Evaluation of classic and novel ultrasound signs of placenta accreta spectrum.

OBJECTIVES: Improvement in the antenatal diagnosis of placenta accreta spectrum (PAS) would allow preparation for delivery in a referral center, leading to decreased maternal morbidity and mortality. Our objectives were to assess the performance of classic ultrasound signs and to determine the value of novel ultrasound signs in the detection of PAS. METHODS: This was a retrospective cohort study of women with second-trimester placenta previa who underwent third-trimester transvaginal ultrasound and all women with PAS in seven medical centers. A retrospective image review for signs of PAS was conducted by three maternal-fetal medicine physicians. Classic signs of PAS were defined as placental lacunae, bladder-wall interruption, myometrial thinning and subplacental hypervascularity. Novel signs were defined as small placental lacunae, irregular placenta-myometrium interface (PMI), vascular PMI, non-tapered placental edge and placental bulge towards the bladder. PAS was diagnosed based on difficulty in removing the placenta or pathological examination of the placenta. Multivariate regression analysis was performed and receiver-operating-characteristics (ROC) curves were generated to assess the performance of combined novel signs, combined classic signs and a model combining classic and novel signs. RESULTS: A total of 385 cases with placenta previa were included, of which 55 had PAS (28 had placenta accreta, 11 had placenta increta and 16 had placenta percreta). The areas under the ROC curves for classic markers, novel markers and a model combining classic and novel markers for the detection of PAS were 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.77-0.90) and 0.88 (95% CI, 0.82-0.94), respectively. A model combining classic and novel signs performed better than did the classic or novel markers individually (P = 0.03). An increasing number of signs was associated with a greater likelihood of PAS. With the presence of 0, 1, 2 and ≥ 3 classic ultrasound signs, PAS was present in 5%, 24%, 57% and 94% of cases, respectively. CONCLUSIONS: We have confirmed the value of classic ultrasound signs of PAS. The use of novel ultrasound signs in combination with classic signs improved the detection of PAS. These findings have clinical implications for the detection of PAS and may help guide the obstetric management of patients diagnosed with these placental disorders. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Superinduction of COX-2 mRNA by cycloheximide and interleukin-1beta involves increased transcription and correlates with increased NF-kappaB and JNK activation.

Many primary response genes, including cyclooxygenase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1beta-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-kappaB binding to COX-2 promoter kappaB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-kappaB by de novo IkappaB alpha synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.

Usefulness of different stimuli in visual evoked potentials.

The goal of this study was to determine the relative usefulness of the flash (FL), pattern reversal (PR) of 56', and PR of 28' in 62 patients (pts) with either MS (34) or non-MS (28) compared with normals (19). An abnormal visual evoked potential was found in 58%, 69%, and 81% of the eyes tested in possible, probable, and definite MS and in 88% of the non-MS group. The 28' PR produced the most abnormal responses, the greatest number with either greater than 3 standard deviations (SD) from the mean or greater than 2 SD in both MS and non-MS groups. The FL was second best at producing the most abnormal responses, but more often produced the only abnormality (29), compared with 28' PR (11). The 56' PR produced the only abnormality in none of the MS pts and in only one of the non-MS pts. In all categories (most abnormal, greater than 3 SD, greater than 2 SD, the only abnormality of greater than 3 SD or greater than 2 SD, and other peaks abnormal), the 28' PR was usually by far the best stimulus for definite (and probable) MS, but equally as effective was the FL in the possible MS pts Our data suggest the usefulness of 28' and not 56' PR, but the FL is especially useful in pts with possible MS.

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report.

