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Biomedical subjects

G Gregory

Publications and source records attributed to G Gregory.

At least 19 recordsLinked to original sources

Fructose- 1,6-bisphosphate did not affect hippocampal neuronal damage caused by 10 min of complete umbilical cord occlusion in fetal sheep.

Fructose-1, 6-bisphosphate (FBP) has a neuroprotective effect in neonatal and adult rats. The purpose of this study was to examine the effects of FBP on hippocampal neuronal damage in fetal sheep asphyxiated by 10 min of complete umbilical cord occlusion. Thirteen fetal sheep at 124 days of gestation were surgically instrumented with catheters. Cardiorespiratory parameters were monitored, and biochemical analyses were performed with the blood samples. During the insult seven fetuses were given FBP (500 mg/kg) and six were given iso-osmotic saline, and hippocampal neuronal damage was examined histologically and scored. Cardiorespiratory changes were the same in both groups, and there was no neuroprotective effect of FBP in this study. However the decrease of serum total Ca level implied the Ca- chelating effect of FBP.

Animals↗

The safety and efficacy of sevoflurane anesthesia in infants and children with congenital heart disease.

UNLABELLED: We tested the hypothesis that sevoflurane is a safer and more effective anesthetic than halothane during the induction and maintenance of anesthesia for infants and children with congenital heart disease undergoing cardiac surgery. With a background of fentanyl (5 microg/kg bolus, then 5 microg. kg(-1). h(-1)), the two inhaled anesthetics were directly compared in a randomized, double-blinded, open-label study involving 180 infants and children. Primary outcome variables included severe hypotension, bradycardia, and oxygen desaturation, defined as a 30% decrease in the resting mean arterial blood pressure or heart rate, or a 20% decrease in the resting arterial oxygen saturation, for at least 30 s. There were no differences in the incidence of these variables; however, patients receiving halothane experienced twice as many episodes of severe hypotension as those who received sevoflurane (P = 0.03). These recurrences of hypotension occurred despite an increased incidence of vasopressor use in the halothane-treated patients than in the sevoflurane-treated patients. Multivariate stepwise logistic regression demonstrated that patients less than 1 yr old were at increased risk for hypotension compared with older children (P = 0.0004), and patients with preoperative cyanosis were at increased risk for developing severe desaturation (P = 0.049). Sevoflurane may have hemodynamic advantages over halothane in infants and children with congenital heart disease. IMPLICATIONS: In infants and children with congenital heart disease, anesthesia with sevoflurane may result in fewer episodes of severe hypotension and less emergent drug use than anesthesia with halothane.

Anesthetics, Inhalation↗

Effects of neuroprotective cocktails on hippocampal neuron death in an in vitro model of cerebral ischemia.

Cocktails of neuroprotectants acting at different parts of the ischemic injury cascade may have advantages over single agents. This study investigated, singly and in combination, the neuroprotective efficacy of an energy substrate (3.5 mM fructose 1,6-bisphosphate, FBP), an antagonist of NMDA receptors (1 and 10 microM MK-801), a free-radical scavenger (100 microM ascorbate), an adenosine A1 receptor agonist (10 microM 2-chloroadenosine), and an inhibitor of neurotransmission (2% isoflurane). These agents were evaluated for their ability to prevent loss and morphologic damage of CA1 neurons in rat hippocampal slices when these agents were administered during 30 minutes in vitro ischemia (combined oxygen/glucose deprivation at 37 degrees C) followed by 5 hours of recovery. Ten microM MK-801, alone or in combination with the other compounds, prevented loss of CA1 neurons and preserved their histologic appearance. Isoflurane, which prevents glutamate receptor-dependent cell death in this model, was also protective. Protection against neuron loss was also found when a subtherapeutic concentration of MK-801 (1 microM) was combined with 2-chloroadenosine (which indirectly causes NMDA receptor suppression), but not FBP or ascorbate. The authors conclude that in this model, the strategy of antagonizing NMDA receptors appears more protective than fructose-1,6-bisphosphate, 2-chloroadenosine or ascorbate.

Animals↗

Three-dimensional proton MR spectroscopic imaging of premature and term neonates.

