Software toolbox for analysis of the endometrial myometrial junction - a pilot study.

PURPOSE: To develop and evaluate an algorithm for computerized evaluation and measurement of the endometrial-myometrial junction (EMJ). MATERIALS AND METHODS: The advanced image processing toolbox of the Matlab software package was used for identificiation and quantitative analysis of the EMJ area on three-dimensional (3D) rendered coronal plane uterine images, with clear-cut borders of the EMJ. The algorithm was used to process the images and calculate the geometric parameters characterizing the identified EM The manual measurements of the maximum thickness of the EMJ were compared to automated measurements performed by the algorithm on the same images. RESULTS: For all three interfaces, the mean maximum manual measurement was less than the mean maximui computed measurement. The differences between the two measurements were not statistically significant (p = 0.275, 0.608 and 0.41 for the right wall, left wall, and fundus, respectively). The mean systematic and random errors ranged from 5.4% tol9.3% and 20.4 to 48.6%, respectively. Pearson correlations for the right wall, left wall and fundus (r = 0.642, p = 0.001; r = 0.730, p < 0.001, and r 0.694, p < 0.001, respectively) were good. CONCLUSIONS: Maximum EMJ thickness measurements performed by the innovative Matla software algorithm are as accurate as manual measurements, and have the potential to reduce inter-observer variability.

Evaluation of energy expenditure in children with cerebral palsy using a multi-sensor accelerometer.

AIM: The aim of this paper was to evaluate the validity and reliability of a multisensor accelerometer, the Intelligent Device for Energy Expenditure and Activity (IDEEA, MiniSun, CA), for measuring energy expenditure in children with cerebral palsy (CP). Twenty-one children with CP, age range 4-10 years, with varying degrees of impairment, were recruited for the study. In addition, 7 children with normal development, age range 5.67-8.5 years, were also tested. METHODS: Children were connected to a portable metabolic cart (Cosmed, Rome, Italy) and to the IDEEA by five sensors. Children were asked to perform a series of activities simulating everyday activity, walk on a treadmill for 4 min and climb a staircase for 4 min. During all activities oxygen consumption values were measured and converted to energy units. Energy expenditure as measured by the IDEEA was also recorded. RESULTS: During the simulation of daily activities and during walking at a comfortable speed the IDEEA significantly overestimated the energy expenditure. However significant and relatively high positive correlations (0.70-0.97) were found between the two instruments. Inconsistent results were obtained during walking at increased speed. During a step test similar means were found by the two instruments for children with normal development and children with CP with good correlations between the values measured by the two instruments. Energy expenditure measurement in children with CP were found to be very reliable, with a correlation of 0.998 for repeated measurements during treadmill walking. CONCLUSION: It seems IDEEA, with its present conversion equations, is not suitable for exact evaluation of energy expenditure in children with CP or in young children with normal development. However, in light of the good correlation with the standard method of evaluating energy expenditure and the high test-retest reliability of the IDEEA's measurements, It is suggested that IDEEA may be a valuable tool for clinical follow-up of children with CP for quantitative evaluation of the efficacy of treatment interventions. The establishment of population specific conversion equations is expected to significantly increase the accuracy of energy expenditure evaluation by the IDEEA.

Long-term "protective" effect of aromatase inhibitors on the endometrium of postmenopausal breast cancer patients.

BACKGROUND: Decrement of endometrial thickness was recorded following short-term aromatase inhibitor treatment in breast cancer patients previously treated with tamoxifen. It is necessary to verify if long-term aromatase inhibitor treatment can maintain this phenomenon. METHODS: Prospective long-term comparison of the last ultrasonographic endometrial thickness measurement taken before discontinuation of long-term tamoxifen treatment in 64 postmenopausal breast cancer patients, with further repeated measurements, performed following administration of aromatase inhibitors. RESULTS: There was a significant decrement of endometrial thickness, following 36.5 +/- 15.7 months of tamoxifen treatment, from a mean value of 8.7 +/- 5.2 mm, measured at the last ultrasonographic measurement performed before discontinuation of tamoxifen treatment, down to a mean value of 6.2 +/- 4.6 mm, measured following 5.3 +/- 4.8 months of aromatase inhibitor therapy (P < 0.001). Further ultrasonographic studies revealed the same significant trend. In the first ultrasonographic study performed during aromatase inhibitor treatment, five (7.8%) patients demonstrated a significant increase of endometrial thickness. Hysteroscopy revealed a benign endometrial polyp in three patients and atrophic endometrium in the other 2. In 35 patients (54.7%), endometrial thickness was reduced following the administration of aromatase inhibitors and in 24 patients (37.5%) there was no change in endometrial thickness. With longer duration of aromatase inhibitor therapy, more patients showed decrement of endometrial thickness. CONCLUSIONS: Reversal of endometrial thickening induced by long-term tamoxifen treatment in postmenopausal breast cancer patients is maintained throughout long-term aromatase inhibitor treatment.