The purpose of this study was to evaluate the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in patients with endometrial cancer known to be resistant to standard therapy. Subjects were taken from three groups: (1) recurrent or persistent disease following surgery and/or radiation, (2) advanced disease at diagnosis, and (3) high-risk histology. The combination of carboplatin (pharmacologically dosed at an area under the concentration-time curve of 5) and paclitaxel (135 to 175 mg/m2 over 3 hours) was given intravenously every 4 weeks for eight courses. Data about response, overall and progression-free survival, and toxicity were collected. Response and toxicity were evaluated by physical examinations, x-ray films, and blood tests. Twenty patients have participated to date, including eight considered evaluable for response. Due to limited follow-up, survival and progression-free intervals are not yet assessable. Of patients with measurable disease, five of eight (63%) have had significant reduction in the size of evaluable tumor masses, constituting a partial response. Although two patients had clinical and radiographic complete responses, occult disease was found at surgery. There were no complete responders. Fifteen patients had grade 3 or 4 hematologic toxicity, but none had neutropenic fever or hospitalization for sepsis. One patient was taken off study for grade 3 neuropathy. There was one possible treatment-related death. In this preliminary report, this combination is active against tumors of the endometrium, with acceptable levels of toxicity. Further follow-up will be required to determine the duration of response and whether progression-free and overall survival are influenced by treatment with these drugs.

Evidence that superoxide-anion, produced by PMA-activated human polymorphonuclear leukocytes, is the cytolytic agent for rabbit, but not for sheep red blood cells.

The lysis of sheep and rabbit red blood cells (SRBC and RRBC, respectively) upon exposure to PMA-activated human polymorphonuclear leukocytes (PMN) was investigated. The lysis of these target cells, which was measured by the release of 51Cr, showed different kinetics and scavenger-sensitivity. The lysis of RRBC, which was already detectable within 45 min of incubation, was sensitive to superoxide dismutase (SOD), but was only poorly influenced by scavengers of hydroxyl radical formation, such as desferal or thiourea. In contrast, lysis of SRBC was first detectable after 90 to 135 min of incubation and sensitive to desferal and thiourea, but not to SOD. Finally, only RRBC were sensitive to the artificial superoxide-generating system hypoxanthine/xanthine oxidase. Taken together, these data point at a cytolytic activity of superoxide anion O2- towards RRBC. SRBC are relatively resistant to O2-, but are lysed by an H2O2- and hydroxyl radical-dependent process.

The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta-dependent PGE(2) release via mechanistically distinct processes.

1. In common with human bronchial epithelial cells, pulmonary A549 cells release prostaglandin (PG) E(2) in response to pro-inflammatory cytokines. We have therefore used these cells to examine the effect of the selective mitogen activated protein (MAP) kinase inhibitors; PD098059, a mitogen activated and extracellular regulated kinase kinase (MEK) 1 inhibitor, UO126, a dual MEK1 & MEK2 inhibitor, and SB203580, a p38 MAP kinase inhibitor in the IL-1beta-dependent release of PGE(2). 2. Following IL-1beta treatment the extracellular regulated kinases (ERKs) and the p38 MAP kinases were rapidly phosphorylated. 3. PD09059, UO126 and SB203580 prevented IL-1beta-induced PGE(2) release at doses that correlated closely with published IC(50) values. Small or partial effects at the relevant doses were observed on induction of cyclo-oxygenase (COX) activity or COX-2 protein suggesting that the primary effects were at the level of arachidonate availability. 4. Neither PD098059 nor SB203580 showed any effect on IL-1beta-induced arachidonate release. We therefore speculate that the MEK1/ERK and p38 kinase cascades play a role in the functional coupling of arachidonate release to COX-2. 5. In contrast, UO126 was highly effective at inhibiting IL-1beta-dependent arachidonate release, implicating MEK2 in the activation of the PLA(2) that is involved in IL-1beta-dependent PGE(2) release. 6. We conclude that the MEK1, MEK2 and p38 MAP kinase inhibitors, PD098059, UO126 and SB203580, are highly potent in respect of inflammatory PG release. Finally, we conclude that these inhibitors act via mechanistically distinct processes, which may have anti-inflammatory benefits.

Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p.

Eight extended dyslexic families with at least four affected individuals were genotyped with twelve genetic markers spanning the Rh (rhesus factor) locus. Eleven of these markers were located on the short arm and the other was on the long arm of chromosome 1. Five theoretically derived phenotypes were used in the linkage analyses: 1) phonemic awareness; 2) phonological decoding; 3) rapid automatized naming; 4) single word reading; and 5) vocabulary. In addition, a lifetime diagnosis of dyslexia was used as a phenotype. Both parametric and non-parametric genetic analyses were completed. The results supported the importance of a putative locus on 1p. In addition, two-locus analyses assuming the interaction between a 1p locus and a 6p locus, previously shown to be of interest for dyslexia, were conducted. As a result, the nonparametric linkage (NPL) scores for rapid automatized naming and phonological decoding were significantly increased. In particular, the NPL scores for rapid automatized naming exceeded 5.0 for certain markers. These results provide strong evidence for separate but jointly acting contributions of the 1p and 6p loci to the reading impairments associated with rapid naming and suggestive evidence for a similar mechanism involving phonological decoding.

