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Chromosome 6 abnormalities in ovarian surface epithelial tumors of borderline malignancy suggest a genetic continuum in the progression model of ovarian neoplasms.

PURPOSE: We used conventional cytogenetics, molecular cytogenetics, and molecular genetic analyses to study the pattern of allelic loss on chromosome 6q in a cohort of borderline epithelial ovarian tumors. EXPERIMENTAL DESIGN: Fifteen tumor samples were collected from patients undergoing surgery for ovarian tumors. The tumors of borderline malignancy, classified according to the standard criteria, included 4 mucinous and 11 serous tumors. Cytogenetic and molecular cytogenetic (with yeast artificial chromosome clones from 6q26-27) studies were performed on tumor areas contiguous to those used for histological examination ensuring the appropriate sampling. Moreover loss of heterozygosity analysis was performed using PCR amplification of eight microsatellite markers mapping on 6q27 (D6S193, D6S297), 6q26 (D6S305, D6S415, D6S441), 6q21 (D6S287), 6q16 (D6S311), and 6q14 (D6S300). RESULTS: Deletions of this chromosome arm, in particular of 6q24-27, were the most frequent lesions found in this set of tumors. In a tumor with a normal karyotype the only detectable alteration was a deletion of approximately 300 kb within the D6S149-D6S193 interval at band 6q27. This is, to date, the smallest deletion described for borderline tumors. CONCLUSION: Alterations in the above-mentioned interval are a common finding in advanced ovarian carcinomas but also in benign ovarian cysts, implying that some tumors of borderline malignancy may arise from benign tumors and that malignant ones may evolve from tumors of borderline malignancy. Genes located in 6q27 seem to be crucial for this mechanism of early events in ovarian tumorigenesis.

Adenocarcinoma, Mucinous↗

[Clinicopathologic analysis of ovarian serous and mucinous borderline tumors].

OBJECTIVE: To understand the clinicopathological features of ovarian borderline tumors and evaluate the significance of various histological appearances. METHODS: Forty-five patients with borderline tumors were analyzed retrospectively. The stage distribution was stage I, 34 patients, stage II, 4 patients and stage III, 7 patients. RESULTS: Forty-five cases of borderline tumors accounted for 25.4% of ovarian epithelial malignant tumors. The ratio of serous borderline tumors (SBTs) to mucinous borderline tumors (MBTs) was approximately 1:1.3. Nine of eleven SBTs with exophytic growth presented peritoneal implants, of which two were invasive and seven noninvasive. Two SBTs and 1 MBT recurred after 5, 4, and 1 years respectively. Thirty-three cases were followed from 2 to 9 years. The 5-year survival rate was 100% (Kaplan-Meir method). CONCLUSIONS: The prognosis of the SBTs is favorable. SBTs with exophytic growth are often associated with peritoneum implants.

Adenocarcinoma, Mucinous↗

[Posttraumatic stress disorder, dissociation and self-destructive behavior in borderline patients]

We studied traumatic childhood experiences, comorbid posttraumatic stress disorders (PTSD), dissociation and self-destructive behavior in 30 inpatients with a borderline personality disorder. A standardized interview for the assessment of PTSD, the Dissociative Experience Scale and the Symptom-checklist were administered. Results were compared to a control of inpatients with neurotic disorders matched for gender and age. Borderline patients showed significantly more childhood sexual and physical abuse as well as emotional neglect than the control patients. Of the borderline patients, 67% met criteria for PTSD and only 13% of the control group. Dissociative symptoms were significantly more frequent in borderline patients and predicted in combination with PTSD symptoms and self-destructive behavior. We discuss our findings with respect to their etiological and clinical significance and propose a model for self-destruction in borderline patients which focusses on dissociation and trauma.

Journal Article↗

[Evolution of surgical treatments in patients with borderline ovarian tumors].

OBJECTIVES: The aim of this study was to evaluate a type and range of primary operation of patients with borderline ovarian tumours. MATERIAL AND METHODS: The analysis included 129 patients operated for ovarian tumours of borderline malignancy in the Gynaecological Department of Medical University of Gdańsk between 1978-2000. The two types of primary operations were defined: conservative and radical. The dependency of type of operation on such factors as age of patients, parity, stage and histological type on was assessed. RESULTS: The group of 42 patients were treated with conservative surgery and 87 underwent radical treatment. 36 from 42 patients (85.7%) were treated by USO. A conservative surgery was mainly performed in young patients with mucinous borderline tumor in stage IA. The risk of recurrence was 4.8% in the group of patients treated conservatively and 8.0% in group of patients treated radically. 5-years survival was, 98.2% and 87.2% respectively. CONCLUSIONS: The type of the primary operation depends on age, parity, stage and histological type of borderline ovarian tumors. A conservative surgery is a proper treatment for young women with borderline ovary tumours in stage Ia. For older, perimenopausal women TAH with BSO is suggested.

