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Biomedical subjects

P H Jones

Publications and source records attributed to P H Jones.

At least 19 recordsLinked to original sources
PubMed1999

Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy.

BACKGROUND--Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL-C or raising HDL-C. METHODS AND RESULTS--Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL-C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82+/-0.06 mmol/L (31. 7+/-2.2 mg/dL), versus 1.23+/-0.29 mmol/L (47.4+/-11.2 mg/dL) in patients with baseline HDL-C >/=0.91 mmol/L. Among patients on placebo, those with low HDL-C had significantly more angiographic progression than those with higher HDL-C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065+/-0.036 mm versus 0.274+/-0.045 mm in placebo patients (P=0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0. 036+/-0.021 mm and 0.083+/-0.019 mm (P=0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P=0.01); among low-HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. CONCLUSIONS--Although the predominant lipid-modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL-C received the greatest angiographic and clinical benefit.

Adult↗
PubMed1998

Future of lipid-lowering trials: what else do we need to know?

Convincing clinical trial evidence shows that lipid-lowering therapy can be effective in primary and secondary prevention of coronary artery disease events. At least 2 studies indicate that this benefit extends to persons with only mild or moderate hypercholesterolemia. The benefits of lipid-lowering therapy in certain subpopulations, however, remains to be elucidated. The effects in women, African Americans, the elderly, and patients with concomitant coronary artery disease risk factors such as diabetes and hypertension are only recently being studied in large, well-designed trials. Other trials, described herein, are studying the benefits of therapy in persons with coronary artery disease and low levels of high-density lipoprotein (HDL) cholesterol (but normal or only mildly elevated total or low-density lipoprotein [LDL] cholesterol). Future trials are needed to assess prospectively the value of aggressive lipid-lowering therapy on coronary artery disease events in diabetic patients with and without coronary artery disease. New drug therapies and innovative uses for existing therapies are being developed that may have an important impact on the prevention of coronary artery disease.

Aged↗
PubMed1998

Long-term effects of low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. Liposorber Study Group.

The short-term effectiveness of low-density lipoprotein (LDL) apheresis using a dextran sulfate cellulose adsorption column technique was previously examined in a 9-center, 22-week controlled trial in 64 patients with familial hypercholesterolemia (FH) who did not adequately respond to diet and drug therapy. Forty-nine patients (40 treatment, 9 controls) subsequently received LDL apheresis procedures as part of an optional follow-up phase. This study reports on the long-term safety, lipid lowering, and clinical efficacy of LDL apheresis for the 5-year period that includes both the initial controlled study and follow-up phase. During this time, patients received a total of 3,902 treatments of which 3,314 treatments were given during the follow-up phase. Adverse events were infrequent, occurring in 142 procedures (3.6%). Immediate reduction in LDL cholesterol was 76% both in homozygotes and in heterozygotes. Patients with homozygous FH had a progressive decrease in pretreatment LDL cholesterol level along with an increase in high-density lipoprotein (HDL) cholesterol level. There was no appreciable change in pretreatment lipoprotein level over time in heterozygotes. The rate of cardiovascular events during therapy with LDL apheresis and lipid-lowering drugs was 3.5 events per 1,000 patient-months of treatment compared with 6.3 events per 1,000 patient-months for the 5 years before LDL apheresis therapy. These findings support the long-term safety and clinical efficacy of LDL apheresis in patients with heterozygous and homozygous FH who are inadequately controlled with drug therapy.

Adolescent↗
PubMed1997

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

Adult↗
PubMed1997

Effectiveness of atorvastatin for reducing low-density lipoprotein cholesterol to National Cholesterol Education Program treatment goals.

Atorvastatin is a highly efficacious hydroxymethylglutaryl-coenzyme A reductase inhibitor that has been shown to reduce low-density lipoprotein cholesterol by 40% to 60%. Monotherapy with atorvastatin (10 to 80 mg/day) is well-tolerated, convenient, and appears to be effective for achieving National Cholesterol Education Program treatment goals in most patients, regardless of risk status.

Anticholesteremic Agents↗
PubMed1997

Epithelial stem cells.

New molecular markers for epidermal stem cells have enabled their isolation both in vitro and from the epidermis lying between hair follicles. Micro-dissection experiments have localised a second population of stem cells within hair follicles. Epidermal stem cells have a patterned distribution in vivo. The patterning can be reconstituted in vitro, showing that it is generated by interactions between keratinocytes and that the differentiation of epidermal stem cells is regulated by signals from other keratinocytes. Recent evidence from transgenic mice suggests that stem cell behaviour in the gut may be regulated by similar cell-cell interactions in vivo. Candidate genes for mediating these interactions are the homologues of Drosophila cell fate patterning genes such as Notch and Wingless and the Cadherin family of cell-cell adhesion molecules. The roles of stem cells and of mutations of the Patched gene in epithelial carcinogenesis are discussed.

Animals↗
PubMed1997

Physician education in hyperlipidemia management: the impact on collaboration.

