Interaction of intense laser pulses with atomic clusters.
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Journal Article↗
Biomedical subjects
T Donnelly
Publications and source records attributed to T Donnelly.
Strong x-ray emission from high-temperature plasmas produced by intense irradiation of clusters.
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Journal Article↗
MIF as a glucocorticoid-induced modulator of cytokine production.
Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. Yet, in contrast to other hormonal systems, no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Recent investigations of the protein macrophage migration inhibitory factor (MIF), which was discovered originally to be a T-lymphocyte-derived factor, have established it to be a pro-inflammatory pituitary and macrophage cytokine and a critical mediator of septic shock. Here we report the unexpected finding that low concentrations of glucocorticoids induce rather than inhibit MIF production from macrophages. MIF then acts to override glucocorticoid-mediated inhibition of cytokine secretion by lipopolysaccharide (LPS)-stimulated monocytes and to overcome glucocorticoid protection against lethal endotoxaemia. These observations identify a unique counter-regulatory system that functions to control inflammatory and immune responses.
Animals↗
Advanced glycation endproducts promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits.
BACKGROUND: Reactive glucose-protein intermediates and advanced glycation endproducts (AGEs) are shown to colocalize with atheromatous lesions and to trigger complex chemical and biological responses through interaction with vessel wall elements. In diabetes and renal insufficiency, atherosclerosis is common, as are elevated levels of serum and vascular tissue AGEs. In the present study, AGEs supplied exogenously to normal animals elicited vascular and renal pathology. MATERIALS AND METHODS: Nondiabetic rabbits were injected intravenously with low doses of AGE-modified rabbit serum albumin (AGE-RSA, 16 mg/kg/day) for 4 months alone, or combined with a brief terminal period (2 weeks) of a cholesterol-rich diet (CRD) (2% cholesterol, 10% corn oil). AGE-RSA associated expression of vascular cell adhesion molecules and the development of atheromatous changes within the aorta were determined by immunohistology. RESULTS: The AGE content of aortic tissue increased by 2.2-fold in AGE-treated and by 3.2-fold in AGE + CRD-treated rabbits compared with normal saline-treated control rabbits (p < 0.025 and 0.001, respectively). Serum AGE levels in AGE groups rose up to 3-fold above the controls (p < 0.025 and p < 0.01). Ascending aortic sections from AGE-treated rabbits showed significant focal intimal proliferation, enhanced endothelial cell adhesion with infrequent intimal macrophages. oil-red-O staining lipid deposits and positive focal expression of vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), a pattern not observed in controls. These AGE-induced changes were markedly enhanced in animals cotreated with AGEs and a brief period of CRD. Lesions consisted of multifocal atheromas, containing foam cells, massive lipid droplets, and strong endothelial expression of VCAM-1 and ICAM-1 restricted to the affected areas. CONCLUSIONS: This study provides in vivo evidence for a causal relationship between chronic AGE accumulation and atherosclerosis independent of diabetic hyperglycemia, and suggests the utility of this animal model for the study of diabetic vascular disease in relation to glycation.
Albumins↗
Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol.