Sarcoidosis.

Much has been learned over the last decade about the genetic predisposition to different patterns of sarcoidosis and its pathogenesis. These major advances have been possible through the very rapid evolution of newer molecular technology. The last two years have also seen the publication of an international statement on sarcoidosis that defines very clearly the presentation, clinical features, diagnosis and treatment of sarcoidosis and also clearly identifies areas where we need to know more. This review aims to highlight key issues that have emerged over the last five years. Specific focus is given to genetic predisposition and trigger factors-molecular epidemiology. The more novel approaches that have been taken to attempt to treat this disease more effectively are also addressed.

Alteration in vomeronasal system anatomy in alcelaphine antelopes: correlation with alteration in chemosensory investigation.

Ruminants typically have an incisive papilla and incisive ducts located on the hard palate just behind the dental pad which are involved in transferring fluid-borne stimulus material from the oral cavity to the vomeronasal organs (VNOs) during flehmen. This behavior in males is presumably involved in the detection of chemosensory cues in female urine which indicate sexual status. Two species of alcelaphine antelopes, topi and Coke's hartebeest, were found to lack the incisive papilla and incisive ducts constituting the oral connection to the VNOs. This distinctive anatomical feature is complemented in these species not only by lack of flehmen behavior, but also a de-emphasis on chemosensory interest in female urine during sexual encounters. The common wildebeest, which is also an alcelaphine antelope, lacks the incisive papilla, but has small incisive ducts. Wildebeest males do perform flehmen to urine from females. However, during flehmen in the wildebeest, intermittent nostril licking apparently delivers the stimulus material to the VNOs via the nasal route, possibly compensating for reduced oral access to the VNOs. These observations on alcelaphine antelopes would appear to represent a unique feature among the world's ruminants.

A rapid and sensitive micro-assay to determine the capacity of quinones to undergo redox cycling.

Using a series of aziridinyl-benzoquinones it is shown that the conversion of oxyhemoglobin to methemoglobin in sheep erythrocytes is correlated with the capacity of each quinone to undergo redox cycling. Based on these findings a semiquantitative assay is developed for the rapid screening of redox cycling quinones.

Inhibitory activity of Jatropha multifida latex on classical complement pathway activity in human serum mediated by a calcium-binding proanthocyanidin.

This study isolates and characterizes the anti-complement constituent(s) present in the latex of Jatropha multifida, in an attempt to explain the traditional application of the latex in the treatment of infected wounds. Guided by the inhibition of classical pathway (CP) complement activity in human serum, a polymer was isolated which could be characterized as a proanthocyanidin. The polymer inhibits CP activation of the complement cascade, while alternative pathway (AP) activation is relatively insensitive to the polymer. This is due to the selective depletion of Ca2+, but not Mg2+, from the incubation medium.

Two functionally and chemically distinct immunomodulatory compounds in the gel of Aloe vera.

An aqueous extract of Aloe vera gel was analyzed guided by modulatory activity with regard to the in vitro activation of human complement and of human polymorphnuclear leucocytes (PMN). Upon ultrafiltration a high (h-Mr) and a low (l-Mr) molecular mass fraction were obtained. Pre-incubation of human pooled serum with the h-Mr fraction resulted in a depletion of classical and alternative pathway complement activity. In contrast, only the l-Mr fraction could inhibit the production of free oxygen radicals by activated PMNs. The latter activity cannot be attributed to non-specific effects like toxicity, interference with stimulant binding or scavenger activity.

Immunodulatory compounds from Picrorhiza kurroa: isolation and characterization of two anti-complementary polymeric fractions from an aqueous root extract.