Adult↗

In vivo adaptive response of the peripheral conduit artery in patients with borderline systolic hypertension.

OBJECTIVE: To investigate elastic changes of the radial artery, a medium-sized muscular peripheral conduit artery, in patients with borderline systolic hypertension. METHODS: Using a non-invasive high-resolution echo-tracking device coupled to a photoplethysmography (Finapres system) allowing simultaneous arterial diameter and finger blood pressure monitoring, we measured radial artery elastic parameters of 20 patients with borderline systolic hypertension and 20 normal subjects according to Langewouters model. RESULTS: The diameter of the radial artery of control subjects and those with borderline systolic hypertension at the isobaric level of 100 mmHg and mean arterial pressure was similar, but the compliance and distensibility at similar conditions in patients with borderline systolic hypertension did not further reduced and even increased. CONCLUSION: In patients with borderline systolic hypertension, the adaptive responses of the radial artery compliance and distensibility to increased pressure were directed to maintain its elasticity, contributing to the homeostasis of the cardiovascular system.

Adaptation, Physiological↗

Immunohistochemical characterization of ovarian borderline tumors of intestinal and mullerian types.

A panel of monoclonal antibodies (MAbs) including MOv2, MOv8, anti-CA 19-9, and anti-carcinoembryonic antigen (CEA), and a polyclonal antibody against CEA, was applied to three types of ovarian borderline tumors. The tumors included 19 intestinal-type mucinous borderline tumors (IMBTs), 22 endocervical-like mucinous borderline tumors (EMBTs), and 23 mixed-epithelial borderline tumors (MEBTs); the latter two tumors are of mullerian type. Statistically significant differences in the percentage of positive IMBTs compared to the mullerian tumors were seen for anti-CEA and MOv8; strikingly different staining patterns were also seen. IMBTs were more often and more diffusely CEA-positive than were the mullerian tumors; within the mullerian tumors, only one type of cell, the indifferent eosinophilic cell, was consistently CEA positive. The MAbs MOv2, MOv8, and anti-CA 19-9 showed more extensive positivity in the mullerian tumors than in the IMBTs. This study highlights the differences in cell types between IMBTs and these two types of mullerian borderline tumors.

Antibodies, Monoclonal↗

Measurement of fractional flow reserve in patients with multi-vessel coronary artery disease and borderline lesions prevents unnecessary revascularisation procedures.

BACKGROUND: Patients with multi-vessel coronary artery disease (CAD) are selected for percutaneous coronary interventions (PCI) or surgical revascularisation. The appropriateness of "ad hoc" PCI of borderline lesions (<70% of lumen diameter) in patients with a multi-vessel CAD has not been proven. However, delayed PCI of another lesion and gaining additional information from non-invasive tests is not a widely accepted strategy. When left anterior descending (LAD) coronary artery is one of the affected vessels, selection for surgical revascularisation is most likely. AIM: To assess long-term outcome in patients with multi-vessel CAD and borderline lesions, including LAD, in whom fractional flow reserve (FFR) in all affected vessels was measured and used for selection for PCI or conservative treatment. METHODS: The study group consisted of 16 patients with stable angina (11 males, mean age 60+/-9 years) with 34 lesions localised in the main epicardial coronary arteries [LAD / left main (LM) / right coronary artery (RCA) / intermediate branch (IB) / circumflex artery (Cx) - 15/1/5/5/8] of which at least two were borderline stenoses. Each lesion underwent FFR measurement. "Ad hoc" PCI was performed when FFR was <0.75, and conservative therapy was instituted when FFR was >0.75. RESULTS: Of 34 lesions, in 8 (23%) the FFR value was <0.75 and these lesions were treated with PCI (LAD/IB/Cx - 3/2/3). In the remaining 26 (77%) lesions, FFR was >0.75 and conservative therapy was instituted. During the mean follow-up of 15+/-6 months (range 6-28 months, median 15 months) in 8 of 9 conservatively treated patients no aggravation of anginal symptoms nor other coronary events were observed. One patient developed acute myocardial infarction due to thrombus occluding a borderline LAD lesion. Of 8 lesions treated with PCI (baseline FFR = 0.63+/-0.10 vs post-PCI FFR = 0.92+/-0.08, p=0.0002), in one case an in-stent restenosis in LAD occurred 9 months after PCI. Of a total of 26 lesions which were conservatively treated (mean FFR 0.91+/-0.05), in 2 (7.7%) the progression of CAD was noted. CONCLUSIONS: In patients with multi-vessel CAD and borderline lesions, FFR measurement identifies those, who can be treated conservatively with a good long-term outcome, and prevents unnecessary PCI.

