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Biomedical subjects

P Ellis

Publications and source records attributed to P Ellis.

At least 37 records · Page 2Linked to original sources
PubMed2000

No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials.

CP-122,288 is a highly potent inhibitor of neurogenic plasma extravasation in animal models at doses without vasoconstrictor effect. We evaluated the acute antimigraine efficacy of intravenous and oral CP-122,288 in two double-blind studies. In a crossover design, patients randomly received 31.25 microg of CP-122,288 intravenously, placebo, or both. In the oral study, patients received placebo or one of four doses of CP-122,288 between 3.125 and 312.5 microg, using a novel "up and down" design for randomization. Both studies were stopped prematurely when target efficacy could not be achieved. Responder rates were 29% for CP-122,288 versus 30% for placebo (difference, -1%; 95% CI, -24-22%; intravenous study) and an overall rate of 25% for CP-122,288 versus 0% for placebo (difference, 25%; 95% CI; 10-40%; oral study). CP-122,288 was not clinically effective at doses and plasma concentrations in excess of those required to inhibit neurogenic plasma extravasation in animals. Neurogenic plasma extravasation is unlikely to play a crucial role in the pathophysiology of migraine headache.

Administration, Oral↗
PubMed1999

Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro.

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), which has been shown to be a clinically effective treatment for erectile dysfunction. Its action results from increased levels of cyclic guanosine monophosphate (cGMP), which is normally degraded by PDE5. This cyclic nucleotide is a second messenger for nitric oxide, which is involved in the regulation of numerous functions, including vascular smooth muscle tone. In an attempt to better predict the effects of sildenafil on cardiovascular function, the distribution of PDE activity was determined with anti-PDE1 and anti-PDE5 antibodies in the human cardiac ventricle and saphenous vein, and in vitro studies were performed on the isolated human cardiac ventricle, corpus cavernosum, saphenous vein, and mesenteric artery as well as on rabbit aorta, dog coronary artery, dog trabecular tissue, and rabbit and human platelets. The major PDE activity in the human cardiac ventricle was shown to be calcium/calmodulin-dependent PDE1, but there was no detectable level of PDE5. In contrast, the human saphenous vein contained PDEs 1, 4, and 5, and the human mesenteric artery contained PDEs 1, 2, 3, 4, and 5. The distribution of PDE5 in the cardiovascular system is consistent with the observed pharmacodynamic and clinical effects of sildenafil. Sildenafil, unlike milrinone, a selective PDE3 inhibitor, had no effect on the isolated trabeculae carneae; this is consistent with the lack of PDE5 expression in cardiac myocytes. Sildenafil selectively increased cGMP levels in coronary vascular smooth muscle tissue but produced no change in cyclic adenosine monophosphate (cAMP) levels, which is consistent with the drug's selectivity for PDE5. In phenylephrine-contracted isolated rabbit aortic rings, sildenafil enhanced the relaxation induced by the nitric oxide donor glyceryl trinitrate, suggesting that sildenafil may potentiate the hypotensive effects of nitric oxide donor agents on the vasculature, an effect that has been observed clinically. Human platelets were found to contain PDE5, which was inhibited by 50% (IC50) by sildenafil at a concentration of 6.3 nM, consistent with the IC50 value in the corpus cavernosum. Sildenafil alone had no direct effect on platelet function, but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets. The pharmacodynamic and adverse event profiles observed in clinical trials with sildenafil are consistent with the in vitro profile of the tissue distribution of PDE5 and its known mechanism of action as a selective inhibitor of PDE5.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1999

The generation of human dendritic and NK cells from hemopoietic progenitors induced by interleukin-15.

