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Biomedical subjects

L Ferguson

Publications and source records attributed to L Ferguson.

At least 37 records · Page 2Linked to original sources

Casemix update.

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Critical Care↗

Casemix update.

Explore the source record for details and available documents.

Delivery of Health Care↗

Intracarotid saline infusion improves outcome from incomplete ischemia in rats.

Previous studies suggest that rheological changes associated with ischemia may produce postischemic hypoperfusion. We tested whether intracarotid or intravenous infusions of saline improve neurological outcome from incomplete cerebral ischemia in rats. Rats were anesthetized with 1.4% isoflurane in air, and ischemia was produced by unilateral carotid artery ligation combined with hemorrhagic hypotension to 30 mm Hg for 30 minutes. Intracarotid (n = 10) or intravenous (n = 10) saline infusion (0.3 ml/min) decreased hematocrit 20% compared with control rats (n = 10). Neurological outcome was significantly improved in rats infused with intracarotid (p less than 0.05) but not intravenous saline during ischemia without a change in brain temperature. Cerebral blood flow, measured in a separate study using laser Doppler flowmetry (n = 5), decreased 70% (p less than 0.01) during carotid ligation and hypotension but was not changed by intracarotid saline infusion (p greater than 0.30). These results show that perfusion of ischemic brain with saline improves outcome by factors not related to changes in hematocrit, brain temperature, or intraischemic tissue blood flow.

Animals↗

Subarachnoid hemorrhage in sickle-cell disease.

The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed.

Adolescent↗

Monitoring mutagenicity in urine and peripheral blood lymphocytes of pharmacists occupationally exposed to anticancer drugs.

Two approaches to mutagenicity monitoring were compared for estimation of possible absorption of cytotoxic drugs by a group of six pharmacists at Auckland Hospital. Blood samples were taken before and after a three week duty roster, from age and sex matched negative controls, and from a matched group of patients on chemotherapy. Peripheral blood lymphocytes were fixed, stained and analysed for sister chromatid exchange (SCE). Urine samples were collected from the pharmacists on the morning following their last day on cytotoxic dispensing duty, as well as from positive and negative controls. Samples were concentrated and analysed for mutagenicity in the bacterial Ames test. Comparison of negative control groups with the pharmacists using either of these test measures gave no evidence for significant absorption of cytotoxics by the pharmacist group as a whole, although values for the positive control groups were raised significantly in a similar comparison. The value for SCE of one pharmacist however, was elevated in the second sample (after three weeks dispensing duty) when compared with the first sample (before duty) and the urine analysis also suggested that this individual might have absorbed some mutagens. The results permit a comparison of these techniques as a means of ongoing monitoring of similar populations within New Zealand.

Antineoplastic Agents↗

"Instant-mix" whole brain photon with neutron boost radiotherapy for malignant gliomas.

From July 1985 through March 1987, 44 consecutive patients with supratentorial, nonmetastatic anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were treated with whole brain photon irradiation with concomitant neutron boost at the University of Chicago. All patients had biopsy proven disease and surgery ranged from biopsy to total gross excision. Whole brain photon radiation was given at 1.5 Gy per fraction, 5 days weekly for a total dose of 45 Gy in 6 weeks. Neutron boost radiation was prescribed to a target minimum dose that included the pre-surgical CT tumor volume plus 1 cm margin. Neutrons were administered 5-20 minutes prior to photon radiation twice weekly and a total dose of 5.2 Gyn gamma was administered over 6 weeks. Median follow-up was 36 months. The median survival was 40.3 months for anaplastic astrocytoma (10 patients) and 11 months for glioblastoma multiforme (34 patients) and 12 months for the overall group. Variables that predicted longer median survival included histology (AA vs. GBM), age (less than or equal to 39 years vs. older), and extent of surgery (total gross or partial excision vs. biopsy) whereas tumor size and Karnofsky performance status did not have a significant influence. The median survival of the anaplastic astrocytoma group was better than expected compared to the RTOG 80-07 study (a dose-finding study of similar design to this study) and historical data. Reasons for this are discussed.

Adult↗

American Express emphasizes service, training and R&D. Interview by Carolyn Dunbar.

Larry Ferguson, president of the Health Systems Group of American Express Information Services Company, tells Computers in Healthcare what has happened in the year since the company acquired enough "critical mass" through purchasing McDonnell Douglas Health Systems Company to become a major player in the healthcare computing industry.

Commerce↗

Incidence of the radial steal syndrome in patients with Brescia fistula for hemodialysis: its clinical significance.

