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Left ventricular diastolic function and responses to adrenergic stimuli in borderline arterial hypertension.

OBJECTIVE: To detect the existence of a possible relationship between arterial hypertension and adrenergic reactivity to pressure stimuli, and changes in left ventricular diastolic function (LVDF). PATIENTS: Fifty-nine young subjects with borderline arterial hypertension and ten sex- and age-matched controls were investigated. After three medical examinations, the subjects were divided into hypertensive and borderline groups on the basis of the blood pressure reading at visit 3. A complete echocardiographic study was performed in 25 of the 59 subjects. DESIGN: Blood pressure was measured in baseline conditions and during pressure stimuli (mental stress, handgrip and cold pressor tests). LVDF was evaluated primarily by means of filling velocities during diastolic phases taken from the left ventricular volume curve (obtained from a complete echocardiographic study). RESULTS: No significant changes in blood pressure responses were observed for the borderline or hypertensive groups during the adrenergic test. The echocardiographic indices of diastolic function were statistically different for the two groups when compared with the control group. The LVDF parameters correlated significantly with systolic blood pressure and diastolic blood pressure measured at the time of the echocardiogram, but not with blood pressure measured occasionally. CONCLUSIONS: Blood pressure increases similarly during adrenergic stimuli in both the hypertensive and borderline groups. The correlation between systolic blood pressure, diastolic blood pressure and LVDF parameters may indicate a very early onset of reduced compliance of the left ventricle, even in a preclinical phase of hypertension.

Adolescent↗

Early impairment of coronary flow reserve and increase in minimum coronary resistance in borderline hypertensive patients.

OBJECTIVE: To evaluate relations between coronary flow velocity and myocardial oxygen demand at rest, as well as coronary vasodilator capacity and flow reserve, in asymptomatic subjects with borderline hypertension as compared to normotensive controls and patients with sustained high blood pressure (HBP) and without left ventricular hypertrophy (LVH). SUBJECTS AND METHODS: Forty-two asymptomatic males were studied: 13 healthy normotensive volunteers; 12 subjects with borderline HBP and 17 asymptomatic subjects with sustained systemic hypertension. Coronary flow velocity in left anterior descending artery and coronary flow reserve were assessed by transesophageal echo-doppler at baseline and during intravenous adenosine infusion. Left ventricular mass, peak systolic wall stress (PSWS; Pa), and midwall fractional shortening (MFS; %) were obtained from M-mode images of the left ventricle in transthoracic long-axis view and in transesophageal transgastric view. RESULTS: Coronary flow velocity at baseline was not significantly different in the three groups, despite significantly higher rate-pressure product (RPP) in the hypertensive groups as compared with controls. Only in control subjects, was resting coronary flow velocity significantly correlated with RPP (y = 4279 + 200x, r = + 0.58, P < 0.05) and PSWS (y = 17.2 + 5.1 x, r = + 0.62, P < 0.05). Coronary reserve was 3.5 +/- 0.65 in controls and significantly lower (P < 0.05) in borderline hypertensive (2.87 +/- 0.46) and in sustained hypertensive subjects (2.66 +/- 0.56). Minimum coronary resistance was significantly increased in both hypertensive groups (1.30 +/- 0.29 and 1.39 +/- 0.48 mmHg/s per cm) as compared to normotensive controls (0.93 +/- 0.20 mmHg/s per cm, P < 0.01). CONCLUSIONS: In asymptomatic subjects with borderline hypertension and without LVH, a significant reduction in coronary flow reserve is already detectable and appears almost entirely related to an impaired coronary vasodilator capacity rather than to an increased myocardial oxygen demand.

Adenosine↗

Hemodynamic patterns in the natural history of borderline hypertension.

