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Effect of Disodium Cromoglycate (DSCG) and Antihistamines on Postirradiation Cerebral Blood Flow and Plasma Levels of Histamine and Neurotensin. COCKERHAM, L. G., PAUTLER, E. L., CARRAWAY, R. E., COCHRANE, D. E., AND HAMPTON, J. D. (1988). . 10, 233-242. In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and visual cortical blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100 Gy, whole-body, y irradiation. Systemic blood pressures were monitored simultaneously. Systemic arterial plasma histamine and neurotensin levels were determined preirradi-ation and postirradiation. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 23% of the preirradiation level within 10 min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10 min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The cortical blood flow for the same animals showed a steady decrease to 29% of the preirradiation levels by 60 min postirradiation. Animals given the mast cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before irradiation did not exhibit an abrupt decline in blood pressure but displayed a gradual decrease to a level 33% below preirradiation levels by 60 min postirradiation. Also, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. The plasma neurotensin levels in the irradiated animals, treated and untreated, indicated a nonsignificant postirradiation increase above control levels. However, the postirradiation plasma histamine levels in both irradiated groups showed an increase of approximately 1600% above the preirradiation levels and the postirradiation control levels. These findings implicate histamine in the postirradiation hypotension, but not necessarily in the direct responsibility for the decrease in regional cerebral blood flow seen immediately postirradiation in the primate. [ABSTRACT FROM PUBLISHER]

Sexual minority men are at increased risk for anal squamous cell carcinoma. Our objective was to compare screening engagement among individuals randomized to self-collect an anal canal specimen at home or to attend a clinic appointment. Specimen adequacy was then assessed for human papillomavirus (HPV) DNA genotyping. A randomized trial recruited cisgendered sexual minority men and transgender people in the community and assigned them to use a home-based self-collection swabbing kit or attend a clinic-based swabbing. Swabs were sent for HPV genotyping. The proportions of participants completing screening in each study arm and the adequacy of their specimens for HPV genotyping were assessed. Relative risks were estimated for factors associated with screening. A total of 240 individuals were randomized. Age (median, 46 years) and HIV status (27.1% living with HIV) did not differ by study arm. A total of 89.2% and 74.2% of home-arm and clinic-arm individuals returned the swab, respectively (P = .003), difference between groups, 15.0% (95% CI 5.4%-24.6%). Among black individuals, 96.2% and 63.2% in the home and clinic arms screened (P = .006). Among individuals with HIV, 89.5% and 51.9% in the home and clinic arms screened (P < .001). Self-collected swabs and clinician-collected swabs were comparable in adequacy for HPV genotyping (96.3% and 93.3%, respectively). People at highest risk for anal cancer may be more likely to screen if they are able to self-collect swabs at home rather than attend a clinic., (© 2023 UICC.)

Background: Circadian transcription factors that regulate cell-autonomous circadian clocks can also increase human immunodeficiency virus (HIV) transcription in vitro. We aimed to determine whether circadian variation in HIV transcription exists in people with HIV (PWH) on antiretroviral therapy (ART)., Methods: We performed a prospective observational study of male PWH on ART, sampling blood every 4 hours for 24 hours. Using quantitative polymerase chain reaction, we quantified expression of circadian-associated genes, HIV deoxyribonucleic acid (DNA), and cell-associated unspliced (CA-US) ribonucleic acid (RNA) in peripheral blood CD4+ T cells. Plasma sex hormones were quantified alongside plasma and salivary cortisol. The primary outcome was to identify temporal variations in CA-US HIV RNA using a linear mixed-effect regression framework and maximum likelihood estimation., Results: Salivary and plasma cortisol, and circadian genes including Clock, Bmal1, and Per3, varied with a circadian rhythm. Cell-associated unspliced HIV RNA and the ratio of CA-US HIV RNA/DNA in CD4+ T cells also demonstrated circadian variations, with no variation in HIV DNA. Circulating estradiol was highly predictive of CA-US HIV RNA variation in vivo., Conclusions: Cell-associated unspliced HIV RNA in PWH on ART varies temporally with a circadian rhythm. These findings have implications for the design of clinical trials and biomarkers to assess HIV cure interventions., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The fungi Paecilomyces variotii is a potential pathogen in immunocompromised and immunocompetent patients. Their rare association with clinical disease results in scarce literature regarding susceptibility and treatment. Here, we discuss a case involving successful treatment of probable P. variotii pneumonia with posaconazole after treatment failure with voriconazole. The current literature related to antifungal susceptibility profiles, microbiological identification methods and clinical management of infections caused by this organism is also reviewed., (© 2016 Blackwell Verlag GmbH.)

