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Biomedical subjects

D Weinstein

Publications and source records attributed to D Weinstein.

At least 37 records · Page 2Linked to original sources

Mapping pathophysiological features of breast tumors by MRI at high spatial resolution.

Magnetic resonance imaging (MRI) is a noninvasive method that reveals anatomical details in vivo and detects lesions for diagnosis. Although standard breast MRI cannot clearly delineate breast cancer, contrast-enhanced MRI enables the detection of breast masses with high sensitivity. Dynamic studies demonstrated that malignant lesions were characterized by a faster signal enhancement rate than benign ones. Dynamic MRI of human breast cancer in mice revealed high heterogeneity in the distribution of contrast-enhanced curves and derived pathophysiological features, indicating the importance of high spatial resolution. With clinical MRI, it is difficult to achieve simultaneously high spatial and temporal resolution. In previous dynamic studies, the emphasis was on high temporal resolution and mainly empiric analyses. We describe here a new model-based method that optimizes spatial resolution by using only three time points, and yet characterizes tumor heterogeneity in terms of microvascular permeability and extracellular fraction. Mapping these pathophysiological features may aid diagnosis and prognosis assessment, while the high spatial resolution may improve the capacity to detect smaller lesions. The method was tested in human breast tumors implanted in mice and in a limited number of benign and malignant breast lesions of patients.

Animals↗

Genomic imprinting and the endometrial cycle. The expression of the imprinted gene H19 in the human female reproductive organs.

H19 is an imprinted maternally expressed gene, which is not translated to protein and functions as an RNA molecule. It is closely related to the oppositely imprinted paternally expressed insulin-like growth factor 2 (IGF-2). While the biological function of H19 is not understood IGF-2 is a growth factor that plays a role in human follicular and endometrial differentiation. We examined the expression of H19 in the endometrium and ovary during the menstrual cycle by in situ hybridization applied to paraffin sections of human endometrium and ovaries at different stages of differentiation. In the endometrium, H19 expression was confined to the stroma and fluctuated with endometrial dating to reach its peak in the late secretory stage. IGF-2 was also prominently expressed in late secretory endometrium, but its expression was evident both in the stroma and glandular epithelium. Expression of H19 was not found in primordial, primary, and preantral follicles of the ovary, but prominent expression was evident in the theca of antral and cystic atretic follicles, and focal expression was noted in the granulosa of corpora lutea. An association between H19 expression during the menstrual cycle and the differentiation state of the human female reproductive tract, which is under hormonal control, is suggested.

Cell Differentiation↗

Altered G-protein coupling of a frontal cortical low affinity [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin serotonergic binding site in Alzheimer's disease.

In Alzheimer's disease (AD), there are marked deficits in the function of both the cholinergic and serotonergic systems. We and others have shown altered muscarinic M1 receptor/G-protein coupling in the superior frontal cortex (Brodmann areas 8 and 9) from AD patients. In the present study, we investigated whether similar receptor/G-protein alterations would occur at the 5-HT1A receptor in the same brain area. Using [3H]8-OH-DPAT as a radioligand, two binding sites with high and low affinity were found. The high affinity site (Kd = 1 nM), which is consistent with the classical 5-HT1A receptor, was not affected in AD either in the absence or presence of the non-hydrolyzable guanine nucleotide analog, GppNHp (100 microM). On the other hand, although there was no change in the affinity of [3H]8-OH-DPAT at the low affinity site (Kd = 8-10 nM), agonist binding was less sensitive to inhibition by GppNHp in AD (-29%) compared to age-matched controls (-51%). Based on these findings, alterations in receptor/G-protein coupling of both cholinergic and serotonergic receptors may be one explanation why neurotransmitter replacement drug therapies have been unsuccessful thus far in the treatment of AD.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Predictive score for vaginal birth after cesarean section.