BACKGROUND AND PURPOSE: Previous studies have primarily used single-voxel techniques to obtain MR spectra from the neonatal brain. In this study, we applied 3D MR spectroscopic imaging techniques to detect the spatial distribution of MR spectroscopic imaging-detectable compounds in premature and term infants. The goals were to test the feasibility of obtaining 3D MR spectroscopic images of newborns, assess the spatial variations of metabolite levels, and determine age-dependent differences in MR spectroscopic imaging data. METHODS: MR spectroscopic imaging data were acquired from nine premature (postconceptional age, 30-34 weeks) and eight term (postconceptional age, 38-42 weeks) neonates, all with normal clinical and neurologic outcomes. A specialized point-resolved spectroscopy sequence with very selective saturation pulses was used to select a region encompassing the majority of the brain. Phase encoding in three dimensions was performed in a 17-minute acquisition time to obtain 3D spectral arrays with a 1.0 cm(3) nominal spatial resolution. RESULTS: This study showed the feasibility of detecting the 3D distributions of choline, creatine, and N-acetylaspartate resonances in the neonatal brain. Significant spectral differences were detected among anatomic locations and between the premature and term groups. CONCLUSION: This initial study indicates that 3D MR spectroscopic imaging of the neonatal brain can detect anatomic and age-dependent variations in metabolite levels. This technique seems to be a powerful tool to assess the metabolic differences between anatomic regions and to follow the changes in cellular metabolites with brain maturation. This study also indicates the need for determining topologic and age-matched normative values before metabolic abnormalities in neonates can be accurately assessed by MR spectroscopy.

Aspartic Acid↗

Bright stars in the sky?

Actions to improve the health of people in rural and remote areas are supported by people's ability as individuals and as a community to take part actively in the design, management and evaluation of their own health services. To do this successfully, people need information about their health, resources to support their actions and political support or legitimacy. This article focuses on the third requirement. At the beginning of 2000, there seems to be strong political interest in improving the status of rural communities and rural services overall, including rural health and health services. The constellation of events that contribute to this encouraging state of affairs includes the Regional Australia Summit that was held in October 1999, the existence of a strategic framework for rural health that was agreed on by all health jurisdictions (Healthy Horizons), improved clarity about the relative state of health and health service utilisation in rural and remote areas, and the Prime Minister's recent commitment to improve rural services. The next major national opportunity to convert these positive signs into action comes with the Federal Budget in May 2000, the content of which will be closely watched by people concerned about improving health in country areas.

Australian Capital Territory↗

'Infront outback' goes national.

The National Rural Health Alliance, the Toowoomba Hospital Foundation and the Cunningham Centre have agreed to merge the two biennial conferences for rural and remote health that have been running in alternate years since 1991. This means that in March 2001, the National Rural Health Conference will, for the first time, incorporate 'Infront Outback', the Australian Rural and Remote Health Scientific Conference. There will, therefore, be one major biennial rural heath conference, dealing coherently with health scientific research and policy development. The recommendations to governments and national bodies that result should be even stronger and more highly regarded than has been the case to date.

Australia↗

Non-government organisations to combine for work on chronic disease in Aboriginal peoples, Torres Strait Islanders and rural and remote populations.

As a result of the National Health Priority Area Report on Cardiovascular Health and in particular, its remote and indigenous section, a consortium of five organisations ran a national workshop in Townsville in October 1999 on heart disease in Aboriginal peoples, Torres Strait Islanders and rural and remote populations. One of the priority areas identified at this workshop was the need for a more coordinated approach to chronic diseases and for the formation of an alliance of non-government organisations (NGOs) to work towards this and to undertake a lobbying and advocacy role. A meeting of a wide range of NGOs working in chronic disease, led by the National Heart Foundation of Australia, was held in Sydney in May 2000. At the Sydney meeting it was agreed that an alliance of NGOs could be formed for the development of a chronic disease strategy for Aboriginal peoples, Torres Strait Islanders and rural and remote populations. The NGOs drafted a 'Statement of Intent', which would inform their work on both heart disease and on broader work to address chronic preventable disease in the target populations. There is a considerable amount of procedural work to be done before the proposed alliance becomes a reality but the prospect of closer collaboration between the NGOs working in chronic disease has much to offer, especially for the population groups that were the focus of the Townsville workshop. This 'alliance' initiative comes at a time when there are national and State/Territory moves on broader aspects of what could become a 'national chronic disease prevention and management strategy'.