The Brescia fistula is the method of choice for providing vascular access in patients who have chronic kidney failure that requires hemodialysis. This study investigated hand hemodynamics in patients with Brescia fistulas to determine the incidence of radial steal and its relationship to symptoms of arterial insufficiency of the hand. Twenty-three patients, one of whom had symptoms of arterial insufficiency, were studied. Thumb systolic blood pressure was determined by photoplethysmography under resting conditions and with the fistula, radial, and ulnar arteries occluded successively by digital pressure. The brachial pressure was determined by Doppler ultrasonography and the thumb/arm pressure ratio was determined for each experimental condition. The presence of a Brescia fistula resulted in a 40% reduction of the thumb blood pressure (median thumb/arm ratio = 0.61), which returned to normal (median ratio = 1.03) when the fistula was occluded. Occlusion of the radial artery distal to the fistula resulted in a significant increase in thumb blood pressure (median ratio = 0.89; p less than 0.001), indicating the presence of radial steal. This phenomenon occurred in 21 of the 24 fistulas (88%) studied. This study demonstrated that the radial steal phenomenon occurs in most patients with Brescia fistulas but in only a small number of these patients do symptoms of arterial insufficiency develop.

Adult↗

Quantitative studies of the rate of insulin internalization in isolated rat hepatocytes.

We studied internalization of 125I-labelled insulin in isolated rat hepatocytes. Using the acidification technique, we were able to dissociate the ligand from its cell-surface receptors, and thus to separate internalized from surface-bound insulin. Because during the first 5 min of incubation of 125I-labelled insulin with freshly isolated hepatocytes there is no loss of internalized label, the ratio of the amount of internalized ligand to the amount of cell-surface-bound ligand may serve as an index of insulin internalization. Within the first 10 min of insulin's interaction with hepatocytes, the plot of the above ratio as a function of time yields a straight line. The slope of this line is referred to as the endocytic rate constant (Ke) for insulin and denotes the probability with which the insulin-receptor complex is internalized in 1 min. At the insulin concentration of 0.295 ng/ml, the Ke is 0.049 min-1. It is independent of insulin concentration until the latter exceeds 1 ng/ml. At the insulin concentration of 3.2 ng/ml, the Ke accelerates to 0.131 min-1. With the Ke being the probability of insulin-receptor-complex internalization, 4.9% of occupied insulin receptors will be internalized in 1 min at an insulin concentration of 0.295 ng/ml, and 13.1% of occupied insulin receptors will be internalized in 1 min at 3.2 ng/ml. When the insulin concentration decreases from 3.2 to 0.3 ng/ml, the Ke decreases accordingly. The half-time of occupied receptor internalization is 15.4 min at the lower insulin concentration and 5.3 min at the higher insulin concentration.

Animals↗

Mechanisms of the fasting-induced dissociation of insulin binding from its action in isolated rat hepatocytes.

Fasting leads to an increase in insulin binding to isolated rat hepatocytes from 12 to 17%. This increase was accounted for by changes in the affinity of insulin receptors without alteration in their number. In contrast, the responsiveness of hepatocytes to insulin was markedly diminished in fasted rats. Both basal and insulin-stimulated rates of 14C-glucose incorporation into glycogen were significantly decreased in fasted animals. When insulin-induced 14C-glucose incorporation into glycogen was expressed as a percent above the basal rate, hepatocytes isolated both from control and fasted animals showed the same magnitude of maximal response (66 +/- 13% in fed and 59 +/- 12% in fasted animals, respectively). However, more insulin must be bound to hepatocytes isolated from fasted animals in order to elicit the same percent of insulin's maximal effect. Incubation of 'fed' hepatocytes in the serum obtained from fasted rats significantly diminished their responsiveness to insulin. An addition of insulin (100 ng/ml), glucose (10 mM) and antibodies to glucagon (1:100) eliminated the inhibitory effect of 'fasted' serum on 'fed' hepatocytes. A 48-hour fast increased significantly the microviscosity (decreased fluidity) of hepatocyte plasma membranes and altered membrane phospholipid composition. These changes correlated with enhanced insulin binding to isolated membranes. Moreover, in response to insulin, plasma membranes isolated from 'fasted' hepatocytes generated only one half the amount of the second messenger (PDH activator) observed in membranes of fed animals. The amount of PDH activator generated by incubation of plasma membranes with insulin correlated inversely with both insulin binding and membrane microviscosity. We conclude that 1) fasting induces both coupling defect and post-receptor changes in insulin's action; 2) both extracellular and intracellular factors contribute to fasting-induced dissociation of insulin binding from insulin action; 3) insulin/glucagon ratio may influence hepatocyte responsiveness to insulin; 4) alterations in plasma membrane fluidity and phospholipid composition may alter insulin binding and contribute to its dissociation from the subsequent action; 5) membranes isolated from 'fasted' hepatocytes generate less mediator of insulin action than do membranes isolated from 'fed' hepatocytes.

Animals↗