OBJECTIVE: Our purpose was to evaluate the relative weight of the different variables that may influence the chances of vaginal birth after one cesarean delivery, with the aim of developing a predictive score for success of such a trial. STUDY DESIGN: In this retrospective study, which covered a 10-year period (1981 to 1990), 471 women who attempted vaginal birth at a level III university hospital after one abdominal delivery were studied as to the subsequent delivery outcome. An attempt to identify possible prognostic factors for success of such a trial was made. RESULTS: A trial of labor was successful in 368 (78.1%) of women and 103 (21.9%) had a repeat cesarean section. Variables of significant predictive value were vaginal birth before cesarean section (odds ratio 1.8), malpresentation (odds ratio 1.9), pregnancy-induced hypertension (odds ratio 2.3), and Bishop score > or = 4 (odds ratio 6.0). Cephalopelvic disproportion and failure to progress did not demonstrate a significant predictive value (odds ratio 0.81) for success or failure in subsequent delivery. In fact, 63.8% of women with this indication have successfully undergone vaginal delivery. Maternal age (odds ratio 0.9) had no bearing on vaginal delivery success rates, whereas both macrosomia (odds ratio 0.2) and intrauterine growth retardation tended to decrease the chances for vaginal birth after cesarean section. CONCLUSIONS: A trial of labor after one cesarean section should be encouraged in most women who are willing to attempt it, provided no obstetric contraindication exists. A scoring system that may help to identify women with a greater chance for vaginal delivery is proposed.

Adult↗

Vaginal birth after cesarean section: current opinion.

Although the current literature attests to the merits of a trial of labor in the patient with a prior cesarean section, some controversies remain. For example, can women with two or more sections be allowed a trial of labor and can patients who undergo a trial of labor receive oxytocin or prostaglandins for induction? Also, do certain indications for previous cesarean section such as relative cephalopelvic disproportion/failure to progress or the diagnosis of breech or twins in the present pregnancy constitute an indication for elective repeat cesarean delivery? These questions along with some other controversies are discussed in the light of newly accumulated data in the English literature and our own experience over the last decade in a major university-based tertiary medical center.

Anesthesia, Epidural↗

Intrapartum fetal pulse oximetry: present and future.

Pulse oximetry is widely used to monitor the patient's well-being in anesthetic and neonatal practice. As a result of recent technologic and theoretical advances, it has emerged as a clinical tool in intrapartum fetal monitoring. Oximeters record both pulse rate and arterial oxygen saturation of the fetus and they may be adapted to derive an estimate of peripheral perfusion. Reflectance oximetry is more accurate than transmission oximetry in intrapartum fetal management. This method uses the pulsatile changes of red and infrared light reflected from tissue to estimate arterial oxygenation. Pulse oximetry is cheap, non-invasive, simple to operate, relatively accurate and has a fast response time. Factors adversely affecting the accuracy of the pulse oximeter output include transducer displacement, peripheral vasoconstriction, hypotension, anemia, presence of intravascular dyes, meconium staining, fetal hair and scalp edema. Fetal pulse oximetry is limited by a wide normal range and inadequate calibration. The amniochorionic membranes however do not affect oximetry readings so that this method may be applied before rupture of the membranes, i.e. before labor. Once successfully developed, fetal pulse oximetry could potentially be used in combination with other monitoring techniques to reduce instrumental and operative interventions during labor and improve perinatal outcome.

Female↗

Management of labor and labor complications.

Obstetricians assume a dual role in the provision of health care for both mother and fetus during labor. Not only do they function as consultants for medical and surgical problems peculiar to labor, but they also assume a more broad-based role in the prevention of labor complications to achieve the best possible health maintenance for both patients. This includes the provision of continuous health care throughout pregnancy, delivery, and postpartum management. A summary of the common problems of management of labor and labor complications is provided, including fetal monitoring during labor, augmentation of labor, vaginal delivery after cesarean section, epidural analgesia and its effects on delivery, and fecal incontinence after delivery.

Anesthesia, Epidural↗

Antenatal bleeding and fetal heart rate.

Objective of the paper was to determine the fetal heart rate (FHR) changes that occur in preterm fetuses whose mothers have suffered antepartum bleeding, versus uncomplicated controls. Over a 12-year span, 91 patients with significant antenatal bleeding (bleeding requiring inhospital observation) were examined and compared to 75 controls with uncomplicated normal pregnancies. None of the women were in labor and all were evaluated at 25-37 weeks' gestation. Excluded were: patients with any other complication (i.e., premature rupture of membranes, intrauterine growth retardation, diabetes, hypertension, collagen vascular disease, postuterine surgery, substance abuse and twins). Analysis of the FHR tracings included baseline heart rate, long-term FHR variability, and number and amplitude of FHR accelerations in 20-min segments. There was no difference in baseline heart rate in the preterm fetuses of pregnancies complicated by antepartum bleeding versus controls. However, the parameters associated with FHR reactivity (number of accelerations in 20 min, and amplitude of accelerations) were higher to a statistically significant degree in fetuses of pregnancies complicated by antenatal bleeding than in controls. Fetuses of mothers suffering antenatal bleeding exhibited significant higher rates of reactive FHR patterns at earlier gestational ages than did controls. In conclusion, there is a significant increase in FHR reactivity in pregnancies in which significant antenatal bleeding occurs, suggesting a probable acceleration in fetal central nervous system maturation in these fetuses.

