Hypertension--time to move on.
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Cardiovascular Diseases↗
Biomedical subjects
A Rodgers
Publications and source records attributed to A Rodgers.
Gonadotropin-releasing hormone and chorionic gonadotropin gene expression in human placental development.
Control of human chorionic gonadotropin (hCG) synthesis during pregnancy is poorly understood, although in vitro data suggest a role for placental gonadotropin releasing hormone (GnRH) in its regulation. To study GnRH regulation during placental development, placental tissue of different gestational ages was analyzed for GnRH and beta hCG mRNA content. cRNA probes to exonic/intronic sequences of GnRH and beta hCG transcripts were constructed and used to perform solution hybridization/nuclease protection and in situ hybridization assays. The levels of GnRH mRNA were approximately 0.1-1% of that of beta hCG mRNA, in agreement with its suggested paracrine, rather than endocrine, role. While beta hCG mRNA content decreased significantly from first trimester to term (643 to 21.6 pg/microgram RNA), there was no significant change in GnRH mRNA (0.179 to 0.155 pg/microgram RNA). While beta hCG mRNA was localized almost exclusively in syncytiotrophoblasts, GnRH mRNA was present in all cell types of the placenta, including the stroma. In the course of performing sense-strand controls in the in situ hybridization, we noted that the placenta appeared to express more antisense GnRH than sense GnRH mRNA, again, in all cell types. Solution hybridization/nuclease protection analysis with exon 1 and exon 3 probes confirmed this observation, showing that there is two to three times more antisense GnRH RNA than sense GnRH mRNA. These studies suggest that GnRH gene expression and its role in regulating hCG production in human placenta is complex and does not fit a simple model for paracrine regulation of hCG.
Chorionic Gonadotropin↗
Phase II multicenter open-label study of carboplatin and pegylated liposomal doxorubicin in uterine and cervical malignancies.
The results of a multicenter phase II study investigating carboplatin and pegylated liposomal doxorubicin (PLD) in patients with recurrent/metastatic uterine and cervical malignancies (UCM) are presented here. Fifty-three subjects with measurable, untreated, advanced UCM were enrolled. Fifty-one were evaluable for response. Prior combined-modality treatment was permitted if a component of primary therapy. Patients received carboplatin AUC = 5 with PLD 35 mg/m(2) intravenously once every 4 weeks. Overall response rate was 33% (35% stable disease). Overall survival (OS) at six months was 86% (95% CI 76%-96%). Six-month progression-free survival (PFS) was 43% (95% CI 30%-57%). Median PFS was 22.9 weeks (range 16.0-35.3) and median OS was 49.1 weeks (range 41.4-75.1). The most frequent grade 3-4 nonhematological adverse events were: abdominal pain (n = 7), fatigue (4), vomiting (4), nausea (3), and shortness of breath (3). There was 1 report of grade 3 hand-foot syndrome and none of grade 4. Twelve patients had first infusion reactions with only 1 discontinuing treatment. Grade 3-4 neutropenia occurred in 26/230 cycles (11.3%). There were no treatment-related deaths. The combination of carboplatin and PLD is well tolerated with sufficient activity to justify additional evaluation in clinical trials and might be suited to the addition of a taxane.
Adolescent↗
Income, health, and the National Lottery.
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Gambling↗
Primary and secondary prevention of stroke.
Data from prospective observational studies indicate that usual levels of blood pressure are directly and continuously related to the risk of stroke. a prolonged difference in usual diastolic blood pressure levels of just 5 mmHg would eventually confer about a one-third difference in stroke risk, with similar proportional effects in hypertensives and non-hypertensives. The results of randomised trials of blood pressure lowering drugs in hypertensive patients suggest that much or all of this long-term potential stroke avoidance can be achieved within just a few years of beginning treatment. Overall in 17 randomised trials of antihypertensive treatment, a net blood pressure reduction of 10-12 mmHg systolic and 5-6 mmHg diastolic, conferred a reduction in stroke incidence of 38% SD 4, with similar reductions in fatal and non-fatal stroke. Additionally, the sizes of the reductions were similar in trials in mild, moderate or more severe hypertension, in trials in older or younger patients and in trials in patients with or without a history of cerebrovascular disease. Because the proportional effects of treatment were similar in all these groups, the absolute effects of treatment on stroke varied in direct proportion to the background risk of stroke. The greatest benefits were, therefore, observed among those with a history of cerebrovascular disease, those above the age of 60 years, and those with more severe hypertension.
