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1.
Cleft Palate Craniofac J ; 60(12): 1665-1673, 2023 12.
Article in English | MEDLINE | ID: mdl-35821585

ABSTRACT

Cherubism is a rare disorder characterized by proliferative fibro-osseous lesions that result in bilateral bony hyperplasia of the face. Management varies based on symptom severity and includes longitudinal follow-up, pharmacotherapy, and/or surgical debulking. Off-label treatment with denosumab, a human monoclonal antibody that binds RANKL and inhibits osteoclast function to reduce bone resorption, can be beneficial in suppressing the proliferation of bone to minimize the need for surgery and to control postoperative reproliferation. Close follow-up is needed to maintain appropriate electrolyte levels. The present case demonstrates the achievement of symptomatic control with denosumab in a child with severe refractory cherubism.


Subject(s)
Cherubism , Child , Humans , Cherubism/drug therapy , Cherubism/surgery , Denosumab/therapeutic use , Mandible/surgery , Maxilla/surgery
2.
Nature ; 504(7478): 119-21, 2013 Dec 05.
Article in English | MEDLINE | ID: mdl-24305162

ABSTRACT

After the initial burst of γ-rays that defines a γ-ray burst (GRB), expanding ejecta collide with the circumburst medium and begin to decelerate at the onset of the afterglow, during which a forward shock travels outwards and a reverse shock propagates backwards into the oncoming collimated flow, or 'jet'. Light from the reverse shock should be highly polarized if the jet's magnetic field is globally ordered and advected from the central engine, with a position angle that is predicted to remain stable in magnetized baryonic jet models or vary randomly with time if the field is produced locally by plasma or magnetohydrodynamic instabilities. Degrees of linear polarization of P ≈ 10 per cent in the optical band have previously been detected in the early afterglow, but the lack of temporal measurements prevented definitive tests of competing jet models. Hours to days after the γ-ray burst, polarization levels are low (P < 4 per cent), when emission from the shocked ambient medium dominates. Here we report the detection of P =28(+4)(-4) per cent in the immediate afterglow of Swift γ-ray burst GRB 120308A, four minutes after its discovery in the γ-ray band, decreasing to P = 16(+5)(-4) per cent over the subsequent ten minutes. The polarization position angle remains stable, changing by no more than 15 degrees over this time, with a possible trend suggesting gradual rotation and ruling out plasma or magnetohydrodynamic instabilities. Instead, the polarization properties show that GRBs contain magnetized baryonic jets with large-scale uniform fields that can survive long after the initial explosion.

3.
Nature ; 478(7370): 493-6, 2011 Oct 26.
Article in English | MEDLINE | ID: mdl-22031441

ABSTRACT

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1 AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163 ± 6 kilometres, density 2.52 ± 0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ∼1 nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.

4.
Nature ; 462(7274): 767-9, 2009 Dec 10.
Article in English | MEDLINE | ID: mdl-20010682

ABSTRACT

The nature of the jets and the role of magnetic fields in gamma-ray bursts (GRBs) remains unclear. In a baryon-dominated jet only weak, tangled fields generated in situ through shocks would be present. In an alternative model, jets are threaded with large-scale magnetic fields that originate at the central engine and that accelerate and collimate the material. To distinguish between the models the degree of polarization in early-time emission must be measured; however, previous claims of gamma-ray polarization have been controversial. Here we report that the early optical emission from GRB 090102 was polarized at 10 +/- 1 per cent, indicating the presence of large-scale fields originating in the expanding fireball. If the degree of polarization and its position angle were variable on timescales shorter than our 60-second exposure, then the peak polarization may have been larger than ten per cent.

