[Quality of life in menopause. Experimental research]. / Qualità di vita nella menopausa. Una ricerca sperimentale.

Psychophysiological relationship in menopausal women was explored by the comparison of stress level and resistance to stress and related symptoms: socio-economic and cultural variables and willingness to participate into a specific therapeutic program were taken into account. One hundred women, aged 44-59 years (54.2 +/- 5.64), that consecutively were referred to an out-patient menopausal Clinic, were studied by a questionnaire that evaluates quality of life (qol) derived and adapted from the Sickness Impact Profile and the Functional Living Test; moreover the test MSP (psychological stress measurement), translated from the original and adapted to Italy, was used. Psychological complaints of women examined are minimal: adaptation tests are substantially normal, and stress index measurements are even lower in comparison with a gender and age matched population group. Our results suggest that after a short period of psychological tension at the onset of climaterium, women acquire a positive, stable status, well different from stereotypes and prejudices around psychological disturbance associated with menopause. Minimal relevance of perceived disturbance seems the reason that limits the women's need and request for a specific therapy. Menopausal depression seems more related to life changes than to hormonal alterations. Reduced physical fitness, increased risk of parental death, difficulty to cope with new roles, apart the care of adult sons or daughters. A critical point is socio-economic level and the possibility to maintain a satisfying work. Contextual conditions, and specially degree of instruction, type of role change inside the family and number of sons, appears the most evident and relevant variables that mediate psychophysical conditions and perceived quality of life.

Relationship between cardiac function and insulin resistance in obese patients.

Both overweight and insulin resistance predispose to atherosclerosis and cardiovascular diseases, independently of other risk factors. We studied the relationship between insulin resistance and heart function and dimension in 39 patients with different degrees of obesity. Twenty-six women and 13 men with body mass index (BMI) ranging 26.1-41 kg/m2 (mean +/- SD = 33.9 +/- 3.8), without diabetes, hypertension and heart, liver or kidney diseases were studied. Patients were subdivided into 2 groups, 25 with overweight or grade I obesity (group A) and 14 with severe (grade II or III) obesity (group B). Insulin sensitivity was evaluated by the Insulin Tolerance Test (ITT), performed after an overnight fast and K(ITT) was calculated. Echocardiographic measurements were also assessed. Between the two groups no significant difference was observed for either K(ITT) (group A, K(ITT) = 5.47 +/- 1.30; group B, K(ITT) = 4.57 +/- 1.53) or the ejection fraction (EF%) (group A, 71.40 +/- 6.63; group B, 69.86 +/- 7.43). No correlation was observed between BMI and both the EF% and other echocardiographic measurements. In patients with mild obesity (group A) a significant negative correlation between EF% and KITT (r = -0.62,p < 0.001) was observed. In mild obesity, therefore, cardiac function changes occur in relation to the level of insulin resistance but these changes are not related to mass and/or volume changes. The cause(s) of this relationship is not clear, but most likely involves metabolic or endocrine factors. The increased EF% in moderately obese patients that are insulin-resistant may provide an initial compensatory mechanism but may also contribute to a late cardiac damage.

[Heart failure and nutritional status in hemodialysis]. / Insufficienza cardiaca e stato nutrizionale in emodialisi.

