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P Phillips

Publications and source records attributed to P Phillips.

At least 91 records · Page 5Linked to original sources

A protein kinase C-like activity involved in the chemotactic response of Dictyostelium discoideum.

During the developmental life cycle of the cellular slime mould Dictyostelium discoideum cells aggregate in response to pulses of extracellular cAMP. This chemotactic agent stimulates a number of signalling pathways in the cell including the activation of a phospholipase C activity leading to the transient generation of inositol 3,4,5-trisphosphate and diacylglycerol. The role of diacylglycerol in chemotactic response and development of Dictyostelium is not known. We have evidence to suggest that two protein kinase C-like enzymes exist in Dictyostelium due to the different cellular responses to two inhibitors specific for protein kinase C. One enzyme is preferentially sensitive to D-erythro-sphingosine, a diacylglycerol analogue, and is required for growth. A second is preferentially inhibited by bisindolylmaleimide GF109203X and is required for chemotaxis. We have identified protein kinase C-like kinase activity in Dictyostelium cell extracts which appears as the cells aggregate. This activity is stimulated by diacylglycerol, especially biologically relevant diacylglycerol species, and phosphorylates a peptide substrate which is an efficient substrate for mammalian protein kinase Cs. This activity is a candidate for the effector of diacylglycerol generated during the aggregative phase of Dictyostelium development and defines a role for diacylglycerol in the chemotactic response.

Animals↗

Clinical and angiographic implications of coronary stenting in thrombus-containing lesions.

OBJECTIVES: This study sought to determine the results of coronary stenting in thrombus-laden lesions. BACKGROUND: The angiographic evidence of intracoronary thrombus has classically been considered a formal contraindication to stent implantation. However, with increasing use of stenting, the indications for this technique have widened to include treatment of patients who have an acute coronary syndrome or lesions with adverse anatomic features. METHODS: We studied 86 consecutive patients (mean age +/- SD 61 +/- 11 years, 14 women) undergoing coronary stenting of a thrombus-containing lesion; the procedure was performed electively in 39% and after angioplasty failure in 61%. Sixty-four patients (75%) were treated for unstable angina, and 19 (22%) underwent the procedure during an acute myocardial infarction. A specific protocol that included clinical and late angiographic follow-up was used. RESULTS: Angiographic success was obtained in 83 patients (96%). Five patients (6%) died during the hospital stay despite angiographic success; four of these had cardiogenic shock, and one (1%) had subacute stent thrombosis. Non-Q wave myocardial infarction developed in five additional patients (6%), and four of these five had data consistent with distal embolization. Of the 78 patients discharged with angiographic success, 67 (86%) were event-free and clinically improved at last follow-up visit (12 +/- 11 months). During the follow-up period, eight patients required repeat angioplasty, one patient required heart transplantation, and two patients died. Quantitative angiography demonstrated excellent angiographic results after stenting (minimal lumen diameter 0.31 +/- 0.4 vs. 2.77 +/- 0.6 mm). Late angiographic follow-up (5.5 +/- 1 months) was obtained in 50 patients with 54 lesions (93% of eligible), revealing a minimal lumen diameter of 2.0 +/- 1 mm and restenosis (lumen narrowing > 50%) in 18 lesions (33%). CONCLUSIONS: Coronary stenting constitutes an effective therapeutic strategy for patients with thrombus-containing lesions, either after failure of initial angioplasty or electively as the primary procedure. Coronary stenting in this adverse anatomic setting results in a high degree of angiographic success, a low incidence of subacute thrombosis and an acceptable restenosis rate.

Adult↗

Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group.