5.
Regul Pept ; 146(1-3): 147-56, 2008 Feb 07.
Article in English | MEDLINE | ID: mdl-17900712

ABSTRACT

Plasma concentrations of the hormone gastrin are elevated by Helicobacter pylori infection and by gastric atrophy. It has previously been proposed that gastrin acts as a cofactor during gastric carcinogenesis and hypergastrinemic transgenic INS-GAS mice are prone to developing gastric adenocarcinoma, particularly following H. pylori infection. We hypothesised that the increased risk of carcinogenesis in these animals may partly result from altered susceptibility of gastric epithelial cells to undergo apoptosis. Gastric corpus apoptosis was significantly increased 48 h after 12Gy gamma-radiation in mice rendered hypergastrinemic by transgenic (INS-GAS) or pharmacological (omeprazole treatment of FVB/N mice) methods and in both cases the effects were inhibited by the CCK-2 receptor antagonist YM022. However, no alteration in susceptibility to gamma-radiation-induced gastric epithelial apoptosis was observed in mice overexpressing progastrin or glycine-extended gastrin. Apoptosis was also significantly increased in gastric corpus biopsies obtained from H. pylori-infected humans with moderate degrees of hypergastrinemia. We conclude that hypergastrinemia specifically renders cells within the gastric corpus epithelium more susceptible to induction of apoptosis by radiation or H. pylori. Altered susceptibility to apoptosis may therefore be one factor predisposing to gastric carcinogenesis in INS-GAS mice and similar mechanisms may also be involved in humans.


Subject(s)
Apoptosis , Disease Susceptibility , Gastric Mucosa/pathology , Gastrins/blood , Stomach Neoplasms/etiology , Animals , Anti-Ulcer Agents/pharmacology , Benzodiazepines/pharmacology , Cells, Cultured , Gamma Rays , Gastric Mucosa/drug effects , Gastric Mucosa/radiation effects , Helicobacter pylori , Humans , Mice , Mice, Transgenic , Omeprazole/pharmacology , Receptor, Cholecystokinin B/antagonists & inhibitors
6.
Ulster Med J ; 75(3): 200-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16964812

ABSTRACT

OBJECTIVE: To study the outcome following treatment for proximal femoral fracture in elderly people. METHODS: All consecutive males and females admitted to the acute fracture service at the Royal Victoria Hospital and the Belfast City Hospital for the 3 years from 1999 to 2001 were studied. The data was collected by trained research nurses. Variables gathered included age, sex, marital status, mental state, pre-injury Barthel score and the American Society of Anaesthesiology (ASA) physical status grading. The information was gathered on admission to hospital and at four, six and 12 months after the injury. RESULTS: The total number of patients studied between January 1999 to December 2001 was 2834 of whom 77% were female and 23% were male. The mean (median) length of stay in the acute fracture service was 10.7 (9 days). The mean (median) length of stay in the rehabilitation ward was 35.3 (24 days). The 30-day mortality was 6.9%, the four-month mortality 15.6 % and one year mortality 22.3 %. Of those subjects living at home at the time of fracture 68% remained at home at one year. Factors predicting successful return home were higher mental test score, younger age, female sex, higher Barthel score, better pre-injury mobility and better ASA score. Of those able to walk independently outdoors before injury 40% regained this ability by 12 months. Factors predicting return of pre-injury mobility were poorer pre-injury mobility, younger age, higher mental test score, better ASA category, higher Barthel score, and previous residence at home. The proportion admitted from their own home and discharged by 56 days was 56%. CONCLUSION: The standardised measurement of outcome in hip fracture subjects enables comparison between units and facilitates improvement in standards of care available to the increasing number of elderly patients presenting with proximal femoral fracture.


Subject(s)
Femoral Neck Fractures/mortality , Femoral Neck Fractures/rehabilitation , Hospitals, Public/statistics & numerical data , Outcome Assessment, Health Care , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Femoral Neck Fractures/surgery , Hip Fractures/mortality , Hip Fractures/rehabilitation , Hip Fractures/surgery , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Northern Ireland/epidemiology , Patient Discharge/statistics & numerical data , Prospective Studies , Quality Indicators, Health Care , Survival Analysis
7.
Nature ; 439(7075): 437-40, 2006 Jan 26.
Article in English | MEDLINE | ID: mdl-16437108

ABSTRACT

In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.