Australia↗

Evolution of brain injury after transient middle cerebral artery occlusion in neonatal rats.

BACKGROUND AND PURPOSE: Stroke in preterm and term babies is common and results in significant morbidity. The vulnerability and pathophysiological mechanisms of neonatal cerebral ischemia-reperfusion may differ from those in the mature cerebral nervous system because of the immaturity of many receptor systems and differences in metabolism in neonatal brain. This study details the neuropathological sequelae of reperfusion-induced brain injury after transient middle cerebral artery (MCA) occlusion in the postnatal day 7 (P7) rat. METHODS: P7 rats were subjected to 3 hours of MCA occlusion followed by reperfusion or sham surgery. Diffusion-weighted MRI was performed during MCA occlusion, and maps of the apparent diffusion coefficient (ADC) were constructed. Contrast-enhanced MRI was performed in a subset of animals before and 20 minutes after reperfusion. Triphenyltetrazolium chloride (TTC) staining of the brain was performed 24 hours after reperfusion. Immunohistochemistry to identify astrocytes (glial fibrillary acidic protein), reactive microglia (ED-1), and neurons (microtubule-associated protein 2) and cresyl violet staining were done 4, 8, 24, and 72 hours after reperfusion. RESULTS: On contrast-enhanced MRI, nearly complete disruption of cerebral blood flow was evident in the vascular territory of the MCA during occlusion. Partial restoration of blood flow occurred after removal of the suture. A significant decrease of the ADC, indicative of early cytotoxic edema, occurred in anatomic regions with a disrupted blood supply. The decline in ADC was associated with TTC- and cresyl violet-determined brain injury in these regions 24 hours later. The ischemic core was rapidly infiltrated with reactive microglia and was surrounded by reactive astroglia. CONCLUSIONS: In P7 rats, transient MCA occlusion causes acute cytotoxic edema and severe unilateral brain injury. The presence of a prominent inflammatory response suggests that both the ischemic episode and the reperfusion contribute to the neuropathological outcome.

Animals↗

Clinical multi-colour fluorescence imaging of malignant tumours--initial experience.

PURPOSE: The detection of malignant tumours relies on a variety of diagnostic procedures including X-ray images and, for hollow organs, endoscopy. The purpose of this study was to present a new technique for non-invasive tumour detection based on tissue fluorescence imaging. MATERIAL AND METHODS: A clinically adapted multi-colour fluorescence system was employed in the real-time imaging of malignant tumours of the skin, breast, head and neck region, and urinary bladder. Tumour detection was based on the contrast displayed in fluorescence between normal and malignant tissue, related to the selective uptake of tumour-marking agents, such as haematoporphyrin derivative (HPD) and delta-amino levulinic acid (ALA), and natural chromophore differences between various tissues. In order to demarcate basal cell carcinomas of the skin, ALA was applied topically 4-6 h before the fluorescence investigation. For urinary bladder tumour visualisation (transitional cell carcinoma of different stages including carcinoma in situ), ALA was instilled into the bladder 1-2 h prior to the study. Malignant and premalignant lesions in the head and neck region were imaged after i.v. injection of HPD (Photofrin). Finally, the extent of in situ and invasive carcinomas of the breast was investigated in surgically excised specimens from patients that received a low-dose injection of HPD 24 h prior to the study. The tumour imaging system was coupled to an endoscope. Fluorescence light emission from the tissue surface was induced with 100-ns-long optical pulses at 390 nm, generated from a frequency-doubled alexandrite laser. With the use of special image-splitting optics, the tumour fluorescence, intensified in a micro-channel plate, was imaged in 3 selected wavelength bands. These 3 images were processed together to form a new optimised-contrast image of the tumour. This image, updated at a rate of about 3 frames/s, was mixed with a normal colour video image of the tissue. RESULTS: A clear demarcation from normal surrounding tissue was found during in vivo measurements of superficial bladder carcinoma, basal cell carcinoma of the skin, and leukoplakia with dysplasia of the lip, and in in vitro investigations of resected breast cancer. CONCLUSIONS: The initial clinical experience of using multi-colour fluorescence imaging has shown that the technique has the potential to reveal malignant tumour tissue, including non-invasive early carcinoma and also precancerous tissue. Further investigations are needed to fully develop the method.