A randomized trial was conducted to compare the efficacy and safety of fluconazole versus that of amphotericin B in the treatment of candidemia in non-neutropenic adults. Enrollment was stratified by disease severity (APACHE II score). Patients were randomized (1:1) to receive amphotericin B 0.6 mg/kg/day (cumulative dose 8 mg/kg) or fluconazole 800 mg intravenous loading dose, then 400 mg daily for four weeks (intravenous for at least 10 days). Patients were monitored for six months. A total of 106 patients were enrolled. A protocol amendment implemented midway through the trial required patients to be removed from the study and treated with amphotericin B if species identification indicated candidemia due to Candida glabrata or Candida krusei. Baseline characteristics were similar for the two groups; 103 patients (fluconazole, 50; amphotericin B, 53) met the major enrollment criteria. The intention-to-treat analysis indicated successful therapy in 50% of fluconazole recipients compared to 58% of the amphotericin B group (p = 0.39; one-sided 95% CI, -8 to 24%). The efficacy analysis included 84 patients (fluconazole, 42; amphotericin B, 42); successful outcomes were observed in 57% and 62% of cases in the fluconazole and amphotericin B groups, respectively (p = 0.66: one-sided 95% CI, -12 to 22%). The mortality at day 14 for the fluconazole group was 26% and for the amphotericin B group 21% (p = 0.52; chi-square test) and remained similar throughout the course of follow-up, Drug-related adverse events were more frequent with amphotericin B than with fluconazole and prompted switching of therapy for two (4%) and zero cases, respectively. Fluconazole and amphotericin B were associated with similar clinical response rates and survival in the treatment of candidemia among non-neutropenic patients; however, drug-related adverse events were more frequent with amphotericin B.

Adult↗

Angioscopic evaluation of angiographically complex coronary lesions.

Coronary angioscopy (CA) provides direct visualization of the endoluminal surface of coronary vessels. The usefulness of CA during coronary angioplasty of angiographically complex lesions remains to be established. This study was designed to determine the value of CA to elucidate the underlying substrate of angiographically complex lesions. Forty-seven consecutive patients with angiographically complex lesions were studied with CA before coronary intervention. Mean age of the group was 59 +/- 9 years; six patients were women. Forty (85%) patients had unstable angina. Complex angiographic lesions included coronary occlusions (n = 23) (14 with Thrombolysis in Myocardial Infarction coronary flow grade 0 and nine with flow grade 1), lesions with intraluminal filling defects suggestive of thrombus or ulceration (n = 8), and lesions that were highly eccentric (n = 16). Items analyzed with CA included red thrombus (lining or protruding) and plaque color (yellow, white, or mixed). In all patients, CA visualized the protruding material causing the angiographic appearance. At this site CA detected red thrombus in 34 (72%) patients (14 protruding, 20 lining) and atherosclerotic plaque in 45 (96%) patients. At the site of the angiographically complex lesion, plaque was classified as predominantly yellow in 24 patients, mixed in 12, and white in nine. The incidence of thrombus on CA was higher for occluded vessels (91%) or lesions with intraluminal filling defects or ulceration (87%) than in eccentric lesions (37%) (p < 0.05). However, plaque coloration was not significantly different among these three angiographic subgroups. Initial procedural success (without stent requirement) was lower in lesions showing protruding thrombus on CA (64% vs 91 %, p < 0.05). Thus most angiographically complex lesions contain thrombus. On CA red thrombus was more frequently identified on occluded vessels and lesions with filling defects or ulceration than in eccentric lesions. Yellow or mixed plaques are common in these patients, suggesting lipid-laden plaques as the underlying pathologic substrate of angiographically complex lesions.

Aged↗

A comparison of the reported early experiences of a group of student nurses with those of a group of people outside the helping professions.

In order to investigate the psychodynamic concepts of "reparation' and "compulsive caring' as possible motivations for a career in nursing, a questionnaire was given to two groups of respondents, 115 nursing students and 97 people not involved in any of the helping professions. Both groups were asked whether or not they had experienced specific, potentially distressing events and circumstances in their childhood and teenage years. The null hypothesis was that there would be no statistically significant differences between the two groups on frequency of affirmative responses to these questions. Chi-square tests were used to determine the differential frequency of responses. The nursing students had a higher percentage of affirmative responses to 11 of the 14 questions, and statistically significant differences were identified. The nursing students had a significantly greater total number of recollected adverse experiences, and there was a significantly greater number of nursing students recollecting at least one. Significance on this result was maintained when males and females were analysed separately and together, with a higher level of significance reached for males than for females. Statistically significant differences between the two groups on their responses to specific questions were greatest for the questions about separations from mother or main carer and about the occurrence of major difficulties not covered in other questions. There is strong evidence for a rejection of the null hypothesis, the implications of which are discussed.

