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Biomedical subjects

T Hawkins

Publications and source records attributed to T Hawkins.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of serum on secretion of prostacyclin and endothelin-1 by decidual endothelial cells from normal and preeclamptic pregnancies.

OBJECTIVE: Increasing circumstantial evidence suggests that the maternal endothelial cell is centrally involved in the syndrome of preeclampsia, and a number of reports have described the presence of a factor(s) that alters endothelial cell function in serum from women with preeclampsia. We have previously described differences between endothelial cells from the decidual vascular bed and those from the umbilical vein. The purposes of this study were (1) to examine the effect of serum from normal and preeclamptic women on secretion of vasoactive substances by maternal decidual endothelial cells, (2) to compare these results with those from umbilical vein endothelial cells, widely used as a surrogate for endothelial cells in general, (3) to compare responses to these sera by decidual endothelial cells from normal and preeclamptic pregnancies, and (4) to determine whether these responses are amplified by preincubation in test sera. STUDY DESIGN: Endothelial cells were isolated from umbilical veins and from decidual biopsy specimens collected at caesarean section delivery, from both normal and preeclamptic women. Cells were maintained in culture until passage 2, when secretion by the three endothelial cell populations of the vasodilator prostacyclin (measured as its stable metabolite, 6-keto-prostaglandin F1 alpha) and the vasoconstrictor endothelin-1 was compared in the presence of serum from preeclamptic or gestational age-matched normal pregnant women. RESULTS: Prostacyclin secretion by all endothelial cell populations was higher in the presence of serum from preeclamptic women than in medium containing serum from gestational age-matched normal pregnant women. Values for endothelin were not significantly different in cells incubated in serum from normal or preeclamptic women. Preincubation of decidual cells from preeclamptic women in test serum, particularly in preeclamptic serum, resulted in more marked stimulation of prostacyclin secretion. CONCLUSIONS: Preeclamptic serum contains a factor(s) that stimulates prostanoid secretion from endothelial cells. This effect was observed in both umbilical vein and decidual cells. Cells from preeclamptic women were more susceptible to perturbation of their secretion by this factor. Serum from preeclamptic women did not specifically affect endothelin-1 secretion.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Secretion of prostaglandins and endothelin-1 by decidual endothelial cells from normal and preeclamptic pregnancies: comparison with human umbilical vein endothelial cells.

OBJECTIVE: An increasing amount of circumstantial evidence points to the maternal endothelial cell as centrally involved in the syndrome of preeclampsia. The purposes of this study were (1) to compare the secretion of vasoactive substances by maternal decidual endothelial cells with that of umbilical vein endothelial cells, widely used as a surrogate for endothelial cells in general, and (2) to compare secretion of the same vasoactive substances by decidual endothelial cells from normal and preeclamptic pregnancies. STUDY DESIGN: Endothelial cells were isolated from umbilical veins and from decidual biopsy specimens collected at cesarean section delivery from both normal and preeclamptic women. Cells were maintained in culture until passage 2, when secretion by the three endothelial cell populations of the vasodilators prostaglandin E2 and prostacyclin and the vasoconstrictor endothelin-1 was examined. In addition to control incubations, their responses to stimulation and suppression of secretion were compared. RESULTS: In control incubations normal decidual endothelial cells secreted lower amounts of prostacyclin, prostaglandin E2, and endothelin than did human umbilical vein endothelial cells. All cell types had qualitatively similar responses to the stimuli used, but quantitatively different responses were noted between human umbilical vein endothelial cells and normal decidual endothelial cells for all metabolites examined. Preeclamptic decidual endothelial cells secreted significantly more prostaglandin E2 than did normal decidual endothelial cells in response to stimulation. CONCLUSIONS: We have delineated levels of secretion of vasoactive substances by human late pregnancy decidual endothelial cells and their responses to manipulation of secretory pathways. There are differences between this endothelial cell population and human umbilical vein endothelial cells (which are widely used as a surrogate for maternal endothelial cells). The differences between normal and preeclamptic decidual endothelial cells in prostaglandin E2 secretion may point to altered regulation of arachidonic acid metabolic pathways in preeclampsia.

Cells, Cultured↗
PubMed1995

Hematopoietic stem cell transplantation in Australia in 1993.