A 3-month double-blind multicenter trial compared the efficacy and safety of perindopril, a new angiotensin-converting enzyme (ACE) inhibitor, with atenolol in mild-to-moderate essential hypertension. A total of 190 patients, 49 of whom were diabetic, entered the perindopril-atenolol comparison. Of these, 163 had been previously treated and had a 4-week run-in period on placebo; 27 had previously been untreated and received placebo for 2 weeks. At entry, all patients who had a supine diastolic blood pressure (DBP) of 95-115 mm Hg were randomized to receive perindopril 2 mg or atenolol 25 mg, once daily. Patients were assessed at 2 weekly intervals for the first month and then monthly for 2 more months. If supine DBP was greater than 90 mm Hg, treatment was increased by stepwise doubling of dose up to 8 mg perindopril or 100 mg atenolol once daily, and later by the addition of hydrochlorothiazide 25 mg, (indapamide 2.5 mg in diabetic patients) once daily. The two groups were homogeneous prior to treatment except for supine and erect heart rate, which were higher in the perindopril group than in the atenolol group (p less than 0.05). Mean supine DBP was 101.1 +/- 0.6 mm Hg in the perindopril group (n = 94) and 99.9 +/- 0.6 mm Hg in the atenolol group (n = 96). After 3 months' active treatment, 74% of patients in the perindopril group achieved a supine DBP of less than or equal to 90 mm Hg and 73% of patients in the atenolol group achieved the same goal. Monotherapy controlled supine DBP in 67% of the perindopril group and 63% of the atenolol group. The decrease in supine DBP was not significantly different between the two groups (-12.9 +/- 0.9 versus -14.7 +/- 0.9 mm Hg) but the decrease in erect DBP was lower in the perindopril group (-10.3 +/- 0.9 versus - 13.4 +/- 1.0 mm Hg, p less than 0.02). Heart rate was reduced in the atenolol group (p less than 0.001). Sixteen patients withdrew from the study; nine were attributed to adverse events, two in the perindopril group and seven, including one death, in the atenolol group. Cough was spontaneously reported by 13% patients of the perindopril group and 1% patients of the atenolol group. In 5% of the perindopril cases this was mild and associated with upper respiratory tract infection. The nature and incidence of other symptoms were similar with both drugs.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Normal and diffusely abnormal myocardium in humans: functional and metabolic characterization with P-31 MR spectroscopy and cine MR imaging.
The current study tested the concept that cine magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy might be used to provide a comprehensive evaluation of the functional and metabolic status of the myocardium in humans. Thirteen patients with congestive cardiomyopathy and eight healthy volunteers were imaged at 1.5 T with the one-dimensional chemical shift imaging technique for localization of P-31 MR spectroscopy and an electrocardiographically referenced gradient refocused sequence for imaging of the heart. Prominent peaks in the PDE and PME regions were observed in cardiomyopathic patients, but only the former peak was measured. The PCr/beta-ATP peak ratio was not significantly lower in cardiomyopathic patients compared with healthy subjects (1.51 +/- 0.08 vs 1.54 +/- 0.04). The ratios of PDE/PCr (0.80 +/- 0.07 vs 0.54 +/- 0.10) (P less than or equal to .01) and PDE/beta-ATP (1.19 +/- 0.10 vs 0.84 +/- 0.08) (P less than or equal to .05) were significantly higher in patients with dilated cardiomyopathy compared with healthy volunteers. Left ventricular systolic wall thickening was significantly lower and left ventricular peak and end-systolic wall stress and mass were significantly higher in cardiomyopathic patients compared with healthy volunteers. Thus, localized, gated P-31 MR spectroscopy combined with cine MR imaging allowed identification of both abnormal myocardial phosphate metabolism and abnormal ventricular function. While this study suggests that increased myocardial PDEs may be a marker for abnormal myocardium, the sensitivity and specificity of this marker need to be further evaluated.
Adenosine Triphosphate↗
Blood pressure and vasoactive hormones with improved glycaemic control in patients with diabetes mellitus.
To assess the effects of improved glycaemic control on arterial pressure and plasma levels of vasoactive hormones, we studied 5 male insulin dependent (Type 1) diabetic patients before and one month after commencement of rigorous control of blood glucose levels. On each occasion, continuous ambulatory intra arterial pressure monitoring for a 10-hour period, together with hourly venous sampling for plasma glucose and vasoactive hormone determinations, was performed under standardised conditions of diet and posture. Mean (+/- SEM) plasma glucose before and after improved glycaemic control was 9.4 +/- 0.3 and 6.6 +/- 0.4 mmol/l respectively (P less than 0.001). There was a small but significant fall in arterial pressure in each patient as well as for the group overall (mean arterial pressure fall 4.8 +/- 1.2 mmHg, p less than 0.01) after improved glycaemic control. The fall in individual (10 hr mean) diastolic arterial pressure levels correlated with concomitant falls in plasma glucose levels (r = 0.92, p less than 0.05) but not with changes in any of the other variables measured.
Adolescent↗
Effect of cholecystokinin on pancreatic carcinogenesis in the hamster model.
