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.

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.

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.

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.

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 value of transvaginal ultrasonography in the prediction of endometrial pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated patients.

OBJECTIVE: There is no established ultrasonographic endometrial cutoff value for the diagnosis of endometrial pathologies in asymptomatic postmenopausal tamoxifen (TAM)-treated patients. We attempted to seek the most accurate cutoff value. MATERIALS AND METHODS: Multiple ultrasonographic cutoff points were evaluated by logistic regression analysis based on 279 patients who had transvaginal ultrasonographic examinations followed by endometrial histopathological analysis. Performance characteristics were calculated with correlation to the endometrial histological findings. We also calculated how many endometrial pathologies could have been left undiagnosed and the number of endometrial samplings, with different cutoff values, which could have been avoided. RESULTS: There was a gradual increase in specificity and a gradual decrease in sensitivity of the ultrasonographic studies with the increase of endometrial thickness. More overall and more various endometrial pathologies were identified with the increase in cutoff values. The best cutoff value appeared to be 15 mm (sensitivity 37.9%, specificity 87.2%, positive predictive value 63.0%, and negative predictive value 70.2%). However, by avoiding performance endometrial sampling up to this cutoff value, 62.2% endometrial pathologies including 48 endometrial polyps, one case of endometrial hyperplasia with atypia, and one case of endometrial cancer may have been left undiagnosed. At the same time, endometrial sampling in 78.5% of cases may have been avoided. CONCLUSION: In asymptomatic postmenopausal breast cancer tamoxifen-treated patients, the use of wider ultrasonographic endometrial cutoff values could be associated not only with the performance of fewer endometrial samplings, but also with a higher possibility of endometrial pathologies, including endometrial cancers, being left undiagnosed.

The value of sonohysterography in the prediction of endometrial pathologies in asymptomatic postmenopausal breast cancer tamoxifen-treated patients.

BACKGROUND: The study evaluated the efficacy of sonohysterography in identifying endometrial pathologies in asymptomatic postmenopausal tamoxifen (TAM)-treated patients by evaluating its performance characteristics. MATERIALS AND METHODS: Multiple assessments of sonohysterography evaluations of intrauterine mass diameter were evaluated by logistic regression analysis based on overall 85 patients (who had transvaginal ultrasonographic endometrial thickness of >/=8 mm) followed by hysteroscopy and endometrial histological findings. Performance characteristics were calculated with correlation to the endometrial histological findings. RESULTS: The mean endometrial thickness was 14.6 +/- 6.2 mm, and the mean intrauterine mass diameter detected by SIS was 11.6 +/- 10.4 mm. There was a gradual decrease in sensitivity and gradual increase in specificity of the SIS studies with the increase in intrauterine mass diameter. False-negative and false-positive of SIS were 2.4% and 8.2%, respectively. ROC curve analysis of intrauterine mass revealed 5 mm as the best accurate cutoff value for the diagnosis of endometrial pathologies, with a sensitivity of 74.1%, specificity of 93.0%, and positive predictive value of 88.3% and negative predictive value of 84.2%. The risk of endometrial pathology was elevated by 1.37-fold, with any additional millimeter of diameter of the intrauterine mass. The mean diameter of the intrauterine mass gradually increased the greater the severity of the histological findings. CONCLUSIONS: Sonohysterography improves the accuracy of diagnosis of intrauterine mass in asymptomatic postmenopausal tamoxifen-treated patients. The size of the intrauterine mass correlates with the severity of the endometrial pathology.

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.

Granulosa cell tumors of the ovary: do they have any unique ultrasonographic and color Doppler flow features?

The aim of this study was to describe the ultrasonographic and Doppler flow attributes of granulosa cell tumors (GCT) of the ovary and to compare these attributes to those of epithelial tumors of the ovary. Among 13,475 gynecological patients who were scanned in our ultrasound unit between 1992 and 1996, seven patients had GCT. The final diagnosis was confirmed, postoperatively, by pathologic examination and by applying the WHO classification. The ultrasonographic findings of the GCT patients were compared to those recorded in a second group of 29 patients who had been diagnosed with epithelial tumor of the ovary. The sonographic appearance of GCT of the ovary was semi-solid and the endometrium was thick in six of the seven patients. Doppler flow studies of vessels within or in the contour of the lesions showed the resistive index (RI) to be 0.448 +/- 0.018. The epithelial tumors had a similar appearance and flow pattern except for the presence of ascites in one-third of the patients. Ultrasound scanning, including color Doppler flow, did not contribute data that could assist in differentiating between GCT and epithelial tumors of the ovary.

Psychotherapy of adults with comorbid attention-deficit/hyperactivity disorder and psychoactive substance use disorder.

Psychotherapy for comorbid attention-deficit/ hyperactivity disorder (ADHD) and psychoactive substance use disorder (PSUD) is described. The authors suggest that relapse prevention is an appropriate initial treatment because it is well suited to manage both substance abuse and comorbid symptomatology such as impulsivity, distractibility, and avoidance associated with ADHD. Clinical vignettes describe typical interactions between patients and their therapists, highlighting opportunities for therapists to focus on overlapping symptoms. ADHD is one of the most common comorbid diagnoses with PSUD, and it is important that efficacious psychotherapies be developed to complement psychopharmacological approaches. Clinicians should consider psychotherapy as part of a multimodal treatment approach that includes medication and perhaps family therapy. Additional contributions from clinicians who have experience conducting psychotherapy with this population are needed in order to develop effective treatments.