The status of hemopoietic stem cell transplantation in Australia from January 1, 1993 to December 31, 1993 is reported. A total of 523 hematopoietic stem cell transplants were carried out throughout Australia during this 12 month period: 296 autologous transplants, 223 allogeneic transplants, and 4 syngeneic transplants. These were carried out by transplant programs in 20 hospitals, and the total number of transplants represented a 9.4% increase on the total number performed in 1992 (n = 478). Of the 296 autologous transplants, 133 utilized blood stem cells only, 125 marrow stem cells only, and 38 both. The most common indications for autologous transplant were non-Hodgkin's lymphoma (n = 92), acute myeloid leukemia (n = 53), breast cancer (n = 37), Hodgkin's disease (n = 33), and myeloma (n = 25). The most common indication for allogeneic transplantation was chronic myeloid leukemia (n = 59), acute myeloid leukemia (n = 56), acute lymphoblastic leukemia (n = 43), and severe aplastic anaemia (n = 14). The number of allogenic transplants performed for individual diseases was comparable between 1992 and 1993, but increases in the number of autologous transplants for non-Hodgkin's lymphoma (26%), Hodgkin's disease (45%), breast cancer (48%), and myeloma (20%) were seen.

Australia↗
PubMed1995

Rescue thrombolysis: alteplase as adjuvant treatment after streptokinase in acute myocardial infarction.

BACKGROUND: In acute myocardial infarction patients who do not reperfuse their infarct arteries shortly after thrombolytic treatment have a high morbidity and mortality. Management of this high risk group remains problematic, especially in centres without access to interventional cardiology. Additional thrombolytic treatment may result in reperfusion and improved left ventricular function. METHODS: Failure of reperfusion was assessed non-invasively as less than 25% reduction of ST elevation in the electrocardiographic lead with maximum ST shift on a pretreatment electrocardiogram. 37 patients with acute myocardial infarction who showed electrocardiographic evidence of failed reperfusion 30 minutes after 1.5 MU streptokinase over 60 minutes were randomly allocated to receive either alteplase (tissue type plasminogen activator (rt-PA) 100 mg over three hours) (19 patients) or placebo (18 patients). 43 patients with electrocardiographic evidence of reperfusion after streptokinase acted as controls. Outcome was assessed from the Selvester Q wave score of a predischarge electrocardiogram and a nuclear gated scan for left ventricular ejection fraction 4-6 weeks after discharge. RESULTS: Among patients in whom ST segment elevation was not reduced after streptokinase, alteplase treatment resulted in a significantly smaller electrocardiographic infarct size (14% (8%) v 20% (9%), P = 0.03) and improved left ventricular ejection fraction (44 (10%) v 34% (16%), P = 0.04) compared with placebo. This benefit was confined to patients who failed fibrinogenolysis after streptokinase (fibrinogen > 1 g/l). In patients in whom ST segment elevation was reduced after streptokinase, infarct size and left ventricular ejection fraction were not significantly different from those in patients treated with additional alteplase. CONCLUSION: Patients without electrocardiographic evidence of reperfusion after streptokinase may benefit from further thrombolysis with alteplase.

Drug Therapy, Combination↗
PubMed1995

Comparison of simultaneous renal clearances of true endogenous creatinine and subcutaneously administered iothalamate in man.

125I-iothalamate and true endogenous creatinine clearances, measured over two short collections periods of 1 and 2 h, were compared simultaneously in 70 patients with a variety of renal diseases and a wide range of renal function. Reproducibility of the iothalamate clearance was 18.5% and that of the creatinine clearance 12.2%. The slope of the regression was not significantly different from 1 (95% confidence interval, CI, 0.964-1.155) for the whole group, nor in any subgroup chosen. The intercept at 12.6 ml/min (CI = 5.0-20.2) indicates that there is some creatinine secretion, but this was constant at all levels of GFR. It is concluded that although the clearance of true creatinine obtained during short collection periods consistently overestimates GFR by a constant proportion, it is a reproducible and accurate measure of GFR suitable for use in the clinical setting.

Adult↗
PubMed1994

Thallium-technetium-subtraction scintigraphy in secondary hyperparathyroidism.