Collaboration of health care professionals is likely beneficial in modifying patient behavior in the treatment of hyperlipidemia. The purpose of this study was to determine whether limited instruction and demonstration of collaborative management of hyperlipidemia in a continuing medical education (CME) would change physicians' office practices, as determined 1 year later by questionnaire. Collaborative practice was defined as physicians working with other allied health care professionals as a team to increase patients' medication compliance and other behavioral outcomes. A 19-credit hour CME Lipid Disorders Training Program (LDTP) was offered emphasizing the collaborative approach to hyperlipidemia patient management. Physicians (n = 196) were surveyed 1 year after LDTP. The response rate was 52.5%, nonrespondents were similar in locations. About 51% of respondents reported increased collaborative practice; of these respondents, 68% reported saving time, 78% reported improved patient outcomes, 76% improved office efficiency, and 90% increased patient satisfaction. According to self-reporting by these physicians, increased collaboration practices after attending the LDTP course led to improved patient outcomes.

Education, Medical, Continuing↗
PubMed1997

Effects of lipid lowering therapy on progression of coronary and carotid artery disease.

Recent data have extended the benefit of lipid lowering therapy to patients with only mildly to moderately elevated LDL-cholesterol, which is typical of patients with coronary artery disease. Meta-analysis of clinical trials of statin therapy with similar sample sizes indicated that the LDL-cholesterol level on treatment was as good a predictor of angiographic benefit as was the percentage reduction in LDL-cholesterol. We review evidence that management of triglyceride-rich lipoproteins, HDL, fibrinogen, lipoprotein particle size, LDL-oxidation, and lipoprotein (a) may also favorably influence atherosclerotic progression. Angiographic and arterial ultrasound trials of lipid lowering therapy have demonstrated benefits on disease progression that are consistent with benefits on myocardial infarction, stroke, and death reported in larger, lengthier trials.

Arteriosclerosis↗
PubMed1996

Isolation and characterization of human epidermal stem cells.

1. The keratinocytes in human epidermis are constantly turned over and replaced by a population of stem cells located in the basal epidermal layer. Until recently there were no markers allowing the isolation of viable epidermal stem cells. However, it has now been shown that epidermal stem cells can be isolated both in vitro and direct from the epidermis as they express high levels of functional beta 1 integrin family receptors for extracellular matrix proteins. 2. The evidence for integrins as stem cell markers and the insights that have been gained into stem cell behaviour are reviewed.

Animals↗
PubMed1996

Functional significance of CD9 association with beta 1 integrins in human epidermal keratinocytes.

CD9 is a member of the tetraspan (TM4) family of proteins and is abundantly expressed in the epidermis. As CD9 forms complexes with beta 1 integrins and the integrins are known to regulate keratinocyte behaviour, we investigated CD9 expression and function in human epidermal keratinocytes. CD9 was present in all the living layers of the epidermis, whereas the beta 1 integrins were largely confined to the basal layer; the same relative distribution was found in stratified cultures of keratinocytes. There was extensive co-localisation of CD9 and beta 1 integrins on microvilli and at cell-cell borders of basal keratinocytes; however, in contrast to the integrins, CD9 was not found in focal adhesions. CD9 was detected in beta 1 integrin immunoprecipitates and also in immunoprecipitates of CD44 and syndecan, but not of cadherins. CD9 was associated with alpha 3 beta 1 but not alpha 5 beta 1; small amounts of CD9 also co-immunoprecipitated with antibodies to alpha 2 beta 1 and alpha 6 beta 4. Antibodies to CD9 did not affect the proportion of keratinocytes that adhered to laminin 1, type IV collagen and fibronectin, but did inhibit motility of keratinocytes on tissue culture plastic. Like antibodies to the beta 1 integrin subunit, anti-CD9 inhibited suspension-induced terminal differentiation. These results suggest that CD9 may play a role in regulating keartinocyte motility and differentiation.

Antigens, CD↗
PubMed1996

Effect of gemfibrozil on levels of lipoprotein[a] in type II hyperlipoproteinemic subjects.

Plasma lipoprotein[a] (Lp[a]) levels are highly correlated with angiographically demonstrable coronary heart disease, and elevated Lp[a] is an independent risk factor for atherosclerosis. Previous studies have provided evidence that the levels of Lp[a] and triglyceride are related, suggesting that Lp[a] might be altered by gemfibrozil, a drug well known for its efficacy in reducing plasma triglycerides. Accordingly, 18 type IIa and 16 type IIb hyperlipoproteinemic males aged 35-58 were treated for 3 months with 600 mg of gemfibrozil twice daily. The efficacy of the drug in altering lipid and lipoprotein levels was different in the two type groups. In type IIa and IIb subjects the respective changes in median levels were: total cholesterol, -7.5 and -8.5% triglycerides, -35.6 and -54.4%; HDL-cholesterol, +9.0 and +11.0%; and Lp[a], -17.2 and +6.1%. Before and after gemfibrozil treatment, 7 type IIa and 10 type IIB subjects were given a 100 g/2 m2 oral-fat load; triglycerides and Lp[a] were measured post-prandially at 0, 2, 4, 6, 8, and 10 h. The differences between before- and after-gemfibrozil post-prandial curve integrated areas (PPCIA) were compared for triglycerides and Lp[a]. The changes in median PPCIA for triglycerides in types IIa and IIB were -54% and -53%, and for Lp[a] were -8% and +8%, respectively. These results indicate i) that the levels of Lp[a] are about 2 times higher in type IIa than IIb subjects, and ii) that although gemfibrozil elicits a rather uniform decrease in fasting and post-prandial triglyceride levels in type IIa and IIb patients, the drug causes heterogeneous changes in Lp[a], suggesting that different metabolic mechanisms may be dominant in subjects showing opposing effects.

