Renal cyst uptake following I-131 treatment for thyroid cancer.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
M Graham
Publications and source records attributed to M Graham.
Low rates of cutaneous adverse reactions to alcohol-based hand hygiene solution during prolonged use in a large teaching hospital.
We assessed cutaneous adverse reactions (CARs) to alcohol-based hand rub (ABHR) after the introduction of a hand hygiene culture change program at our institution. CARs were infrequent among exposed health care workers (HCWs) (13/2,750; 0.47%; 1 CAR per 72 years of HCW exposure) and were not influenced by the duration or intensity of ABHR use but were associated with the presence of irritant contact dermatitis.
Anti-Infective Agents, Local↗
Radiotherapy patterns of care study in lung carcinoma.
PURPOSE: For the first time, a lung Patterns of Care Study was conducted to determine the national patterns of radiation (RT) practice in patients treated for nonmetastatic lung cancer in 1998 to 1999. MATERIALS AND METHODS: A national survey of randomly selected RT institutions in the United States was conducted using two-stage cluster sampling, stratified by practice type. Patients with nonmetastatic lung cancer (Karnofsky performance score [KPS] > or = 60), who received RT as definitive or adjuvant therapy, were randomly selected. To determine national estimates, sample size was weighted by the relative number of institutions per strata and the number of patient records reviewed per the number of patients eligible. Accordingly, 42,335 patient records from 58 institutions were reviewed by trained research associates. The unweighted sample size (or number of patients) was 541. RESULTS: The histologies were small-cell lung cancer (SCLC) in 14.5% of patients versus non-small-cell lung cancer (NSCLC) in 85.5% of patients. The median age was 67 years (range, 29 to 92 years); 61% of patients were male, and 38% were current smokers. Bone scans and brain imaging were not obtained in 34% and 52% of clinical stage (CS) III NSCLC patients, respectively. Regarding treatment strategies, for SCLC and CS III NSCLC, chemotherapy plus RT was used significantly more than RT alone (P <.05); in CS I NSCLC, RT alone was the primary treatment (P <.05). Overall, 58% of patients received systemic therapy. On multivariate analysis, factors correlating with increased use of chemotherapy included younger age, histology (SCLC > NSCLC), increasing CS, increasing KPS, and lack of comorbidities. Only 3% of all patients were treated on prospective clinical trials. CONCLUSION: This study establishes the general patterns of care for lung carcinoma in RT facilities within the United States. As supported by clinical trials, patients with limited-stage SCLC and CS III NSCLC received chemotherapy plus RT more than they received RT alone. Further improvements in staging, smoking cessation, and increased accrual to clinical trials must be encouraged.
Adult↗
Interference study of the chi c0(13P0) in the reaction -pp-->pi0pi0.
Fermilab experiment E835 has observed (-)pp annihilation production of the charmonium state chi(c0) and its subsequent decay into pi(0)pi(0). Although the resonant amplitude is an order of magnitude smaller than that of the nonresonant continuum production of pi(0)pi(0), an enhanced interference signal is evident. A partial wave expansion is used to extract physics parameters. The amplitudes J=0 and 2, of comparable strength, dominate the expansion. Both are accessed by L=1 in the entrance (-)pp channel. The product of the input and output branching fractions is determined to be B((-)pp-->chi(c0))xB(chi(c0)-->pi(0)pi(0))=(5.09+/-0.81+/-0.25)x10(-7).
Journal Article↗
Dehydroepiandrosterone 7-hydroxylase CYP7B: predominant expression in primate hippocampus and reduced expression in Alzheimer's disease.
