Ptchd1 deficiency induces excitatory synaptic and cognitive dysfunctions in mouse.

Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1-/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

New sonographic marker of borderline ovarian tumor: microcystic pattern of papillae and solid components.

OBJECTIVE: To describe and evaluate the utility of a new sonographic microcystic pattern, which is typical of borderline ovarian tumor (BOT) papillary projections, solid component(s) and/or septa, as a new ultrasound marker that is capable of distinguishing BOT from other adnexal masses, and to present/obtain histologic confirmation. METHODS: In this retrospective study, we identified women with a histologic diagnosis of BOT following surgical resection who had undergone preoperative transvaginal ultrasound (TVS) examination. All images were reviewed for presence or absence of thin-walled, fluid-filled cluster(s) of 1-3-mm cystic formations, associated with solid component(s), papillary projections and/or septa. From the same cases, histopathologic slides of each BOT were examined for presence of any of these microcystic features which had been identified on TVS. To confirm that the microcystic TVS pattern is unique to BOTs, we also selected randomly from our ultrasound and surgical database 20 cases of epithelial ovarian cancer and 20 cases of benign cystadenoma, for review by the same pathologists. To confirm the novelty of our findings, we searched PubMed for literature published in the English language between 2010 and 2018 to determine whether the association between microcystic tissue pattern and BOT has been described previously. RESULTS: Included in the final analysis were 62 patients (67 ovaries) with preoperative TVS and surgically confirmed BOT on pathologic examination. The mean patient age at surgery was 39.8 years. The mean BOT size at TVS was 60.7 mm. Of the 67 BOTs, 47 (70.1%) were serous, 15 (22.4%) were mucinous and five (7.5%) were seromucinous. We observed on TVS a microcystic pattern in the papillary projections, solid component(s) and/or septa in 60 (89.6%) of the 67 BOTs, including 46 (97.9%) of the 47 serous BOTs, 11 (73.3%) of the 15 mucinous BOTs and three (60.0%) of the five seromucinous BOTs. On microscopic evaluation, 60 (89.6%) of the 67 samples had characteristic 1-3-mm fluid-filled cysts similar to those seen on TVS. In seven cases there was a discrepancy between sonographic and histologic observation of a microcystic pattern. The 20 cystadenomas were mostly unilocular and/or multilocular and largely avascular. None of them or the 20 epithelial ovarian malignancies displayed microcystic characteristics, either on TVS or at histology. On review of 23 published articles in the English medical literature, containing 163 sonographic images of BOT, we found that, while all images contained it, there was no description of the microcystic tissue pattern. CONCLUSION: We report herein a novel sonographic marker of BOT, a 'microcystic pattern' of BOT papillary projections, solid component(s) and/or septa. This was seen in the majority of both serous and mucinous BOT cases. Importantly, based on comparison of sonographic images and histopathology of benign entities and malignancies, the microcystic appearance seems to be unique to BOTs. No similar description has been published previously. Utilization of this new marker should help to identify BOT correctly, discriminating it from ovarian cancer and benign ovarian pathology, and should ensure appropriate clinical and surgical management. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Cesarean scar pregnancy and early placenta accreta share common histology.

OBJECTIVE: To determine, by evaluation of histological slides, images and descriptions of early (second-trimester) placenta accreta (EPA) and placental implantation in cases of Cesarean scar pregnancy (CSP), whether these are pathologically indistinguishable and whether they both represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester. METHODS: The database of a previously published review of CSP and EPA was used to identify articles with histopathological descriptions and electronic images for pathological review. When possible, microscopic slides and/or paraffin blocks were obtained from the original researchers. We also included from our own institutions cases of CSP and EPA for which pathology specimens were available. Two pathologists examined all the material independently and, blinded to each other's findings, provided a pathological diagnosis based on microscopic appearance. Interobserver agreement in diagnosis was determined. RESULTS: Forty articles were identified, which included 31 cases of CSP and 13 cases of EPA containing histopathological descriptions and/or images of the pathology. We additionally included six cases of CSP and eight cases of EPA from our own institutions, giving a total of 58 cases available for histological evaluation (37 CSP and 21 EPA) containing clear definitions of morbidly adherent placenta. In the 29 cases for which images/slides were available for histopathological evaluation, both pathologists attested to the various degrees of myometrial and/or scar tissue invasion by placental villi with scant or no intervening decidua, consistent with the classic definition of morbidly adherent placenta. Based on the reviewed material, cases with a diagnosis of EPA and those with a diagnosis of CSP showed identical histopathological features. Interobserver correlation was high (kappa = 0.93). CONCLUSIONS: EPA and placental implantation in CSP are histopathologically indistinguishable and may represent different stages in the disease continuum leading to morbidly adherent placenta in the third trimester.