Left ventricular function is impaired in long-term maintenance dialysis as a consequence of several inter-related conditions. Aim of the study was to assess if different degree of malnutrition can affect diastolic and systolic function of dialysis patients. Bio-electrical whole-body multifrequency impedance analysis (BIA) allows a dynamic assessment of body composition according to a multi-compartment model. This allows an assessment of lean (FFM) and fat mass (FAT), metabolically active cell mass (BCM) and a BIA Nutritional Index (NI). We studied 73 patients (53 M, 20 F), aged 54.41 +/- 3.1 yrs, on maintenance bicarbonate dialysis since 57.3 +/- 61.8 mths, by BIA, performed before and after a dialysis. I-PTH and serum albumin are correlated (r = -0.55, p < 0.001); the same trend is shown by I-PTH vs fat free mass (r = -0.47, p < 0.001) and vs NI (r = -0.51, p < 0.001). Ejection fraction (EF) is correlated with age (r = -0.50, p < 0.001) and with I-PTH (r = -0.59, p < 0.001). Moreover, albumin and EF are closely related (r = 0.36, p < 0.01), as well as EF vs FFM (r = 0.47, p < 0.001), and EF vs NI (r = 0.37, p < 0.01). A/E ratio, assumed as index of left ventricular diastolic function, shows a correlation vs albumin (r = -0.33, p < 0.01), BCM (r = -0.34, p < 0.01) and NI (r = -0.40, p < 0.01), but not with I-PTH. Malnutrition, defined both by BIA measurements and lower serum albumin, could exert unfavourable effects on left ventricular systolic and diastolic function of patients on long-term haemodialysis, even independently by hyperparathyroidism.

[Quality of life in hemodialyis patients: the effect of educational status]. / Qualità della vita in emodialisi: interferenza del grado di istruzione scolastica.

INTRODUCTION: Hemodialysis has a major influence on the quality of life of chronic renal failure patients. Great attention is currently paid to the development of supporting programmes for this patient group. Aim of this study was to evaluate the quality of life in maintenance dialysis and to research the influence of various factors related to treatment and ESRD on quality of life, taking into account also the level of school instruction. PATIENTS AND METHODS: Reduced functional abilities, as measured by the Sickness Impact Profile (SIP), and Functional Living Test (FLT), derived by Karnofsky Activity Scale were assessed; Hospital Anxiety and Depression Scale (HAD) and semistructured interviews, including a clinical grading of symptoms were considered vs. age, duration of dialysis, level of school instruction. The study was performed with 40 hemodialysis patients, aged 57.4 +/- 14.9 years (range 22-79), treated since at least three years. RESULTS: Significant (P < 0.05) independent correlates with higher SIP scores (greater disability) and Functional Living Test were lower educational level, and the score of Hospital Anxiety and Depression Scale (HAD). No correlation was found for any of the three scales vs. age and vs. dialytic age; no gender difference was observed. DISCUSSION: A greater care in considering Quality of Life questionnaires is warranted, especially for the severe interference of instruction level of patients on results. QALY (Quality Adjusted Life Years), used as a tool for decision-making in clinical and political subsets, can include critical bias that invalidate conclusion.

[Hyperthyroidism, therapy with erythropoietin, malnutrition and systolic function in hemodialysis: echocardiography study]. / Iperparatiroidismo, terapia con eritropoietina, malnutrizione e funzione sistolica in emodialisi: studio ecocardiografico.

Secondary hyperparathyroidism is a frequent condition of dialysis patients. Endocrine derangements, with disturbance of calcium metabolism are complex, involving bone, heart (left ventricular hypertrophy-dilatation), bone marrow (anemia and erythropoietin resistance), muscle (increase of body fat mass) and insulin resistance. Aim of the study was to assess how these conditions are inter-correlated in the same patients. 45 patients (m 20, f 25; years 61.8 +/- 11.6) in maintenance bicarbonate three-weekly hemodialysis since > 3 years were studied. Cardiac function was assessed by echocardiography (EF%: left ventricular ejection fraction), which showed an inverse correlation both with parathormone (iPTH vs EF%: r = -0.64; p < 0.001) and with erythropoietin (rHu-EPO vs EF%: r = -0.62; p < 0.001). This suggests the possibility of a multi-endocrine resistance in dialysis patients with chronic renal failure, secondary to the degree of malnutrition. Lower lean mass is correlated with hyperparathyroidism (iPTH vs fat mass%: r = 0.37; p < 0.01), with lower left ventricular systolic function (EF% vs fat mass%: r = -0.41; p < 0.005) and with rHu-EPO resistance. Moreover, patients with higher iPTH show a hypercatabolic disposition, assessed as protein catabolic rate (PCR/kg vs iPTH r = 0.54; p < 0.001). This pattern can be a consequence of chronic renal failure, but bio-compatibility of materials can be involved as well.