8.
Toxicol Sci ; 88(1): 242-9, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16120746

ABSTRACT

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related chemicals are potent cardiovascular teratogens in developing piscine and avian species. In the present study we investigated the effects of TCDD on murine cardiovascular development. Pregnant mice (C57Bl6N) were dosed with 1.5-24 microg TCDD/kg on gestation day (GD) 14.5. At GD 17.5, fetal mice exhibited a dose-related decrease in heart-to-body weight ratio that was significantly reduced at a maternal dose as low as 3.0 microg TCDD/kg. In addition, cardiocyte proliferation was reduced in GD 17.5 fetal hearts at the 6.0-microg TCDD/kg maternal dose. To determine if this reduction in cardiac weight was transient, or if it continued after birth, dams treated with control or 6.0 microg TCDD/kg were allowed to deliver, and heart weight of offspring was determined on postnatal days (P) 7 and 21. While no difference was seen on P 7, on P 21 pups from TCDD-treated litters showed an increase in heart-to-body weight ratio and in expression of the cardiac hypertrophy marker atrial natriuretic factor. Additionally, electrocardiograms of P 21 offspring showed that the combination of in utero and lactational TCDD exposure reduced postnatal heart rate but did not alter cardiac responsiveness to isoproterenol stimulation of heart rate. These results demonstrate that the fetal murine heart is a sensitive target of TCDD-induced teratogenicity, resembling many of TCDD-induced effects observed in fish and avian embryos, including reduced cardiocyte proliferation and altered fetal heart size. Furthermore, the combination of in utero and lactational TCDD exposure can induce cardiac hypertrophy and bradycardia postnatally, which could increase the risk of cardiovascular disease development.


Subject(s)
Cardiomegaly/chemically induced , Environmental Pollutants/toxicity , Fetal Development/drug effects , Heart Rate/drug effects , Heart/drug effects , Polychlorinated Dibenzodioxins/toxicity , Teratogens/toxicity , Animals , Animals, Suckling , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Cardiomegaly/metabolism , Cardiomegaly/pathology , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Female , Gene Expression Profiling , Heart/physiopathology , Heart Rate/physiology , Mice , Mice, Inbred C57BL , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/drug effects , Organ Size/drug effects , Pregnancy , Prenatal Exposure Delayed Effects , RNA, Messenger/metabolism
9.
Oncogene ; 20(41): 5878-87, 2001 Sep 13.
Article in English | MEDLINE | ID: mdl-11593393

ABSTRACT

Epithelial ovarian cancers (EOCs) arise in the Ovarian Surface Epithelium (OSE). This tissue is a simple, poorly committed mesothelium which exhibits characteristics of epithelial and mesenchymal cells when grown in culture. In contrast, EOCs frequently exhibit properties of complex epithelial tissues of the female reproductive tract, such as oviductal, endometrial and cervical epithelia, and show induction of expression of epithelial markers such as E-cadherin. Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF receptor 2-IIIb) is a spliced variant of FGF receptor 2 that binds the ligands FGF-1 and FGF-7 with high affinity, and is expressed exclusively by epithelial cells. We have studied the expression of FGF receptor 2-IIIb and its ligands in primary cultures of normal human OSE, EOC cell lines and snap frozen tissue from EOCs. Expression of FGF receptor 2-IIIb mRNA is undetectable in normal OSE, but is expressed in 16/20 (80%) of EOCs. FGFs 1 and 7 mRNAs are expressed in normal OSE, whilst only 4/20 (20%) and 12/20 (60%) of EOCs demonstrated expression for these ligands respectively. However, FGF-7 protein was detected in 70% (mean level=0.7 ng/ml) of ascitic fluids obtained from patients with EOC. FGFs 1 and 7 stimulate DNA synthesis in EOC cell lines that express FGF receptor 2-IIIb. Moreover, DNA synthesis in these cell lines can be partially blocked by blocking antisera to FGFs 1 and 7. It is suggested that induction of expression of FGF receptor 2-IIIb may play a role in the development of EOCs by rendering the OSE susceptible to paracrine and/or autocrine stimulation by its requisite FGF ligands.