Adult↗

Fructose-1,6-bisphosphate preserves adenosine triphosphate but not intracellular pH during hypoxia in respiring neonatal rat brain slices.

BACKGROUND: Fructose-1,6-bisphosphate (FBP) sometimes provides substantial cerebral protection during hypoxia or ischemia. 31P/1H nuclear magnetic resonance spectroscopy of cerebrocortical slices was used to study the effects of FBP on hypoxia-induced metabolic changes. In addition, 13C-labeled glucose was administered and 13C nuclear magnetic resonance spectroscopy was used to search for FBP-induced modulations in glycolysis and the pentose-phosphate pathway. METHODS: In each experiment, 80 slices (350 microm) obtained from ten 7-day-old Sprague-Dawley rat litter mates were placed together in a 20-mm nuclear magnetic resonance tube, perfused, and subjected to 30 min of hypoxia (PO2 < 3 mmHg). Nine experiments were performed, with n = 3 in each of three groups: (1) no treatment with FBP; (2) 60 min of prehypoxia treatment with FBP (2 mM); and (3) 60 min of posthypoxia treatment with FBP (2 mM). 31P/1H Interleaved nuclear magnetic resonance spectra at 4.7 T provided average adenosine triphosphate, intracellular pH, and lactate. Cresyl violet stains of random slices taken at predetermined time points were studied histologically. Some experiments had [2-13C]glucose in the perfusate. Slices from these studies were frozen for perchloric acid extraction of intracellular metabolites and studied with high-resolution 13C nuclear magnetic resonance spectroscopy at 11.75 T. RESULTS: With no pretreatment with FBP, hypoxia caused an approximately 50% loss of adenosine triphosphate, an approximately 700% increase in lactate, and a decrease in intracellular pH to approximately 6.4. Pretreatment with FBP resulted in no detectable loss of adenosine triphosphate, no increase in lactate, and minimal morphologic changes but did not alter decreases in intracellular pH. 13C Nuclear magnetic resonance spectra of extracted metabolites showed that pretreatment caused accumulation of [1-13C]fructose-6-phosphate, an early pentose-phosphate pathway metabolite. Posthypoxic treatment with FBP had no effects compared with no treatment. CONCLUSIONS: During severe hypoxia, pretreatment with FBP completely preserves adenosine triphosphate and almost completely preserves cell morphology but does not alter hypoxia-induced decreases in intracellular pH. Pretreatment also substantially augments the flux of glucose into the pentose-phosphate pathway.

Adenosine Triphosphate↗

Pharmacologic hemoglobin reversal: the importance of lipid intermediaries and the proposed involvement of the cAMP and phosphatidylinositol second messenger systems.

Humoral and microenvironmental influences have played a major role in recent research into reversing the Hb F to Hb A switch. Early research in this area focused on hormonal influences and showed both thyroid hormone and prolactin could induce small but statistically significant reversals in hemoglobin phenotype. Recent research has focused on the effect of certain lipids in this process. The current study shows a synergy between thyroid hormone and prolactin in inducing a significant switch in adult rat hemoglobin patterns toward the neonatal pattern. Further, it is hypothesized that this synergy is due to the hormones' effect on lipid intermediaries whose effect in turn are proposed to be mediated by the cAMP and phosphatidylinositol second messenger systems.

Animals↗

National rural health policy and the role of the National Rural Health Conferences.