Interleukin-15 (IL-15) is a pleiotropic cytokine that induces the generation and differentiation of lymphoid cells and shares many biological activities with IL-2. We have shown here the development of dendritic cells (DC) from human CD34+ hemopoietic precursor cells cultured for 2-4 weeks with IL-15 alone. DC generated with IL-15 have typical morphological, immunocytochemical, phenotypic, and functional characteristics of mature DC. Dual flow cytometry analysis performed weekly demonstrated increasing co-expression of CD1a or CD83 with HLA-DR, CD80, CD86, IL-2R alpha, beta, and gamma. Two populations of cells were distinguished among CD34+ progeny. Small and medium-size cells were mainly natural killer (NK) cells (72.6-85.2% CD56+) and low numbers of DC (9.1-21.3% CD1a+). Large cells were mostly DC (75.4-95.4% CD1a+). Isolated CD34+ cells did not express IL-2R subunits but after 2-3 days in culture with IL-15, they were found to express IL-2Rgamma. Induced expression of IL-2Rgamma on CD34+ cells may explain the primary mechanism of IL-15-regulated differentiation of hemopoietic precursor cells. Thus, our data suggest that IL-15 stimulates CD34+ cells to differentiate into NK and DC and may represent a new growth and survival factor for lymphoid DC.

Antigens, CD34↗
PubMed1999

Dermatologic complications in HIV.

The skin is unique in its accessibility for the diagnosis of diseases acquired because of decreased immunity in human immunodeficiency virus (HIV) infection. A majority of HIV-infected patients will have dermatologic problems at some time during their illness. Many of the cutaneous conditions identified will provide the means by which systemic opportunistic infections, neoplasms, and complications of therapy can be identified. The skin provides an opportunity for the recognition of new or foreign conditions as well as exotic manifestations of diseases that complicate HIV infection. A high degree of suspicion and a willingness to examine the entire skin thoroughly and frequently can enable practitioners to reduce the morbidity and mortality associated with HIV infection.

HIV Infections↗
PubMed1999

Student and faculty learning styles in a Canadian and a Chilean self-directed, problem-based nursing program.

A descriptive comparative study was conducted to identify and compare/contrast the learning styles of nursing faculty and entry-level students in 2 self-directed (SDL), problem-based (PBL) nursing programs. The Kolb LSI-1985 was administered to 94 first-year generic students, 63 post-R.N. students, and 22 faculty members in a Canadian university nursing program. A Spanish translation was completed by 37 incoming nursing students and 13 faculty members in a Chilean university. One-way ANOVA analysis of group mean scores showed significant differences among the 4 student groups in the active experimentation learning mode. Post hoc tests confirmed that Chilean students are less likely to be active learners than their teachers or Canadian students, a finding of significance in preparing students to assume self-direction of their learning. Canadian faculty had higher abstract conceptualization scores than Chilean faculty, which has implications for faculty development of educator roles for SDL/PBL.

Adult↗
PubMed1998

Changes in balance and locomotion measures during rehabilitation following stroke.

BACKGROUND AND PURPOSE: This study aimed to examine the utility of a number of measures of balance and locomotion for the purpose of measuring change in a group of stroke patients undergoing in-patient rehabilitation. The aim was to select a core group of measures based on empirical evidence of usefulness rather than personal preference. METHODS: Twenty-nine stroke patients undergoing in-patient rehabilitation (mean age 71.8 +/- 10.5 years; 66% male) participated in the study. A prospective design was utilized with repeated measurement undertaken at four, six and eight weeks post-stroke. Static standing, the Clinical Test of Sensory Interaction of Balance (CTSIB) (Shumway-Cook & Horak, 1986), functional reach (FR), repetitive reach (RR), step test (ST), gait velocity, stride length and the Motor Assessment Scale (Carr et al., 1985) (walking item) were assessed at each interval. RESULTS: All measures of dynamic balance showed significant change over the four-week measurement period (p < 0.0036). Factor analysis identified two factors which grouped tests into static and dynamic, with a trend towards a third factor incorporating bipedal dynamic tests. Tests of static balance suffered from ceiling effects, whereas dynamic tests of balance and gait suffered from floor effects. Dynamic tests were more responsive (Standardized Response Measure (SRM) > 0.75) to change over the rehabilitation period than static tests. CONCLUSIONS: The findings suggest that a clinically useful and responsive balance and mobility test battery should include one component of the CTSIB (Shumway-Cook & Horak, 1986), RR (step stance), ST and gait velocity.