Adult↗
Blood pressure lowering for the prevention of cognitive decline in patients with cerebrovascular disease. PROGRESS Management Committee. Perindopril Protection Against Recurrent Stroke Study.
Cerebrovascular disease and high blood pressure both appear to increase the risk of vascular dementia. PROGRESS aims to investigate whether blood pressure lowering with an angiotensin coverting enzyme inhibitor-based regimen will reduce the risk of cognitive impairment in patients with a history of stroke or transient ischaemic attack. A total of at least 6000 patients will be randomised to receive perindopril (+/- indapamide) or matching placebo(s), with treatment and follow-up scheduled to continue for at least 4 years. Substudies will investigate the effects of treatment on cognitive decline in subgroups defined by apo-E genotype and on white matter lesions assessed by magnetic resonance imaging. Final results from the study should be available in 2001.
Angiotensin-Converting Enzyme Inhibitors↗
The associations of diastolic blood pressure with the risk of stroke in Western and Eastern populations.
This paper reviews evidence from two overviews of prospective, observational studies of the association of diastolic blood pressure (DBP) with the risk of stroke in populations from the US and Europe and populations from China and Japan. The Western overview included seven studies involving a total of 405,511 individuals. During a mean follow-up period of 11 years, 843 strokes were observed. The Eastern overview included 18 cohorts involving a total of 124,774 participants. During a mean follow-up duration of 9 years, 1,798 strokes were observed. The shape of the association between usual DBP and the risk of stroke was similar in Western and Eastern populations, but in Eastern populations the size of the association was about 50% steeper than that in Western populations. This may be due, at least in part, to cerebral haemorrhage comprising a greater proportion of total stroke in Eastern populations. This finding, together with the high stroke rates in many Eastern Asian populations, suggests that the potential benefits of blood pressure lowering may be greater in Eastern Asia.
Adolescent↗
Blood pressure and the global burden of cardiovascular disease.
Cardiovascular disease is responsible for a large and increasing proportion of death and disability worldwide. Half of this burden occurs in Asia. This study assessed the possible effects of population-wide (2% lower DBP for all) and targeted (7% lower DBP for those with usual DBP > or = 95 mmHg) BP interventions in Asia, using data from surveys of blood pressure levels, the Global Burden of Disease Project, Eastern Asian cohort studies and randomised trials of blood pressure lowering. Overall each of the two interventions would be expected to avert about one million deaths per year throughout Asia in 2020. These benefits would be approximately additive. About half a million deaths might be averted annually by each intervention in China alone, with about four-fifths of this benefit due to averted stroke. The relative benefits of these two strategies are similar to estimates made for US and UK populations. However, the absolute benefits are many times greater due to the size of the predicted CVD burden in Asia.
Blood Pressure↗
1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization.
The present Guidelines were prepared by the Guidelines Sub-Committee of the World Health Organization-International Society of Hypertension (WHO-ISH) Mild Hypertension Liaison Committee, the members of which are listed at the end of the text. These guidelines represent the fourth revision of the WHO-ISH Guidelines and were finalised after presentation and discussion at the 7th WHO-ISH Meeting on Hypertension, Fukuoka, Japan, 29th Sept-1st Oct, 1998. Previous versions of the Guidelines were published in Bull WHO 1993, 71:503-517 and J Hypertens 1993, 11:905-918.
Adult↗