Background: Patient information leaflets (PILs) are often used to reinforce and provide further information relating to treatment choices, risks, and alternatives. An assessment of the quality of commonly used orthodontic patient information leaflets is lacking., Methods: A cross-sectional assessment of patient information leaflets from two international orthodontic societies was undertaken. The quality of each leaflet was assessed using the DISCERN instrument. The readability of each leaflet was assessed using the Flesch Reading Ease instrument, Flesch-Kincaid Grade Level and Simple Measure of Gobbledygook (SMOG) index. Descriptive statistics followed by univariate analysis was conducted., Results: Thirty-six patient information leaflets were identified. Reporting of DISCERN instrument items relating to aims, description of sources, details of additional sources, consequences of no treatment, possible treatment options, and support for a shared decision process was of low quality. The overall quality score for the total sample was 44. The median Flesch Reading Ease, Flesch-Kincaid Grade Level, and SMOG index scores were 70 (interquartile range (IQR) 53.3-73.9), 7.2 (IQR 6-9.7), and 7.3 (IQR 6.7-9.1), respectively. There was a significant difference between the quality (-8.00, 95% CI: -14.62, -1.38, p < 0.001), Flesch Reading Ease (-22.30, 95% CI: -26.77, 17.83, p < 0.001) and the Flesch-Kincaid Grade Level (3.80, 95% CI: 2.74, 4.86, p < 0.001) scores between the two societies' PILs., Conclusions: In relation to the DISCERN instrument, the quality of orthodontic PILs is deemed of moderate quality. There is a significant difference between the quality scores and the readability of PILs from different societies.

Subcellular distribution of the apoptosis inhibitor survivin and its ability to relocalize as a result of cell cycle phase or therapeutic insult has led to the hypothesis that these subcellular pools may coincide with different survivin functions. The PIK kinases (ATM, ATR and DNA-PK) phosphorylate a variety of effector substrates that propagate DNA damage signals, resulting in various biological outputs. Here we demonstrate that subcellular repartitioning of survivin in MCF-7 cells as a result of UV light-mediated DNA damage is dependent upon DNA damage-sensing proteins as treatment with the pan PIK kinase inhibitor wortmannin repartitioned survivin in the mitochondria and diminished it from the cytosol and nucleus. Mitochondrial redistribution of survivin, such as was recorded after wortmannin treatment, occurred in cells lacking any one of the three DNA damage sensing protein kinases: DNA-PK, ATM or ATR. However, failed survivin redistribution from the mitochondria in response to low-dose UV occurred only in the cells lacking ATM, implying that ATM may be the primary kinase involved in this process. Taken together, this data implicates survivian's subcellular distribution is a dynamic physiological process that appears responsive to UV light-initiated DNA damage and that its distribution may be responsible for its multifunctionality.

Objective: To determine the relationship of HIV infection, demographic, and cardiovascular disease (CVD) risk factors with mortality in the recent highly active antiretroviral therapy era., Methods: Vital status was ascertained from 2004 to 2007 in 922 HIV infected and 280 controls in the Study of Fat Redistribution and Metabolic Change in HIV infection; 469 HIV infected were included in analysis comparing HIV with similar age controls. Multivariable exponential survival regression (adjusting for demographic and CVD factors) estimated hazard ratios (HRs) for death., Results: After 5 years of follow-up, the overall adjusted mortality HR was 3.4 [95% confidence interval (CI): 1.35-8.5]; HR was 6.3 among HIV infected with CD4 < 200 (95% CI: 2.2-18.2), 4.3 with CD4 200-350 (95% CI: 1.14-16.0), and 2.3 with CD4 > 350 (95% CI: 0.78-6.9). Among HIV infected, current smoking (HR = 2.73 vs. never smokers, 95% CI: 1.64-4.5) and older age (HR = 1.61 per decade, 95% CI: 1.27-2.1) were independent risk factors for death; higher baseline CD4 count was associated with lower risk (HR = 0.65 per CD4 doubling, 95% CI: 0.58-0.73)., Conclusions: HIV infection was associated with a 3-fold mortality risk compared with controls after adjustment for demographic and CVD risk factors. In addition to low baseline CD4 count, older age and current smoking were strong and independent predictors of mortality in a US cohort of HIV-infected participants in clinical care.

Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA) and serotonin (5-HT). To investigate the relationship among these responses, rhesus monkeys (Macaca mulatta) received physiological saline (i.v.), disodium cromoglycate (DSCG), antihistamines (AH, mepyramine and cimetidine), or methysergide (METH), then were given 25 Gy whole-body irradiation. Monkeys receiving DSCG, AH or METH had higher post-irradiation mean arterial blood pressure (MBP) than saline-treated controls. Compared to levels in controls, post-irradiation hippocampal blood flow (rCBF) levels were higher in monkeys receiving DSCG, AH or METH. Treatment with the 5-HT2 receptor antagonist methysergide was the most effective in maintaining both rCBF and MBP after irradiation. Results support the hypothesis that the irradiation-induced cerebral ischemia and, to some extent, the hypotension is mediated by serotonin through 5-HT2 receptor sites.

Methyl bromide is widely used as an insecticidal fumigant in food supplies, warehouses, barges, buildings, and furniture. Its popularity as a fumigant is largely attributable to its high toxicity to many pests, the variety of settings in which it can be applied, its ability to penetrate the fumigated substances, and its rapid dissipation following application. Because of its frequent use around humans and human-related activities and its high acute toxicity, methyl bromide-related fatal accidents have occurred. The primary route for human exposure to methyl bromide is inhalation. In California, the most frequent cause of death from methyl bromide exposure in recent years has been unauthorized entry into structures under fumigation. The most frequently reported lesions included pulmonary edema, congestion, and hemorrhage. In recent years, a great deal of effort has been given to the characterization of the toxicity of methyl bromide because of its commercial value and its direct and indirect economic importance. Methyl bromide is acutely very toxic. Subchronically and chronically, the principal target site for methyl bromide appears to be the central nervous system. However, there was no evidence for carcinogenic activity of methyl bromide following the normal environmental exposure routes of inhalation or oral intake through residue on foods. Methyl bromide is clearly genotoxic in vitro and in vivo, as evidenced by the positive results from various tests. The mechanism of toxicity for methyl bromide is currently uncertain, although its alkylating property as well as the possibility of forming a reactive intermediate through metabolic transformation remain attractive hypotheses.

One of the observations of endotoxic or septic shock in canines is the report of concurrent hypoglycemia. Canines exposed to supralethal gamma radiation also develop acute systemic hypotension. This study was performed in order to determine if hypoglycemia develops in the canine concurrent with radiation-induced hypotension. Systemic arterial mean blood pressure (MBP) was measured via femoral arterial catheter. Blood for plasma glucose determinations was obtained from the systemic arterial circulation at the level of the abdominal aorta and from the hepatic portal vein. Plasma glucose levels were determined on a Beckman Glucose Analyzer which employs the enzymatic reaction of beta-D-glucose and oxygen. Glucose levels and MBP were monitored for one hour before and for one hour after exposure to 100 Gy, whole-body, gamma radiation or sham radiation for the control animals. Concurrent with postradiation hypotension, we measured a significant decrease in plasma glucose levels in both the systemic arterial circulation and in the hepatic portal vein. Arterial glucose levels in the sham radiated animals showed a slight rise two minutes after sham radiation, falling back to pretreatment, base line levels four minutes later and remaining at that level for the remainder of the hour. Arterial levels in the radiated animals showed a sharp decline two minutes postradiation, falling even further to twenty percent below preradiation levels by one hour postradiation. Venous blood glucose levels in sham radiated animals showed an initial increase and a gradual decrease to five percent below pretreatment base line levels; while glucose levels in radiated animals showed an immediate postradiation decrease continuing to twenty percent below preradiation levels by one hour postradiation. These findings suggest impaired hepatic gluconeogenesis, resulting in postradiation hypoglycemia.

A possible mechanism by which disodium cromoglycate (DSCG) prevents a decrease in regional cerebral blood flow but not hypotension in primates following whole body gamma-irradiation was studied. Several studies have implicated superoxide radicals (O2-.) in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively. O2-. is formed during radiolysis in the reaction between hydrated electrons (e-aq) and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge e-q and possibly prevent the formation of O2-. was studied. Hydrated electrons were produced by photolysis of potassium ferrocyanide solutions. The rate constant, k = 2.92 x 10(10) M-1s-1 for the reaction between e-aq and DSCG was determined in competition experiments using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). This spin trap reacts rapidly with e-aq followed by protonation to yield the ESR observable DMPO-H spin adduct. The results show that DSCG is an efficient e-aq scavenger and may effectively compete with oxygen for e-aq preventing the radiolytic formation of O2-..