Between 1983 and 1992 thallium-technetium subtraction scintigraphy (TTS) was performed on 74 patients with clinical and biochemical evidence of hyperparathyroidism. Twenty-five of the 53 investigations since 1988 were conducted on patients with renal failure with a suspicion of secondary hyperparathyroidism. In a retrospective study we have evaluated radioisotope scintigraphy for patients with adenoma and for renal failure patients with possible parathyroid hyperplasia. Thirty of 74 patients underwent neck exploration. Scintigraphy detected 17 of 24 parathyroid adenomas (sensitivity 71%). In contrast, in six renal patients who came to operation, scintigraphy localised only 5 of 20 hyperplastic parathyroid glands (sensitivity 25%) and in one renal patient we localised a parathyroid adenoma. A review of the literature shows low detection rates for hyperplasia by TTS to be a common observation. Based on these findings a rational approach is offered for parathyroid localisation in renal patients prior to neck exploration.

Adenoma↗
PubMed1994

Radiopharmaceutical uptake as a marker of sternal blood supply following internal mammary artery harvesting.

To evaluate the impact of internal mammary artery harvesting on sternal blood supply after open heart surgery, a conventional bone scan was performed 7 days after operation in 30 patients. After administration of 370 MBq of technetium 99 m-medronic acid complex, imaging was carried out at the level of the sternum and including the humerus as a reference. A quantitative analysis of uptake (sternum/humerus uptake index) was performed and compared in three different groups of patients: group A, ten patients who had only vein grafts or valve surgery; group B, ten patients with single internal mammary artery harvesting; and group C, ten patients with bilateral internal mammary artery harvesting. These results were compared with 24 non-surgical subjects as a control (group D). Although intervention had a significant influence in raising the uptake index of the surgical groups (A = 3.34; B = 3.09 and C = 3.48) when compared with normal subjects (D = 2.45) (P < 0.01), there was not a statistically significant difference among the three surgical groups (P > 0.05). It was concluded that the vascular supply of the sternum is not entirely dependent upon the internal mammary arteries and that mobilization of both vessels does not cause per se additional serious impact to the bone vascularization after midline sternotomy, at least beyond day 7 after operation.

Coronary Artery Bypass↗
PubMed1994

Bone marrow transplantation in Australia during 1992. Australian Bone Marrow Transplant Recipient Data Registry.

Australia has a population of 17.5 million people distributed in six states and two territories. The first allogeneic transplants were performed in the early 1970s. There are now 19 hospitals registered with the Australian Bone Marrow Transplant Recipient Data Registry. In 1992 a total of 478 transplant procedures were carried out, of which 228 were allografts and 250 were autografts. The principal indications for allografting were acute leukaemia and chronic myeloid leukaemia; the principal indications for autografting were non-Hodgkin's lymphoma, acute myeloid leukaemia and myeloma. In general the patterns of indications and donor use do not differ from those seen in most European countries and North America.

Acute Disease↗
PubMed1994

The impact of membership in a health maintenance organization on hospital admission rates for acute chest pain.

OBJECTIVE: We evaluate the impact of membership in a staff-model health maintenance organization (HMO) on hospital admission rates for patients presenting to an emergency department with acute chest pain. DATA SOURCES AND STUDY SETTING: Primary prospective data were gathered from all 3,006 patients presenting with a chief complaint of chest pain to the emergency department (ED) of a university teaching hospital from October 1987 to November 1989. STUDY DESIGN: Prospective cohort analysis used clinical data to stratify patients into groups at high (> or = 25%), medium (8-24%), and low risk (< or = 7%) of acute myocardial infarction (AMI). Insurance status was determined as either HMO, Medicare, commercial, Medicaid, or self-pay. Triage decisions were recorded, and patient outcomes of AMI and other final diagnoses were determined for all patients. DATA COLLECTION METHODS: Clinical data were recorded by the physicians in the ED as part of a detailed protocol. Insurance data were recorded separately by the ED staff as part of the hospital administrative database. Patient outcomes were recorded daily by research nurses for hospitalized patients; for patients who were discharged from the ED, telephone or physician follow-up was accomplished within seven days after discharge. PRINCIPAL FINDINGS: HMO patients were more likely to be admitted to the hospital than patients in other insurance groups in both the medium- and low-risk patient categories. Within the low-risk category, after controlling for clinical differences in a multiple logistic model, HMO membership retained an independent positive association with hospital admission compared to all other insurance groups except Medicaid. CONCLUSIONS: For patients with acute chest pain who were at medium and low risk of acute myocardial infarction, HMO membership was associated with higher rates of hospital admission. These findings suggest that organizational factors beyond financial incentives may exercise an important influence on hospitalization rates for HMO patients.