Case-Control Studies↗

High maternal serum chorionic gonadotropin level in Downs' syndrome pregnancies is caused by elevation of both subunits messenger ribonucleic acid level in trophoblasts.

A unique product of human placenta is CG. Its concentration in maternal blood rises exponentially until 9-10 weeks' gestation, thereafter, it decreases to about 20% of the maximum, remaining constant from 16-17 until 40 weeks. High second-trimester maternal blood level indicates an increased risk for Downs' Syndrome (DS). This study's aim was to determine whether changes occur in the genetic expression of CG subunits in cultured trisomy-21 trophoblasts compared with various gestational age controls. Second-trimester trisomy-21 trophoblasts secrete 10 times more CG than gestational age-matched controls during the first day in culture: 878 (range, 235-2230) IU/g vs. 87 (range, 20-150) IU/g (P < 0.05). This high secretion closely resembles quantities secreted by first-trimester normal trophoblasts: 7500 (range, 3,850-10,000) IU/g. Both subunits' messenger RNA content are substantially increased, CG beta much more than CG alpha, although these genes are not located on chromosome 21. We conclude that at least one cause of high second-trimester maternal blood CG in DS pregnancies is a rise in alpha and beta CG messenger RNA levels in the trophoblast. We propose that at 12-14 weeks, when rapid decrease in maternal blood CG levels can be found, higher than normal values may indicate an increased risk for DS.

Cells, Cultured↗

Assessment of pain threshold and pain tolerance in women in labour and in the early post-partum period by pressure algometry.

The changes in the pressure pain threshold (PPThr) and pressure pain tolerance (PPTol) in 41 parturients have been studied during the active phase of labour and in the early post-partum period. The sensitivity to pressure stimuli was examined with an electronic pressure algometer placed on the sternum during the interval between painful contractions, after extradural analgesia and 24 h after childbirth. Prior to extradural analgesia, mean (+/- SD), PPThr and PPTol were 4.9 +/- 1.6 kg 0.25 cm-2 and 6.9 +/- 1.8 kg 0.25 cm-2, respectively. Similar values were recorded 1 h after induction of the extradural block when the pain of labour was abolished. At 24 h post-delivery, a significant decrease in both PPThr and PPTol was noted (P < 0.001). The lack of influence of extradural analgesia on pressure algometry values, and the elevated sensitivity to pain in the early post-partum period, may be related to the influence of pregnancy and labour on the appreciation of pain.

Adult↗

Experimental investigation of an infolded bowel segment as an anti-incontinence mechanism without interposing the ileo-cecal valve.

A technique for using bowel segment as an anti-incontinence mechanism was developed in an animal model and evaluated urodynamically. Variously modified bowel segments were investigated alone and later attached to a colonic reservoir to establish their value in preventing urinary incontinence while allowing easy catheterization. Using careful surgical technique, intussuscepted, tapered and plicated bowel segments were constructed. The maximum segmental closure pressure and functional length were evaluated in all preparations. The three bowel segments remained continent during slow filling and up to reservoir capacity. The recordings demonstrated both highest maximal closure pressure and longest functional length in the plicated system when evaluated both alone and following reservoir attachment. These recording differences occurred both with the reservoir full and empty. These results demonstrate the value of a plicated bowel segment in the maintenance of urinary continence when attached to a compliant urinary reservoir without using the ileo-cecal valve in this model.

Animals↗

Human fetal auditory threshold improvement during maternal oxygen respiration.

It has been suggested that the near full-term fetus in-utero has a sensori-neural hearing loss compared to the neonate due to the relative hypoxia resulting from placental oxygenation compared to pulmonary oxygenation. This hypothesis was tested by estimating the threshold of the fetus to vibrio-acoustic stimulation applied to the maternal abdomen while the mother was breathing room air and again when breathing oxygen. Fetal response was assessed by maternal perception of fetal movement and by objective demonstration of movement by ultrasound. It has been shown that the fetal responses are to the acoustic component of the stimulus, that the acoustic stimulus is not overly attenuated or masked, and that maternal oxygen inhalation enhances fetal oxygenation. The results showed that the threshold was lower and/or the response was stronger when the mother was breathing oxygen compared to when she was breathing room air. Thus it is confirmed that in-utero the fetus has an hypoxia-induced sensori-neural hearing loss. At birth, with the shift to more efficient pulmonary oxygenation, there is an improvement in auditory threshold.