Cyclosporin A reverses chemoresistance in patients with gynecologic malignancies.

Multidrug resistance is a major obstacle in successful systemic therapy of gynecologic malignancies. The objectives of this study are to evaluate the activity of cyclosporin A used to overcome drug resistance in a variety of gynecologic malignancies. Forty women (29 with ovarian cancer, 7 with uterine cancer, 3 with cervical cancer, and 1 with choriocarcinoma) were treated with cyclosporin A, 4 mg/kg intravenously, 6 hours before and 18 hours after the specific chemotherapeutic agent, to which the tumor had developed drug resistance. All patients had shown resistance to the chemotherapy agent used in combination with cyclosporin A. All patients had been heavily pretreated (mean, 2.8 previous chemotherapy regimens). Overall, among 38 available patients with gynecologic malignancies, a 29% objective response rate was observed. Twenty-six (65%) of all patients received three or more cycles of cyclosporin A. There was a 25% response rate for patients with ovarian cancer patients and 50% for those with uterine cancer. There were no responses among the three patients with cervical cancer, and the patient with choriocarcinoma had a complete response. All patients were evaluable for toxicity. Leukopenia and nausea were the most common toxic reactions, but in most cases they were transient, and only three patients required a treatment delay. The most common grade 3 or 4 toxicity was thrombocytopenia, which was observed in 22% of the patients. Cyclosporin A is well tolerated and has significant potential for reversal of chemoresistance in heavily pretreated patients with ovarian and uterine malignancies.

Advanced ovarian carcinoma presenting with a cerebrovascular accident.

Ovarian carcinoma usually presents in an indolent manner, most often nonspecifically with complaints of abdominal pain or swelling, bloating, constipation, anorexia, early satiety, and evidence of ascites. We present a case of ovarian cancer with a cerebrovascular accident (CVA) as the presenting symptom, with minimal classic presenting signs and symptoms. The patient is a 43-year-old female with no cardiovascular risk factors who presented with a left parietal lobe infarct and advanced ovarian carcinoma. The patient underwent an extensive workup for the etiology of her CVA and possible hypercoagulation syndrome and eventually had surgical treatment. Ovarian carcinoma with a thromboembolic event as the initial presenting symptom is extremely rare. Although this patient did not appear to have hypercoagulability, consideration of this diagnosis should be given to patients presenting in this manner.

Melanoma complicating pregnancy.

The incidence of malignant melanoma is rising, and this may be the most frequently encountered malignancy during pregnancy. Because effective treatment of advanced or metastatic disease remains elusive, the key to adequate therapy is surveillance for early disease with prompt diagnostic work-up and treatment. Review of the most prominent reports in the literature fails to yield a consensus on whether pregnancy contributes to a worse prognosis. It seems clear that after controlling for all known prognostic variables, prognosis is unchanged; however, groups of patients diagnosed during pregnancy may have a disproportionately high incidence of high-risk primary lesion sites and increased tumor thickness. Surgical treatment during pregnancy should be prompt, with appropriate avoidance of general anesthesia during the first trimester. There is as yet insufficient evidence to warrant the use of adjuvant chemotherapy or biologic therapy during pregnancy.

Abdominal incisions from creation to closure.