This paper gives a review of cross-sectional and long-term hemodynamic studies in mild and borderline hypertension at different ages. Since the term borderline and mild are frequently used rather loosely, the selection criteria and blood pressure during the hemodynamic study should be noted. For two decades it has been assumed that subjects below 40 years of age with mild or borderline hypertension usually have a higher resting cardiac index (CI) and heart rate (HR) than normotensive age-matched controls. This assumption is supported by numerous previous and recent invasive studies in young males. However, a true hyperkinetic circulatory system with abnormally low arteriovenous oxygen difference is not typical. The whole-body oxygen consumption is increased, and cardiac output is normal when related to the oxygen uptake. Thus, the so-called whole-body autoregulation theory should not be applied to explain the chain of hemodynamic events including a fall in cardiac index and an increase in total peripheral resistance over time. Recent noninvasive studies in children and adolescents with mild or borderline hypertension have generally not demonstrated higher cardiac indexes in mildly hypertensive groups, and blood pressure increases have been due to increased total peripheral resistance. Possible explanations for these different findings in subjects supposed to be in the initial phase of essential hypertension are discussed. Our laboratory performed invasive long-term follow-up studies of central hemodynamics at rest and during exercise at 10 years and 17 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cellular and humoral factors in borderline hypertension.

In this article, we review the data about Na+ and K+ lymphocyte content in young subjects with borderline hypertension. These data indicate that many borderline subjects have an abnormally high lymphocyte Na+ content (Nai) and that their pressor response to stress and exercise is directly related to Nai. Lymphocyte K+ content (Ki) is increased in about 50% of borderline subjects. Subjects in whom Ki is high, in comparison with those having a normal Ki, have a lower Nai and lower diastolic blood pressure. This suggests that these subjects have an activation of some compensatory mechanism, possibly an increase in sodium pump function. A humoral factor causing an increase in Nai was detected not only in the plasma from essential hypertensives, but also in the plasma from borderline subjects and from normal subjects with familial hypertension having high Nai. This indirect evidence of a plasma factor impairing Na+ transport was confirmed by direct measurements of the plasma ability to inhibit Na+/K+ adenosine triphosphate. Moderate short-term dietary salt restriction reduces Nai and, proportionally, pressor response to stress. In the long-term, resting blood pressure is also reduced. Dietary K+ supplementation reduces pressor response to handgrip but not resting blood pressure. Intralymphocytic Na+ content is a good predictor of future sustained hypertension, since subjects with normal Nai do not develop hypertension within 5 years, whereas subjects with high Nai develop hypertension in 31% of cases. These subjects also have an altered pressor response to mental stress and do not respond to the low-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation↗

Hyperadrenergic borderline hypertension is characterized by suppressed aggression.

The effect of suppressed aggression on the reactivity of the sympathetic nervous and cardiovascular systems has been investigated in two groups of 24 subjects each with either borderline hypertension or normal blood pressure and no family history of hypertension. Groups were matched for sex and age (18-24 years). Suppressed aggression was defined by the newly standardized Rosenzweig Picture-Frustration test, a projective method assessing the reaction to everyday stress. Responses of blood pressure, heart rate, and venous plasma catecholamines were measured before and during application of mental stressors, using the Stroop color-word conflict test and mental arithmetic. In an analysis of covariance for repeated measures, which eliminates the influence of anxiety, borderline hypertensive subjects with suppressed aggression had significantly higher heart rates and diastolic blood pressures and a greater noradrenaline reactivity than borderline hypertensive subjects without suppressed aggression or normotensive subjects. Suppressed aggression may lead to a hyperadrenergic form of early borderline hypertension and thereby contribute to higher blood pressure.

Adolescent↗

Behavioral determinants of 24-hour blood pressure patterns in borderline hypertension.

Borderline hypertension is a heterogeneous condition; only a minority of patients will progress to fixed essential hypertension or suffer cardiovascular damage. Ambulatory blood pressure monitoring can detect the subgroup of borderlines with sustained blood pressure elevation outside the office setting and can also provide a measure of blood pressure variability. Patients in the former group may be at greatest risk for cardiovascular complications while the latter have been theorized to be at risk for progression to fixed hypertension. Evidence we have gathered utilizing ambulatory monitoring does not support the contention that there is a subgroup of borderline hypertensives with excessive blood pressure variability in natural settings. Such recordings have been of benefit in identifying patients with excessive pressor responses to office visits. Future studies employing ambulatory monitoring may be useful in the detection of clinically important subgroups of borderline hypertension.