Comparison of estimation of volume of fetomaternal hemorrhage using Kleihauer-Betke test and microcolumn gel method in D-negative nonisoimmunized mothers.

In this study we assessed the efficay of the microcolumn gel method in the detection and quantification of the volume of fetomaternal hemorrhage (FMH) in comparison with the Kleihauer-Betke test (KB) in nonisoimmunized D- mothers. We collected blood samples from 80 D- indirect antiglobulin test-negative mothers over a span of more than 1 year. FMH was determined by KB and microcolumn gel method, and the results were compared. FMH was recorded as less than 4 mL by KB if no fetal cells were seen after examining 25 fields using 10x objective. If fetal cells were seen, slides were examined furhter to quantify FMH. By microcolumn gel method, FMH was reported as less than 0.1 percent, 0.1 percent, 0.2 percent, and 0.4 percent or greater. None of the patients had FMH greater than 15 mL by KB . Sixty-two patients (77.5%) had FMH less than 4mL by KB. In all these cases , FMH was less than or equal 0.2 percent (approximately 4mL) by microcolumn gel method. The mean volume of FMH in the remaining 18 (22.5%) cases by KB was 8.3 ± 1.7 mL. Fifteen (83.3%) of these 18 cases had FMH of at least 0.4 percent (approximately 8 mL) by gel technology. Three cases (16.7%) that differed from KB results had FMH of 0.2 percent by microcolumn gel method with a maximal FMH of 6.4 mL by KB. FMH was significanlty increased in cesarean delivery (mean FMH 9.5 ± 0.8 mL, range 7.9-10.4 mL, p=0.001) abd abtepartum hemorrahge (mean FMH 9.5 ± 0.9 mL, range 7.9-10.4 mL, p< 0.001). Microcolumn gel method is an effective screening test . Technologies like KB and flow cytometry are better options for detecting a large volume of FMh. Antepartum hemorrhage and cesarean delivery are risk factors for FMH. the 300-µg dose of cases. We need to analyze the relative cost-effectiveness of universal administration of 300µg of Rh immune globulin vs. FMH quantitation with subsequent administration of titrated doses.

Multi-fidelity modelling of shark skin denticle flows: insights into drag generation mechanisms.

We investigate the flow over smooth (non-ribletted) shark skin denticles in an open-channel flow using direct numerical simulation (DNS) and two Reynolds averaged Navier-Stokes (RANS) closures. Large peaks in pressure and viscous drag are observed at the denticle crown edges, where they are exposed to high-speed fluid which penetrates between individual denticles, increasing shear and turbulence. Strong lift forces lead to a positive spanwise torque acting on individual denticles, potentially encouraging bristling if the denticles were not fixed. However, DNS predicts that denticles ultimately increase drag by 58% compared to a flat plate. Good predictions of drag distributions are obtained by RANS models, although an underestimation of turbulent kinetic energy production leads to an underprediction of drag. Nevertheless, RANS methods correctly predict trends in the drag data and the regions contributing most to viscous and pressure drag. Subsequently, RANS models are used to investigate the dependence of drag on the flow blockage ratio (boundary layer to roughness height ratio), finding that the drag increase due to denticles is halved when the blockage ratio δ/h is increased from 14 to 45. Our results provide an integrated understanding of the drag over non-ribletted denticles, enabling existing diverse drag data to be explained.

Reporting of delayed adverse donor reactions in whole blood donors: Just the tip of an iceberg!