Adult↗
PubMed1995

Extending the benefit of lipid-regulating therapy to primary prevention.

In recent years, a number of published secondary prevention trials have further strengthened the rationale for aggressive lipid-regulating therapy in patients with established coronary artery disease. However, the role of lipid-regulating therapy in primary prevention is less well characterized. Several large primary prevention trials, using a variety of interventions, are ongoing in different populations. These include the Air Force Coronary/Texas Atherosclerosis Prevention Study, the West of Scotland Coronary Prevention Study, the Women's Health Initiative, and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. These investigations will extend the results of earlier primary prevention trials and further characterize the rationale for intervention.

Aged↗
PubMed1995

Stem cell patterning and fate in human epidermis.

Within human epidermis there are two types of proliferating keratinocyte: stem cells, which have high proliferative potential, and transit-amplifying cells, which are destined to undergo terminal differentiation after a few rounds of division. We show that, in vivo, stem cells express higher levels of the alpha 2 beta 1 and alpha 3 beta 1 integrins than transit-amplifying cells and that this can be used both to determine the location of stem cells within the epidermis and to isolate them directly from the tissue. The distribution of stem cells and transit-amplifying cells is not random: patches of integrin-bright and integrin-dull cells have a specific location with respect to the epidermal-dermal junction that varies between body sites and that correlates with the distribution of S phase cells. Stem cell patterning can be recreated in culture, in the absence of dermis, and appears to be subject to autoregulation.

Adult↗
PubMed1995

Lung function and exercise capacity in survivors of childhood leukaemia.

The survival from acute lymphoblastic leukaemia in childhood is now approximately 60-70%, and from acute myeloid leukaemia, up to 50%. However, there is little information on the effects of intensive chemotherapy and radiotherapy used in the treatment of these conditions on lung function and exercise capacity in the long term. Severity survivors of acute leukaemia from one centre in the UK were studied. Measurements of lung volumes, spirometry and transfer factor were made. Each child also performed a standard, symptom-limited maximal exercise test on a cycle ergometer. Predictive equations for indices of lung function and exercise tolerance were calculated from 146 age- and sex-matched control subjects. The results of the survivors of leukaemia were compared to these. There was a significant reduction of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), and transfer for carbon monoxide (DLCO; P < 0.05 for each measurement), in the survivors of leukemia when compared to the control subjects. In addition, there was a mild but significant reduction of both maximal and submaximal indices of exercise capacity in the leukaemic group. A multivariate analysis was carried out to identify those variables acting independently to reduce lung volumes. For FEV1, FVC and TLC, these were craniospinal irradiation, cyclophosphamide and chest complications during treatment. For a reduction in DLCO, the significant factors were administration of anthracyclines, craniospinal irradiation and bone marrow transplantation. Survivors of acute leukemia have impaired pulmonary function and exercise capacity. Long-term cardiopulmonary follow-up may be necessary and new regimens devised which reduce long-term toxicity without compromising survival rates.

Adolescent↗
PubMed1995

Sleep nasendoscopy: what benefit to the management of snorers?

It has been proposed that sleep nasendoscopy (SN) will improve the success rate of the uvulopalatopharyngoplasty operation by identifying those patients with palatal snoring. The aim of this study was to test the efficacy of SN in the management of snorers who do not have obstructive sleep apnoea. This study compared a group of 26 snorers managed without SN (group A) to a group of 27 snorers managed with SN (group B). The post-operative results of group A were 61 per cent cured, 27 per cent better and 8 per cent unchanged. Group B results were 76 per cent cured, 19 per cent better and 5 per cent unchanged. However, if patients with only palatal snoring had surgery, the results for group B would have been 94 per cent cured, 6 per cent better and 0 per cent unchanged (95 per cent C.I. of difference +0.14, +0.54, p = 0.017). The results confirm the predictive power of SN in identifying success following uvulopalatopharyngoplasty. A simple grading system is suggested to aid in treatment planning. Patients are divided into three categories on SN: palatal snorers, mixed snorers and non-palatal (tongue base) snorers. It is proposed that uvulopalatopharyngoplasty may cure palatal snorers but mixed snorers will need additional therapies to eliminate their snoring although uvulopalatopharyngoplasty may improve the symptoms.

Endoscopy↗
PubMed1995

Trials of lipid-lowering therapy in primary prevention of coronary heart disease.

The effectiveness of lipid-regulating therapy in the primary prevention of coronary heart disease requires further investigation. The only data available are from trials conducted before the advent of more potent lipid-regulating agents, but several large trials currently in progress are expected to provide valuable evidence about the role of lipid-regulating intervention in primary prevention.

Antihypertensive Agents↗