Aged↗
PubMed1998

Fatal Staphylococcus aureus infective endocarditis: the dental implications.

Infective endocarditis remains an important and life-threatening infection despite improvements in diagnosis and management. There is currently a greater role for nosocomial acquisition of organisms and immunosuppression in the pathogenesis of this disease and emergence of a broader spectrum of infective organisms including those not commonly isolated from the mouth such as staphylococci. We report a case of infective endocarditis caused by Staphylococcus aureus in which the patient developed disseminated intravascular coagulation and multiple septic infarcts resulting in a frontal lobe brain abscess. Multiple dental extractions were complicated by delayed postextraction hemorrhage and the immediate cause of death was abdominal hemorrhage. The dental management in infective endocarditis should be planned in consultation with the attending physician, and should take into account both the causative organism and the presence of complications. When the oral cavity cannot be proven as the bacterial source for infective endocarditis, the immediate dental management should be directed toward improving the patient's oral hygiene and providing pain relief. Definitive long-term treatment, including any extractions, is ideally delayed until the patient has fully recovered from the infective endocarditis and its attendant complications.

Brain Abscess↗
PubMed1998

Clinical prognostic and predictive factors for primary chemotherapy in operable breast cancer.

PURPOSE: This study aimed to identify clinical factors that are of prognostic significance or that predict for subsequent treatment outcome in patients with large operable breast cancer treated with primary chemotherapy (PCT) at our institution. METHODS: One hundred eighty-five patients received the following regimens: CMF or MMM (76 patients), ECF (75 patients), AC or FEC (34 patients), followed by surgery, with radiotherapy (RT) given to those with breast conservation. A number of common clinical variables were assessed in relation to local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). RESULTS: Clinical responders had improved DFS (P = .009) and OS (P = .08) compared with nonresponders. There was no association between clinical or pathologic complete remission (CR) and survival. Pretreatment clinical axillary node positivity was a significant predictor of worsened DFS (P = .0001), OS (P = .0001), and LRFS (P = .03). Patients remaining clinically node-positive postchemotherapy had an inferior outcome compared with those becoming node-negative (DFS, P = .03; OS, P = .03) but pathologic axillary node status was not shown to predict for survival. Twenty-nine patients in clinical CR following PCT who electively did not have surgery and were treated with RT alone had significantly increased local recurrence rate compared with partial responders having surgery and RT (P = .02). There were no differences in DFS or OS between these groups. On multivariate analysis, clinical axillary node status was the only independent predictor of OS and DFS, and LRFS. CONCLUSION: Pretreatment and posttreatment clinical axillary node status is a major predictor of outcome following PCT. Complete clinical response does not define a more favorable subgroup compared with those not obtaining CR.

Adult↗
PubMed1998

Ventriculoperitoneal shunt knot: a rare cause of bowel obstruction and ischemia.

Small-bowel obstruction caused by knotting of a peritoneal shunt catheter is an extremely rare and severe complication of a ventriculoperitoneal (VP) shunt. In the 1-week-old female infant reported here who had a VP shunt, inability to remove the peritoneal catheter was followed by small-bowel obstruction and necrosis due to intestinal strangulation in a tight loop of the catheter. An uncomplicated primary resection of the necrotic segment was followed by placement of a temporary ventriculoatrial shunt. The authors suggest that when withdrawal of the peritoneal part of a VP shunt meets with resistance, an intraoperative radiograph should be obtained to assess the position of the remaining catheter. If knotting is observed, an attempt to straighten the catheter with a guide wire is worthwhile. Should this fail, immediate laparoscopy or laparotomy is indicated.