Many of the techniques involved in creating and closing a surgical incision are based on tradition. Over the last several decades, randomized studies have addressed some of the steps in this process. Animal data and human data often have conflicting results. Randomized trials in human subjects indicate: 1) The incision can be made with one, rather than two, scalpels. 2) There is no advantage to using a laser rather than a scalpel when creating the incision. 3) Subcutaneous Penrose drains carried through the incision increase the infection rate. Closed suction drains in the subcutaneous space are rarely indicated. 4) The surgeon does not need to close peritoneum. 5) Time can be saved by closing the fascia in a continuous rather than interrupted fashion without causing an increase in postoperative wound separation or hernia formation. 6) Closing Camper's fascia after a cesarean delivery reduces the incidence of wound separation. 7) The cosmetic appearance of an incision is not improved by closing skin in a subcuticular rather than interrupted fashion.

p53 gene mutation analysis and antisense-mediated growth inhibition of human ovarian carcinoma cell lines.

Targeting dysfunctional gene expression in the cancer cell with gene-specific therapeutics requires knowledge of the structure and expression of the designated gene. Because of the prevalence of p53 dysfunction in epithelial ovarian carcinoma, modulation of the expression of this tumor suppressor gene is an attractive target for gene therapy. We sequenced the p53 gene and analyzed its expression in 10 ovarian cancer cell lines. Only five cell line mutations were encountered, three associated with a loss of heterozygosity. Thus, neither p53 mutation nor allelic loss is required for ovarian carcinogenesis or propagation of ovarian cancer cell lines in vitro. SSCP screening, but not immunohistochemical staining, correlated with results of direct genomic sequencing. All p53 immunohistochemical-negative cell lines differed from that reported by another laboratory, underscoring the importance of the knowledge of target gene expression in a given cell line in a given laboratory. We designed pilot studies of antisense oligodeoxynucleotides directed against the p53 gene based on our sequence data. Differential growth inhibition of the A2780-CP-20 cell line (mutant p53 protein), but not of the OVCAR-3 cell line (wild-type p53 protein) confirmed the potential usefulness of this strategy.

Stage I squamous cell cervical carcinoma in pregnancy: planned delay in therapy awaiting fetal maturity.

PURPOSE: It is not known whether intentional delay to allow fetal maturity in patients with Stage I cervical carcinoma diagnosed during pregnancy will affect the survival of these patients. The purpose of this study is to report our experience with invasive squamous cervical carcinoma after planned delay in therapy for fetal indications, to assess maternal morbidity due to treatment delay, and to report maternal and fetal survival. METHODS: Between 1989 and 1994, eight pregnant women with Stage I squamous cervical carcinoma, who declined immediate therapy in order to improve fetal outcome, were prospectively followed until the late third trimester. Serial MRIs were used to follow the lesion in two patients. RESULTS: Stage IB cervical cancer was diagnosed in seven pregnant women. All lesions were less than 2.5 cm. The mean diagnosis-to-treatment interval was 109 days (range, 21-201; median, 112). One woman conceived in the cycle after diagnosis and had a diagnosis-to-treatment interval of 282 days. All were delivered by cesarean section-radical hysterectomy late in the third trimester. There was no clinical progression of disease detected during any of the pregnancies. Serial MRI examination confirmed stable disease in one patient and suggested an increase in tumor volume in one patient that was not pathologically confirmed. All are alive and disease free after a mean follow-up of 37 months (range, 13-68; median, 33). Neonatal morbidity was encountered in one infant (spontaneous pneumothorax). CONCLUSIONS: With a median follow-up of 33 months, patient-requested delays in therapy between 3 and 40 weeks (mean, 19) did not affect progression.

Comparison of a novel redox dye cell growth assay to the ATP bioluminescence assay.

Antisense oligodeoxynucleotides (ASOs) are being studied with increasing frequency to determine their potential role as anticancer drugs. The overwhelming majority of this research continues to be done in vitro. Reliable and accurate determination of cell proliferation and/or inhibition, therefore, is essential for the production of meaningful results. The Alamar Blue assay, a colorimetric/fluorometric redox dye assay, was recently marketed by Alamar Biosciences (Sacramento, CA). In order to determine a potential role for this assay in ASO research, it was extensively tested on ovarian cancer cells in culture under a variety of conditions including uninhibited cell growth, cell kill with cytotoxic chemotherapeutic agents, and growth inhibition with ASOs. Results were compared directly with the ATP bioluminescence assay. We conclude that the Alamar Blue assay correlates poorly with the ATP assay, and it should be used only as a rapid preliminary screening assay. The ATP bioluminescence assay should continue to be considered as the standard in this setting.