Subject(s)
Fibroblast Growth Factor 2/metabolism , Fibroblast Growth Factors/metabolism , Neoplasm Proteins/metabolism , Ovarian Neoplasms/metabolism , Ovary/metabolism , Receptors, Fibroblast Growth Factor/metabolism , Adult , Aged , Aged, 80 and over , Ascites/metabolism , Cadherins/metabolism , DNA, Neoplasm/biosynthesis , Female , Fibroblast Growth Factor 1 , Fibroblast Growth Factor 7 , Humans , Middle Aged , RNA, Messenger/metabolism , Receptor, Fibroblast Growth Factor, Type 2 , Tumor Cells, Cultured/metabolism
10.
Fertil Steril ; 72(3): 467-71, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10519618

ABSTRACT

OBJECTIVE: To evaluate the use of percutaneous testicular sperm aspiration in the assessment of azoospermia and its association with seminiferous tubule microliths. DESIGN: Case report. SETTING: Tertiary care fertility center in a university hospital. PATIENT(S): Male undergoing infertility evaluation. INTERVENTION(S): Testicular biopsy and percutaneous testicular aspiration. MAIN OUTCOME MEASURE(S): Serum hormone analysis, sperm concentration in semen, spermatogenesis in samples from testicular biopsies and aspirations, and microlith composition. RESULT(S): A patient presented for infertility evaluation with a history of severe oligospermia that progressed to azoospermia. The serum testosterone concentration (357 ng/dL) and LH concentration (9.2 mIU/mL) were normal and the serum FSH concentration (18.3 mIU/mL) was elevated. Testicular biopsy results indicated spermatogenic hypoplasia with limited spermatozoa. Seminiferous tubules obtained by percutaneous testicular aspiration were structurally aberrant, with multiple diverticula. Microliths averaging 120 microm in diameter were observed within and blocking the seminiferous tubules. The microliths were composed of calcium phosphate (hydroxyapatite) in both the core and peripheral regions. Electron microscopy revealed a high degree of collagen-like material within the peripheral zone. CONCLUSION(S): The presence of seminiferous tubule microliths is associated with the development of azoospermia. In patients with a low incidence of seminiferous tubule microliths and aberrant seminiferous tubule architecture, percutaneous testicular aspiration may provide a diagnostic advantage over testicular biopsy.


Subject(s)
Calcinosis/diagnosis , Oligospermia/etiology , Seminiferous Tubules/abnormalities , Testicular Diseases/diagnosis , Adult , Biopsy , Calcinosis/complications , Calcinosis/pathology , Female , Follicle Stimulating Hormone/blood , Humans , Hydrogen-Ion Concentration , Luteinizing Hormone/blood , Male , Microscopy, Electron , Oligospermia/pathology , Sperm Count , Sperm Motility , Spermatogenesis , Testicular Diseases/complications , Testicular Diseases/pathology , Testis/pathology , Testosterone/blood
11.
Thorax ; 54(4): 334-8, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10092695

ABSTRACT

BACKGROUND: Resection is the treatment of choice for lung cancer, but may cause impaired cardiopulmonary function with an adverse effect on quality of life. Few studies have considered the effects of thoracotomy alone on lung function, and whether the operation itself can impair subsequent exercise capacity. METHODS: Patients being considered for lung resection (n = 106) underwent full static and dynamic pulmonary function testing which was repeated 3-6 months after surgery (n = 53). RESULTS: Thoracotomy alone (n = 13) produced a reduction in forced expiratory volume in one second (FEV1; mean (SE) 2.10 (0.16) versus 1.87 (0.15) l; p<0.05). Wedge resection (n = 13) produced a non-significant reduction in total lung capacity (TLC) only. Lobectomy (n = 14) reduced forced vital capacity (FVC), TLC, and carbon monoxide transfer factor but exercise capacity was unchanged. Only pneumonectomy (n = 13) reduced exercise capacity by 28% (PVO2 23.9 (1.5) versus 17.2 (1.7) ml/min/kg; difference (95% CI) 6.72 (3.15 to 10.28); p<0.01) and three patients changed from a cardiac limitation to exercise before pneumonectomy to pulmonary limitation afterwards. CONCLUSIONS: Neither thoracotomy alone nor limited lung resection has a significant effect on exercise capacity. Only pneumonectomy is associated with impaired exercise performance, and then perhaps not as much as might be expected.