Neurosteroids such as dehydroepiandrosterone (DHEA), pregnenolone and 17beta-estradiol are synthesized by cytochrome P450s from endogenous cholesterol. We previously reported a new cytochrome P450 enzyme, CYP7B, highly expressed in rat and mouse brain that metabolizes DHEA and related steroids by hydroxylation at the 7alpha position. Such 7-hydroxylation can enhance DHEA bioactivity in vivo. Here we show that the reaction is conserved across mammalian species: in addition to mouse and rat, DHEA hydroxylation activity was present in brain extracts from sheep, marmoset and human. Northern blotting using a human CYP7B complementary deoxyribonucleic acid (cDNA) probe confirmed the presence of CYP7B mRNA in marmoset and human hippocampus; CYP7B mRNA was present in marmoset cerebellum and brainstem, with lower levels in hypothalamus and cortex. In situ hybridization to human brain revealed higher levels of CYP7B mRNA in the hippocampus than in cerebellum, cortex, or other brain regions. We also measured CYP7B expression in Alzheimer's disease (AD). CYP7B mRNA was significantly decreased (approximately 50% decline; P<0.05) in dentate neurons from AD subjects compared with controls. A decline in CYP7B activity may contribute the loss of effects of DHEA with ageing and perhaps to the pathophysiology of AD.
Adipates↗
Cysteine residues of SNAP-25 are required for SNARE disassembly and exocytosis, but not for membrane targeting.
The release of neurotransmitter at a synapse occurs via the regulated fusion of synaptic vesicles with the plasma membrane. The fusion of the two lipid bilayers is mediated by a protein complex that includes the plasma membrane target soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (t-SNAREs), syntaxin 1A and synaptosome-associated protein of 25 kDa (SNAP-25), and the vesicle SNARE (v-SNARE), vesicle-associated membrane protein (VAMP). Whereas syntaxin 1A and VAMP are tethered to the membrane by a C-terminal transmembrane domain, SNAP-25 has been suggested to be anchored to the membrane via four palmitoylated cysteine residues. We demonstrate that the cysteine residues of SNAP-25 are not required for membrane localization when syntaxin 1A is present. Analysis of the 7 S and 20 S complexes formed by mutants that lack cysteine residues demonstrates that the cysteines are required for efficient SNARE complex dissociation. Furthermore, these mutants are unable to support exocytosis, as demonstrated by a PC12 cell secretion assay. We hypothesize that syntaxin 1A serves to direct newly synthesized SNAP-25 through the Golgi transport pathway to the axons and synapses, and that palmitoylation of cysteine residues is not required for targeting, but to optimize interactions required for SNARE complex dissociation.
Animals↗
A time-to-treatment analysis in the medicine versus angiography in thrombolytic exclusion (MATE) trial.
Patients with acute coronary syndromes who are considered ineligible for thrombolytic therapy are at high risk of recurrent ischemia and death. This trial randomized 201 patients to triage angiography in the first 24 hours of hospital admission versus conventional medical care. Of the 165 patients who underwent angiography that was either protocol-driven or on the basis of physician preference, those who underwent angiography within 6 hours of symptom onset had a reduction in early and late adverse events. The rates of in-hospital recurrent ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for trend), and rates of cumulative recurrent myocardial infarction or death were 0%, 12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively from symptom onset. Future trials of invasive versus conservative therapy should focus on performing angiography within 6 hours of symptom onset.
Adult↗
Pharmacokinetics and pharmacodynamics of an antisense phosphorothioate oligonucleotide targeting Fas mRNA in mice.
ISIS 22023 is a modified phosphorothioate antisense oligonucleotide targeting murine Fas mRNA. Treatment of mice with ISIS 22023 reduced Fas expression in liver in a concentration-dependent and sequence-specific manner, which completely protected mice from fulminant death induced by agonistic Fas antibody. In this study, we characterized the relationships in mice between total dose administered, dose to the target organ, and ultimately, the intracellular concentration within target cell types to the pharmacologic activity of ISIS 22023. After subcutaneous injection, ISIS 22023 distributed to the liver rapidly and remained in the liver with the t(1/2) ranging from 11 to 19 days, depending on dose. There were apparent differences in patterns of uptake and elimination in different types of liver cells. Oligonucleotide appeared within hepatocytes rapidly, whereas the peak concentrations in Kupffer cells were delayed until 2 days after dose administration. Hepatocytes cleared oligonucleotide the most rapidly, whereas Kupffer cells appeared to retain oligonucleotide longer. The reduction of Fas mRNA levels (pharmacodynamic response) paralleled the increase of oligonucleotide concentration in mouse liver with maximum mRNA reduction of 90% at 2 days after a single 50 mg/kg subcutaneous administration. Moreover, the pharmacodynamics of ISIS 22023 correlated better with the pharmacokinetics in hepatocytes, supporting the concept that the presence of oligonucleotide in target cells results in reductions in mRNA and, ultimately, pharmacologic activity. These results provide a comprehensive understanding of the kinetics of an antisense drug at the site of action and demonstrate that the reductions in mRNA induced by this antisense oligonucleotide correlate with its concentrations in cell targets.