Aged↗

[Structural and functional characteristics of cardiovascular system in elderly patients with borderline hypertension].

Structural and functional state of the heart and vessels was studied in elderly patients with borderline hypertension. Remodeling in these patients was compared with that in patients of the same age with normal or higher blood pressure levels. Analysis revealed substantial contribution in remodeling of both age and hypertensive factors. Compared with subjects with normal blood pressure patients with hypertension had greater myocardial mass, higher frequency of left ventricular hypertrophy with cases of concentric hypertrophy and isolated hypertrophy of interventricular septum. Elderly patients with borderline hypertension had more pronounced disturbances of diastolic function. Overall characteristics of patients with borderline hypertension were similar to those found in the elderly with higher level of hypertension. Presence of borderline hypertension was associated with higher than age specific stiffness of vessels. Character and degree of remodeling of the heart and vessels in the elderly patients with borderline hypertension evidence for elevated risk of cardiovascular complications.

Aged↗

Borderline coronary lesions may lead to serious coronary events--long-term outcome in 65 conservatively treated patients.

BACKGROUND: The choice of optimal therapy in a patient with borderline coronary lesion is difficult. The long-term outcome of conservatively treated patients has not yet been well defined. AIM: To analyse long-term outcome in patients with a borderline lesion in a single coronary artery who were selected for conservative treatment. METHODS: The study group consisted of 65 patients (mean age 59.4+/-7.4 years, 48 males) with (1) stable angina (CCS class I/II), (2) isolated single borderline coronary lesion (40-70% stenosis demonstrated by quantitative coronary angiography) and (3) no demonstrable ischaemia during non-invasive tests. Patients with heart failure, left ventricular ejection fraction <50% or acute coronary syndrome within 6 months preceding the study were not included. All patients were prescribed statins, angiotensin converting enzyme inhibitors and aspirin. Follow-up end-points included cardiac death, new myocardial infarction (MI) with or without ST segment elevation and revascularisation of the target coronary artery. RESULTS: The follow-up duration was 18.4+/-8.5 months (range 12-33, median 18 months). Forty nine (75%) patients remained free from angina during daily activity. Coronary events occurred in 16 (25%) patients, including three (5%) serious complications -- sudden death, new MI with ST elevation and new MI without ST elevation. The remaining 13 (20%) patients underwent percutaneous revascularisation of the target coronary artery. Coronary angiography was repeated in 16 (25%) patients. When the patients were divided into two groups according to the follow-up results (with or without coronary event), no differences in the clinical characteristics, lesion localisation and length or degree of stenosis were noted. CONCLUSIONS: (1) Conservatively treated patients with stable angina and borderline coronary stenosis have a high rate of coronary events, especially revascularisation, during a long-term follow-up. (2) Clinical parameters and quantitative coronary angiography do not identify those patients with borderline coronary lesions who are at increased risk of future coronary events.

Angina Pectoris↗

[The activity and properties of Na,K-ATPase in the erythrocytes and the Na-pump inhibitor in the plasma of subjects with borderline arterial hypertension].

The activity and properties of Na,K-ATPase in erythrocytes and their membrane preparations (ghosts) from 34 subjects with borderline hypertension and 21 normotensive controls were studied. The Na,K-ATPase activity was found to be by 43% lower as compared to control group. No changes in the Na,K-ATPase activity were revealed in the ghosts of borderline subjects. This suggests that the plasma of borderline subjects contains an inhibitor of Na,K-ATPase. The plasma level of sodium pump inhibitor was measured in 21 borderline hypertensive subjects. It was found to be about 19% compared with the control group. These findings suggest presence of Na,K-ATPase inhibitor in the plasma of borderline subjects, which is likely to be involved in the development of hypertension.

Adult↗

Renal eicosanoids and renal hemodynamics in early borderline hypertension.