Expression of L-selectin and efficient binding to high endothelial venules do not modulate the dissemination potential of murine B-cell lymphoma.

The homing receptor L-selectin is essential for the migration of naive lymphocytes into peripheral lymph nodes. In contrast to naive lymphocytes, activated and memory cells down-regulate L-selectin and enter peripheral lymph nodes by an L-selectin-independent mechanism. In view of the concept that lymphomas present the malignant counterparts of normal lymphocytes at a defined stage of differentiation, it has been suggested that in contrast to lymphomas with a memory/activated cell phenotype, L-selectin is essential for dissemination of lymphomas that represent naive cells. 38C-13 is a murine B-cell lymphoma with an immature naive cell phenotype. 38C-13 cells express high levels of L-selectin and bind to lymph node high endothelial venules in an L-selectin-dependent manner. In this study we demonstrate that treatment of 38C-13 tumor-bearing mice with anti-L-selectin antibodies did not inhibit tumor dissemination to peripheral lymph nodes. Moreover, L-selectin-negative 38C-13 variant cells disseminated as efficiently as wild-type cells. Thus, in spite of its expression, L-selectin is not required and does not affect the metastatic potential of the tumor. L-selectin of the malignant cells and of normal lymphocytes appears to be functionally different. Thus, whereas antibody cross-linking of L-selectin resulted in down-modulation of the receptor in normal lymphocytes, cross-linking had no effect on L-selectin expression in 38C-13 cells, suggesting that, in spite of comparable levels of surface expression in normal and malignant cells, L-selectin may be functionally impaired in some malignant cells.

The increase of renal pelvis dilatation in the fetus and its significance.

OBJECTIVE: To determine the effects of the changes in fetal renal pelvis dilatation on post-natal diagnosis and outcome. METHODS: Prenatal sonographic fetal renal anteroposterior diameters of > or = 4 mm in the second trimester, which persisted to > or = 7 mm in the third trimester, were the inclusion criteria. Fifty-six fetuses and 73 renal units with normal karotypes and a solitary sonographic finding of renal pyelectasis, which met the inclusion criteria, were followed, post-natally, until the age of 30 months. The neonates were categorized into three groups, according to their final diagnosis: No hydronephrosis, pelvi-ureteric junction obstruction and hydronephrosis from other causes. The neonates were also categorized according to their outcome: no treatment, follow-up only and surgical treatment. RESULTS: In 17 neonates (30.4%), and 19 renal units, the diagnosis of hydronephrosis was excluded post-natally. In 39 neonates (69.6%), and 54 renal units, an urinary tract pathology was confirmed. The dynamics of pyelectasis in the second and third trimesters of pregnancy differed significantly among the neonates when categorized according to the final diagnosis (P < 0.05), or according to outcome (P < 0.05). CONCLUSION: It is possible to predict, and distinguish between, long-term conservative and surgical treatments of renal pelvis dilatation in the third trimester of pregnancy.

[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.

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.

Prenatal sonographic detection of a lipomeningocele as a sacral lesion.

We present a case of a lipomeningocele in a newborn. Prenatal sonography revealed dysraphia and a 3.8 x 4.3 cm, semisolid, echogenic mass that was continuous with the sacral area and bulged posteriorly under the skin. The mass was diagnosed after birth as a lipomeningocele based on the results of MRI. This diagnosis was confirmed histologically.

A model for educating humanistic physicians in the 21st century: the new medicine, patient, and society course at Tel Aviv University.

BACKGROUND: The impact of the social and behavioral sciences on medical education has often been limited due to a variety of organizational, curricular and professional barriers. The new "Medicine, Patient, and Society (MPS)" program in Tel Aviv attempts to rectify this educational shortcoming by exploring new ways to help students acquire the knowledge, attitudes and skills needed for becoming humanistic physicians and for helping patients (and themselves) adopt healthy behaviors. To work toward this goal, this program integrates the biomedical and psychosocial aspects of health care, providing developmentally appropriate learning experiences according to levels of training, together with a variety of educational methods, including learner-centered approaches. OBJECTIVES: To implement and evaluate the MPS pilot program. METHODS: The MPS program uses a "seamless" model of behavioral science education. This integrated curriculum interweaves several elements: behavioral science topics (presented through multiple approaches), clinical experiences, practical medical skills, and an independent project. During the program's first year there is a strong focus on "health" rather than "disease," with activities designed to encourage healthy behaviors, including smoking cessation, stress management, birth control, AIDS education, life cycle and preventive health services. Assessment of the pilot for first-year students included standardized questionnaires, student focus groups, participant observation of educational activities, and committee feedback. RESULTS: Students' quantitative evaluations indicated high levels of satisfaction with the MPS program, but their qualitative evaluations revealed some concerns. Participant observations and focus groups added unexpected insights. Student concerns included performance fears, difficulties with "learner-centered" education, and incompatibilities between more traditional first-year courses and the MPS program. Long-term follow-up will be needed to determine the impact of this emphasis on health during the first year. We assume it serves as a helpful foundation for students before they focus on disease and its sequelae in their later years.