Long-term follow-up of postmenopausal breast cancer patients following discontinuation of tamoxifen therapy.

BACKGROUND: There is a need to evaluate the extent of endometrial pathologies that might develop in postmenopausal breast cancer patients following discontinuation of tamoxifen (TAM) therapy. METHODS: The medical records of 153 postmenopausal breast cancer patients who remained untreated following discontinuation of tamoxifen therapy were evaluated for various clinical features, for endometrial thickness measurements, as detected by transvaginal ultrasonography, and for various endometrial pathologies detected. The last endometrial thickness measurement performed before discontinuation of tamoxifen was compared with endometrial thickness measured following discontinuation of tamoxifen. RESULTS: Patients were followed for 37.5+/-31.3 months. There was a gradual and significant decrement of endometrial thickness measured at the last ultrasonographic study performed before cessation of tamoxifen, compared to that observed in all four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Endometrial thickness gradually and significantly decreased in correlation with the time intervals of the four ultrasonographic studies performed following discontinuation of tamoxifen (P=0.001). Overall, 40 hysteroscopies were performed in 38 (24.8%) patients. No tissue was obtained in 18 (11.8%) patients. Overall endometrial pathologies were diagnosed in 22 (14.4%) patients. Benign endometrial polyps were the most frequent endometrial pathology recovered: 17 (11.1%) patients. No endometrial malignancy was diagnosed. The rate of endometrial pathologies considerably decreased with the extension of time following discontinuation of tamoxifen therapy. CONCLUSIONS: Long-term follow-up of postmenopausal breast cancer patients who remained untreated following discontinuation of TAM therapy did not reveal any malignant endometrial pathology. Only few benign endometrial pathologies were diagnosed, which became fewer in time.

Hemorrhagic corpus luteum is associated with ovarian edema.

BACKGROUND: Most cases of ovarian edema are thought to result from intermittent ovarian/adnexal torsion. This study describes how, in some cases, this etiology was ruled out even though the edema was unexplained. STUDY OBJECTIVE: To evaluate the association between ovarian edema and hemorrhagic corpus luteum. SETTING: Department of gynecology in an urban medical center. PARTICIPANTS: Five patients admitted to the department of gynecology with a sonographic diagnosis of ovarian edema of unexplained etiology. RESULTS: Laparoscopy performed on three of five patients in whom a diagnosis of unexplained ovarian edema revealed hemorrhagic corpus luteum and ovarian edema. The remaining two patients displayed typical sonographic imaging of hemorrhagic corpus luteum and ovarian edema and they were managed expectantly. The affected ovaries were between 4.8 and 10 times larger than the unaffected ovaries. During follow-up, the affected ovaries returned to their normal size and appearance. CONCLUSIONS: Hemorrhagic corpus luteum can cause ovarian edema without interrupting the blood flow supply. The outcome of expectant management without any surgical intervention is the gradual disappearance of the ovarian edema in these patients and the return of ovaries to a normal sonographic appearance.

The plant lectin FRIL supports prolonged in vitro maintenance of quiescent human cord blood CD34(+)CD38(-/low)/SCID repopulating stem cells.