Radiation-induced systemic hypotension is accompanied by increased intestinal blood flow (IBF) and an increased hematocrit (HCT) in dogs. Histamine infusion leads to increased IBF and intestinal edema with consequent secretion of fluid into the intestinal lumen. This study was performed to determine whether these effects could be diminished by prior administration of H1 and H2 histamine blockers. Dogs were given an iv infusion of mepyramine (0.5 mg/min) and cimetidine (0.25 mg/min) for 1 hr before and for 1 hr after radiation (H1 and H2 blockers, respectively). Mean systemic arterial blood pressure (MBP), IBF, and HCT were monitored for 2 hr. Systemic plasma histamine levels were determined simultaneously. Data obtained indicated that the H1 and H2 blockers, given simultaneously, were successful in blocking the increased IBF and the increased HCT seen after 100 Gy, whole-body, gamma radiation. However, the postradiation hypotension was only somewhat affected, with the MBP falling to a level 28% below the preradiation level. Plasma histamine levels reached a sharp peak, as much as 20% above baseline, at 4 min postradiation. These findings implicate histamine in the radiation-induced increase in IBF and HCT but not for the gradual decrease in postradiation blood pressure.

Radiation-induced early transient incapacitation (ETI) is accompanied by severe systemic hypotension, during which arterial blood pressure often decreases to less than 50 per cent of normal. One haemodynamic compensatory mechanism is increased peripheral resistance due to vasoconstriction. This vasoconstriction in the small intestine of dogs is disproportionately increased during haemorrhagic or endotoxic shock, and intestinal ischaemia is frequent. In an attempt to elucidate mechanisms underlying radiation-induced ETI and the gastrointestinal radiation syndrome, canine intestinal submucosal blood flow was measured by the hydrogen polarographic technique, both before and after exposure to gamma radiation. Systemic blood pressures, blood gases and haematocrits were determined simultaneously. Data obtained from 12 sham-irradiated dogs and 12 irradiated dogs indicated that 90 Gy, whole-body, gamma radiation produced a 31 per cent decrease in systemic mean blood pressure beginning within 20 min post-irradiation and lasting for at least 90 min. However, the intestinal submucosal blood flow did not decrease as anticipated, but it exhibited an actual post-irradiation increase. This increase in post-irradiation intestinal submucosal blood flow began within 5 min after irradiation and lasted for at least 90 min. Post-irradiation haematocrits were 10.5 per cent higher than those obtained before irradiation and those obtained from sham-irradiated subjects. Histopathological examination of ileal mucosa revealed significant pathologic lesions in some irradiated animals within two hours after exposure.

Radiation-induced early transient incapacitation (ETI) is often accompanied by severe systemic hypotension. However, postradiation hypotension does not occur with equal frequency in all species and is not reported with consistency in the canine. In an attempt to clarify the differences in reported canine postradiation blood pressures, canine systemic blood pressures were determined both before and after exposure to gamma radiation of either 80 Gy or 100 Gy. Data obtained from six sham-radiated beagles and 12 radiated beagles indicated that 100 Gy, whole-body, gamma radiation produced a decrease in systemic mean blood pressure while 80 Gy, whole-body, gamma radiation did not. Analysis of this data could be consistent with a quantal response to a gamma radiation dose between 80 Gy and 100 Gy.

Phospholipids were utilized as a membrane marker to test for transformation-induced alteration of cellular membranes of cultured crown gall cells of Vinca rosea L. Fully transformed cells contained less than half the amount of phospholipids (7.8 micrograms lipid P per gram fresh weight) of normal V. rosea cells (21.4 micrograms lipid P per gram fresh weight). The normal V. rosea callus cells were not significantly different (P > 0.05) in phospholipid content from partially transformed crown gall cells (20.7 micrograms lipid P per gram fresh weight). Stimulation to rapid growth of the partially transformed cells by adding higher concentrations of inorganic salts and auxin did not significantly alter their phospholipid content (23.1 micrograms lipid P per gram fresh weight). These findings suggest that the transformation process is directly responsible for an alteration of the cellular membranes and that the membrane alteration cannot be attributed to secondary effects associated with the rapid growth of these neoplastic cells.Five classes of phospholipids were identified and quantified. Average percentage of total phospholipids contained in each class were as follows: phosphatidylcholine, 38.5 +/- 4.3; phosphatidylethanolamine, 22.2 +/- 0.8; phosphatidylinositol, 12.3 +/- 2.9; phosphatidylserine, 0.8 +/- 0.4; phosphatidic acid, 4.7 +/- 1.3. Several unidentified phospholipids were also quantified. The relative amounts of the various classes of phospholipid compounds in normal and crown gall cells of V. rosea were not significantly different.