Dandy-Walker Syndrome↗
PubMed1996

Real-time spike detection in EEG signals using the wavelet transform and a dedicated digital signal processor card.

This paper describes a complete real-time system for EEG signal analysis. Specific software and hardware have been designed to provide biologists with an efficient tool, which allows a complete study of the different states of vigilance as well as the paroxysmal activities. The analysis method which is based on the wavelet transform is first presented and compared to the standard spectral approach. The dedicated digital signal processor card, based on the Motorola 96002 processor chip, that has been designed to support real-time acquisition and real-time processing of EEG signals is then presented. We finally illustrate the proposed method by processing real EEG signals of rats, and show that it opens up new prospects in the domain of EEG-based diagnosis. We propose a new representation, called globalization, that provides a global view and better detection of paroxysmal activities.

Algorithms↗
PubMed1996

An H-YDb epitope is encoded by a novel mouse Y chromosome gene.

Rejection of male tissue grafts by genotypically identical female mice has been explained by the existence of a male-specific transplantation antigen, H-Y (ref. 1), but the molecular nature of H-Y antigen has remained obscure. Hya, the murine locus controlling H-Y expression, has been localized to delta Sxrb, a deletion interval of the short arm of the Y chromosome. In mice, H-Y antigen comprises at least four distinct epitopes, each recognized by a specific T lymphocyte clone. It has recently been shown that one of these epitopes, H-YKk, is a peptide encoded by the Y-linked Smcy gene, presented at the cell surface with the H-2Kk major histocompatibility complex (MHC) molecule. However, deletion mapping and the analysis of variable inactivation of H-Y epitopes has suggested that the Hya locus may be genetically complex. Here we describe a novel mouse Y chromosome gene which we call Uty (ubiquitously transcribed tetratricopeptide repeat gene on the Y chromosome). We identify the peptide WMHHNMDLI derived from the UTY protein as an H-Y epitope, H-YDb. Our data formally demonstrate that H-Y antigen is the product of more than one gene on the Y chromosome.

Amino Acid Sequence↗
PubMed1996

Therapeutic monitoring of continuous infusion etoposide in small-cell lung cancer.

PURPOSE: To investigate the feasibility of therapeutic monitoring of etoposide at different plasma concentrations of the drug, and the resulting pharmacodynamic effects of such an approach. PATIENTS AND METHODS: Forty-nine previously untreated small-cell lung cancer (SCLC) patients received single-agent etoposide every 3 weeks by continuous infusion over 5 days. Plasma etoposide concentrations were monitored 18 and 66 hours into the infusion to permit dose modification. The first cohort of 15 patients began treatment with etoposide 2 micrograms/mL, with dose escalation to 3 micrograms/mL for cycles 3 and 4 and 4 micrograms/mL for cycles 5 and 6, toxicity permitting. The second cohort of 34 patients commenced at 3 micrograms/mL, with dose escalation to 4 and 5 micrograms/mL on cycles 3 and 5, respectively. RESULTS: Mean plasma etoposide concentration during the first treatment cycle was 93.4% +/- 26.6% of the target level at 18 hours (57% of patients within +/- 20% of the target) and 98.9% +/- 14.5% of the target level at 66 hours (82% of patients within +/- 20%). Hematologic toxicity was more pronounced in those treated with 3 micrograms/mL versus 2 micrograms/mL (median nadir neutrophil count, 1.3 v 2.6 x 10(9)/L, P = .032). Tumor responses, typically documented by the third cycle, were similar in each cohort (71% in patients commenced at 2 micrograms/mL and 70% at 3 micrograms/mL). Treatment cohort was not independently predictive of survival. CONCLUSION: Therapeutic monitoring of infusional etoposide is feasible and dramatically reduces interpatient pharmacokinetic variability. Although this was a small nonrandomized trial, the observation of different hematologic toxicity at the two starting concentrations but similar antitumor activity further suggests that these effects may be associated with different plasma etoposide concentrations.

Antineoplastic Agents, Phytogenic↗