Subject(s)
Exercise Tolerance , Lung Neoplasms/surgery , Pneumonectomy , Thoracotomy , Exercise Test , Humans , Lung Neoplasms/physiopathology , Middle Aged , Pneumonectomy/adverse effects , Postoperative Period , Respiratory Function Tests
12.
Postgrad Med J ; 75(887): 537-9, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10616686

ABSTRACT

The study was set up to investigate the awareness of elderly patients and medical doctors of medical restrictions to driving. Separate questionnaires were completed by patients and doctors. All were interviewed face-to-face, without prior warning and their immediate answers were recorded. In total, 150 elderly patients from the acute elderly care wards, rehabilitation wards and day hospital, and 50 doctors (including all grades from consultant to junior house officer) were interviewed. The main outcome measures were numbers of patients currently driving and previously driving; patients' awareness of how their medical condition affected their ability to drive; doctors' spontaneous knowledge of medical conditions which restrict driving, current licensing policy, and restrictions for five specific medical conditions (epilepsy, myocardial infarction, stroke, 5-cm abdominal aortic aneurysm, and diabetes). Only 21 patients were current drivers, and six of these should not have been driving. While 103 perceived themselves eligible to drive, 46 had medical restrictions to driving. Seventeen of the 47 patients who perceived themselves not eligible to drive possibly did not have restrictions to driving. Doctors' knowledge of the current licensing policy and action to be taken if a patient was not eligible to drive was very poor. Knowledge of medical restrictions to driving was scanty, with few doctors giving the correct driving restrictions for the five specific conditions. We recommend that education of doctors regarding medical restrictions to driving should begin at an undergraduate level and be continued throughout their postgraduate career.


Subject(s)
Automobile Driving/legislation & jurisprudence , Health Knowledge, Attitudes, Practice , Age Factors , Aged , Aged, 80 and over , Female , Humans , Male , Medical Staff, Hospital , Middle Aged , Patient Education as Topic , Surveys and Questionnaires
13.
Eur J Clin Invest ; 28(1): 33-40, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9502185

ABSTRACT

BACKGROUND: Patients with acute cardiac failure have excess body water, and it is commonly assumed that this is also so in patients with stable chronic cardiac failure (CCF). METHODS: To investigate this, we measured total body water (TBW) using stable isotope dilution and single-frequency bioelectrical impedance (BIA), and also extracellular volume (ECV) using bromide dilution in 12 patients with CCF and eight matched control subjects. RESULTS: TBW [kg(-1) bodyweight] was similar in the two groups [median 18O dilution 53.2% (range 46.5-57.1%) in patients vs. 54.8% (47.9-62.7) in control subjects; BIA 56.6% (42.7-73.1) vs. 58.0% (52.0-68.6)]. ECV was also similar in the two groups [0.25 Lkg(-1) (0.20-0.29) vs. 0.25 (0.19-0.35)]. There was a strong correlation between stable isotope and BIA measurements of TBW for all subjects (r = 0.76), but BIA overestimated TBW by a mean difference of 2.4 kg (limits of agreement of -4.1 kg to +8.9 kg). Body fat content was similar in the two groups, whether measured by skinfold anthropometry, whole-body densitometry or by 18O dilution. Resting energy expenditure (REE), calculated from indirect calorimetry, and total energy expenditure (TEE), calculated from the ratio of 2H to 18O elimination rate after drinking doubly labelled water, were also similar in the two groups. CONCLUSION: It is concluded that the patients with stable CCF in this study had normal ECV and TBW, and so excess body water did not account for their persistent symptoms.


Subject(s)
Body Composition , Energy Metabolism , Heart Failure/physiopathology , Aged , Aged, 80 and over , Body Water , Bromides , Chronic Disease , Densitometry , Deuterium , Electric Impedance , Extracellular Space/metabolism , Heart Failure/blood , Heart Failure/urine , Humans , Male , Middle Aged , Oxygen Isotopes , Potassium Compounds , Reproducibility of Results
14.
Ir J Med Sci ; 166(4): 257-9, 1997.
Article in English | MEDLINE | ID: mdl-9394079

ABSTRACT

Sixty-two women (mean age 68.7 +/- 0.9 yr) with postmenopausal spinal osteoporosis were treated with cyclical etidronate therapy (400 mg for 2 weeks alternating with 12 weeks of 1 gm elemental calcium and 400 IU Vitamin D3) for a minimum of 2 yr. Bone mineral density (BMD) of the lumbar spine (g/cm2) increased significantly (p < 0.0001) after yr 1 (4.1 +/- 0.5 per cent) and yr 2 compared with yr 1 (2.2 +/- 0.5 per cent). The response rate was 89 per cent after yr 1 and 84 per cent after yr 2. BMD of the hip (30 patients) increased by 1.5 +/- 0.9 per cent after yr 1 and 5.5 +/- 1.1 per cent (p < 0.0001) after yr 2 when compared with baseline. The response rate was 63 per cent after yr 1 and 80 per cent after yr 2. Smaller numbers of patients continued with treatment up to 4 yr with no adverse long-term effects.