Ex vivo maintenance of human stem cells is crucial for many clinical applications. Current culture methods rely on optimized combinations of cytokines. Although these conditions provide some level of stem cell support, they primarily induce proliferation and differentiation, resulting in reduced repopulation capacity. The recently identified legume lectin FRIL has been shown to preserve human cord blood progenitors up to a month in suspension culture without medium changes. To test whether FRIL also preserves human SCID repopulating stem cells (SRC), we cultured human CD34(+) cord blood cells in medium containing FRIL, with or without subsequent exposure to cytokines, and tested their repopulating potential. We report that FRIL maintains SRC between 6 and 13 days in culture. Incubation of CD34(+) cells with FRIL results in significantly lower numbers of cycling cells compared with cytokine-stimulated cells. CD34(+) cells first cultured with FRIL for 6 days and subsequently exposed to cytokines for an additional 4 days generated significantly more mononuclear and progenitor cells and higher levels of engraftment in NOD/SCID mice compared with CD34(+) cells cultured with FRIL alone. Similar results were obtained with CD34(+)CD38(-/low) cells, including expansion of SRC that were cultured in FRIL followed by cytokine stimulation. Moreover, CD34(+) cells precultured with FRIL successfully engrafted primary and more importantly secondary recipients with lymphoid and myeloid cells, providing further support that FRIL maintains SRC for prolonged periods.FRIL's ability to preserve quiescent primitive cells in a reversible manner may significantly expand the time and range of ex vivo manipulations of human stem cells for clinical applications.

A cell line with unusual characteristics from an ovarian carcinoma patient: modulation of sensitivity to antitumour drugs.

A cell line (GZL-8) was established by cloning from ascitic fluid of an untreated ovarian carcinoma patient. The cells grew rapidly, accumulated lipids and showed chromosomal alterations. One of the marker chromosomes showed characteristics of a Y-like chromosome. This unusual finding was confirmed by DNA hybridisation using specific probes to the Y chromosome. The cells stained with fluorescent antibodies to desmoplakin and cytokeratins 8, 18, 19, and weakly with vimentin but not with desmin. The presence of epithelial membrane antigen, human milk fat globulin, alpha-lactalbumin, alpha-fetoprotein, placental alkaline phosphatase and oestrogen receptor-related antigen was demonstrated by indirect immunoperoxidase staining, but no CA-125 antigen could be detected. The cells showed positive reaction with antibodies to P-glycoprotein. The function of the P-glycoprotein transport system was demonstrated by the rhodamine-123 release test. The cells were initially responsive to doxorubicin, and to high concentrations of cisplatin. Growth inhibition by doxorubicin, especially at low doses was enhanced by the addition of verapamil or tamoxifen. This was shown by the soft agar clonogenic assay, by direct cell counting and by the MTT reducing test. Our results show that combination between drug and sensitivity modulators may be of potential clinical value in ovarian cancer.

Inhibition of 6-phosphogluconate dehydrogenase by glucose 1,6-diphosphate in human normal and malignant colon extracts.

Increased activity of 6-phosphogluconate dehydrogenase was found in human colon tumors as compared to the adjacent unaffected mucosa. Glucose 1,6-diphosphate (Glc-1,6-P2), an endogenous potent regulator of glucose metabolism, markedly inhibited the activity of 6-phosphogluconate dehydrogenase (6-PGD) in extracts of the normal and malignant human colon. Glc-1,6-P2 also inhibited the activity of hexokinase in these extracts. The endogenous levels of Glc-1,6-P2 in the colon and tumors were measured. Since the pentose cycle can be inhibited by Glc-1,6-P2, means to increase endogenous levels of Glc-1,6-P2 or to introduce it into cells, might result in antitumor effects.

Three-dimensional first trimester fetal volumetry: comparison with crown rump length.

BACKGROUND: Ultrasonographic volumetry measurements of human fetus have become possible using three-dimensional ultrasound systems. OBJECTIVE: To evaluate the weekly increase of fetal volume during the first trimester of normal pregnancies compared to the crown rump length and creating a first trimester fetal volume nomogram. METHODS: Crown rump length and three-dimensional ultrasonographic volumetry measurements performed on 72 first trimester fetuses using virtual organ computer aided analysis (VOCAL). RESULTS: A significant direct correlation (r = 0.939) was found between the calculated fetal volumes and crown rump lengths. A 6-12 weeks gestation fetal volume nomogram was proposed. CONCLUSION: Fetal volume database in the first trimester may serve as a reference table for diagnosis of early pregnancy failure.

