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The relationship of hyperinsulinemic state to left ventricular hypertrophy, microalbuminuria, and physical fitness in borderline and mild hypertension.

The relationship of the hyperinsulinemic state to left ventricular hypertrophy, left ventricular geometric patterns, microalbuminuria, and physical fitness were studied in 52 middle-aged unmedicated men with borderline and mild hypertension. Left ventricular mass index and relative wall thickness were assessed by echocardiography. Physical fitness was determined by symptom-limited maximal treadmill stress testings. The urinary concentration of microalbumin and C-peptide was measured in 24-h urine samples by radioimmunoassey. The 24-h urinary C-peptide excretion rate was correlated with left ventricular mass index (r = 0.46), relative wall thickness (r = 0.41), treadmill time (r = -0.35), normalized treadmill time (r = -0.52), systolic blood pressure at peak exercise (r = 0.29), and 24-h urinary microalbumin excretion (r = 0.48). Stepwise multiple regression analysis identified the left ventricular mass index, the 24-h urinary albumin excretion, and the normalized treadmill time as variables in the equation for the 24-h urinary C-peptide excretion. Thus, the hyperinsulinemic state is related to left ventricular hypertrophy, microalbuminuria, and impaired physical fitness in patients with borderline and mild hypertension.

Adult↗

Effects of alpha1-blockade on the forearm vascular resistance responses to lower body negative pressure in young borderline hypertensives.

To determine whether alpha1-blockade affects the forearm vascular resistance responses to lower body negative pressure (LBNP) in borderline hypertensives, six hypertensives (HTN; mean arterial pressure [MAP] = 109.9 +/- 1.7 mm Hg, mean +/- SE) and seven normotensives (NTN; MAP = 81.5 +/- 1.4 mm Hg) underwent exposures of LBNP at pressures of -10, -20, and -40 mm Hg during systemic alpha1-receptor blockade (BLK) and during placebo (PLA). Resting forearm vascular resistance (FVR) was greater in HTN than in NTN during PLA (34.8 +/- 5.4 v 17.5 +/- 3.1 units; P < .05), but not during BLK (28.1 +/- 5.2 v 25.3 +/- 9.9 units). When expressed as a percentage of resting FVR, LBNP evoked an increased FVR (P < .001) that did not differ significantly between BLK and PLA in either group. FVR was higher (P < .001) in HTN than in NTN throughout both trials; at -40 mm Hg of LBNP during BLK, the increase in FVR was greater (P < .05) in HTN than in NTN (131 +/- 42 v 48 +/- 15%). MAP (relative to resting) was maintained throughout LBNP during PLA but, at -40 mm Hg, was lower (P < .01) during BLK for both groups. HR was elevated in BLK and was increased at -40 mm Hg (P < .01) for each group in each trial. This increase was greater during BLK (P < .05). These data suggest that borderline hypertensives have a greater vasoconstrictor response to LBNP than do normotensives and alpha1-blockade does not appear to attenuate this response.

Adrenergic alpha-1 Receptor Antagonists↗

Left ventricular geometric patterns and QT dispersion in borderline and mild hypertension: their evolution and regression.

To investigate whether QT dispersion increases in borderline and mild hypertension during a longitudinal observation of > 3 years and whether it is improved with medications, left ventricular geometric patterns and QT dispersion were studied with special regard to their longitudinal changes in 85 male borderline and mild hypertensive subjects with left ventricular mass index < 125 g/m2. These subjects were followed for > 3 years without medication. Thirty-two patients with a left ventricular mass index > 125 g/m2 at the end of follow-up period were further observed using antihypertensive drugs for an additional 3 years. Echocardiograms and electrocardiograms were obtained at the beginning and end of the follow-up period. At the end of the follow-up period, subjects were classified into four groups based on ventricular geometric patterns determined by left ventricular mass index and relative wall thickness in diastole. The QT dispersion was greater in patients with concentric hypertrophy (56+/-18 msec) than in patients with normal geometry (41+/-17 msec) (P < .05) and increased significantly in the former group during the follow-up period. After medication, the left ventricular mass index regressed and the QT dispersion decreased (from 55+/-21 to 50+/-26 msec, P < .01) in these patients. Thus, these findings suggest that changes in the QT dispersion reflect both concentric evolution and regression of left ventricular hypertrophy.

