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Biomedical subjects

S Watson

Publications and source records attributed to S Watson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Dose intensification--a phase I study of ifosfamide with vinorelbine (Navelbine): rationale and study design in advanced non-small cell lung cancer.

A phase I trial of a combination of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) and ifosfamide given on a novel schedule on 3 consecutive days with granulocyte colony-stimulating factor was conducted to establish the maximum tolerated dose of vinorelbine and the dose-limiting toxicities of this regimen. Doses of vinorelbine were escalated in cohorts of patients. Of the 29 patients enrolled at the time of data analysis, 26 were evaluable for toxicity. At the first dose level (ifosfamide 2.0 g/m2 days 1, 2, and 3; vinorelbine 15 mg/m2 days 1, 2, and 3), two of three patients had dose-limiting toxicities. The dose of ifosfamide was decreased by 20%, and dose escalation of vinorelbine was restarted. At the vinorelbine dose level of 35 mg/m2/d for 3 days, three of four patients had dose-limiting toxicities. The recommended phase II doses were established as 1.6 g/m2/d ifosfamide for 3 days and 30 mg/m2/d vinorelbine for 3 days. This study established that granulocyte colony-stimulating factor was needed for approximately 8 days. We are currently examining the feasibility of two dose levels of vinorelbine (25 mg/m2 and 30 mg/m2/d for 3 days) in combination with ifosfamide (1.6 g/m2/d) given every 2 weeks.

Adult↗
PubMed1995

Paclitaxel and ifosfamide: a multicenter phase I study in advanced non-small cell lung cancer.

Both paclitaxel and ifosfamide have significant single-agent activity in non-small cell lung cancer. We designed a phase I study combining escalating doses of paclitaxel, administered by 24-hour infusion, with ifosfamide given at a dose of 1.6 g/m2 daily x 3. Paclitaxel dose levels were 135, 170, 200, 250, and 300 mg/m2. The goal of the study was to determine the maximum tolerated dose and dose-limiting toxicities of paclitaxel when used in this combination. Dose escalation was possible because of the use of filgrastim, a granulocyte colony-stimulating factor. Twenty-five patients at three institutions were treated. The dose-limiting toxicity of the combination was granulocytopenia, with other toxicities being generally mild to moderate. The maximum tolerated dose of paclitaxel was 300 mg/m2, and the recommended phase II dose is 250 mg/m2. There was a suggestion of a dose-response curve with paclitaxel as all three partial responses were seen at the 250 mg/m2 dose level. An additional II patients had objective regression or stable disease lasting for 9 to 30 weeks. A phase II study of this combination is currently being planned by the Cancer and Leukemia Group B.

Adult↗
PubMed1994

Responsiveness of the somatosensory system after nerve injury and amputation in the human hand.

We studied the responsiveness of the somatosensory system in humans after prolonged deprivation of peripheral input. Eight patients with traumatic transection of the median or ulnar nerve and 6 patients with amputation of a finger or hand underwent microneurography and intraneural stimulation. Bundles of nerve fibers were electrically stimulated through a microelectrode placed in the affected nerve proximally to the site of damage or in the case of amputees, in a nerve fascicle supplying the stump. During intraneural stimulation the subjects with nerve injuries reported distinct percepts in the hypoesthetic skin. Their projections were usually confined to the territory of a single or two adjacent palmar digital nerves, similar to the fascicular territories of healthy nerves in control subjects, but there was much less microneurographically recordable afferent activity than in normal subjects. In amputees intraneural stimulation evoked sensations in a phantom digit or digits in over three fourths of the fascicles studied. We conclude that (1) the somatosensory system remains able to process information from a nerve fascicle that has lost its cutaneous territory, and (2) somatosensory localization remains accurate despite the presumed central reorganization that takes place after nerve division or amputation. This lack of functional adaptation has important implications with regard to our understanding of human central nervous system plasticity.

Adolescent↗
PubMed1994

Assessing iron status in children with chronic renal failure on erythropoietin: which measurements should we use?