Simultaneous local recurrence of retroperitoneal paraganglioma with liver metastases.

A 68-year-old woman with a history of a nonfunctional paraganglioma resected 23 years previously presented with an abdominal mass. Tumor metastases to the liver were seen at the second operation. The tumor had a more pleomorphic appearance, but was otherwise similar to the original tumor. We discuss the difficulty of predicting the later malignant behavior of the tumor from the original biopsy specimen.

The use of far distal arterial bypass for limb salvage.

Thirty-four distal arterial reconstructions to the ankle and the foot for limb salvage were performed in 33 patients, 11 of whom underwent additional operative procedures. The follow-up period is up to 4 years. The operative mortality rate was 9.09%. The 6 month, 1 year and 2 year accumulated patency rates calculated by life table analysis were 85%, 86.7% and 77.3%, respectively. Limb salvage was achieved not only in patients with patent grafts but also in a considerable number of patients whose grafts were occluded between 3 and 24 months postoperatively.

Microhysteroscopy and endometrial biopsy results following failed diagnostic dilatation and curettage in women with postmenopausal bleeding.

OBJECTIVE: The aim of this study was twofold: firstly to evaluate and compare the diagnostic precision of the microhysteroscopy (MH) and endometrial biopsy in a group of menopausal women in whom D&C had failed to obtain an adequate endometrial sample, and secondly to quantitate the value of a hysteroscopy in determining endometrial sampling in these patients. METHODS: A Hamou type II CO2 microhysteroscope (MH) was used to evaluate the endocervical canal and the uterine cavity, followed by endometrial sampling. RESULTS: Thirty-nine women were assessed using MH and endometrial biopsy. Histopathology results were available for diagnosis in 29 of them (74.3%). In the remaining ten patients, the MH diagnosis was atrophic endometrium. Biopsy results corroborated with MH in 86.2% (25/29) of the patients with tissue samples. The analysis (r) of this concordance rate was statistically significant (r = 0.96). Sample results for patients with MH determined pathological and normal endometrium corroborated in 83% and 91%, respectively, inclusive of three cases of endometrial adenocarcinoma. The sensitivity, specificity and predictive values for MH alone were 93.7%, 76.9% and 83.3%, respectively. CONCLUSIONS: These significant results are indicative that this simplified endoscopic method surpasses all blind hospital or office endometrial sampling methods. Therefore, we suggest that MH and endometrial sampling should be the initial assessment tool for any type of indication requiring endometrial and uterine cavity assessment.

Low molecular heparin (Enoxaparin) as an alternative treatment of acute deep venous thrombosis in gynecologic oncology patients.

While heparin has been the standard treatment in established deep vein thrombosis (DVT), it carries associated potential hazards of hemorrhage and induction of thrombocytopenia. Enoxaparin (Rhone-Poulenc Rorer Pharm. Inc., France) is a low molecular weight heparin which has antithrombotic properties, and has been demonstrated effective in prophylaxis of DVT, apparently without severe treatment related bleeding complications. Six patients with genital malignancies, presenting with Doppler sonography confirmed deep venous thrombosis, were treated with Enoxaparin. A uniform dosage of 2 mg/kg/day in two divided doses was administered subcutaneously for 10 days during hospitalization and then continued on an out-patient basis. The clinical symptoms of venous thromboses diminished in all six patients. Enoxaparin represents an effective treatment of DVT, with the potential advantage of a lessening hemorrhagic complications. With administration of low molecular heparin, the activated partial thromboplastin time (aPTT) is not dramatically altered, making laboratory monitoring unnecessary. Our clinical findings demonstrate an easily applied therapy for gynecologic oncology patients, which is potentially safer to use, less costly, and less dependent on laboratory monitoring than the normal regimen.

A second primary malignancy in a cohort of patients with epithelial ovarian cancer--characteristics of diagnosis.