Evaluation of hyperbaric oxygen as a chemosensitizer in the treatment of epithelial ovarian cancer in xenografts in mice.

BACKGROUND: Resistance to chemotherapy is common in bulky hypoxic tumors such as epithelial ovarian cancer. Hyperbaric oxygen (HBO) oxygenates hypoxic tissues and promotes neovascularization. These unique properties of HBO may help overcome chemotherapy resistance by increasing both tumor perfusion and cellular sensitivity. This study was undertaken to determine if HBO increases the response of epithelial ovarian cancer to cisplatin chemotherapy. METHODS: In Phase I, 64 nu/nu mice were divided into four groups and subcutaneously inoculated with cells from the A2780 human epithelial ovarian cancer cell line. Group 1 served as controls. Group 2 received weekly intraperitoneal cisplatin (3.15 mg/kg). Group 3 was exposed to HBO (dives) at 2.4 atmospheres absolute pressure for 90 minutes, 7 days a week. Group 4 received both cisplatin and HBO. In Phase II, 72 mice were divided into two groups and similarly inoculated. Both groups received weekly intraperitoneal cisplatin (2.5 mg/kg). Group 1 was not exposed to HBO. Group 2 was exposed to HBO for 5 days a week. RESULTS: Dramatic tumor neovascularization was found in tumors of mice exposed to HBO (P = 0.0001). There was significant (P = 0.014) tumor growth retardation in Phase I for mice receiving both cisplatin and HBO compared with those treated with cisplatin alone. This significance was noted after just two doses of cisplatin but subsequently lost due to reduced numbers of mice. In Phase II, neovascularization was detectable after 10 HBO treatments (2 weeks) and was maximal after 15 treatments (3 weeks). CONCLUSIONS: Hyperbaric oxygen increases vascularity in bulky tumors such as epithelial ovarian cancer. There appears to be a relationship between increased vascularity and enhanced response to chemotherapy that merits further investigation.

Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer.

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.

In vitro growth effects of colony-stimulating factors in ovarian cancer.

Human recombinant colony-stimulating factors may be used to treat or prevent neutropenia caused by marrow toxic chemotherapeutic agents administered to patients with cancer. Despite their common clinical use, little is known about the potential adverse effects that these cytokines may have on the growth of malignant cells. Indeed, several in vitro reports have indicated that colony-stimulating factors may act as stimulating growth factors in some human malignancies. To evaluate these effects in ovarian cancer, we investigated the possible growth effects of granulocyte colony-stimulating factor (G-CSF/Filgrastim) and granulocyte-macrophage colony-stimulating factors (GM-CSF/Sargramostim) on four established ovarian cancer cell lines, as well as five primary ovarian cancer cultures over a wide range of pharmacologic doses. Cell viability was measured by an ATP bioluminescence assay and expressed as a percentage of untreated control cultures. G-CSF showed no growth-stimulating effects in any of the four established cell lines tested. In the OVCAR-3 cell line, a decrease in growth (> 10%) was seen at 10, 100, and 1000 ng/ml after 5 days of continuous treatment. In the same cell line, GM-CSF caused an increase (> 10%) in growth at the same doses. However, these changes did not demonstrate statistical significance in a dose-dependent fashion. In the five primary cultures treated with G-CSF, only one demonstrated statistically significant increases in growth in a dose-dependent manner. GM-CSF treatment had no significant growth alterations in these same five primary cultures. These results would suggest that colony-stimulating factors may act as growth factors in some but not all ovarian cancer cells. Further investigations into the receptor status of ovarian cancer cells for these cytokines are underway to clarify this issue.