Chi-Square Distribution↗

An explanation and the clinical significance of the failure of microcolumn tests to detect weak ABO and other antibodies.

Shear forces are proposed to explain the failure of antiglobulin and 'neutral' (no antiglobulin) microcolumn tests at 37 degrees C to detect weak ABO incompatibilities and other weak antibodies, clearly detectable by spin-tube methods. These shear forces can be minimized in a microcolumn test using a biphasic centrifugation phase. Although this biphasic test is not suitable for routine use, it may be of use as an investigational method for reference laboratories. This failure of microcolumn test to detect weak ABO incompatibilities is of little clinical significance as the antibodies are dubiously active at 37 degrees C.

ABO Blood-Group System↗

The Family Atherosclerosis Risk Intervention Study (FARIS): risk factor profiles of patients and their relatives following an acute cardiac event.

BACKGROUND: Relatives of patients with coronary heart disease have a heightened risk of cardiovascular disease. Attendance at a family-based screening clinic after an acute cardiac event could motivate patients and relatives to modify their lifestyles. AIMS: The Family Atherosclerosis Risk Intervention Study (FARIS) aimed to determine (i) whether a high proportion of patients and relatives would attend a special screening and prevention programme; (ii) whether the risk factor profiles of relatives would be worse than those in the general community; and (iii) whether ongoing management of patients and families together in a special clinic would improve risk factor profiles. METHODS: Consecutive patients, together with spouse, siblings and offspring, aged 18 to 69 years, were randomly allocated three months after an acute cardiac event to attend a special outpatient clinic, a screening and advice group, or a control group. Risk factor measures were total cholesterol, HDL cholesterol (HDLC), systolic blood pressure (SBP), body mass index (BMI) and smoking behaviour. This paper presents the risk factor profiles of all FARIS attenders and compares those of family members, age adjusted, with risk factors measured in a multicentre urban cross-sectional survey conducted in the same period. Differences between groups were compared using t-tests for numerical variables and ANOVA and chi-square for categorical variables. RESULTS: Six hundred and twenty-eight patients and 1723 family members were enrolled, representing 85.9% and 82.7% of eligible patients and relatives respectively. Risk factors were significantly worse amongst family members than among those in the population survey.

Adult↗

Vasopressin synergistically stimulates DNA synthesis in normal and regenerating rat liver cell cultures in the presence of hepatocyte growth factor.

Liver regeneration is significantly impaired in rats with both alpha-adrenergic hepatic denervation and hereditary vasopressin deficiency. This may implicate a direct role for these agonists in the process of compensatory hyperplasia. The mitogenic capacities of norepinephrine, vasopressin and hepatocyte growth factor (HGF), either alone or in combination were investigated by [3H]thymidine incorporation into hepatocyte cultures prepared from normal and regenerating rat livers. The results show that normal hepatocytes incorporate less [3H]thymidine in response to HGF than do regenerating hepatocytes. In addition, physiological concentrations of vasopressin cause a synergistic stimulation of [3H]thymidine uptake in rat liver cells in the presence of HGF.

Animals↗

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas.

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 +/- 6% at 2 years and 68 +/- 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 +/- 11% vs. 75 +/- 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 +/- 7% compared with a rate of 39 +/- 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

Adolescent↗

Common dilemmas in diabetic care.

This article looks at some commonly encountered problems faced by doctors managing diabetes. The increasing prevalence of diabetes, dilemmas relating to insulin use, the use of insulin pens and home blood glucose technologies, concerns with commonly prescribed drugs in the diabetic patient, and advice regarding travel, are discussed.

Administration, Oral↗

The eye in diabetes. Key points for the general practitioner.

Diabetic retinopathy is a common complication in people with diabetes. General practitioners can arrange annual screening for diabetic eye disease to detect early changes and prevent severe damage. Due to an ageing population the number of people with type II diabetes will increased dramatically during the next 20 years. This article outlines how general practitioners can prevent progressive loss of vision in their patients.

Australia↗