To examine the effect of cholecystokinin (CCK) on pancreatic carcinogenicity in the hamster model, two sets of experiments were carried out. In one study, CCK (20 IDU/kg body wt) was given 3 h before, simultaneously with or 3 h after a single dose (20 mg/kg body wt) of N-nitrosobis(2-oxopropyl)amine (BOP). In another experiment, hamsters were treated similarly except that both CCK (20 IDU/kg body wt) and BOP (2.5 mg/kg body wt) were given weekly for 20 weeks. The results showed that CCK in the first experiment (single BOP dose) inhibited pancreatic cancer induction in a statistically significant fashion when given either 3 h prior to (P less than 0.05) or simultaneously with BOP (P less than 0.0005); however, CCK, when administered after BOP did not alter the cancer incidence as compared with hamsters treated with BOP alone. In the second experiment (chronic BOP treatment) the pattern and the incidence of pancreatic tumors were not affected by CCK.
Adenoma↗
Long-term immunization against the beta-subunit of ovine luteinizing hormone (oLH beta) has no adverse effects on pituitary function in rhesus monkeys.
One postulated safety hazard of contraceptive methods based on immunization against gonadotropic hormones is the possibility that circulating antibodies which crossreact with pituitary hormones may impair pituitary function through the deposition of immunoglobulin and/or complement suggesting immune complexes. In order to evaluate this possibility in rhesus monkeys actively immunized against the beta-subunit of ovine luteinizing hormone (oLH beta), we used three approaches to study the effects of long-term immunization on pituitary function: a) evaluation of pituitary responsiveness to challenge with a GnRH-agonist; b) examination of pituitary histology and immunostaining with gonadotropin antisera; and c) examination of pituitary cells for deposition of immune complexes. Our results indicate that circulating anti-oLH beta antibodies did not result in significant impairment of pituitary function in rhesus monkeys.
Animals↗
Problems in the assessment of outcome in a back pain clinic.
A sample of 72 patients attending the rheumatological back pain clinic of a district general hospital were interviewed at home, before their visit, about their expectations of the clinic. They also completed a Back Pain Disability Questionnaire. Fifty of the patients were recontacted by mail 3 months after their first clinic attendance and asked to complete the Back Pain Disability Questionnaire together with satisfaction questionnaires. Patients' reports, both with regard to expectations and satisfaction, particularly emphasized the importance of communication. One-third of the follow-up sample rated their clinic attendance as unhelpful, and although such views correlated with lack of improvement in pain and disability, other factors are involved in patients' evaluations. Significant correlations were obtained between subjective outcomes and health locus of control, social class and previous hospital treatment. Patient satisfaction may be a valuable measure of outcome in assessing the efficacy of back pain treatment.
Adult↗
Persistent production of colony-stimulating factor (CSF-1) by cloned bone marrow stromal cell line D2XRII after X-irradiation.
The adherent stromal layer in long-term bone marrow cultures (LTBMC) provides the cellular environment necessary for the in vitro proliferation and differentiation of pluripotential hematopoietic stem cells. The role of humoral hematopoietic growth factors, colony-stimulating factors (CSF) in the regulation of hematopoietic cell production in this system is poorly understood. We have recently isolated and cloned an adherent cell line, D2XRII, derived from murine LTBMC. Plateau phase 25 cm2 cultures of 2 X 10(6) D2XRII cells in 8.0 ml produced CSF-1 (M-CSF) at around 100-150 units/0.1 ml medium. Following X-irradiation there was a dose-dependent decrease in the production of CSF-1 to a plateau of 50% of control levels at 10,000 rad. Higher doses did not produce a further decrease. The X-ray dose reducing CSF-1 production to 50% was 100-fold above the lethal dose as measured by clonagenic survival following trypsinization and replating. Trypsinized replated viable adherent but nondividing X-irradiated D2XRII cells were maintained for up to 8 weeks after irradiation and demonstrated continuous production of CSF-1. The data indicate significant divergence of two biologic effects of X-irradiation on plateau-phase marrow stromal cells: physiologic function of adherence and CSF-1 production, versus proliferative integrity. This divergence of effects may be very relevant to understanding the mechanism of X-irradiation-associated marrow suppression and leukemogenesis.
Animals↗
Record linkage study of hypokalaemia in hospitalized patients.