To study the modulatory role of renal eicosanoids on renal hemodynamics and electrolyte excretion, pressor doses of norepinephrine (NE) were infused in 10 control subjects (mean age, 26 y) and 13 patients (mean age, 25 y) with borderline hypertension. The highest NE dose used (150 ng/kg/min) produced comparable increases in mean blood pressure in control subjects (20 +/- 2 mmHg) and in patients (23 +/- 3 mmHg). NE induced a significant increase in renal vascular resistance (p less than 0.01, both groups), with a smaller decrease in glomerular filtration rate resulting in a concomitant increase in filtration fraction (p less than 0.01, both groups). The renal hemodynamic changes tended to be more pronounced in borderline hypertension. NE infusion led to similar decreases in electrolyte clearances in the two groups. Urinary prostaglandin (PG)E2, PGF2 alpha (p less than 0.01), and 6-keto-PGF1 alpha increased with NE infusion. Urinary thromboxane (TX)B2 increased slightly in control subjects and decreased in borderline hypertension (p less than 0.05). The 6-keto-PGF1 alpha/TXB2 ratio, an index of vasodilation, was significantly increased (p less than 0.05) in borderline hypertension. These results demonstrate that in both groups pressor infusion of NE induced significant modifications in renal hemodynamics and in urinary electrolyte and eicosanoid excretion. The vasodilatory component of the renal eicosanoid system appears hyperresponsive in borderline hypertension, which may represent an early antihypertensive defense mechanism.

6-Ketoprostaglandin F1 alpha↗

The association of borderline hypertension with target organ changes and higher coronary risk. Tecumseh Blood Pressure study.

The Tecumseh project investigates the evolution of hypertension in a healthy population. Of 946 subjects aged 18 through 38 years, 124 had clinic blood pressure readings higher than 140/90 mm Hg (the mean for borderline hypertensive subjects was 130/94 mm Hg). Compared with normotensive subjects, borderline hypertensive subjects had higher home blood pressures (mean, 12/7 mm Hg higher). Their childhood and postpubertal blood pressures were elevated (6/4 mm Hg higher than normal at age 6 years and 12/7 mm Hg higher than normal at age 21 years), and hypertensive target organ changes were detected. Borderline hypertensive subjects also had elevated minimal forearm resistance (0.22 U higher than normal), decreased stroke index (1.8 mL/m2 lower than normal), and impaired ventricular diastolic relaxation (mitral Doppler peak early diastolic blood flow [E] to peak late diastolic blood flow [A] ratio 0.13 lower than normal). Borderline hypertensive subjects had significant abnormalities in other coronary risk factors (cholesterol levels were 0.39 mmol/L higher, triglyceride levels were 0.45 mmol/L higher, high-density lipoprotein levels were 0.08 mmol/L lower, insulin levels were 38 pmol/L higher, and 16.5% more of them were overweight). Borderline hypertension is neither transient nor innocuous. Its association with other predictors of atherosclerosis calls for clinical attention.

Adolescent↗

[A study on evaluation of circulating anticoagulant in borderline cases].

Detection of circulating anticoagulant (CA) is clinically important in patients with SLE, habitual abortion and other hemorrhagic and thrombotic disorders. We have studied CA in 83 patients with such disorders. Thirty-one of 83 (37%) had positive CA and 16 of 83 (19%) had negative CA, while 36 of 83 (44%) showed borderline pattern of CA. The experiment was undertaken to detect CA clearly in patients with borderline CA, by using diluted APTT or PT reagents. When we used 5% diluted reagent in APTT or 50% diluted reagent in PT, constant value of clotting time showed 1.8% or 1.2%, respectively. Seven of 10 with borderline CA cases tested here revealed positive CA by using diluted reagents. Furthermore 2 of remaining 3 with borderline CA cases showed positive anti-cardiolipin antibodies, suggesting of presence of lupus anticoagulants. These results suggest that CA in borderline cases should be considered to be positive and to be possibly derived from lupus anticoagulants.

Autoantibodies↗

[Incidence of hypertension and borderline hypertension with reference to complex professional stress in above ground and under ground workers in ore mining].

Comprehensive health care for working people requires a deeper insight into the relationship between work load and biological reactions. This is necessary to be able to adequately influence the field of industrial medicine. The incidence of both hypertension and borderline-hypertension in a group of 200 face workers with complex work load as well as 150 pithead metal workers aged between 25 and 45 was measured over a period of 5 years (1981-1986). The hypertension incidence was 0.90% in the group of face workers and 1.46% with the pithead metal workers, while the incidence of borderline-hypertension was 1.30% for the face workers and 2.12% for the pithead metal workers. A statistically significant difference between those people working above ground and those working underground was not apparent. No relationship was found between age, Broca-index, habit of smoking, shift work, the total time away from home and the development of an increase in blood pressure. Both a hypertension incidence totalling 1.14% and an incidence of borderline-hypertension of 1.66% were found in the test group aged between 25 and 45. This roughly corresponded to the nationally statistical level and was in line with the relevant literature. There was no discernable effect with regard to developing hypertension and borderline-hypertension, respectively, as a result of complex work load in the test group. The incidence rates require regular blood pressure tests on normotensive miners and pithead workers, respectively, as a prerequisite for early detection and registering as well as an adequate therapy of both hypertension and borderline-hypertension.

