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Biomedical subjects

P Ellis

Publications and source records attributed to P Ellis.

At least 55 records · Page 3Linked to original sources
PubMed1995

A phase I and pharmacology study of an oral platinum complex, JM216: dose-dependent pharmacokinetics with single-dose administration.

JM216 [bis-acetato-ammine-dichloro-cyclo-hexylamine-platinum (IV)] is an oral platinum complex with in vivo activity against murine and human tumor models and a lack of nephro- and neurotoxicity in rodents. During a phase I study of a single-dose schedule, JM216 was given in dry-filled hard gelatin capsules by mouth without hydration or diuresis. In all, 37 patients were given a total of 88 courses at doses ranging from 60 to 700 mg/m2. The study was stopped before the MTD was reached because of nonlinear pharmacokinetics. Myelosuppression was manifest by leucopenia or thrombocytopenia and showed marked variability at 420-700 mg/m2. Vomiting was mild and controllable by antiemetics in approximately 50% of courses. The onset of vomiting was delayed to 4 h after during ingestion. There was no nephro-, oto- or neuro-toxicity. A partial response was recorded in a patient with recurrent ovarian cancer, and significant falls in plasma tumour markers (CA125) were seen in two further cases. Plasma pharmacokinetics were linear and showed moderate interpatient variability at dose levels of < or = 120 mg/m2. At dose levels of > or = 200 mg/m2, Cmax and AUC increased less than proportionally to dose. This was associated with greater interpatient pharmacokinetic variability and reduced urinary platinum recovery. A significant sigmoidal relationship existed between ultrafilterable plasma AUC and the percentage of reduction in platelet count (r2 = 0.78). Nonlinear absorption was a limitation to this single-dose schedule of oral NM216; however, little non-haematological toxicity was seen at doses associated with myelosuppression and antitumour activity. Clinical studies of divided dose schedules using doses within the range of pharmacokinetic linearity (< or = 120 mg/m2) are now being investigated.

Administration, Oral↗
PubMed1995

The in vivo pharmacological profile of a 5-HT1 receptor agonist, CP-122,288, a selective inhibitor of neurogenic inflammation.

1. The aim of the present study was to investigate the in vivo pharmacological profile of CP-122,288, an indole-derivative with a conformationally restricted N-methylpyrrolidinyl basic side chain in the C-3 position. This C-3 substituent structurally differentiates CP-122,288 from the 5-HT1D receptor agonist sumatriptan, which possesses an N,N-dimethylaminoethyl group. [Formula: see text] 2. When administered prior to electrical stimulation of the trigeminal ganglion, CP-122,288 (0.3-300 ng kg-1, i.v.) produced a dose-related inhibition of plasma protein extravasation in rat dura mater (minimum effective dose, MED, 3 ng kg-1 i.v., P < 0.05; maximal inhibition of plasma extravasation at 30 ng kg-1 i.v., P < 0.01). Sumatriptan produced a similar inhibition of plasma leakage in the dura, but at much higher dose levels (MED, 100 micrograms kg-1 i.v., P < 0.05). Thus, CP-122,288 is of the order of 10(4) fold more potent than sumatriptan. 3. At all doses tested, CP-122,288 did not inhibit plasma protein extravasation measured in extracranial tissues such as the lower lip, eyelid, and conjunctiva. 4. In a separate series of studies in the anaesthetized rat, CP-122,288 (0.003-3 micrograms kg-1 i.v.) produced no change in either heart rate or mean arterial blood pressure, thus demonstrating that doses of CP-122,288 which inhibit plasma protein leakage in rat dura, are devoid of hemodynamic effects. 5. Following a 5 min period of electrical stimulation of the trigeminal ganglion, a 20 min period of sustained neurogenically-driven plasma extravasation, occurring in the absence of electrical stimulation, was initiated. By administration of the compound 5 min after completing the phase of electrical stimulation, this protocol permitted the evaluation of the activity of CP-122,288 on an ongoing and established inflammatory event. CP-122,288 (30 and 300 ng kg-1, i.v., P < 0.01 and P < 0.05, respectively) produced a complete inhibition of plasma protein leakage which was consistent with its effects when administered prior to trigeminal ganglion stimulation. 6. In the anaesthetized dog, CP-122,288 and sumatriptan, at 1-300 micrograms kg-1, i.v., produced a dose-dependent reduction in carotid arterial blood flow and coronary arterial diameter. These data demonstrate that sumatriptan inhibits neurogenic inflammation in the rat (MED, 100 micrograms kg-1, i.v.), and produces vasoconstriction in the dog, over a similar dose-range. Interestingly, doses of CP-122,288 that inhibit neurogenic inflammation in rat dura mater (0.3-300 ng kg-1) were demonstrated to be devoid of vasoconstrictor activity in either the carotid or coronary vascular beds of dog. 7. These data demonstrate that in the rat, CP-122,288 is a highly potent and selective inhibitor of neurogenic inflammation in intracranial tissues, at doses which are devoid of vasoconstrictor activity in dog. Potentially, CP-122,288 may be of use for the acute treatment of migraine, without the risk of cardiovascular side-effects.

Anesthesia↗
PubMed1994

Management of carcinomas of the upper gastrointestinal tract.

Patients with oesophageal, gastric, and pancreatic carcinomas present a common and difficult problem for the clinician. Surgery is the best option for curative treatment but overall survival figures remain low. Recent improvements in our understanding of the biology of these tumours and improvements in their clinical staging, along with the development of combined modality approaches to local-regional disease, have led to renewed optimism that survival figures may be improved. This is particularly so for oesophageal and gastric carcinomas. In addition, there have been advances in the palliative management of all three tumours. This article examines some of these developments and looks at future prospects.