Two aqueous root extracts of Picrorhiza kurroa, one prepared by extraction at 4 degrees C and the other by refluxing, were purified using the guidance of modulation of classical (CP) and alternative (AP) pathway complement activity. By means of methanol extraction and gel filtration chromatography, two polymeric fractions were isolated from the cold water extract. A methanol-soluble polymeric fraction (CS1) was highly active in inhibiting CP complement activity exclusively, whereas a methanol-insoluble polymeric fraction (CI1) exhibited an inhibitory effect on both CP and AP complement activity. Preliminary chemical analysis of the anti-complementary fractions revealed the presence of structures of carbohydrate and of peptide nature in CS1 and CI1. The modulation of CP complement activity by CS1 was studied in more detail. Its inhibitory effect was proven to be based on complement consumption rather than on chelation of Ca2+ and/or Mg2+ or on stabilization of the target cells in the complement-assay. The purification of the aqueous extract prepared by refluxing, resulted in the isolation of a polymeric fraction with the same qualities as CS1. However, a fraction with properties similar to CI1 could not be isolated from this extract.

Characterization of anti-complement compounds from Azadirachta indica.

The crude aqueous extract of Azadirachta indica bark possesses an inhibitory activity on both classical (CP) and alternative pathway (AP) activation of human complement. Purification of the compounds with the guidance of the AP-inhibitory activity involved extraction with methanol, dialysis, ion-exchange procedures and gel-permeation chromatography. This sequence yielded two polymers, NB-I and NB-II, one a highly active compound with a relatively low molecular weight (NB-II) and the other a less active compound with a high molecular weight (NB-I). The polymers were characterized by using colour reactions, TLC, GLC and HPLC after hydrolysis and gel-permeation chromatography as peptidoglycans. The carbohydrate part consisted predominantly of glucose. Arabinose, galactose and mannose were present in minor amounts (NB-II) or only as traces (NB-I). Protein was present for 5.5% in NB-I and for 9.8% in NB-II.

Selecting pet dogs on the basis of cluster analysis of breed behavior profiles and gender.

Using a computer-generated data base of rankings of 56 breeds of dogs on 13 behavioral traits, a factor analysis was performed to determine the extent to which a few general underlying behavioral tendencies are manifested in specific characteristics. Three factors, referred to as reactivity, aggression, and trainability, accounted for 81% of the variance in the 13 behavioral traits. Subsequently, a cluster analysis was performed to generate 7 clusters of dog breeds on the basis of similarity in scores for each of the 3 main factors. The clusters reflected to some degree the conventional groupings of dogs into working, sporting, hound, and terrier breeds. A quantitative analysis of the ranking of male dogs vs female dogs for the 13 characteristics revealed that males differed from females on 10 traits. It was concluded that these gender and cluster profiles will allow people to select a breed or gender of dog that is most likely to match the emotional and physical needs of the person who will provide a home for the pet.

Selective predictive value of rapid automatized naming in poor readers.

This study considers the differential predictive value of rapid naming tests for various aspects of later reading, where the differential is between nondisabled and poor readers. Two large-N longitudinal samples of students who have been evaluated from third through eighth grades are studied: (a) a randomly accessed, normally distributed group including students with varying degrees of reading ability (N = 154), and (b) a group of poor readers whose single-word reading in third grade is at or below the population 10th percentile (N = 64). Outcomes in fifth and eighth grade were measured in both groups. Single-word reading in both grades was strongly predicted from third-grade rapid naming only within the poor readers, even when IQ, socioeconomic status, and third-grade single-word reading were statistically controlled. Although rapid naming had predictive value within the large, normally distributed group, its predictive power was entirely absent in the average-reading nondisabled students who were between the 10th and 90th percentiles (n = 122). The fact that rapid naming has predictive power only for poor readers but not for average readers is interpreted as suggesting that impaired readers are qualitatively different from the normal-reading population and are not simply the "tail" of a normal distribution of reading ability. It also seems that it is the automaticity of retrieval, not the knowledge of names itself (as in confrontational naming tasks), that gives the predictive power in rapid naming. These data are considered in light of the one- and two-factor theories of the underlying processes involved in reading disability or dyslexia.