Adult↗

No relevant seasonal influences on office and ambulatory blood pressure: data from a study in borderline hypertensive primary care patients.

Our objective was to study seasonal influences on office and ambulatory blood pressure. We therefore designed a prospective 7-month study of 47 borderline hypertensive patients in a primary care setting. We used no interventions. Our main outcome measures were the differences between summer and winter office and ambulatory blood pressures and 95% confidence intervals. Results showed that winter minus summer differences ranged from 0 to 3 mm Hg. Only one significant difference was found: ambulatory systolic daytime pressure was significantly higher (3 mm Hg) in winter than in summer. Our results do not confirm the data of earlier studies in hypertensives. In view of the small and clinically irrelevant winter-summer differences, it seems unnecessary to modify antihypertensive treatment of borderline hypertensives according to the season.

Adult↗

Bone anchored hearing aid wearers with significant sensorineural hearing losses (borderline candidates): patients' results and opinions.

Bone anchored hearing aids (BAHA) have been implanted in Birmingham since 1988. Since this time confidence has grown in the fitting and rehabilitation of BAHA wearers, with corresponding increase in the implantation and rehabilitation of more difficult and borderline candidates. This study analyses the results of 16 borderline BAHA candidates who have been assessed and fitted with a BAHA at Birmingham Children's Hospital and Queen Elizabeth Hospital, and who have had at least one post-fitting review. All of these subjects had mean bone conduction (BC) thresholds, in the better hearing ear, in excess of 45 dBHL in the frequency range 0.5-4 kHz, when initially assessed. The age range at the time of the study was 10-84 years, with a mean age of 60 years. The study demonstrates the benefits that these patients achieved with the BAHA compared to their previous aid, both audiologically and in terms of comfort and reduction in ear discharge.

Adolescent↗

Evidence of a borderline region between E1cb and E2 elimination reaction mechanisms: a combined experimental and theoretical study of systems activated by the pyridine ring.

We report a combined experimental and theoretical study to characterize the mechanism of base-induced beta-elimination reactions in systems activated by the pyridyl ring, with halogen leaving groups. The systems investigated represent borderline cases, where it is uncertain whether the reaction proceeds via a carbanion intermediate (E1cb, A(xh)D(H) + D(N)) or via the concerted loss of a proton and the halide (E2, A(N)D(E)D(N)) upon base attack. Experimentally, the Taft correlation for H/D exchange, in OD(-)/D(2)O with noneliminating substrates (1-methyl-2-(2-Xethyl)pyridinium iodide), is used to predict the expected values of the rate constants for the elimination reactions with N-methylated substrates and F, Cl, Br as the leaving group. The comparison indicates an E1cb irreversible mechanism with F, but the deviation observed with Cl and Br does not allow a conclusive assignment. The theoretical calculations show that for the N-methylated substrate with a fluoride leaving group the elimination proceeds via formation of a moderately stable carbanion. No stable anionic intermediate is instead found when the leaving group is Cl or Br, as well as for any of the nonmethylated species, indicating a concerted elimination. The methylated substrate with Cl shows however only a moderate increase in reactivity compared to the fluorinated substrate, despite the change in mechanism. Very interestingly, our analysis of the computed two-dimensional potential energy surface for the reaction with a F leaving group indeed evidences the lack of a net distinction between the E1cb and E2 reaction paths, which appear to merge smoothly into each other in these borderline cases.

Journal Article↗

Ab initio molecular dynamics simulations of elimination reactions in water solution: exploring the borderline region between the E1cb and E2 reaction mechanisms.

We report a theoretical study, based on ab initio molecular dynamics simulations in water solution, of the mechanism of base-induced beta-elimination reactions in systems activated by the pyridyl ring, with halogen leaving groups. The systems investigated represent borderline cases, where it is uncertain whether the reaction proceeds via a carbanion intermediate (E1cb, A(xh)D(H) + D(N)) or via the concerted loss of a proton and the halide (E2, A(N)D(E)D(N)) upon base attack. Recent theoretical and experimental evidence points toward the lack of a net distinction between the E1cb and E2 reaction paths, which seem to merge smoothly into each other in these borderline cases (Alunni, S.; De Angelis, F.; Ottavi, L.; Papavasileiou, M.; Tarantelli, F. J. Am.Chem. Soc. 2005, 127, 15151-15160). In this study, we explore the dynamics on the potential energy surface for the reaction of 2-(2-fluoroethyl)-1-methyl pyridinium with OH- by means of Car-Parrinello simulations in water solution. Our results indicate that the reaction mechanism effectively evolves through the potential energy region of the carbanion: the carbon-fluoride bond breaks only after the carbon-hydrogen bond, confirming the conclusions of a recently reported study of the potential energy surface for this system.