Adult↗
PubMed1994

Diagnosis of lymphoma in a continuous ambulatory peritoneal dialysis patient by peritoneal fluid cytology.

A 72-year-old woman with diabetic nephropathy receiving continuous ambulatory peritoneal dialysis for 1 year presented with recurrent episodes of sterile cloudy dialysate. Abdominal ultrasound and computed tomography demonstrated retroperitoneal masses. Cytology of the dialysis fluid revealed large atypical lymphocytes with light chain restriction, strongly suggestive of lymphoma. Fine-needle aspiration of the retroperitoneal masses showed cells with identical cytologic and immunocytochemical staining characteristics. This is the first report of de novo lymphoma diagnosed in a continuous ambulatory peritoneal dialysis patient by cytologic analysis of the dialysis effluent.

Aged↗
PubMed1994

A survey of college health services: how widely are protocols used in the college health setting?

We developed a survey to assess the prevalence and use of protocols in college health services, using the college health nurse as the primary focus. Three thousand and twenty copies of the survey were mailed to individual and institutional members of the American College Health Association (ACHA), and 812 surveys were returned, yielding a return rate of 25%. The data, which came from all 50 states, Canada, and Guam, were then compiled and analyzed using computer software dBase III. The generalizability of the results are somewhat limited because some surveys were returned with unanswered questions and because duplicate surveys were received from some facilities.

Health Surveys↗
PubMed1993

Utilization of medical services by drug abusers in detoxification.

To establish the extent of health services, including inpatient, emergency room, and outpatient care utilized by illicit drug users during the previous year, we surveyed 77 drug abusers, who were not known to be HIV-positive, entering a detoxification unit and a comparison group of 70 drug nonusers. Over the previous year, drug abusers had a greater number of visits to their usual source of care, to emergency rooms, and to other sites than drug nonusers. Drug abusers were significantly more likely to have been hospitalized during the past year. Using a logistic model including sociodemographic factors, drug abusers were 2.3 times as likely to use an emergency room and 6.7 times as likely to be hospitalized as drug nonusers. We conclude that drug abusers are heavy users of health services compared to a group of drug nonusers.

Ambulatory Care↗
PubMed1993

Monitoring the standard of deputizing services.

The standard of medical care provided by deputizing services is important for patients receiving care and for doctors using the service. The monitoring of these standards is discussed here in terms of what should be measured, how this should be done, and who should carry out this monitoring. The features to be taken into account include professional values, accessibility, clinical competence, and ability to communicate. Various bodies, such as the deputizing services, family health services authorities, and individual doctors and patients will usefully be involved in assessing standards. The future might hold radical solutions to the management of out-of-hours calls. These solutions could involve patients, general practitioners and the deputizing services. The result must be that patients receive the best possible care.

Contract Services↗
PubMed1992

Sucrose promotes the functional activity of blood vessels after cryopreservation in DMSO-containing fetal calf serum.

The cryoprotective effect of sucrose has been investigated using 3 different vascular smooth muscle preparations, namely canine saphenous veins and arteries and porcine circumflex coronary arteries following storage in liquid nitrogen (at -196 degrees C). Contractile responses to noradrenaline, 5-HT, prostaglandin F2 alpha and KCl and relaxant responses to substance P and 5-HT were determined on fresh tissues and after cryostorage in fetal calf serum (FCS) containing either 1.8 M dimethyl sulfoxide (DMSO), or 0.1 M sucrose or both agents combined. The data demonstrate that the addition of sucrose to the DMSO-containing cryomedium promotes the preservation of both contractile and relaxant activity of cryostored blood vessels, though sucrose alone did not confer any noticeable protection.

Animals↗
PubMed1992

Neutrophils from patients undergoing hip surgery exhibit enhanced movement under spinal anaesthesia compared with general anaesthesia.

The purpose of this research was to investigate whether the effects of regional anaesthesia on neutrophil migration differ from those due to general anaesthesia during major orthopaedic surgery in human patients. Eighteen patients underwent spinal or general anaesthesia (halothane or isoflurane) for surgery (six patients in each group). Blood samples were taken prior to induction of anaesthesia and after surgery was in progress for one hour. The movement of isolated neutrophils was measured in both samples in the chemotactic chamber toward lipopolysaccharide activated pooled serum. In addition plasma concentrations of catecholamines were determined in the blood samples. Neutrophils extracted from peripheral blood during spinal anaesthesia and surgery moved further towards a complement-derived attractant than neutrophils obtained from patients undergoing surgery under general anaesthesia with halothane or isoflurane and surgery (156.4 +/- 7.6 microns vs 114.3 +/- 6.1 microns or 119 +/- 8.4 microns respectively, P < 0.05). Increased concentrations of adrenaline were present in both general anaesthetic groups whereas the spinal group had lower concentrations than those prior to anaesthesia and surgery. It is considered unlikely that these differences in neutrophil reactivity are due to the direct effects of anaesthetic agents employed. The effects are likely to be the result of differing effects of spinal anaesthesia on the stress response or immunological mediators.

Adult↗
PubMed1992

Environmentally contaminated families: therapeutic considerations.

The unique stress for families of exposure to environmental toxins is discussed in terms of the physical characteristics of such contaminants and resultant adaptational dilemmas, the agent or cause of the injury, and institutional responses to the contamination. Recommendations for mental health professionals working with contaminated families are presented.

Adaptation, Psychological↗