Behavior↗

Comparison of pain perception in normotensives and borderline hypertensives by means of a tooth pulp-stimulation test.

Recent studies indicate a reduced sensitivity to pain in genetically and experimentally hypertensive rats. A similar finding is also reported for human established hypertension. However, to our knowledge, no data have been reported in borderline hypertension. The aim of this study was to assess in subjects with borderline hypertension the sensory and pain thresholds by a noninvasive pulp-stimulation test performed with a commercial pulp tester that delivered stepwise increased electrical stimuli to four healthy teeth. The data reported are the means of measurements. In order to assess the possible importance of differences in the selection of the controls, two distinct groups of normotensives were chosen, one of volunteers and the other of outpatients. Significantly higher values for the pain and sensory thresholds were observed in borderline hypertensives compared with pooled normotensives. No significant effect on pain perception could be observed for sex, whereas a significant tendency toward higher threshold levels was found for younger subjects. In two normotensive groups, the sensory and pain thresholds were significantly higher in volunteers than in patients. These results suggest that changes in pain perception are present not only in established hypertension but also in borderline hypertension and, moreover, that differences in the selection of normotensive controls can have important influences on the results.

Adult↗

Arterial distensibility in young normotensive subjects and in patients with borderline and essential hypertension.

We evaluated the indices of arterial distensibility in a group (N = 40) of normotensive subjects and patients with borderline or established hypertension by measuring intra-arterial pressure, pulse wave velocity, and a mathematical modification of MOEN's formula to calculate arterial distensibility. Multiple linear regression analysis including six hemodynamic variables (systolic pressure [SP], diastolic pressure, mean arterial pressure, cardiac output, stroke volume, total peripheral resistance) and age showed that SP and age are the best predictor indices for arterial distensibility (P less than .025; both inversely correlated with arterial distensibility) and for pulse wave velocity (P less than .001; both positively correlated with pulse wave velocity). Patients aged 48 years and under (N = 35) with no evidence of target organ damage showed significant differences in arterial distensibility (F = 5.41; P less than .01) among normal, borderline, and established hypertensive subjects; arterial distensibility was lower in those with borderline (P less than .025) and established hypertension (P less than .01) when compared with the normal group. We concluded that arterial distensibility is decreased in borderline as well as in established essential hypertension without target organ involvement and that age and systolic pressure are the best predictors of arterial distensibility.

Adult↗

Ambulatory blood pressure monitoring and borderline hypertension.

Blood pressure fluctuates during daytime hours in response to changes in activities and to daily life stressors. Lifestyle factors may influence changes in blood pressure through a modulation of the sympathetic nervous system s activity, which is often elevated in subjects with borderline hypertension. In the HARVEST smoking, consumption of coffee, intake of alcohol, physical activity habits, and use of oral contraceptives influenced daytime blood pressure to a greater extent than did office blood pressure and had an effect on sympathetic tone (determined by measuring levels of urinary catecholamines). Subjects with borderline hypertension have a greater than normal risk of cardiovascular morbidity and mortality, but few data on the relation between ambulatory blood pressure and hypertensive complications during the early stage of hypertension are available. In the HARVEST the impact of ambulatory blood pressure on the walls of the left ventricle and on left ventricular mass in women was remarkable, whereas it was weak for men. The assessment of left ventricular systolic function confirmed that ejective performance in many young borderline hypertensive subjects is greater than normal. However, in 9.2% of the HARVEST participants left ventricular contractility evaluated by midwall measurement was found to be depressed. Although the prevalence of microalbuminuria (rate of excretion of urinary albumin > or = 30mg/24h) appeared to be low (6.1%), rate of excretion of albumin was highly statistically significantly correlated to 24h blood pressure. Ambulatory blood pressure monitoring is useful for identifying those borderline hypertensive subjects for whom antihypertensive treatment should be started.

Blood Pressure↗

The management of borderline tumours of the ovary.