Iron deficiency severely limits the efficacy of recombinant human erythropoietin (EPO). In order to determine how best to identify and monitor children at risk of developing iron deficiency, we serially measured several parameters of iron status in nine children before and during a 24-week period of EPO therapy. Serum ferritin was the best predictor of development of iron deficiency, five of the nine children developed iron deficiency, characterised by a poor haemoglobin response or evidence of microcytosis and hypochromia; all had a serum ferritin of 60 micrograms/l or less at the start of EPO. Haemoglobin response was also related to change in mean red cell volume (MCV); a falling MCV, irrespective of absolute value, accompanying a poor response to EPO. Iron treatment in five children resulted in significant improvements in haemoglobin and iron status parameters. Although MCV remained low, there was a marked increase in red cell volume distribution width after iron, which may be of value in monitoring the response to iron therapy. We suggest that children with a serum ferritin of 60 micrograms/l or less and those who develop a falling MCV during EPO treatment should receive high-dose oral iron supplementation before and during treatment with EPO.

Administration, Oral↗
PubMed1994

Evaluation of an automated DNA profiling system employing multiplex amplification of four tetrameric STR loci.

We have examined the performance and reproducibility of an automated DNA profiling system which is based on the multiplex amplification of 4 tetrameric STR loci-HUMVWFA31/A. HUMTH01, HUMF13A1 and HUMFES/FPS. The system was able to type 100 pg of purified, undegraded, genomic DNA. At lower concentrations of DNA (below 100 pg), allelec drop-out occurred due to stochastic differences in allele copy number. Minor variation of individual PCR reagent concentrations or cycling temperatures did not result in a significant effect on the efficiency of amplification of any of the 4 loci in the quadruplex system. More substantial variation of reagent concentrations or cycling temperatures outside the optimum range of the system resulted in a reduction or complete loss of signal for one or more loci. This was also observed at high ionic strength or extreme pH. However, under all reagent concentrations and conditions studied, no artefact bands that could potentially result in the mistyping of a sample were apparent within the read region (130-240 bases) of the gel. Evaluation of both native and denaturing polyacrylamide gels revealed that, although native gels displayed faster run times, the sizing precision of such gels for certain STR loci was lower than that of denaturing gels. Also, artefact bands may be present within the read region of native gels. In conclusion the quadruplex amplification system described, coupled with automated fluorescence-based detection on denaturing polyacrylamide gels, appeared to be a robust and reliable system for individual identification.

Alleles↗
PubMed1994

An exploratory study into a methodology for the examination of decision making by nurses in the clinical area.

This study was undertaken to explore decision making in the clinical area and why it is that some nurses make seemingly irrational decisions. In the past simulations and decision frames have been used by psychologists and clinician researchers to examine decision making, although none of these methods were reported to have been used in the clinical area. In the study 11 subjects were observed in the clinical area for 2 hours each and a total of 18 decisions were made by these subjects. Each observation was followed by an interview in which the decisions were further explored and three simulations and four decision framed questions were also employed as comparative tools. The subjects were also asked about their decision making strategies. The method of using observation to collect data was effective and the effect of experience was highlighted as one of the main factors influencing decision making. The other methods proved useful as tools to examine particular aspects of decision making. The effect of experience on decision making has wide reaching effects on future nurse education, as well as having professional implications in the area of autonomy, accountability and responsibility. Further research in this area is then recommended.

Clinical Nursing Research↗
PubMed1994

The new star of cable TV: smart cards.

Cable television viewers in New York are tuning in to an unusual new ad campaign for health care smart cards. Berdy Medical Systems Inc. of Rochelle Park, N.J., is running the ads in the hopes that card-carrying consumers will press their physicians and hospitals to jump on the automation bandwagon and buy electronic records software.

Entrepreneurship↗
PubMed1994

How automation is breaking the cash flow logjam.

As financially strapped hospitals look for ways to improve their cash flow, they are turning to automation to streamline claims processing and shorten the payment cycle. By using the latest automation tools, hospital business offices are making the most of their limited staff resources.

Computer Communication Networks↗
PubMed1994

A phase II study of cisplatin, 5-fluorouracil, and leucovorin augmented by vinorelbine (Navelbine) for advanced non-small cell lung cancer: rationale and study design.