Journal Article↗

Increased expression of fascin, motility associated protein, in cell cultures derived from ovarian cancer and in borderline and carcinomatous ovarian tumors.

Fascin bundles actin microfilaments within dynamic cellular structures such as microspikes, stress fibers and membrane ruffles. Fascin overexpression induces membrane protrusions and increased cell motility, and is highly expressed in various transformed cells, and in specialized normal cells including neuronal, endothelial and dendritic cells. In breast cancer, fascin expression correlates with high-grade tumors. To investigate whether fascin might be a predictor factor for ovarian cancer progression, eighteen cell cultures derived from ovarian cancer, and thirty four archival paraffin-embedded material of normal versus borderline and carcinomatous ovaries were stained by immunocytochemistry and immunohistochemistry with fascin Mab 55K-2. Overall expression of the fascin protein was found in 50% (9/18) of cell cultures derived from original samples of ovarian tumors. Expression of fascin protein was found in 67% (6/9) of cell cultures derived from patients diagnosed with stage IV disease, and 33% (3/9) of cell cultures from patients diagnosed with stage II/III. There was no clear relationship between fascin expression and histologic types, tumor grade, or DNA ploidy. However, 75% of cell cultures, which developed into a xenograft after intraperitoneal inoculation, showed fascin expression, while 86% of non-tumorigenic cell cultures did not show fascin expression. Expression of fascin in these established ovarian tumor cell cultures was significantly associated with the ability for these cells to grow intraperitoneally (P < 0.05). Furthermore, fascin was never expressed in normal epithelial ovarian tissues, but was present in all pathologic ovaries. Both diffuse and focal patterns were observed in borderline ovarian tumors (67% and 33%), advanced primary ovarian cancer (67% and 33%) and metastatic ovarian cancer (89% and 11%). Therefore, our data suggest that fascin could serve as a prognostic factor for abnormal ovarian epithelial pathology and could be a novel target for the treatment of ovarian cancer.

Carrier Proteins↗

Standard setting for OSCEs: trial of borderline approach.

OSCE examinations were held in May and June 2002 for all third and fourth year and some fifth year medical students at the University of Leeds. There has been an arbitrary pass mark of 65% for these examinations. However, we recognise that it is important to adopt a systematic approach towards standard setting in all examinations so held a trial of the borderline approach to standard setting for third and fifth year examinations. This paper reports our findings. The results for the year 3 OSCE demonstrated that the borderline approach to standard setting is feasible and offers a method to ensure that the pass standard is both justifiable and credible. It is efficient, requiring much less time than other methods and has the advantage of using the judgements of expert clinicians about actual practice. In addition it offers a way of empowering clinicians because it uses their expertise.

Adult↗

Confirmatory factor analysis of DSM-IV borderline, schizotypal, avoidant and obsessive-compulsive personality disorders: findings from the Collaborative Longitudinal Personality Disorders Study.

OBJECTIVE: To test the diagnostic constructs implied by DSM-IV Axis-II personality disorders by examining relationships between different combinations of DSM-IV criteria. METHOD: Confirmatory factor analysis was used to test the borderline, schizotypal, avoidant and obsessive-compulsive personality disorder constructs in a large treatment-seeking sample (N= 668) from a multisite study. A model based on the three DSM-IV Axis II clusters was also tested. Both models were tested against a unitary 'generic' model constructed from four criteria sets combined. RESULTS: Goodness-of-fit for both the three-cluster and four disorder models was significantly better than the unidimensional model, and the four-disorder model was significantly better than the three-cluster model. Results were replicated using data from 2-year follow-up obtained by interviewers blind to original Axis II diagnoses at baseline. CONCLUSION: Support is provided for the DSM-IV disorder-level classification for schizotypal, borderline, avoidant and obsessive-compulsive personality disorders in a treatment-seeking sample.

Adolescent↗

Intra-arterial blood pressure and heart rate reactivity to behavioral stress in normotensive, borderline, and mild hypertensive men.