Algorithms↗
A phase I/II study of external beam radiation, brachytherapy, and concurrent chemotherapy for patients with localized carcinoma of the esophagus (Radiation Therapy Oncology Group Study 9207): final report.
BACKGROUND: A multiinstitutional, prospective study of the Radiation Therapy Oncology Group (RTOG) was designed to determine the feasibility and toxicity of chemotherapy, external beam radiation, and esophageal brachytherapy (EB) in a potentially curable group of patients with adenocarcinoma or squamous cell carcinoma of the esophagus. A preliminary analysis indicated a 17% 1-year actuarial risk of treatment-related fistulas. A final analysis of this study was considered important to determine the median survival time, local control, and late toxicity associated with this treatment regimen. METHODS: Planned treatment was 50 grays (Gy) of external beam radiation (25 fractions given over 5 weeks) followed 2 weeks later by EB (either high-dose-rate 5 Gy during Weeks 8, 9, and 10, for a total of 15 Gy, or low-dose-rate 20 Gy during Week 8). Chemotherapy was given during Weeks 1, 5, 8, and 11, with cisplatin 75 mg/m(2) and 5-fluorouracil 1000 mg/m(2)/24 hours in a 96-hour infusion. RESULTS: Of the 49 eligible patients, 45 (92%) had squamous histology and 4 (6%) had adenocarcinoma. Forty-seven patients (96%) completed external beam radiation plus at least 2 courses of chemotherapy, whereas 34 patients (69%) were able to complete external beam radiation, EB, and at least 2 courses of chemotherapy. The estimated survival rate at 12 months was 49%, with an estimated median survival of 11 months. Life-threatening toxicity or treatment-related death occurred in 12 (24%) and 5 (10%) cases, respectively. Treatment-related esophageal fistulas occurred in 6 cases (12% overall, 14% of patients starting EB) at 0.5-6.2 months from the first day of brachytherapy, leading to death in 3 cases. CONCLUSIONS: In this study, severe toxicity, including treatment-related fistulas, occurred within 7 months of brachytherapy. Based on the 12% incidence of fistulas, the authors continue to urge caution in employing EB, particularly when used in conjunction with chemotherapy.
Adenocarcinoma↗
Strain differences to the effects of aversive frequency ultrasound on behaviour and brain topography of c-fos expression in the rat.
Previous studies have shown that ultrasound at 20 kHz produces an escape (defence) response in the hooded Lister rat. This study compares the ultrasound-induced behavioural response in the hooded Lister and albino Wistar rat. Ultrasound (continuous tone, square wave, 20 kHz) produced an initial characteristic startle response (brisk running) in the hooded Lister rat that was followed immediately after cessation of the ultrasound by a period of freezing behaviour. In contrast, Wistar rats showed no initial escape response but a prolonged period of freezing that started during the ultrasound and continued for a period after the end of the ultrasound. Immunohistochemical assessment of c-fos expression also showed a difference between the two strains with preferential expression in the dorsal region of the rostral and caudal periaqueductal grey (PAG) in the hooded Lister rat, while the expression occurred in the ventral PAG in the Wistar rats. In summary, the two strains exhibit distinct defensive behaviours and patterns of neuronal activation in response to the same aversive signal. It remains to be determined whether these differences relate to neuronal circuitry or perception of the signal, but analysis of the mechanisms involved may help our understanding of the heterogeneity of anxiety disorders.
Animals↗
Increased gelsolin expression and retarded collagen lattice contraction with smooth muscle cells from Crohn's diseased intestine.
