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Biomedical subjects

J B O'Sullivan

Publications and source records attributed to J B O'Sullivan.

At least 19 recordsLinked to original sources

An audit of ultrasound-assisted catheter insertion in patients receiving chemotherapy.

BACKGROUND AND AIMS: Hickman catheters have been shown to provide safe long-term venous access for patients with malignant diseases. In many centres, catheters are placed using fluoroscopic guidance. We hypothesised that ultrasound-assisted catheter placement by surgeons in the operating theatre would be a simple, safe and effective alternative technique with reduced infective complication rates. METHODS: Hickman catheter insertions between May 1998 and March 2002 were studied. The data were collected from the Hospital Inpatient Enquiry database and the case notes of all patients were reviewed. Percutaneous catheter placement with tunnelling was performed in the operating theatre after scanning the internal jugular vein (IJV) for position, size and patency, using a Pie 100LC Scanner (Pie Medical, Maastricht). A standard chest radiograph confirmed catheter position at the end of the procedure. RESULTS: Fifty-eight patients (30 males and 28 females) had 65 Hickman catheters inserted. The median age was 60 years (range 32-82 years). Catheter placement was achieved in all patients, 59 in the right IJV and six in the left. Ultrasound scanning demonstrated that the right IJV was thrombosed in six patients (10%), thus avoiding unnecessary attempts at cannulation. The Hickman catheters remained in situ for a combined total of 5857 days (median, 89 days, range 4-485 days). Immediate complications occurred in two patients (pneumothorax in both). One patient required a chest drain. The overall sepsis rate was 3.92 per 1000 catheter days. Systemic sepsis was slightly higher (2.21 per 1000 catheter days) than superficial sepsis (1.71 per 1000 catheter days). In all the patients who developed systemic sepsis the catheter had to be removed (n = 13). All the superficial infections were treated successfully with antibiotics (n = 10 patients). Two catheters developed thrombosis. CONCLUSION: We conclude that ultrasound-assisted percutaneous placement of Hickman catheters in the operating suite is a simple, safe and effective technique and may help to reduce infective complications.

Adult↗

Long-term effects of angiotensin-converting enzyme inhibition on renal medullary neutral lipid in spontaneously hypertensive rats.

Short-term treatment of young spontaneously hypertensive rats (SHR) with angiotensin-converting enzyme (ACE) inhibitors reduces systolic blood pressure. Renal medullary neutral lipids (RMNLs) have vasodilator properties that may explain the effects of ACE inhibition. We measured RMNL levels of SHR treated between 6 and 10 weeks of age with (1) vehicle, (2) ramipril 1 mg. kg-1. d-1, (3) the bradykinin B2 receptor antagonist icatibant 0.5 mg. kg-1. d-1, or (4) icatibant 0.5 mg. kg-1. d-1 plus ramipril 1 mg. kg-1. d-1. RMNLs were quantified by oil red O fluorescence at 10 and 20 weeks of age. Systolic blood pressure (BP) was measured by tail-cuff plethysmography. Ramipril reduced BP at 10 weeks of age and increased RMNLs compared with controls (0.99+/-0.07% versus 0.56+/-0. 06%, P<0.01). Icatibant alone had no significant effect on RMNLs (0.55+/-0.04%) but attenuated the increase in RMNLs by ramipril (0. 81+/-0.05%). In control SHR, the increase in BP between 10 and 20 weeks of age was associated with a significant increase in RMNLs (0.79+/-0.09%). SHR that had received ramipril had significantly lower BP than controls at 20 weeks of age, but RMNL was not significantly different (0.92+/-0.10%). Therefore, in young SHR, ACE inhibition increases RMNLs and reduces blood pressure, an effect that appears to depend on bradykinin. The changes in RMNLs at the age of 10 weeks paralleled long-term BP effects and may be involved in setting the BP track in SHR.

Angiotensin-Converting Enzyme Inhibitors↗

Cardiac transplantation, perindopril, and left ventricular hypertrophy in spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors reduce blood pressure and cardiac mass but may also have a direct effect on myocardial growth. To test this hypothesis, we studied the effects of perindopril on the weight of transplanted hearts in which the left ventricle does not pump blood. Hearts were transplanted between littermate 10-week-old male spontaneously hypertensive rats, and recipients were treated for 2 weeks with vehicle (n = 10), perindopril (3 mg/kg per day) (n = 9), perindopril (3 mg/kg per day) plus the selective bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg per day) (n = 13), or angiotensin II (200 ng/kg per minute) (n = 12). Perindopril reduced blood pressure and native left ventricular weight and also caused a significant decrease in the weight of the transplanted left ventricle compared with controls. Hoe 140 did not significantly alter blood pressure or native left ventricular weight of perindopril-treated rats but caused a significant increase in the weight of the transplanted left ventricle compared with rats treated with perindopril alone. Angiotensin treatment resulted in a significant increase in blood pressure and native left ventricular weight but no significant change in the weight of the transplanted left ventricle. Blood pressure and left ventricular weight for native but not for transplanted hearts were positively correlated. Therefore, in the absence of mechanical load, the weight of the left ventricle of spontaneously hypertensive rats responds little to angiotensin II but can be reduced by angiotensin-converting enzyme inhibition. The effect of perindopril on transplanted hearts of spontaneously hypertensive rats appears to depend on bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗

Resetting blood pressure in spontaneously hypertensive rats. The role of bradykinin.