PURPOSE OF REVIEW: The treatment of borderline ovarian tumours has been similar to that for their invasive counterparts for a long time. However, in view of the good prognosis for borderline ovarian tumours, their occurrence in a younger age group and the development of less invasive techniques, the question can be asked as to whether a more conservative treatment is warranted. RECENT FINDINGS: Recent articles discuss the mode of surgery (laparotomy or laparoscopy), the possibility of fertility-sparing surgery, the need for restaging procedures and adjuvant therapy. SUMMARY: The ultimate goal in treating patients with borderline ovarian cancer is defining those patients with bad prognostic factors and risk for recurrence and who consequently require more aggressive therapy. A proper staging procedure is crucial to estimate the risk. Translational research might help identify borderline tumours with poor prognosis. Fertility-sparing surgery is often a good option in young patients with Fédération International de Gynécologie et Obstétrie (FIGO) stage I disease or in selected cases with noninvasive implants, since long-term survival does not seem to be negatively influenced by conservative surgery.

Chemotherapy, Adjuvant↗

K-RAS mutations in ovarian and extraovarian lesions of serous tumors of borderline malignancy.

K-RAS mutations are the most frequent molecular genetic alteration in serous ovarian tumors of borderline malignancy (SBOT). The pathogenesis of associated contralateral tumors and extraovarian implants and Müllerian inclusion cysts is obscure. We hypothesized that the comparison of K-RAS mutations in these lesions might help to distinguish multifocal from metastatic foci. Eight cases of SBOT with known K-RAS mutation (RAS+) and two cases without mutation (RAS-) were analyzed for comparison. DNA was extracted from multiple samples of 58 paraffin-embedded and laser-microdissected ovarian and extraovarian lesions (10 ovarian borderline tumors, 8 contralateral tumors, 25 implants, 15 inclusion cysts; total: 97 samples). K-RAS exon 1 was amplified by PCR and analyzed by denaturing gradient gel electrophoresis and cycle sequencing. In 12 of 14 SBOT and in 2 of 2 extraovarian implants, the K-RAS mutation could be found in different areas of the same lesion, indicating monoclonality. All RAS+ ovarian borderline tumors with contralateral tumors (six of six) harbored an identical mutation in both ovaries (in one case, a separate surface borderline tumor component contained a different mutation in addition). In 4 of 5 RAS+ ovarian tumors with extraovarian lesions, RAS mutations were also found in implants (15/21 implants [71%]) and more rarely in inclusion cysts (3 of 12 lesions [25%]). These extraovarian mutations were always identical to the one in the ovary (18 of 18 [100%]). Regarding the contralateral and extraovarian lesions of the two RAS- SBOT, only one extraovarian implant contained a RAS mutation. The demonstration of K-RAS mutations in Müllerian inclusion cysts and implants of SBOT suggests that K-RAS mutations represent a pivotal event during neoplastic transformation of ovarian and extraovarian serous epithelium. Considering our observations, the two putative pathogenetic mechanisms for the development of implants and endosalpingiosis-multifocal tumorigenesis and spread from the ovarian primary tumor-seem to coexist.

Adnexal Diseases↗

Long-term follow-up of 13C-urea breath test results after Helicobacter pylori eradication: frequency and significance of borderline delta13CO2 values.

BACKGROUND: The precise choice of cut-off point for the 13C-urea breath test to define whether it is positive or negative represents a controversial issue. AIM: To quantify the 13C-urea breath test result for several years following Helicobacter pylori eradication, and to evaluate the frequency and the significance of borderline delta13CO2 values. METHODS: Two-hundred H. pylori eradicated patients confirmed by 13C-urea breath test (100 mg of urea, citric acid), and having had repeated this test yearly up to 5 years, were studied. Delta13CO2 values between 2 and 5/1000 were considered as borderline results. RESULTS: Eight H. pylori recurrences were observed during 406 patient-years of follow-up (1.97% yearly). In two of eight reinfected patients, the reinfection was preceded by a negative delta13CO2 value >2/1000. Borderline delta13CO2 values were detected in 4% of the 606 urea breath tests performed, and in 25% when only patients in whom H. pylori recurrence was detected in subsequent urea breath tests were included (P < 0.05). The negative-predictive value of a post-treatment delta13CO2 >2/1000 for the diagnosis of H. pylori recurrence was 99%. CONCLUSIONS: Positive and negative urea breath test results tend to cluster outside the range between 2/1000 and 5/1000. Nevertheless, a borderline urea breath test delta value (e.g. very close to the selected cut-off point) should be interpreted cautiously, and the result should probably be confirmed either by repeating the urea breath test or by other diagnostic methods. On the contrary, a delta13CO2 value <2/1000 very confidently confirms H. pylori eradication.