Acoustic Stimulation↗

Levels of platelet calmodulin for the prediction of progression and severity of adolescent idiopathic scoliosis.

Calmodulin is a calcium-binding receptor protein that regulates the contractile protein systems of skeletal muscle and platelets. The levels of platelet calmodulin were measured in twenty-seven adolescents to determine whether there was a relationship between these levels and the progression or the severity of idiopathic scoliosis. The study included seventeen patients who had idiopathic scoliosis of varying severity and patterns and a control group consisting of ten age and sex-matched subjects: eight patients who were being managed for non-scoliosis-related problems and two normal volunteers. Platelets were isolated from the venous blood of all adolescents. The platelets were homogenized and centrifuged, and the calmodulin-containing supernatant was isolated. The level of calmodulin was then measured with use of a radioimmunoassay that employs competitive binding between native, unlabeled calmodulin and 125I-labeled calmodulin. The results showed that the level of platelet calmodulin in the patients who had a progressive curve (more than 10 degrees of progression in the previous twelve months) (3.83 nanograms per microgram of protein) was significantly higher than the level in the patients who had a stable curve (less than 5 degrees of progression in the previous twelve months) (0.60 nanogram per microgram of protein) (p < 0.01); the levels in the stable group and the control group (0.69 nanogram per microgram of protein) were similar. The level of platelet calmodulin appeared to be an independent and possibly more acute predictor of progression of the curve than the Risser sign alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Sonographic evaluation of fetal head extension and maternal pelvis in cases of breech presentation.

BACKGROUND: To investigate whether sonographic examination of the fetal head extension, pelvic adequacy and fetal position, could replace the traditional x-ray method in the evaluation of the breech in labor. METHODS: Seventy-two parturients admitted in labor with a breech presentation were prospectively evaluated by a newly proposed ultrasonographic approach. The head extension, obstetric conjugate and fetal attitude obtained were further compared to the gold standard radiologic measurements. RESULTS: A highly significant correlation between ultrasonic and x-ray measurements for the fetal head extension (r = 0.8696; p < 0.0001), obstetric conjugate (r = 0.8931; p < 0.0001), as well as high reliability (95.5%) in diagnosing the breech variant by ultrasound have been found. CONCLUSIONS: Ultrasonic evaluation of breech presentation, as performed by the proposed method, is simple, easy to perform and compares well with the standard radiologic studies. It is suggested that modern ultrasonic technique, which carries no risk of ionizing radiation, may replace traditional x-ray examination of the breech in labor.

Breech Presentation↗

Safety of surgical intervention during the second trimester of pregnancy. A case report.

Surgical and anesthetic interventions during pregnancy are not hazard free. While an increase in fetal resorption and the abortion rate during the first trimester is well documented, a second-trimester intervention is assumed to be relatively safe. A case of acute transient oligohydramnios, fetal growth arrest and limb reduction anomaly following second-trimester abdominal surgery is reported for the first time.

Female↗

Ultrastructural characteristics of cytotrophoblast cells during stages of differentiation.

Isolated cytotrophoblast cells from term human placenta were separated into eleven fractions according to cell size, by centrifugal elutriation. Each fraction isolated was examined by electron microscopy to elucidate ultrastructural features consistent with differences in stages of cellular differentiation. As a rule, increasing cell size correlated with evidence of progressive intracellular differentiation. This was represented by the appearance of specialization structures in later fractions, and by changes in the density of organelles and other cellular constituents. Progressive development and maturation of the rough endoplasmic reticulum was also evident. These data are the first to demonstrate successful subfractionation of the heterogeneous cytotrophoblast cell population into distinct groups, each representing different levels of cellular differentiation. These morphologic features of differentiation correlate closely with established biochemical parameters associated with various stages of intermediate cytotrophoblast cell differentiation.

Cell Differentiation↗

Myasthenia gravis and preeclampsia.

Serious diagnostic and therapeutic dilemmas may arise when preeclampsia complicates pregnancy in a myasthenic patient. Four cases of such an association were previously reported in the English-language medical literature and the fifth one is reported here. Based on the literature review and our own case, the problems that may arise when myasthenia gravis is complicated by severe preeclampsia during pregnancy are discussed and guidelines for diagnosis and management are suggested.

Adult↗