma xenograft tumors. CONCLUSIONS: These data suggest that MGI 114 has significant efficacy as a single agent in preclinical studies against pediatric tumors. In addition, based on previous reports and the results presented here, combining MGI 114 with topotecan appears to be an attractive approach to the treatment of pediatric malignancies. After completion of the pediatric phase I studies of MGI 114, consideration should be given to phase II single agent and phase I combination studies with a topoisomerase I inhibitor such as topotecan or irinotecan.
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Effects of hypnotherapy (HT) and self-hypnosis training on extreme dental anxiety in adults aged 19-65 years were compared with group therapy (GT) and individual desensitization (SD) using scales of dental anxiety, dental beliefs, and fear of a next dentist (after specialist treatment). All experimental groups were demographically comparable and showed reduced anxiety and improved dental beliefs compared with 51 control patients. The 25 HT patients did not differ significantly in numbers of dropouts during training compared with the 30 GT patients or 68 SD patients. For patients completing treatment, HT (n = 22) reduced dental anxiety to the same degree as GT (n = 24) and SD (n = 60). HT and SD patients required more therapist hours per patient than did GT, but total dropouts at 1 yr after specialist treatment were significantly greater in HT (13/ 25) than for SD rehearsals (5/34) or SD video (8/32), but not GT (15/30). Hypnotizability was found to vary from patient to patient, with a direct relationship to time saved. But hypnotizability had an inverse relationship to STAI general anxiety level for those who went on to dentists after 1 year. Transference effects were noted for most HT dropout patients as an aversive response to continued dental treatment with other dentists than the specialist.
In medical imaging, the temperature of the developer solution in the film processor affects film speed (radiation dose), film contrast, and film base plus fog. The National Council on Radiation Protection and Measurement (NCRP) Report 99 on Quality Assurance, and the American College of Radiology (ACR) Mammography Quality Control Manual for Radiologic Technologists, indicate that the developer temperature should be within +/- 0.5 degree F (+/- 0.3 degree C) of that recommended by the manufacturer for the specific film/developer combination being used. The accuracy and repeatability of the thermometer is most important. This paper describes the requirements of a thermometer for measuring the temperature of the developer solution and suggests an inexpensive but accurate device for doing so.
The mucosal vaccination of rodents with killed non-typeable Haemophilus influenzae (NTHi) has been previously shown to enhance live NTHi clearance following middle ear challenge. This study assessed the efficacy of mucosal anti-NTHi vaccination during a concomitant viral infection of the respiratory tract. Animals were mucosally immunised with killed NTHi by intra-Peyer's patch primary inoculation and lung (intratracheal) boost. At the time of both immunisations rats were also infected intra-nasally with Sendai virus. Concomitant Sendai virus infection did not influence the efficacy of anti-NTHi vaccination mediated clearance of NTHi from the middle ear. This would suggest that immunisation strategies to prevent bacterial middle ear infection would be effective despite the presence of concomitant viral agents.
Urinary kallikrein excretion (UK), plasma renin activity (PRA), and 24-hour urine volume, sodium, and potassium excretion rates were determined sequentially in 16 normal pregnant women. Throughout gestation, UK was significantly elevated as compared to values obtained in 13 control women (1466 +/- 152 vs 375 +/- 90 U/g creatinine). The highest level was observed in Period 2 of gestation, corresponding to Weeks 17 to 24. PRA was also significantly elevated during pregnancy (11.97 +/- 1,35 vs 1.06 +/- 0.90 ng/ml/hr), with the highest level in Period 2. Mean 24-hour urine volume, sodium, and potassium excretion rates were significantly higher during pregnancy. Nor correlation was found between UK and: PRA, urine volume, and sodium and potassium excretions. These findings indicate a consistent activation of the renal-kallikrein-kinin system during pregnancy. We postulate that this vasodilator system might play a role in the maintenance of normotension in pregnancy, counteracting tha effect of the renin-angiotensin-aldosterone system.
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