In a series of 183 patients with proven cancers of the esophagus and stomach, endoscopic cytology was positive in 155 or 84.7 per cent. Endoscopic biopsy in 173 of these patients was positive in 137 or 79 per cent. At least one of the techiques was positive in 164 patients or 94.8 per cent. These results emphasize the overall accuracy of endoscopic cytology and biopsy and their complementary value in detection of malignancy. Meticulous care in technique is stressed for achievement of such accuracy rates.

In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and hypothalamic blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100 Gy, whole body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 35% of the preirradiation level within 10 min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10 min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The hypothalamic blood flow of the same animals showed a steady decrease to 43% of the preirradiation levels by 60 min postirradiation. The postradiation systemic blood pressure of the allopurinol treated monkeys was not statistically different from the untreated, irradiated monkeys and was statistically different from the control monkeys. However, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. These findings suggest the involvement of free radicals in the postirradiation decrease in regional cerebral blood flow but not necessarily in the postirradiation hypotension seen in the primate.

Radiation-induced hypotension in the beagle is accompanied by increased intestinal blood flow (IBF) and hematocrit (HCT). This study was performed to correlate these radiation-induced changes with plasma histamine (PH) levels following radiation. The histamine (H) levels were monitored in the systemic arterial circulation (SA) and the hepatic portal vein (HPV) before and after radiation. To examine the effect of radiation on the mobilization of total body H stores, Compound 48/80 was given I.V., and H responses were monitored in both control and radiated animals. Data obtained indicated that 100 Gy, whole-body, gamma-radiation produced a decrease in systemic mean blood pressure (BP), an increase in IBF and an increase in HCT. Concurrently, the mean PH/SA values increased and the PH/HPV levels decreased. Compound 48/80 produced a marked increase in PH levels in both control and radiated animals; however, the levels found in the radiated animals were consistently lower than those in the controls, although not statistically different. This implies that H may mediate these observed intestinal responses and that the mobility of histamine is decreased in radiated animals.

The Central Nervous System (CNS) exhibits a high sensitivity to ionizing radiation from conception until after birth. X-irradiation damage of the nervous system during development has been well documented and exposure to ionizing radiation above approximately 10 cGy during perinatal development is contraindicated. Shielding of the embryo or fetus usually prevents gross malformations but high energy irradiation of the pregnant female may result in embryonic growth retardation. This may be especially true when the irradiation is coupled with an ethanol-induced reduction in SOD activity. The synergistic interactions between other drugs and ionizing radiation also have been demonstrated. However, the concentration of endogenous compounds such as histamine and serotonin may be increased in the maternal circulation following irradiation and reach the fetal CNS through a blood-brain-barrier that is more permiable than normal. The introduction of histamine and/or serotonin into the fetal circulation may result in fetal hypotension, edema, cerebral ischemia, and damage to the developing CNS.

Early transient incapacitation (ETI) and/or performance decrement (PD) is a reduction in performance during the first 30 min after exposure to a relatively high, rapidly delivered dose of ionizing radiation. The accelerod provides a sensitive measure of functional impairment in neurotoxic evaluations of chemical agents and demonstrates that the motor performance of gamma-radiation-exposed Sprague-Dawley rats was significantly different from that of sham-radiated controls.

Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with hypotension and a dramatic release of mast cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomenon and the postradiation decrease in cerebral blood flow, primates were exposed to 100 Gy (1 Gy = 100 rads), whole-body, gamma radiation. Pontine and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. Systemic arterial histamine levels were determined preradiation and postradiation. Data obtained indicated that radiated animals showed a decrease in blood flow of 63% in the motor cortex and 51% in the pons by 10 min postradiation. Regional cerebral blood flow of radiated animals showed a slight recovery 20 min postradiation, followed by a fall to the 10 min nadir by 60 min postradiation. Immediately, postradiation systemic blood pressure fell 67% and remained at that level for the remainder of the experiment. Histamine levels in the radiated animals increased a hundredfold 2 min postradiation. This study indicates that regional cerebral blood flow decreases postradiation with the development of hypotension and may be associated temporally with the postradiation release of histamine.