Brief angiotensin-converting enzyme (ACE) inhibition in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure. Bradykinin accumulation may contribute to these long-term effects, and to test this hypothesis we studied the consequences of bradykinin B2 receptor antagonism during ACE inhibitor treatment in young SHR. Male SHR were treated from 6 to 10 weeks of age with water, ramipril (1 mg/kg per day), Hoe 140 (0.5 mg/kg per day), or both ramipril and Hoe 140. Systolic blood pressure and body weight were measured each week from 6 to 20 weeks of age. During treatment, Hoe 140 treatment resulted in lower blood pressures than in controls. Rampiril caused a larger fall in blood pressure over the same period. The ramipril plus Hoe 140 group had the lowest blood pressures of any group during treatment. After treatment, the blood pressure of Hoe 140-treated SHR was similar to that of untreated SHR. After ramipril, blood pressure rose but plateaued significantly below values in controls. In contrast, withdrawal of combined ramipril and Hoe 140 treatment caused a rapid rise of systolic blood pressure to levels significantly higher than in ramipril-treated SHR but less than in controls. The antihypertensive effects of Hoe 140 during the development of genetic hypertension may represent a direct effect of the drug or some alteration in the normal relation between bradykinin and blood pressure. The antagonism by Hoe 140 of the long-term blood pressure reduction after ramipril withdrawal indicates that the persistent effects of ACE inhibitors may in part be due to the accumulation of bradykinin during a critical stage of development.

Aging↗

Cardiovascular hypertrophy in one-kidney, one clip renal hypertensive rats: a role for angiotensin II?

OBJECTIVE: To investigate the role of angiotensin II (Ang II) in cardiovascular hypertrophy in the Goldblatt one-kidney, one clip (1-K, 1C) renal hypertensive rat. METHODS: Six-week-old Wistar-Kyoto (WKY) rats underwent uninephrectomy and left renal artery clipping. After surgery, rats were treated with perindopril, an angiotensin converting enzyme (ACE) inhibitor, or losartan, an Ang II type 1 (AT1) receptor antagonist, for 4 weeks. Untreated 1-K, 1C rats and uninephrectomized (sham) rats served as controls. RESULTS: The rise in systolic blood pressure in the perindopril-treated and losartan-treated rats was not significantly different from that in the untreated 1-K, 1C group throughout the treatment period. At 4 weeks after surgery the heart weight:body weight ratios of the untreated 1-K, 1C and losartan-treated 1-K, 1C groups were significantly greater than for sham-operated normotensive rats and hypertensive perindopril-treated rats. The total number of smooth muscle cells in the thoracic aortae of the 1-K, 1C untreated, losartan-treated 1-K, 1C and sham groups were similar. However, after treatment the aortae of the perindopril-treated group contained significantly fewer smooth muscle cells. The medial cross-sectional wall area and wall: lumen ratio were similar in the 1-K, 1C untreated and perindopril-treated 1-K, 1C groups. CONCLUSION: These results suggest that Ang II, via its effects on cardiac and vascular AT1 receptors, does not contribute to the development of cardiovascular hypertrophy in the 1-K, 1C rat. Attenuation of cardiac and vascular growth after ACE inhibition appears to be mediated by mechanisms independent of the actions of the renin-angiotensin system.

Angiotensin II↗

Criteria critique.

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Diabetes, Gestational↗

Diabetes mellitus after GDM.

The impact of factors that influence diabetes mellitus (DM) and impaired glucose tolerance (IGT) incidence rates among former gestation diabetes mellitus (GDM) patients undermine attempts at interstudy comparisons. The recommended diagnostic standards for GDM by oral glucose tolerance test (OGTT) are the O'Sullivan and Mahan criteria and the World Health Organization (WHO) criteria for IGT, which result in prevalence rates of 2.5 and 7.2%, respectively, when applied to 752 unselected pregnant women. In applying the O'Sullivan and Mahan criteria, the current open-ended definition of GDM without rules either to exclude overt diabetes uncovered by pregnancy or to require a return to a normal OGTT after pregnancy is shown to be a major source of differences in subsequent incidence rates of diabetes. For subsequent nonpregnant diagnoses, the differences between WHO and National Diabetes Data Group criteria and the allowable modifications within each of the diagnostic standards all result in different incidence rates of diabetes. Review of 12 worldwide studies of diabetes among former GDM patients indicated a wide range of incidence rates, from 19 to 87% for combined DM and IGT and 6 to 62% for DM. In applying WHO DM criteria to GDM patients and control subjects, the excess risk of diabetes among GDM patients was 18% in Copenhagen and 30.9% in Boston, MA. The potential impact of varying observation periods within studies was seen when the application of an actuarial method added a further 50% to the Boston incidence rates of both GDM patients and control subjects. Although the variability in diabetes incidence rates is wide, there is broad general agreement on the predictive nature of gestational blood glucose levels.