As the life expectancy of cancer patients has been extended because of earlier diagnosis and improved therapeutic modalities, second primary tumors are being diagnosed more frequently. We have examined the clinical characteristics of 38 second primary tumors in a cohort of patients diagnosed with epithelial ovarian cancer in our department over a 6-year period. The most frequent neoplasm associations were in decreasing order of occurrence: ovary-breast, ovary-endometrium, and ovary-gastro-intestinal tract. Most heterochronous second primary tumors have been diagnosed following patient symptoms and not during routine follow-up of patients with a known primary cancer. Family history was obtained for 30/38 patients (19 with full pedigrees and 11 with partial information). Two of these 30 patients (6.6%) had one affected first degree relative-one with ovarian cancer and one with breast cancer. With an increased risk of developing a second malignancy after having a previous tumor, closer surveillance of patients posttreatment for cancer is warranted.

[Emergency cesarean section in a comatose parturient after head trauma].

Coma in pregnancy and labor is a rare and complicated situation. One of the causes is severe head trauma, which requires neurosurgical consultation and possibly urgent transfer to a neurosurgical unit. This should follow stabilization, confirmation of fetal viability, and cesarean section when indicated. A 38-year-old primigravida at term and in labor, with severe head injury from a vehicular accident is reported. Emergency cesarean section was performed for severe fetal distress during resuscitation. Fetal distress in a comatose parturient with severe head injury may require a short delay in referral to a tertiary trauma center to allow for an emergency cesarean section.

Placental findings contributing to fetal death, a study of 120 stillbirths between 23 and 40 weeks gestation.

BACKGROUND: Intrauterine fetal death is an agonizing, often unpredictable event. Autopsies of stillborn fetuses, including placentas, are performed to clarify the cause of death. Autopsy results are not always easily understood by the patients or their healthcare providers. OBJECTIVE: To evaluate placental causes of death in stillbirths based on autopsy and placental findings that are related to maternal underperfusion, fetal underperfusion, or inflammatory etiologies in hierarchical order. METHODS: Retrospective review of 120 autopsy reports of singleton stillborn fetuses and placentas from 23 to 40 weeks of gestation. RESULTS: Among the placental causes of death there were 54(51%) cases with direct cause or major contributor to death in the etiology of maternal vascular supply abnormalities, 28(26%) cases in the etiology of fetal vascular supply abnormalities and 13(12%) in the etiology of inflammatory lesions. Maternal vascular supply abnormalities were more common in preterm stillbirths and fetal vascular supply abnormalities were more common among term stillbirths. In 88% of stillbirths, the direct cause or a major contributor to death was found in the placentas. The incidence of unexplained death was 8%. CONCLUSIONS: Pathological analysis of the placenta is essential for clarifying causes of stillbirths. Using specific simplified categories for abnormal placental findings may increase the benefits of the autopsy report.

Aromatase inhibitors reverse tamoxifen induced endometrial ultrasonographic changes in postmenopausal breast cancer patients.

OBJECTIVE: Aromatase inhibitors may decrease endometrial thickness in breast cancer patients previously having short-term tamoxifen treatment. There is a necessity to find out if aromatase inhibitors can also decrease endometrial thickness in patients previously treated with long-term tamoxifen treatment. METHODS: Prospective comparison of the last ultrasonographic endometrial thickness measurement taken before discontinuation of long-term tamoxifen treatment in 36 postmenopausal breast cancer patients, with further measurements, performed following aromatase inhibitors administration. RESULTS: There was a significant decrement of endometrial thickness, following 36.2 +/- 16.8 months of tamoxifen treatment, from a mean value of 9.1 +/- 5.8 mm, measured at the last ultrasonographic measurement performed before discontinuation of tamoxifen treatment, down to a mean value of 6.0 +/- 5.0 mm, measured following 5.8 +/- 5.8 months of aromatase inhibitors therapy (P = 0.001). A second ultrasonographic measurement performed in 8 patients following of additional 7.5 +/- 4.0 months of aromatase inhibitors treatment revealed further decrement of mean endometrial thickness to 4.8 +/- 2.1 mm (P = 0.002 compared to baseline). In 28 patients (77.8%), endometrial thickness was reduced following the administration of aromatase inhibitors, in four patients (11.1%) there was no change in endometrial thickness and four (11.1%) patients demonstrated an increase of endometrial thickness. CONCLUSIONS: Aromatase inhibitors may reverse endometrial thickening induced by long-term tamoxifen treatment in postmenopausal breast cancer patients.