Breath Tests↗

Cardiac autonomic mechanisms associated with borderline hypertension under varying behavioral demands: evidence for attenuated parasympathetic tone but not for enhanced beta-adrenergic activity.

Elevated blood pressure in psychophysiological studies of borderline hypertension is frequently attributed to the effects of increased sympathetic tone, and with few exceptions, the potential parasympathetic contributions have not been considered. Furthermore, of the investigations that have addressed vagal influences upon blood pressure, most have employed invasive pharmacological assessment of parasympathetic tone. In this study, cardiac parasympathetic and beta-adrenergic influences in borderline hypertension were evaluated noninvasively employing respiratory sinus arrhythmia as a vagal index and preejection period as a sympathetic index of cardiac functioning. Subjects were 30 borderline hypertensive and 23 normotensive males (age range, 24-45 years). The ECG, blood pressure, impedance cardiography, and respiration were measured during two baselines (initial and post-task), a memory-comparison reaction time task, the cold pressor, and CO2-rebreathing. Results indicated tonic differences between groups in all cardiovascular variables across tasks, with the exception of pre-ejection period, which showed no group effects at all. Hypertensives additionally manifested somewhat heightened systolic blood pressure reactivity and attenuated cardiac parasympathetic responsivity to specific tasks. Our findings provide no support for an exaggerated cardiac beta-adrenergic tonic level or reactivity in borderline hypertensives. On the other hand, the consistently lower magnitude of respiratory sinus arrhythmia in our hypertensives suggests that reduced parasympathetic control may be involved in the pathophysiology of hypertension.

Adult↗

A clinical review of borderline glandular cells on cervical cytology.

OBJECTIVE: To review the diagnoses and diagnostic pathway of women presenting with borderline glandular cells on cervical cytology. To outline the basis of clinical approach of these women. DESIGN: Retrospective review. POPULATION: Forty-three women referred to the hospital department over a 32-month period. METHODS: Review of the casenotes for the demographic data, previous cervical cytology and/or histology report, indication for the smear resulting in borderline glandular cells, colposcopic findings, diagnostic and/or treatment procedures, final diagnosis and current status. RESULTS: The average age was 36.7 years. Twenty-four women (56%) had clinically significant lesions: seven women (16%) presented with cancers, of which one was endometrial in origin, and 17 (40%) with intraepithelial neoplasia (CIN and cervical glandular intraepithelial neoplasia (CGIN)). Sixty-seven percent of all clinically significant lesions were of squamous origin. Thirty-seven had histological diagnosis, while six went on to cytological surveillance. Colposcopy was the most significant predictor for clinically significant lesions (P < 0.05). Punch biopsies and loop excisions were diagnostic when based on abnormal colposcopic findings. Brush cytology was appropriate follow up for asymptomatic, premenopausal women with no colposcopic abnormality. In addition, endometrial sampling was recommended in the peri- and postmenopausal women. CONCLUSION: Borderline glandular cells have a high incidence of clinically significant lesions. Immediate referral for colposcopy and assessment is strongly recommended in women with two borderline glandular smears to avoid delays in potential cancer diagnosis.

Adult↗

Fertility results after conservative treatment of advanced stage serous borderline tumour of the ovary.