BACKGROUND AND OBJECTIVES: The study was planned to determine the incidence and analyze how various epidemiological factors tend to be associated with delayed adverse donor reactions (ADR). MATERIAL AND METHODS: The prospective observational study was conducted in Department of Transfusion Medicine of tertiary care hospital from January to December 2019. Eligible blood donors were observed for any adverse reactions after 15 minutes of removal of phlebotomy needle. Further, telephonic calls were made to each enrolled blood donor on day-2 and day-7 of the whole blood donation. For each day, two calls were made at an interval of 4 hours before declaring the participant to be non-responder. RESULTS: A total of 1540 (84.1%) blood donors responded on day-2 and 1610 (87.9%) responded on day-7 of follow-up. Total 180 (11.2%) blood donors experienced delayed ADRs. Two donors (1.1%) experienced on-site while 178 (98.89%) reported off-site delayed ADRs when followed-up telephonically. The commonest delayed ADRs reported were bruise (n=72; 30.9%), arm-pain (n=61; 26.2%) and generalised weakness (n=44; 18.9%). Female donors (27.3% vs. 11.2%; P=0.004), first time donors (15.2 vs. 9.9%; P=0.002), donors with low body-weight (range of 45-60kg; 15.9% vs. 11.5% vs. 6.1%; P=0.011) and body mass index<18.5 (24% vs. 12.5% vs. 9.7% vs. 11.3%; P=0.028) experienced more delayed ADRs. CONCLUSION: Blood donors do experience delayed ADRs but these are not reported to the blood centers as these are usually mild. However, it is important to capture these delayed adverse donor reactions and report it to National Hemovigilance Program so that strategies can be formulated to prevent their occurrence and recurrence.

Impact of blood donor characteristics on quality of packed red blood cell concentrates.

INTRODUCTION: Impact of blood donor characteristics on quality of packed red blood cell concentrates. OBJECTIVE: To determine the impact of donor factors on the quality of packed red blood cell concentrates. MATERIAL AND METHODS: The analytical cross sectional study was conducted on 505 whole blood donors after approval by the Institutional Ethics Committee and written informed consent from blood donors. Two mL EDTA sample was collected for pre-donation haemoglobin estimation and all relevant donor details were recorded. Whole blood was collected in 350mL double blood bags. PRBCs were prepared as per the departmental SOP. Volume of each PRBC was recorded and sample from each bag was taken for estimation of total haemoglobin content and haematocrit. RESULTS: Of 505 blood donors, 459 (90.9%) were males and 324 donors (64.2%) were less than 30 years of age. The majority of the donors were repeat donors (61%, n=308 repeat donors), vegetarians (52.9%, n=267 vegetarians) and non-smokers (92.7%, n=468). Mean haemoglobin was found to be significantly higher in males (14.9 vs. 13.3; P≤0.001), donors more than 30 years of age (15 vs. 14.7; P=0.042), repeat donors (14.9 vs. 14.7), non-vegetarians (15.1 vs. 14.6; P≤0.001) and smokers (15.3 vs. 14.8g/dL; P=0.020). PRBC units prepared from male blood donors, repeat donors and non vegetarians had significantly higher mean volume and mean total haemoglobin content. Strong positive correlation was observed between haemoglobin of the blood donor and total haemoglobin content of the PRBC and volume of blood collected. CONCLUSIONS: Donor characteristics do have effect on total haemoglobin content of packed red blood cells.

Prenatal diagnosis of unilateral proximal femoral focal deficiency at 19 weeks' gestation: case report and review of the literature.

Proximal femoral focal deficiency (PFFD) represents a rare and complex deformity manifested by hypoplasia of a variable portion of the femur with shortening of the entire limb. The condition may be unilateral or bilateral and is often associated with other congenital anomalies. Recent technological advances in ultrasound imaging offer the opportunity to detect an increasing number of rare skeletal malformation syndromes whose correct diagnosis is essential for adequate counseling and management of the pregnancy. We report a case of fetal non-familial PFFD diagnosed prenatally using two-dimensional and three-dimensional images. Clinical findings, differential diagnosis and management of this rare skeletal dysplasia are discussed and a review of the recent literature is given.