Intra-arterial blood pressure (BP) stress reactivity was studied in newly detected, World Health Organization-classified (1978), age-matched normotensive (NT; n = 33), borderline hypertensive (BHT; n = 30), and hypertensive (HT; n = 32) men recruited through routine health examinations. They underwent a relaxation baseline followed by 8 standardized behavioral challenges. BHT and HT men displayed exaggerated BP reactivity compared with NT men, particularly on perceptual-motor and social tasks, and HT men showed higher reactivity than NT men in the cold pressor test. These results are the first to show reactivity differences between NT men and BHT or HT men in an intra-arterial experiment. Diastolic BP (DBP) discriminated the groups better than systolic BP (SBP) or heart rate (HR). The few differences in SBP compared with DBP among the groups combined with hardly any differences in HR indicate the predominance of vascular factors in middle-aged as opposed to younger men with borderline or mild hypertension.

Adult↗

Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers.

In an effort to understand whether HLA class I and II plays any role in the process of tumorigenesis and metastasis, we have immunohistochemically examined expression of HLA class I and II antigen by using the monoclonal antibodies (mAb) L368 (for beta2m of HLA class I), HC-10 (for HLA-B, C heavy chains), and LGII-612.14 (for HLA class II heavy chain) in 5 borderline serous malignancy (BSM), 20 serous adenocarcinomas (SA), 15 borderline mucinous malignancy (BMM), and 10 mucinous adenocarcinomas (MA) of human ovary tumor case tissues. In BSM, the distribution and intensity of HLA expressions failed to reach statistical significance. In SA, HLA class I beta2-microglobulin (beta2m), HLA-B, C heavy chains and HLA class II heavy chain antigen expressions were down-regulated. Although expressions of HLA-B, C heavy chains and class II heavy chain were down-regulated in metastatic SA, there were no differences in HLA expression levels between primary and metastatic lesions. In BMM, class II heavy chain expressions were down-regulated. In MA, beta2m, HLA-B, C heavy chains and class II heavy chain expressions were also down-regulated. Thus, we could distinguish the reduction or absence of HLA molecule expression was related to malignant potential. Loss of HLA class I and II molecules in invasive ovarian cancers raises the possibility that this could be a factor for tumor cells to retain invasiveness.

Adenocarcinoma↗

Genital tract tumors in Proteus syndrome: report of a case of bilateral paraovarian endometrioid cystic tumors of borderline malignancy and review of the literature.

Proteus syndrome is a rare, sporadic disorder that causes postnatal overgrowth of multiple tissues in a mosaic pattern. Characteristic manifestations include: overgrowth and hypertrophy of limbs and digits, connective tissue nevus, epidermal nevus and hyperostoses. Various benign and malignant tumors and hamartomas may complicate the clinical course of patients with the syndrome. Commonly encountered tumors include hemangiomas, lymphangiomas and lipomas. Tumors of the genital tract occur less often. Bilateral ovarian cystadenomas are regarded as having diagnostic value in Proteus syndrome when occurring within the first two decades of life. We describe a 3-year-old girl with Proteus syndrome who developed bilateral paraovarian villoglandular endometrioid cystadenomatous tumors of borderline malignancy (low malignant potential) of the broad ligament. Desmoplastic tumor implants, presumably noninvasive, were present in biopsies from the pelvic floor, cul-de-sac and omentum. This is the first recognized example of a cystic borderline epithelial tumor of the female genital tract and the first paraovarian tumor reported in a patient with Proteus syndrome. Previously reported tumors and cystic lesions involving the female genital tract and the male genital tract in patients with Proteus syndrome are reviewed. We suspect that specific testicular and paratesticular tumors may prove to have the same diagnostic value in Proteus syndrome as do bilateral cystic ovarian and paraovarian tumors.

Carcinoma, Endometrioid↗

Risk for invasive and borderline epithelial ovarian neoplasias following use of hormonal contraceptives: the Norwegian-Swedish Women's Lifestyle and Health Cohort Study.