The biennial National Rural Health Conference has become as essential feature on the calendar of events for rural and remote health professionals, researchers, public servants and consumers. Since the first conference held in 1991, attendance has grown significantly, factors hindering the achievement of optimal health for all rural and remote Australia have been clearly identified, and recommendations for action have been endorsed by the broad rural health constituency. These recommendations have provided valuable input to the National Rural Health Strategy and many programs and policies of Commonwealth and State departments of health. Significantly, too, the first four conferences have facilitated greater collaboration among rural and remote health professionals and provided a major catalyst in fostering cooperation between consumers, health workers, service providers and governments.

Australia↗

ECG in sickle cell trait at rest and during exercise and hypoxia.

The electrocardiograms of 28 volunteers with sickle cell trait were compared to those of 28 control subjects. Tracings were recorded at rest, at peak exercise, at simulated sea level, and at a simulated altitude of 4,000 m. No differences between the subjects with sickle cell trait and control subjects were observed for the majority of electrocardiographic measurements. Several measurements had statistically significant differences that persisted after correcting for body surface area and physical fitness. The magnitude of the differences does not appear to have physiologic or clinical significance. The observation that the differences were greatest for resting and sea level recordings indicates that sickling is probably not responsible. Further investigation will be needed to substantiate these differences and determine whether these electrical observations have any physiologic implication.

Adolescent↗

Randomized trial of dapsone and aerosolized pentamidine for the prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis.

PURPOSE: Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis are the most frequent pulmonary and central nervous system opportunistic infections associated with human immunodeficiency virus (HIV) infection. We designed a prospective study to compare the effects of aerosolized pentamidine and dapsone in the prophylaxis of these infections in HIV-infected persons with CD4+ lymphocyte counts less than 250/mm3. PATIENTS AND METHODS: Two hundred seventy-eight patients seropositive for HIV who had acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex were randomly assigned to receive intermittent dapsone (100 mg twice weekly) or aerosolized pentamidine (100 mg every 2 weeks). The proportion of patients remaining free of PCP or toxoplasmosis was analyzed with the log-rank test as a function of time, as were the effects of zidovudine or prophylaxis on survival. RESULTS: Dapsone and aerosolized pentamidine demonstrated similar efficacy in the primary and secondary prophylaxis of PCP, with 15 (18%) failures among patients receiving dapsone compared to 15 (14%) among those receiving aerosolized pentamidine (p = 0.4), after a mean length of follow-up of 42 and 44 weeks, respectively. Dapsone was more effective in the primary prophylaxis of toxoplasmic encephalitis, with six toxoplasmic encephalitis events occurring among those receiving aerosolized pentamidine, compared to none among those taking dapsone (p = 0.01). Primary prophylaxis for PCP was more effective than secondary prophylaxis with either therapy. Zidovudine therapy did not prevent PCP yet prolonged the PCP-free interval for those in whom either prophylactic therapy failed. Kaplan-Meier estimates did not show a difference in survival between the patients receiving either therapy, yet zidovudine use was associated with improved survival, independent of race and risk factor (Cox proportional hazards model, p = 0.001). The 1-month survival for patients developing PCP despite prophylaxis was better with those in whom dapsone failed than it was for those in whom aerosolized pentamidine failed (p = 0.08). CONCLUSION: Dapsone is as effective as aerosolized pentamidine in preventing PCP and has the advantage of a lower cost, easier administration, and possibly an additional preventive effect against toxoplasmosis. Zidovudine prolongs the PCP-free interval for patients receiving prophylaxis, regardless of which prophylactic agent is used.

AIDS-Related Opportunistic Infections↗

Effects of simulated altitude and exercise upon ECGs of young black men.

Twenty-five healthy black men between 17 and 21 years of age were evaluated. Their resting and exercise electrocardiograms were recorded at simulated sea level and at a simulated altitude of 4,000 m. Sea level exercise caused a reduction in the amplitudes of R waves and a lowering of J points. Exercise at a simulated altitude of 4,000 m caused a lowering of the J point in several leads and a reduction of the R wave amplitude in lead aVF. Hypoxia caused a reduction in the amplitudes of the T waves and a lowering of the J points in several leads. These effects of exercise and altitude, to a great extent, eliminated the appearance of "early repolarization," which is very common among young black men.

Adult↗