In a randomized phase II study by the Cancer and Leukemia Group B, the cisplatin/5-fluorouracil/leucovorin (PFL) combination produced a 29% response rate in advanced, unresectable non-small cell lung cancer. Vinorelbine (Navelbine; Burroughs Wellcome, Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France), a semisynthetic vinca alkaloid, has also demonstrated single-agent activity in this disease. Therefore, a phase I-II study was designed to investigate the addition of vinorelbine in escalating doses to the PFL combination. The objectives of this study were to establish the maximum tolerated dose of vinorelbine in combination with PFL, and to define the overall response rate in a cohort of patients treated with the maximum tolerated dose. The regimen consisted of vinorelbine in escalating doses starting at 20 mg/m2/d intravenously on days 1 and 5, followed by leucovorin 100 mg orally every 4 hours on days 1 to 5,5-fluorouracil 800 mg/m2/d intravenous continuous infusion days 2 to 5 (96 hours), and cisplatin 100 mg/m2 intravenously 12 to 24 hours after administration of the first dose of vinorelbine. Cycles were repeated every 3 weeks. No dose-limiting toxicity was observed in the first five patients treated with the initial vinorelbine dose. Increasing the dose of vinorelbine to 25 mg/m2 in a second cohort of two patients, however, resulted in grade 4 granulocytopenia in both, and grade 4 diarrhea in one. It was concluded that this dose level was not feasible. During a preliminary analysis, one complete response and three partial responses were observed in 16 patients evaluated; one of these patients had a pathologic complete remission. This early analysis indicates activity for the regimen.

Adult↗
PubMed1993

Crystal structure of an endotoxin-neutralizing protein from the horseshoe crab, Limulus anti-LPS factor, at 1.5 A resolution.

Lipopolysaccharide (LPS), or endotoxin, is the major mediator of septic shock, a serious complication of Gram-negative bacterial infections in humans. Molecules that bind LPS and neutralize its biological effects or enhance its clearance could have important clinical applications. Limulus anti-LPS factor (LALF) binds LPS tightly, and, in animal models, reduces mortality when administered before or after LPS challenge or bacterial infection. Here we present the high resolution structure of a recombinant LALF. It has a single domain consisting of three alpha-helices packed against a four-stranded beta-sheet. The wedge-shaped molecule has a striking charge distribution and amphipathicity that suggest how it can insert into membranes. The binding site for LPS probably involves an extended amphipathic loop, and we propose that two mammalian LPS-binding proteins will have a similar loop. The amphipathic loop structure may be used in the design of molecules with therapeutic properties against septic shock.

Amino Acid Sequence↗
PubMed1993

Non-cardiac benefits of human recombinant erythropoietin in end stage renal failure and anaemia.

Recombinant human erythropoietin (r-HuEpo) is now available to correct the anaemia of end stage renal failure. The clinical consequences of increasing the haemoglobin concentration in children on dialysis are incompletely documented; a placebo controlled study is essential when assessing subjective changes, for example in appetite or other aspects of quality of life. A single blind, placebo controlled crossover study in 11 children with end stage renal failure was performed to assess the clinical benefits resulting from correction of anaemia. Ten of the 11 children completed 36 weeks of the study and seven completed both 24 week limbs. Subcutaneous administration of r-HuEpo twice a week resulted in an increase in haemoglobin concentration, from 73 to 112 g/l. This was associated with an objective improvement in exercise tolerance, and a subjective improvement in physical performance and health, and better school attendance. No consistent effect was seen on appetite, growth, psychosocial functioning, biochemical control, or peritoneal dialysis efficiency. A small but clinically unimportant increase in systolic and diastolic blood pressure was seen in five children. One child on antihypertensive treatment required an increase in dosage during r-HuEpo while another child required a reduction in treatment. These findings, together with the important cardiac benefits previously described during r-HuEpo treatment, support the use of r-HuEpo in all children with end stage renal failure and anaemia.

Anemia↗
PubMed1992

Radiological appearances following limb replantation: a report of 5 cases.

Plain radiographs of the limbs were reviewed after replantation procedures following traumatic amputation in 5 patients at the wrist (2), mid-forearm (2) and knee (1). Following upper limb replantation, rapid development of osteopaenia was initially noted in the juxta-articular regions and metaphyses of the tubular bones of the hand. These changes were followed by diaphyseal cortical bone loss with evidence of subperiosteal, intracortical and endosteal bone resorption. Juxta-articular erosions developed at the margins of the small joints in the hand in all cases. Gradual resolution of bone changes was noted in 3 of the 4 cases where follow-up exceeded 5 years. Following lower limb replantation, there was no evidence of bone loss; however, severe neuropathic joint disease developed within 18 months and progressed over the following 9 years. We suggest that the radiographic changes observed after upper limb replantation reflect regional hyperaemia secondary to neurovascular damage, whilst the changes in the lower limb reflect a similar process in a limb subjected to weight bearing.

Adult↗