The risk of ovarian epithelial neoplasia following use of hormonal contraceptives (HC) was examined in data from the Norwegian-Swedish Women's Lifestyle and Health cohort including 103551 women aged 30-49 years in 1991-92. Follow-up through 2000 produced 214 incident cases of histologically confirmed epithelial ovarian neoplasias (135 invasive and 79 borderline cases). Using the Cox proportional hazard models, ever having used HC was associated with a decreased relative risk of epithelial ovarian cancer of 0.6 (95% CI 0.5-0.8). The effect of duration of HC use was convincing (P for trend <0.0001), and more important than age at start of use or time since first or last use. There was no significant difference between the effects of combined oral contraceptives and progestins-only contraceptives on risk (P=0.98). Similarly, there was no significant difference between the effects of ever use of HC on invasive and borderline ovarian neoplasia (P=0.37). In this cohort, use of HC seems to reduce the risk of epithelial ovarian neoplasia markedly and persistently in relation to the duration of use.

Adult↗

Post exercise hypotension is not mediated by the serotonergic system in borderline hypertensive individuals.

Recent evidence from our laboratory and others have suggested that the mechanism for a decrease in resting blood pressure after an acute bout of exercise is a centrally mediated decrease in total peripheral resistance. This study examined the effect of the central serotonergic system on post exercise hypotension (PEH) in 11 borderline hypertensive individuals (nine male, two female) aged 24.5 +/- 5.1 years. Each subject completed two, 30-min cycling bouts at 70% of VO2peak while under placebo or a selective serotonin re-uptake inhibitor (SSRI) treatment. Blood pressure was recorded directly from the radial artery, and treatments were randomised, double blinded and separated by at least 14 days. Baseline blood pressure was 145/72 mm Hg for systolic (SBP) and diastolic (DBP) respectively. Peripheral measures of serotonin (5-HT) were lower under SSRI treatment, whereas the major 5-HT metabolite, 5-hydroxyindoleacetic acid, was not significantly changed, indicating elevated central 5-HT levels. There was no difference in any of the haemodynamic variables between trials. Despite an increased heart rate for the initial 75 min post exercise, SBP was decreased as much as 23 mm Hg during the initial 60 min post exercise, after which it had returned to normal. DBP was unchanged after exercise. Circulating adrenaline (0.60 +/- 0.14 ng/mL to 1.3 +/- 1.6 ng/ml) and noradrenaline (0.27 +/- 0.31 ng/ml to 4.5 +/- 2.1 ng/ml) were significantly elevated during exercise. Both returned to pre-exercise levels within 15 min post exercise. Unexpectedly, oxygen uptake was slightly (5%), but significantly increased over the entire duration of the SSRI trial. We conclude that the central serotonergic system is not responsible for PEH in our borderline hypertensive population.

Adult↗

The sympathetic nervous system and the renin-angiotensin system in borderline hypertension.

1. Plasma catecholamine levels as well as plasma renin activity and plasma renin concentration were compared in normotensive volunteers and in subjects with borderline hypertension. All subjects were studied at rest and during bicycle ergometry. 2. The two groups of volunteer subjects did not differ in the plasma concentrations of noradrenaline and adrenaline, both at rest and during physical activity. The same was true for plasma renin activity and plasma renin concentration. Furthermore, urinary excretion of noradrenaline, adrenaline and 4-hydroxy-3-methoxymandelic acid was similar in both groups. 3. The results do not support the assumption that there is increased sympathetic activity in subjects with borderline hypertension.

Adolescent↗

Effects of a low-salt diet and of acute salt loading on blood pressure and intralymphocytic sodium concentration in young subjects with borderline hypertension.

1. Three groups of young patients with borderline hypertension were studied for a 12 months period. The first was on a free sodium diet while the second was on a low-salt diet. The third group of patients underwent acute salt loading. 2. After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted. Five patients who were re-checked after 24 months also had a significant increase in blood pressure. 3. Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure. 4. After acute salt loading, borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal.

Adolescent↗

Baroreceptor stimulation and isometric exercise in normotensive and borderline hypertensive subjects.

1. The effects of carotid baroreceptor stimulation (neck chamber) on systemic haemodynamics were determined for normotensive and borderline hypertensive subjects during periods of resting and isometric exercise. 2. Both groups reacted to baroreceptor stimulation with a similar decrease in mean arterial pressure and cardiac index at rest and during isometric exercise, but baseline heart rate decreased more in borderline hypertensive patients. 3. Baroreceptor stimulation elicited the same haemodynamic response at rest and during exercise-induced arterial pressure increase. Since the magnitude of arterial pressure had no bearing on the subsequent response, these data suggest resetting of baroreceptors during this short-term blood pressure increase.

Adult↗