OBJECTIVE: To assess the fertility of patients treated conservatively for a Stage II or III borderline ovarian tumour. DESIGN: A retrospective study. SETTING: Gynaecological oncology department in a French anti-cancer centre. POPULATION: Seventeen patients treated with conservative management for a Stage II (n = 6) or III (n = 11) borderline ovarian tumour were followed up. Fifteen patients underwent a unilateral salpingo-oophorectomy (with contralateral cystectomy in six patients), one had unilateral cystectomy and one a bilateral cystectomy. Fourteen patients had non-invasive implants and three had invasive implants. MAIN OUTCOME MEASURES: Pregnancy rates and outcome. RESULTS: Eight pregnancies were observed in seven patients in a median delay of eight months following the surgical procedure. Six pregnancies were observed spontaneously, one occurred after an ovarian stimulation and one after an IVF procedure. None of these patients recurred under the form of invasive ovarian carcinoma on the spared ovary. Two patients (one with a non-invasive disease and one with an invasive one) had recurrence in the form of evolutive invasive implants, but neither woman died. CONCLUSION: Spontaneous pregnancy can occur after conservative treatment of advanced stage borderline tumour of the ovary (with non-invasive implants). Such management, performed in a close follow up of the patients, does not affect the overall survival. Conservative surgery could be proposed in patients with borderline tumour of the ovary and non-invasive peritoneal implants.

Adolescent↗

Carcinosarcoma-like mural nodule in intestinal-type mucinous ovarian of borderline malignancy: a case report.

Epithelial ovarian tumors of borderline malignancy are tumors with histologic features and biologic behavior between benign and frankly malignant epithelial ovarian neoplasms. To date, we cannot accurately predict the patients who are prone to an aggressive course of disease. Here, we present a 35-year-old patient with carcinosarcoma-like mural nodule in intestinal-type mucinous ovarian tumor of borderline malignancy. Foci of intraepithelial carcinoma (about 10%) without stromal invasion are also noted. Total hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and omentectomy were performed, and the frozen pathology during operation showed mucinous tumor of borderline malignancy of left ovary on April 18, 2002. The patient was followed at our outpatient department for 19 months after operation and was free of the disease without any adjuvant chemotherapy. It is difficult to determine whether intestinal-type borderline mucinous tumors with intraepithelial carcinoma are associated with a worse prognosis compared with those with epithelial atypia alone due to disparate results in the published literature. In contrast, most patients with mural nodules of anaplastic carcinoma have had a malignant, often rapid, course. However, too few cases of carcinosarcoma-like mural nodule in mucinous tumor have been published to warrant a conclusion regarding their prognosis.

Adult↗

The border between the paranoid-schizoid and the depressive positions in the borderline patient.

In this paper some of the mental mechanisms deployed by borderline patients are described and illustrated with clinical material. It is suggested that the term borderline has three distinct but related meanings. First, it refers to a clinical category of patients, borderline between neurosis and psychosis who, while not frankly psychotic, tend to use psychotic mechanisms. Second, it refers to a metaphor representing the subjective experience of these patients who are unable to find a permanent identity but feel themselves sitting on the fence between a variety of different identities in a borderline position. Third, it can refer to a theoretical formulation of the level of development at which these patients function. I propose that in terms of mental mechanisms, they function as if on the border between the paranoid-schizoid and depressive positions as outlined by Melanie Klein. Some of the consequences of the failure to experience and work through depressive anxieties are discussed.

Adult↗

Comparison of conventional susceptibility tests with direct detection of penicillin-binding protein 2a in borderline oxacillin-resistant strains of Staphylococcus aureus.

Six selected strains of Staphylococcus aureus classified as borderline oxacillin-resistant, according to standard disk diffusion and microdilution susceptibility test methods, and seven methicillin-resistant and seven methicillin-susceptible control strains were examined for the presence of penicillin-binding protein 2a (PBP 2a) by fluorography and immunoblotting and for DNA hybridization with a mec-specific probe in a dot blot assay. Oxacillin agar screen tests with and without NaCl supplementation were also performed with all strains. PBP 2a was detected both by fluorography and by immunoblotting in all seven methicillin-resistant control strains and in none of the susceptible controls. PBP 2a was detected in two borderline strains. Results of agar screen tests performed without NaCl supplementation were completely concordant with susceptibility determined by PBP 2a and mec detection methods. Agar screening with NaCl supplementation was less accurate. These findings were confirmed with 20 additional borderline strains. Direct detection methods for the presence of PBP 2a or mec, the gene encoding it, allow accurate and definitive classification of borderline strains. Further efforts to develop a rapid, clinically useful, antibody detection system for PBP 2a are warranted.

Animals↗