Subject(s)
Etidronic Acid/administration & dosage , Osteoporosis, Postmenopausal/drug therapy , Aged , Aged, 80 and over , Bone Density/drug effects , Calcium/administration & dosage , Cholecalciferol/administration & dosage , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Etidronic Acid/adverse effects , Female , Humans , Long-Term Care , Middle Aged , Osteoporosis, Postmenopausal/diagnosis , Treatment Outcome
15.
Diabetes Care ; 20(12): 1814-21, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9405899

ABSTRACT

OBJECTIVE: The hemodynamic, respiratory, and metabolic responses to exercise were studied in IDDM patients and control subjects to detect diabetic cardiomyopathy. RESEARCH DESIGN AND METHODS: Eight subjects aged 25-40 years with diabetes of at least 10 years' duration were compared with eight control subjects aged 21-46 years. All subjects underwent a progressive incremental bicycle exercise test with measurement of gas exchange, blood glucose, lactate, fat metabolite, and catecholamine levels and two steady-state exercise tests with measurement of cardiac output by a CO2 rebreathing method. A new first-pass radionuclide method was used to measure cardiac ejection fractions (EFs) at rest, peak exercise, and steady-state exercise. RESULTS: The peak achieved oxygen consumption was similar in the diabetic and control subjects (29.9 [25.1-34.6] and 31.4 [26.9-35.9] ml.min-1.kg-1, respectively; mean [95% CI]). There were no significant differences in heart rate, double product, ventilation, respiratory exchange ratio, or ventilatory equivalents for oxygen and CO2 during the incremental test. Glucose levels were higher in the diabetic subjects, but there were no significant differences in levels of lactate, catecholamines, free fatty acids, glycerol, or beta-hydroxybutyrate. Left ventricular EF fell from rest to peak exercise within the diabetic group (66.0% [59.6-72.4] at rest; 53.6% [45.6-61.6] at peak; P < 0.05) but this did not differ significantly from the control group (58.7% [52.3-65.1] at rest; 60.3% [48.9-71.7] at peak). Right ventricular EFs were similar in each group, and there was no reduction in peak filling rate to suggest diastolic dysfunction. The cardiac output responses to exercise were also similar in the two groups. CONCLUSIONS: There is no evidence of impairment of the exercise response in subjects with long-standing diabetes, and the apparent fall in left ventricular EF at peak exercise could be related to hemodynamic adaptation.


Subject(s)
Cardiac Output/physiology , Diabetes Mellitus, Type 1/physiopathology , Exercise/physiology , Oxygen Consumption/physiology , Adult , Basal Metabolism/physiology , Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Female , Heart Rate/physiology , Humans , Male , Middle Aged , Reference Values
16.
Clin Sci (Lond) ; 93(3): 195-203, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9337633

ABSTRACT

1. The role of cardiac output limitation in the pathophysiology of exercise in patients with chronic failure remains undefined. During steady-state submaximal exercise, oxygen uptake is similar in patients and control subjects, but it is not known if cardiac output is also similar. We wished to determine if the reduced exercise tolerance of patients with chronic cardiac failure during such exercise is related to reduced cardiac output, or to peripheral factors. 2. Ten male patients with stable chronic failure and ten age-matched male normal controls were studied at rest and during exercise. Each subject performed a familiarization exercise test, a symptom-limited maximal exercise test and two submaximal exercise tests. Cardiac output was measured by a carbon dioxide rebreathing method. We also measured oxygen consumption, ventilation, Borg score of perceived exertion and venous lactate concentration, and ejection fractions. 3. As expected, patients had lower peak oxygen consumption [median (range) 1.18 (0.98-1.76) versus 1.935 (1.53-2.31) l/min; P < 0.001], lower peak venous lactate concentration but a similar overall level of perceived exertion. At the same submaximal workload, patients and control subjects had similar oxygen consumption [0.67 (0.59-0.80) versus 0.62 (0.52-0.82) l/min] and cardiac output [6.92 (5.79-9.76) versus 7.3 (5.99-10.38) l/min] but the patients had a greater perceived level of exertion [Borg score: 4 (1-6) versus 3 (1-5); P < 0.005], higher venous lactate concentration [1.6 (1-3.3) versus 1.14 (0.7-1.7) mmol/l; P < 0.05] and higher heart rate [106 (89-135) versus 87 (69-112) beats/ min; P < 0.005]. 4. During submaximal exercise at a similar absolute workload, patients with cardiac failure have a similar oxygen uptake and cardiac output but greater anaerobiosis and increased fatigue when compared with normal subjects. These findings appear to relate predominantly to changes that occur in the periphery rather than abnormalities of central cardiac function.