Retrospective analysis of biochemical data from 58,167 hospital inpatients revealed that 21% developed hypokalaemia during hospitalization-in 5.2% the serum potassium was less than 3.0 mmol/l. Subsequent evaluation showed a positive correlation between hypokalaemia and both female sex and hospital mortality. Patients with leukaemia and lymphoid tumours, especially when receiving antibiotic or cytotoxic therapy, and patients with gastro-intestinal malignancy were amongst those most frequently experiencing hypokalaemia. There was no significant association with cardiovascular disease. Drug and intravenous fluid administration accounted for the hypokalaemia in 56% of patients. While drug-related hypokalaemia was most commonly seen with diuretics, it was also apparent following use of steroids, insulin and haematinics.
Aged↗
Serum fructosamine concentration as a measure of blood glucose control in type 1 diabetes mellitus.
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Blood Glucose↗
Changes in the management of the pregnant diabetic.
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Congenital Abnormalities↗
Biologic effects of in vitro X-irradiation of murine long-term bone marrow cultures on the production of granulocyte-macrophage colony-stimulating factors.
The production of colony-stimulating factor (CSF) by murine long-term bone marrow culture (LTBMC) was studied by a technique involving measurement of colony formation in agar overlay by fresh marrow target cells. Colonies were removed and microscopically examined for morphology and histochemistry. LTBMCs were exposed to x-irradiation at 200 rad/min prior to the overlay. Nonirradiated control LTBMCs induced 51.5 +/- 11 granulocyte-macrophage colonies per 2 X 10(5) target cells. Irradiation of LTBMCs to 6000 rad revealed a six-fold plateau-maximum increase in the number of colonies. There was occasional appearance of macroscopic mixed colonies containing granulocytes, macrophages, and megakaryocytes over irradiated but not control LTBMCs. Irradiated cells in the adherent stromal layer of LTBMCs continuously produced CSF that was detectable in the cell-free supernatants for up to seven weeks after irradiation and after doses as high as 10,000 rad. Shielding of the x-ray beam over half of the culture surface by a 10-half-value-layer lead block produced increased colony formation by target cells near the exposed surface area. The data indicate that CSF production by adherent cells within LTBMC persists after supralethal doses of x-irradiation. The mechanism of the increased colony formation by target cells overlaid on irradiated stromal cells involves factors relative to the local microenvironment.
Animals↗
Modification of pancreatic carcinogenesis in the hamster model. XI. Inhibitory effect of pilocarpine hydrochloride.
Pilocarpine hydrochloride (PH) was administered as a single sc injection (15 mg/kg body wt) to outbred Syrian golden hamsters either prior to, simultaneously with, or after a single 20-mg/kg body weight dose of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). An additional group was treated with PH, once before and once simultaneously with BOP; another group received PH daily for life after BOP and controls were given BOP only. Surviving hamsters were killed 46 weeks after BOP treatment. PH significantly inhibited pancreatic ductal-ductular cancer induction, whether it was given once before, simultaneously with, or after BOP. A more pronounced inhibitory effect was seen when PH was administered once before and once simultaneously with BOP. However, daily injection of PH did not alter the carcinoma incidence over the BOP control value. The possible mechanisms are discussed.
Animals↗
Blood pressure and diabetic control. Results of indapamide treatment.
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Adult↗
Hyperkalaemia in patients in hospital.
Significant hyperkalaemia occurred in 406 out of 29 063 patients admitted to a major Scottish teaching hospital in one year (1.4%). Mortality was higher in these patients than in control patients and was strongly correlated with the severity of the hyperkalaemia. Overall seven deaths were directly due to hyperkalaemia (out of 58 deaths among patients with hyperkalaemia). Factors contributing to a poor prognosis were severity and speed of onset of hyperkalaemia and the presence of appreciable renal impairment. Patients with hyperkalaemia were older and more likely to be male; this trend was present in all diagnostic subcategories. Genitourinary disease, gastrointestinal disease, and cancer were significantly more common among the patients with hyperkalaemia than the controls. Hyperkalaemia due to drug treatment was invariably mild and non-fatal, whereas genitourinary disease was often associated with moderate to severe hyperkalaemia, which in two cases proved fatal. Use of electrocardiographic monitoring was rare, and although the treatment of hyperkalaemia was effective, it was often used when not required. Hyperkalaemia is a potential hazard in diabetic ketoacidosis, and use of potassium supplements should be carefully monitored during correction of the acidosis.
Diabetic Ketoacidosis↗