Animals in elementary school education in California.

The purpose of this project was to provide preliminary, descriptive data concerning the uses of nonhuman animals in northern California elementary school classrooms. The project comprised a mail survey that was sent to all elementary school teachers in Stanislaus County, California, followed by a workshop with survey respondents. Information gathered included that about animals and the use of animals, the learning objectives for the animal-related instructional activities, and the kinds of resources that would help teachers to improve or expand their existing animal-related activities or to create new ones. Most of the teachers were keeping either live animals or a variety of nonliving specimens in the classroom. They reported that animals and information about animals are popular and effective foci of instruction throughout the primary grades. The majority of respondents stated that live animals, in addition to providing formal lessons in science and cross-curricular instruction, are important for teaching children humane values. They also reported the many drawbacks of maintaining live classroom animals, such as the responsibility and cost of ongoing care, potential health and safety issues for the children, and concerns about the welfare of the animals. Because animals used in precollege education are not subject to legal regulations in the United States, some degree of oversight by the school or school district may help to avert potential problems.

The role of pet dogs in casual conversations of elderly adults.

Casual conversations were recorded as elderly persons routinely walked their dogs through a familiar mobile home park in the United States. Control observations included walks without dogs by owners and non-owners of dogs. All owners talked to and about their dogs. Transcribed conversations indicated that dogs were a primary focus of conversation. A majority of sentences to dogs were imperatives; the owners were instructing the dogs. Dog owners frequently included dogs' names or nicknames in their sentences when they spoke to the dogs and made reference to the dogs' wishes or needs. Speaking to dogs was also associated with frequent repetition of sentences. Passersby talked to the owners about their dogs whether or not the dogs were present. When dog owners spoke with other people, their conversations often concerned activities that were occurring in the present, whereas conversations of non-owners focused on stories about past events. Dog owners reported taking twice as many daily walks as non-owners. Dog owners also reported significantly less dissatisfaction with their social, physical and emotional states.

Companion cats and the social support systems of men with AIDS.

60 male pet owners with AIDS were given a formal questionnaire including items related to demographic, lifestyle, and pet ownership, as well as the Comfort from Companion Animals Scale, the Revised UCLA Loneliness Scale, and the General Health Questionnaire (GHQ-28). The men lived in the San Francisco area and received assistance from Pets Are Wonderful Support (PAWS), a community organization, in caring for their companion dogs or cats. Participants were a convenience sample of pet owners who volunteered from among 500 PAWS clients and who do not necessarily represent a random sample of men with AIDS who keep companion animals. For these men, their comfort from companion animals was significantly associated with having cats but not dogs, closeness with friends, dissatisfaction with their practical support system, and listing pets as a source of support. Loneliness was negatively associated with having a large practical support network, scoring as healthy on the General Health Questionnaire, and living alone. For these male pet owners with AIDS, pet cats appeared to complement their supportive relationships with friends and family that were protective against loneliness.

The role of police dogs as companions and working partners.

Written responses to a questionnaire by 255 officers who used canines in police work were assessed. Almost all officers frequently played with, talked to, petted, and brushed their dogs and believed the dogs benefitted their health and well-being. Officers whose dogs slept indoors, often in the same bedroom, generally said they loved their dogs and they described their dogs as calm rather than active, as indicated by a multiple correspondence analysis. These 96 officers more than the 154 officers whose dogs slept outdoors or in kennels also planned to remain in canine work. Although departments often assumed responsibility for purchasing the dogs, the more experienced officers usually were involved in the final selection of dogs (logistic regression: p < .0001). Compared with 94 officers not involved in selecting their dogs, 106 officers with a specific role in selecting their dogs planned to stay in canine work, as shown by a multiple correspondence analysis. They believed the dogs had saved their lives (p < .01). Over-all, officers reported spending 4.1 hr. on-duty and 2.9 hr. off-duty per week training their dogs, and also played with them for 6.5 hr. per week, assuring a regular pattern of exercise for the officers. Virtually all officers valued canine service and believed the dogs enhanced the department's effectiveness. This study showed that both close companionship with the dog and involvement in selecting the dog were associated both with satisfaction with the dog and with working as a canine officer.