Acute Disease↗
PubMed1993

Secretion of prostanoids by platelets and monocytes in normal and hypertensive pregnancies.

OBJECTIVES: Secretory products of immune cells may induce or potentiate coagulation disturbances and vasoconstriction, both central features of pregnancy-induced hypertension. Women with chronic essential hypertension are at high risk of superimposed pregnancy-induced hypertension. The aim of our study was to compare secretory rates of prostanoids (active in coagulation and vascular reactivity) by peripheral blood monocytes and platelets from nonpregnant controls and from women in the third trimester of pregnancy, normals and those with either pregnancy-induced hypertension or uncomplicated chronic essential hypertension. STUDY DESIGN: From 100 ml blood, peripheral blood monocytes and platelets were isolated; their relative rates of in vitro production of prostacyclin, prostaglandin E2, and thromboxane were measured, and responses to stimulation by arachidonic acid or the calcium ionophore A23187 were compared among the four groups of subjects. RESULTS: Basal peripheral blood monocyte secretory levels of prostanoids were low in all groups, with responses to both stimuli. Cells from women with chronic essential hypertension had a relatively exaggerated rise in thromboxane secretion (and to a lesser extent, prostacyclin) in response to the stimuli used, with a similar but less marked trend for those with pregnancy-induced hypertension. Platelets from women with chronic essential hypertension had particularly high basal secretory levels of thromboxane, with little further response to stimulation by arachidonic acid or A23187. CONCLUSIONS: Our work demonstrates clearly for the first time that peripheral blood monocytes from pregnant women secrete low levels of vasoactive prostanoids and respond to the stimuli used in a manner similar to that of nonpregnant women, and that cells from pregnant women with hypertension have a tendency to increased reactivity that is most marked in those with chronic essential hypertension. Platelets from women with chronic essential hypertension secrete near-maximal amounts of thromboxane in the absence of exogenous stimuli, indicating a degree of prior activation.

Adult↗
PubMed1993

Upper gastrointestinal dysmotility in heart-lung transplant recipients.

Recipient pneumonectomy and the necessity for meticulous hemostasis in heart-lung transplantation can result in injury to the vagus nerves as they course through the posterior mediastinum, with consequent delay in gastric emptying. This has been reported to lead to chronic aspiration and associated pulmonary sequelae. To study the association between delayed gastric emptying, bronchiectasis, and bronchiolitis obliterans after heart-lung transplantation, we performed esophageal manometry, 24-hour pH monitoring, and radioisotopic gastric emptying in 10 patients who underwent heart-lung transplantation. Three patients had grossly delayed liquid and solid emptying that was compatible with complete vagotomy. Six other patients had delayed liquid but normal solid emptying--an unexplained finding that is the reverse of what one would expect from vagal injury. Two of these 9 patients had esophageal dysmotility, but none demonstrated gastroesophageal reflux. One remaining patient had faster than normal gastric emptying for both solids and liquids. Of the 10, 2 patients have radiologic changes of bronchiectasis and 3 have biopsy evidence of obliterative bronchiolitis. There is no relationship between these sequelae and the occurrence of esophageal dysmotility, gastroesophageal reflux, or vagotomy. We conclude that gastric emptying abnormalities can occur after heart-lung transplantation, but such abnormalities are not associated with gastroesophageal reflux and the development of pulmonary sequelae, as previously reported.

Adult↗
PubMed1993

Ventilation perfusion radionuclide imaging in cryptogenic fibrosing alveolitis.

There is increasing interest in ventilation perfusion (V/Q) imaging in cryptogenic fibrosing alveolitis because of the data these scans provide on the dynamic V/Q relationships in such patients undergoing single lung transplantation. However, the full spectrum of V/Q abnormalities in this disease is poorly defined. We therefore analysed the V/Q scans of 45 consecutive patients with advanced cryptogenic fibrosing alveolitis being considered for single lung transplantation. Scans were classified according to the presence, severity and degree of matching of defects in ventilation and perfusion images and the results were compared with the data obtained from lung function tests. Ventilation images showed defects in 13 (29%) and 'washout delay' in 15 (33%) patients; 10 (22%) patients had asymmetric distribution of ventilation with one lung receiving > 60% of total ventilation. Perfusion images showed normal perfusion in 8 (18%), mild defects in 18 (40%) and major defects in 19 (42%) patients. The distribution of perfusion between lungs was significantly asymmetric in 20 (45%) patients. V/Q images were matched in 15 (33%), mildly mismatched in 15 (33%) and severely mismatched in 15 (33%) patients, but the degree of V/Q mismatch did not show a relationship to KCO, PaO2 or A-aO2 gradient. The appearances were atypical of pulmonary embolism in eight patients. V/Q images in cryptogenic fibrosing alveolitis show a diverse range of appearances and may mimic pulmonary embolism. V/Q imaging complements the data obtained from lung function tests and is particularly useful in defining the differential function of each lung which is particularly important in the assessment of patients for single lung transplantation.