Australia↗

Body weight and subsequent diabetes mellitus.

The ten- to 16-year predictive value of body weight for diabetes mellitus was evaluated prospectively in two groups of women with initially normal results of glucose tolerance tests. The incidence of diabetes in 602 high-risk (previous transient gestational glucose intolerance) participants was significantly higher for overweight subjects (46.7%) than for those of normal weight (25.6%). In 328 concurrently selected negative control subjects (without previous intolerance), the difference was not significant (4.5% v 1.9%). Another definition of diabetes, indicating further deterioration, gave similar results, although high-risk overweight women had disproportionately higher incidence rates. Being overweight had no substantial predictive value for diabetes mellitus during this period unless the additional evidence for a high-risk classification was present. Among such persons at high risk, excess weight also predicted the severity of the subsequent diabetic condition.

Body Weight↗

Mortality related to diabetes and blood glucose levels in a community study.

A prospective 29-year population study of diabetes in Oxford, MA, is the basis for a case-control analysis of diabetes mortality rates and their validity. Two case groups were considered, one consisting of previously known diabetics at the study's inception in 1946 and the other defined by hyperglycemia above 140 mg/dl. Mortality rates were significantly higher for diabetics than for age- and sex-matched controls, and disproportionately higher for women largely due to the advantageous mortality experience of nondiabetic women compared to nondiabetic men. Estimated survival experience showed longevity to be shorter by some 10 to 15 years for the female and six to nine years for the male diabetic. Mortality rates were also significantly higher for the hyperglycemic group than for matched controls. Although deaths from cardiovascular causes were predominant, they proved significantly higher for women with known diabetes only. Substantial underreporting of diabetes on the death certificates persisted in every decade of the study. The proportion of prevalent and incident cases of diabetes during the 19-year period of the study, whose diagnosis failed to appear anywhere on the death certificate, was found to be at or above 50%. Among subjects with death certificates that did not list diabetes, 4.4 to 14.1% were known to have diabetes, based on the underlying composition of the sample. Prevalent cases of diabetes had a higher reporting rate than incident cases, suggesting that duration of diabetes may also be a factor in such rates.

Blood Glucose↗

Decisive factors in the tolbutamide controversy.

No increased mortality trend attributable to tolbutamide is shown by an analysis of variance on logit-transformed data from the University Group Diabetes Program (UGDP) study. The UGDP's controversial finding of an increased rate with mortality subgrouped by "cardiovascular" causes is confirmed by the Biometric Committee's report, with reservations that failed to include overriding decisive factors. The basic problem is that inspected data set up the hypothesis (the increased cardiovascular mortality), and that the same data were used to test the hypothesis, so that resulting probability values no longer have the usual meaning. The problem was compounded by multiple testing of the data without adjusting the probability levels. When cardiovascular deaths were redefined as myocardial infarcts and sudden deaths, in an attempt to test a proposed etiologic inotropic hypothesis, no significant increase in cardiovascular mortality was found.

Age Factors↗

Lipid metabolism in pregnancy. II. Postheparin lipolytic acitivity and hypertriglyceridemia in the pregnant rat.

Plasma postheparin lipolytic activity (PHLA) has been measured in rat pregnancy to qualitatively assess mechanisms of triglyceride removal from the circulation. This assessment can be made if the larger plasma volume of pregnancy is considered. A supramaximal dose of heparin avoids dilution of the heparin stimulus to PHLA release. Dilution of the released PHLA is corrected using measurements of plasma volume. In addition, no evidence of circulating inhibitors is present, and timing of PHLA appearance is unaffected by pregnancy. Prior studies of postheparin lipolytic activity in human pregnancy have not taken the effect of plasma volume into account and must therefore be reconsidered in light of the present results. We observed a biphasic pattern in PHLA over the course of gestation. Levels were increased in midgestation (day 12), declined to normal by day 19, and fell rapidly to one-half of control by day 21. Assuming a functional role for the triglyceride lipases represented in PHLA, the data suggest the following hypothesis: triglyceride removal is increased or normal for the greater part of gestation and is decreased only at term. If this hypothesis proves true, the hypertriglyceridemia of pregnancy should be due largely to overproduction, with decreased removal contributing only near term.

Adipose Tissue↗