Intestinal smooth muscle cells (SMC) produce the fibrotic tissue, strictures, that characterize Crohn's disease. These SMC change their phenotype from a contractile muscle form to an inflammation-responsive form that migrates and synthesizes a collagen matrix. It is postulated that the inflammatory responsive SMC form associates differently with its surrounding collagen matrix compared to the normal SMC form. SMC derived from Crohn's diseased and uninvolved bowel were sustained in cell culture. Cultured SMC incorporated in collagen lattices have the capacity to reduce the size of that lattice, referred to as lattice contraction. At day 2, Crohn's SMC-populated collagen lattices were reduced to 21% of their initial area, while non-Crohn's SMC collagen lattices were reduced to 8%. Crohn's SMC demonstrate retarded lattice contraction compared to non-Crohn's SMC. When grown in monolayer culture, Crohn's-derived SMC cover 30% more area than non-Crohn's SMC. By Western blot analysis Crohn's SMC express more gelsolin, an actin-binding protein found elevated in cells exhibiting increased cell motility. Was the increased expression of gelsolin related to retarded collagen lattice contraction? Intracellular levels of gelsolin were elevated by the electroporation of plasma gelsolin protein into suspended non-Crohn's SMC. When incorporated in collagen lattices, gelsolin loaded cells showed retarded lattice contraction compared to SMC loaded with albumin. Crohn's SMC show increased expression of gelsolin, which may be associated with a diminished capacity to reorganize collagen fiber bundles. It is suggested that increased concentrations of gelsolin in Crohn's SMC is consistent with enhanced cell migration as a consequence of the inflammatory state of Crohn's diseased intestine.
Blotting, Western↗
Acoustically elicited behaviours in Lister hooded and Wistar rats.
It has been reported previously that experimenter-presented 20-kHz tones at low intensities produce bursts of locomotor running in Lister hooded rats, but reduced locomotion (freezing) in Wistar rats. Because rats emit 20-kHz tones when stressed, it was proposed that this ultrasound-elicited running and freezing behaviour in Lister hooded and Wistar rats, respectively, represents a model for qualitative strain differences in fear behaviour. The present studies examined the acoustic specificity of acoustically elicited locomotor behaviours in Lister hooded and Wistar rats. In Experiment 1, it was found that brief exposure (i.e., 15 s) of Lister hooded rats to tones at frequencies of 7, 12, or 20 kHz and intensities of 85-95 dB SPL, elicited running behaviour characterised by brief bursts of locomotion followed by periods of quiescence. Somewhat surprisingly, the 7- and 12-kHz tones elicited running behaviour at lower intensities than did the 20-kHz tones. In Experiment 2, it was found that exposure of Lister hooded rats to the 20-kHz acoustic stimulus (91-101 dB, SPL) for a much longer duration, up to 9 min, resulted in episodic bursts of locomotion and convulsions in a significant proportion of subjects. Both the maximal velocity of locomotion and the likelihood of occurrence of convulsions was related to the intensity of the acoustic stimulus. Exposure of Lister hooded rats to white noise for up to 9 min also elicited episodic bursts of locomotion and convulsions in an intensity-dependent manner. The white noise stimulus was found to be a more effective stimulus than the 20-kHz stimulus in this regard. In Experiment 3, it was found that Lister hooded rats exhibited reduced locomotion when they were exposed to a low-intensity 20-kHz acoustic stimulus (e.g., 81 dB, SPL). In Experiment 4, it was found that Wistar rats did not exhibit locomotor bursts or convulsions when presented with 20-kHz tones using stimulus parameters equal to and even greater than those that had been shown to be effective in producing locomotor bursts in Lister hooded rats. Rather, Wistar rats exhibited only reduced locomotion. The present data indicate that (1) running behaviour in Lister hooded rats is not specific for the 20-kHz stimulus. Moreover, (2) when compared to Lister hooded rats, Wistar rats are relatively insensitive to the running and convulsions elicited by acoustic stimuli. Finally, (3) both Lister hooded and Wistar rats exhibited reduced locomotion when presented with the 20-kHz tones, although the range of stimulus intensities that produces freezing behaviour is much more limited in Lister hooded rats because of their propensity to exhibit locomotor bursting and convulsions. Thus, it appears that the difference between the two strains with respect to their unconditioned locomotor responses to novel acoustic stimuli relates to the fact that Lister hooded rats are uniquely susceptible to acoustically elicited locomotor bursts and/or convulsions.