Subject(s)
Cardiac Output/physiology , Exercise Tolerance/physiology , Heart Failure/physiopathology , Stroke Volume/physiology , Adult , Aged , Chronic Disease , Exercise Test , Heart Failure/blood , Heart Failure/psychology , Heart Rate/physiology , Humans , Lactic Acid/blood , Male , Middle Aged , Oxygen Consumption/physiology , Radionuclide Angiography
18.
Eur J Clin Invest ; 27(4): 270-6, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9134374

ABSTRACT

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are known to be elevated in patients with chronic heart failure at rest. While it is known that during exercise the circulating level of ANP increases in patients with heart failure, the response of BNP to exercise in these patients relative to control subjects is unclear. Ten patients with stable chronic heart failure and 10 normal control subjects performed symptom-limited exercise with respired gas analysis. All patients had depressed left ventricular ejection fractions (LVEF). Patients had lower peak oxygen consumption PVo2) than the control group [median (range) 1.18 (0.98-1.76) vs. 1.94 (1.53-2.31) L min-1; P < 0.001]. Circulating plasma levels of ANP and BNP were higher at rest in patients than in control subjects [ANP 335 (140-700) vs. 90 (25-500) pg mL-1; BNP 42 (25-50) vs. 20 (10-20) pg mL-1], and at peak exercise [ANP 400 (200-1000) vs. 130 (10-590); BNP 46 (40-51) vs. 20 (10-30)]. The rise in ANP at peak exercise was significant in patients compared with the resting level, but not in control subjects. For BNP, there was a significant rise in patients but no change in control subjects. The circulating plasma levels of both peptides showed a strong negative correlation with LVEF (ANP, P < 0.005; BNP, P < 0.0001) and, to a less extent, with RVEF. It is possible that BNP may give a better indication of cardiac function.


Subject(s)
Atrial Natriuretic Factor/blood , Exercise , Heart Failure/blood , Nerve Tissue Proteins/blood , Adult , Aged , Chronic Disease , Heart Failure/physiopathology , Humans , Male , Middle Aged , Natriuretic Peptide, Brain , Stroke Volume , Ventricular Function, Left
19.
Eur J Clin Invest ; 26(11): 1018-22, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8957209

ABSTRACT

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.


Subject(s)
Cytokines/blood , Heart Failure/blood , Aged , Aged, 80 and over , Body Mass Index , C-Reactive Protein/analysis , Chronic Disease , Female , Humans , Interleukin-6/blood , Male , Receptors, Tumor Necrosis Factor/blood , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism
20.
Science ; 273(5280): 1365-7, 1996 Sep 06.
Article in English | MEDLINE | ID: mdl-8703065

ABSTRACT

The IIIA and IIIB iron meteorites are considered to have formed in the cores of asteroids. A silicate inclusion within the IIIA meteorite Puente del Zacate consisting of olivine (Fa4), low-calcium pyroxene (Fs6Wo1), chromium diopside (Fs3Wo47), plagioclase (An14Or4), graphite, troilite, chromite, daubreelite, and iron metal resembles inclusions in IAB iron meteorites. The oxygen isotopic composition of the Puente del Zacate inclusion is like chromite and phosphate inclusions in other IIIA and IIIB irons. The Puente del Zacate inclusion may have been derived from the lower mantle of the IIIAB parent asteroid.


Subject(s)
Meteoroids , Oxygen Isotopes , Silicates/analysis
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