Adult↗
PubMed1993

The effect of neonatal sex hormone manipulation on the incidence of diabetes in nonobese diabetic mice.

The nonobese diabetic (NOD) mouse is a model of Type I (insulin-dependent) diabetes. It develops autoimmune pancreatic beta-cell lesions characterized by lymphocytic infiltration and beta-cell destruction. The incidences of diabetes for male and female NOD mice in our colony were 24% and 73%, respectively. In this study, we investigated the effect of neonatal manipulation of the sex hormone profile on the incidence of diabetes in male and female NOD mice. One day after birth, male mice were castrated and female mice were either ovariectomized, given testosterone, or ovariectomized and given testosterone. The mice were maintained for 140 days and blood samples were collected biweekly starting at 42 days old. Diabetes was determined by three consecutive blood glucose levels > 200 mg/dl. Neonatal gonadectomy increased the incidence of diabetes in males but decreased it in females. Females treated with testosterone also had a decreased incidence of diabetes, whereas ovariectomy plus testosterone increased the incidence to 100%. Castration decreased the body weight in males and increased body weight in females. Testosterone treatment with or without ovariectomy also increased body weight. From these studies, we concluded that neonatal hormonal imprinting has a significant influence on the incidence of diabetes in the NOD mouse.

Aging↗
PubMed1991

The specificity of technetium-labelled-leucocyte imaging of aortic grafts in the early postoperative period.

Radio-labelled-leucocyte imaging is becoming accepted as the investigation of choice when infection of prosthetic arterial bypass grafts is suspected. However, alternative sources of inflammation, such as haematoma and, perhaps, the healing and incorporation of newly inserted bypass grafts, are potential causes of false positive results. This study examines the use of technetium-labelled-leucocyte imaging during the postoperative in-hospital period following aortic bypass surgery. Two labelled-leucocyte scans were carried out serially in 20 patients randomly allocated to receive either of two types of Dacron aortic graft in regular use. The earlier scans were undertaken at 2-5 days after surgery and only two of these scans were positive. None of the later scans, undertaken at 7-10 days after surgery, was positive. None of the patients had a graft injection as evidenced by clinical features, leucocyte counts, and C-reactive protein measurements. These results suggest that recent surgery does not in itself significantly reduce the specificity of technetium-labelled-leucocyte imaging.

Aged↗
PubMed1991

The long-term stability of reconstituted exametazime: a clinical and laboratory evaluation.

99Tcm-exametazime has become recognized as an effective agent for in vitro leucocyte labelling. However, the material is relatively expensive and exhibits instability, being recommended for use within 30 min. Following subdivision and low-temperature storage of unlabelled exametazime we have evaluated long-term stability in a clinical setting and provided some laboratory support for the observations. Vials of exametazime were reconstituted with sodium chloride injection BP and subdivided into three aliquots prior to storage at -66 degrees C. At intervals up to 27 days they were used for routine leucocyte labelling with percentage labelling efficiency being recorded. Additional aliquots were tested for lipophilic primary complex and radiochemical impurities using thin layer chromatography over a similar period. Results on 92 patients gave a mean leucocyte labelling efficiency of 37% (range 10-78%). Chromatography supported the patient data. The percentage of primary exametazime remaining after 24 days' storage (55%) compared favourably with that in a freshly prepared aliquot, subdispensed but not stored (66%). Subdivision and refrigerated storage of unlabelled exametazime at -66 degrees C appears to preserve its radiolabelling capacity and the ability of the 99Tcm-exametazime to label leucocytes. This combination of long-term stability and improved cost-effectiveness may promote more widespread utilization of this pharmaceutical in clinical nuclear medicine.

Drug Stability↗