Acoustic Stimulation↗
Impaired culprit vessel flow in acute coronary syndromes ineligible for thrombolysis.
The majority of patients with acute myocardial infarction and other acute coronary syndromes (ACS) are considered ineligible for thrombolysis and do not routinely receive reperfusion therapy. We hypothesized that predictors and outcomes of angiographically impaired culprit vessel flow can be identified and compared. This trial evaluated the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with<24 hours of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy. This analysis was performed in 165 patients, from experimental and control arms, in whom angiography was performed on the index hospitalization with the outcome of interest being target vessel flow (Thrombolysis In Myocardial Infarction [TIMI] grades 0 to 2) on initial angiography. Patients with and without impaired culprit lesion flow were similar with respect to age, gender, diabetes, and prior coronary disease. A family history of premature coronary disease was more common in those with impaired flow, 50.0 versus 28.5% (p=0.02). Abnormal culprit vessel flow was found in 19.2% of patients who underwent angiography within 6 hours of symptom onset; however, after 24 hours this rate was reduced to 11.7%. Impaired culprit lesion flow can be expected in approximately 20% of patients presenting with ACS who are ineligible for reperfusion therapy by conventional guidelines and therefore represents an opportunity for early intervention within 6 hours of the onset of symptoms in these patients.
Actuarial Analysis↗
Development and geometry of isotropic and directional shrinkage-crack patterns.
We have studied shrinkage-crack patterns which form when a thin layer of an alumina/water slurry dries. Both isotropic and directional drying were studied. The dynamics of the pattern formation process and the geometric properties of the isotropic crack patterns are similar to what is expected from recent models, assuming weak disorder. There is some evidence of a gradual increase in disorder as the drying layer become thinner, but no sudden transition, in contrast to what has been seen in previous experiments. The morphology of the crack patterns is influenced by drying gradients and front propagation effects, with sharp gradients having a strong orienting and ordering effect.
Journal Article↗
Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis.
OBJECTIVE: To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. DESIGN: A multicentre randomised double blind placebo controlled trial. SUBJECTS: Infants admitted to hospital with their first episode of RSV positive bronchiolitis. INTERVENTION: Randomisation to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. MAIN OUTCOME MEASURES: Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of anti-wheeze medication during follow up. RESULTS: 161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure. Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Pla, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (CI)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants receiving at least one prescription for anti-wheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6); bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). CONCLUSIONS: There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.
Acute Disease↗
Be careful about drawing conclusions.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Usefulness of intravenous enoxaparin for percutaneous coronary intervention in stable angina pectoris.
This pilot study was designed to determine whether the low molecular weight heparin, enoxaparin, could be used for elective percutaneous coronary intervention (PCI) to provide antithrombotic effects without the full systemic anticoagulation that occurs with the use of unfractionated heparin. Sixty patients were randomized to receive intravenous enoxaparin (1 mg/kg bolus dose) or unfractionated heparin at the time of coronary intervention. Laboratory testing was performed at baseline, 5 minutes, and 4 hours after study drug to test if a single bolus dose of intravenous enoxaparin can consistently achieve therapeutic antithrombotic effect, thus eliminating the need for multiple doses of heparin and closely monitoring levels of anticoagulation during PCI. Thirty percent of patients who received unfractionated heparin required a second bolus of intravenous heparin to achieve the target-activated clotting time of 300 seconds before PCI. Enoxaparin showed antithrombotic properties comparable to that of unfractionated heparin as measured by anti-Xa levels, with less inhibition of thrombin (factor IIa) at the time points measured (p <0.0001). Angioplasty success rates, in-hospital ischemia, bleeding, and vascular complications were similar in both groups. Thus, intravenous enoxaparin has predictable and effective antithrombotic effects during elective PCI. Although the level of anticoagulation attained with enoxaparin is significantly lower than that after unfractionated heparin, no increase in ischemic complications were noted. The use of a single bolus of intravenous enoxaparin, without the need for measuring the activated clotting time or titrating heparin anticoagulation, has the potential for simplifying the performance and perhaps enhancing the safety of PCI.
Aged↗
Is angioplasty safe at community hospitals without cardiac surgery?
Explore the source record for details and available documents.
Angioplasty, Balloon, Coronary↗