Adult↗

Serologic study of specimens with borderline FTA-ABS test reactivity.

The treponemal group-specific absorbed fluorescent antibody test (FTA-ABS) does not yield clearly positive or negative results in all instances. This study was designed to analyze those sera showing borderline reactivity, in order to determine whether additional tests may help to resolve serodiagnostic problem cases. FTA-ABS tests on 23,807 sera submitted to the Wisconsin State Laboratory of Hygiene yielded borderline results with 479 specimens (2%). Patients showing inconclusive FTA-ABS test reactivity were equally distributed among older and younger age groups, and 6% of borderline cases were women. Of all the 479 specimens, only five sera (1%) gave a non-specific hemagglutination with the Treponema pallidum microhemagglutination (MHA-TP) test, with 82.5% of the FTA-ABS test borderline sera yielding negative results with the MHA-TP test. Because recent findings had shown atypical false fluorescence with the FTA-ABS test on sera from patients with antinuclear antibody, the fluorescent antinuclear antibody test (FANA) was also performed on specimens inconclusive with the FTA-ABS test. Only seven sera (1.5%) were reactive by the FANA test, suggesting that antinuclear antibody was not a significant cause of borderline FTA-ABS reactions. The implications of these findings to venereal disease serology laboratory practice are discussed.

Adolescent↗

Nuclear deoxyribonucleic acid heterogeneity of ovarian borderline malignant serous tumors.

Sixteen borderline malignant serous ovarian tumors and seven well-differentiated invasive serous ovarian carcinomas were examined with the technique of Feulgen microspectrophotometry for the determination of nuclear deoxyribonucleic acid (DNA) ploidy patterns (diploid versus aneuploid) and ploidy levels of the stem cell lines. Of the nine stage I-II borderline malignant tumors, only one (11%) was aneuploid. In contrast, four of seven (57%) stage III borderline malignant neoplasms and all stage III carcinomas were aneuploid. The stem cell modal values in all borderline serous tumors were less than triploid (3N) while in five of seven carcinomas stem cell modal values were greater than triploidy. This contrast in ploidy patterns and ploidy levels may explain the differences in biologic behavior between borderline malignant serous tumors and invasive serous carcinomas of the ovary.

Adult↗

Aloneness and borderline psychopathology: the possible relevance of child development issues.

The experience of intense painful aloneness is a common event in the lives of borderline patients, especially those closer to the psychotic spectrum. This experience is defined as an intrinsic aspect of the borderline personality defect and consists of a relative or total inability to remember positive images or fantasies of sustaining people in the patient's present or past life, or being overwhelmed by negative memories and images of these people. The development of borderline aloneness is related to a possible developmental failure, defined by Piaget, Fraiberg, and A.-M. Sandler. These workers describe the child's development of object permanence and evocative memory capacity (Piaget's sensori-motor stage VI). We postulate that a major borderline vulnerability is the tenuous achievement of the capacity for affective object permanence and its regressive loss to recognition memory or earlier when under specific stresses. We relate our hypotheses to possible empathic parental failures during the substages of separation-individuation, especially the rapprochement sub-phase. The treatment implications of our formulations are discussed, with an emphasis on the clarification of the need for the therapist's availability and the use of transitional objects during times of the patient's loss of his affective cognitive capacities. These regressive experiences often emerge as a core transference manifestation during psychoanalytic therapy with borderline patients, and often become the basis of significant therapeutic work.

Child Development↗

Studies on salivary flow in borderline hypertension.

Salivary flow and the influence of drugs on this variable were studied in subjects with borderline hypertension and in normotensive control subjects. Saliva production under resting conditions was 0.85 +/- 0.08 g/min in normotensive subjects and 0.51 +/- 0.04 g/min in borderline hypertensive subjects. In both groups of subjects studied, salivary secretion was decreased by atropine but propranolol and phentolamine had no effect. The stimulating effect of neostigmine on saliva production was more pronounced in normotensive than in borderline hypertensive subjects. Thus, in order to increase salivary flow by 1 g/min 28 +/- 0.9 micrograms/min neostigmine had to be infused intravenously in normotensives compared with 41 +/- 3.8 micrograms/min in borderline hypertensives. The results of the study suggest that subjects with borderline hypertension have a reduced parasympathetic drive to the salivary glands.

Adult↗