Semiclassical evaluation of expectation values.

Semiclassical mechanics allows for a description of quantum systems which preserves their phase information, and thus interference effects, while using only the system's classical dynamics as an input. In particular one of the strengths of a semiclassical description is to present a coherent picture which (to negligible higher-order ℏ corrections) is independent of the particular canonical coordinates used. However, this coherence relies heavily on the use of the stationary phase approximation. It turns out, however, that in some important cases, a brutal application of stationary phase approximation washes out all interference, and thus quantum, effects. In this paper, we address this issue in detail in one of its simplest instantiations, namely the evaluation of the time evolution of the expectation value of an operator. We explain why it is necessary to include contributions which are not in the neighborhood of stationary points and provide new semiclassical expressions for the evolution of the expectation values. The efficiency of our approach is based on the fact that we treat analytically all the integrals that can be performed within the stationary phase approximation, implying that the remaining integrals are simple integrals, in the sense that the integrand has no significant variations on the quantum scale (and thus they are very easy to perform numerically). This to be contrasted with other approaches such as the ones based on initial value representation, popular in chemical and molecular physics, which avoid a root search for the classical dynamics, but at the cost of performing numerically integrals whose evaluation requires a sampling on the quantum scale, and which are therefore not well designed to address the deep semiclassical regime. Along the way, we get a deeper understanding of the origin of these interference effects and an intuitive geometric picture associated with them.

Genetic linkage between the HL-A system and a deficit of the second component (C2) of complement.

From a family of 14 individuals, evidence was obtained suggesting linkage between the HL-A haplotypes and the transmission of a 50 percent deficit in the functional activity of the C2 component of complement.

Entamoeba histolytica: lipid rafts are involved in adhesion of trophozoites to host extracellular matrix components.

Adhesion is an important virulence function for Entamoeba histolytica, the causative agent of amoebic dysentery. Lipid rafts, cholesterol-rich domains, function in compartmentalization of cellular processes. In E. histolytica, rafts participate in parasite-host cell interactions; however, their role in parasite-host extracellular matrix (ECM) interactions has not been explored. Disruption of rafts with a cholesterol extracting agent, methyl-beta-cyclodextrin (MbetaCD), resulted in inhibition of adhesion to collagen, and to a lesser extent, to fibronectin. Replenishment of cholesterol in MbetaCD-treated cells, using a lipoprotein-cholesterol concentrate, restored adhesion to collagen. Confocal microscopy revealed enrichment of rafts at parasite-ECM interfaces. A raft-resident adhesin, the galactose/N-acetylgalactosamine-inhibitable lectin, mediates interaction to host cells by binding to galactose or N-acetylgalactosamine moieties on host glycoproteins. In this study, galactose inhibited adhesion to collagen, but not to fibronectin. Together these data suggest that rafts participate in E. histolytica-ECM interactions and that raft-associated Gal/GalNAc lectin may serve as a collagen receptor.

Natural antibodies to human lymphocytes in murine strains.

Murine strains vary greatly in their content of natural antibodies to human lymphocytes; sera from NZB, B10.BR/TSn, DBA/J, and B10.S mice reacted with more than 90% of the panel of human lymphocytes, yet those from other strains did not react. These levels of natural antibodies to human lymphocytes did not correlate with the H-2 type of mice, but appeared to be a dominant character with incomplete penetrance. Since sera from germfree mice also contained natural antibodies to human lymphocytes, their formation was not influenced substantially by bacteria.

Increased expression of transforming growth factor beta isoforms and basic fibroblast growth factor in complex hyperplasia and adenocarcinoma of the endometrium: evidence for paracrine and autocrine action.

Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential role for TGF-beta s in the normal proliferative endometrium and its possible involvement in the transition to complex hyperplasia and progression to endometrial carcinoma. The angiogenic and mitogenic growth factor, basic fibroblast growth factor, was used for comparison. Differential TGF-beta isoform-specific immunoreactivity was observed in the normal endometrium, which is composed of glandular and stromal cells. There was an increase in TGF-beta 3 but not TGF-beta 1 or TGF-beta 2 in the glandular epithelium from the proliferative to the secretory phase of the menstrual cycle. Immunostaining for TGF-beta 2 was more intense in the stroma than the glands. In contrast, TGF-beta 1 and TGF-beta 3 were near equal intensity in these two endometrial compartments, TGF-beta 3 being the most intense. The glandular epithelium demonstrated a statistically significant stepwise increase in the expression of all three TGF-beta s progressing from the normal proliferative endometrium to simple hyperplasia and on to complex hyperplasia. However, the stromal cells maintained approximately the same level of immunoreactivity for TGF-beta in all these samples. In comparing proliferative endometrium with complex hyperplasia, there was a 5.1-, 3.4-, and 2.6-fold increase in immunostaining in the glands for TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively (P < or = 0.001). There was no further increase in immunoreactivity with progression from preneoplastic complex hyperplasia to carcinoma. Immunoreactive basic fibroblast growth factor was slight in normal endometrium and simple hyperplasia. There was a 4.6- and 4.2-fold increase in immunostaining observed in complex hyperplasia compared with proliferative endometrium in the glandular (P < or = 0.0054) and stromal (P < or = 0.0053) cells, respectively, with no further increase in carcinoma. By in situ hybridization, an increase in mRNA for all TGF-beta isoforms paralleled TGF-beta immunoreactivity. However, in contrast to the increased immunostaining in the glands in complex hyperplasia, there was remarkably more mRNA in the stromal cell compartment. The discordant expression of mRNA and protein was only observed in the pathological endometrium since both were more highly expressed in the stromal cells in normal proliferative endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

Orbital foreign body- Study of a case series.

BACKGROUND: Orbital foreign bodies (OFBs) may remain in the orbital cavity for considerable time and manifest with secondary complications. OBJECTIVE: To report five consecutive cases of orbital trauma with OFBs, who presented at our institute from Jan 2010 to Dec 2013. CASES: The first case of our series with a non-specific history of injury had a chronic granulomatous discharging sinus in the left upper eyelid and an intact globe. The second case, with an injury to the left lower eyelid following an assault, presented late and the manifestations were similar to that of the first case. The third case, of a road traffic accident, had sustained multiple facial and periocular injuries. The nature of all of three OFBs was uncertain by CT- scan, till surgical exploration. The fourth case had sustained injury to his left eye by a flying metal object. X-ray was sufficient to detect the OFB, but as scleral penetration was associated, management was complex. The fifth case had a nonspecific history of injury and the manifestation was similar to that of the first case. The surgical exploration revealed multiple OFB (wood). CONCLUSION: The OFBs pose difficult diagnostic and therapeutic challenges. Management of such cases, at times, calls for innovation in decision making and formulation of strategies.

HLA-compatible paternity in two "fertile eunuchs" with congenital hypogonadotropic hypogonadism and anosmia (the Kallmann syndrome).

Two men are described who fulfill the criteria for both the Kallmann and the fertile eunuch syndrome, and we report the erythrocyte and HLA phenotypes of these men and their children. There were no paternal exclusions noted in red blood cell phenotypes encompassing seven separate red cell systems. The HLA phenotypes indicate that the probability that these men were the fathers of the children was greater than 99.99%.

Histocompatibility (HL-A) factors in familial multiple sclerosis. Is multiple sclerosis susceptibility inherited via the HL-A chromosome?

In order to study a possible hereditary factor leading to multiple sclerosis (MS) susceptibility, histocompatibility (HL-A) types were studied in families where two or more first-degree relatives had MS. Neither the inheritance of a particular parental HL-A chromosome, nor the occurrence of any specific HL-A antigens, could be shown to be necessary or sufficient for the development of MS in family members. The distribution of HL-A chromosomes was essentially the same for affected and unaffected family members. An excess of 3,7 haplotype and W21 antigen was demonstrated, both in affected patients and in unaffected family members, in equal proportions. We conclude that the HL-A chromosome has no direct causal relationship to MS susceptibility, although it may be indirectly associated by population stratification, maternal factors, or some other mechanism.

HLA-DR typing: a comparison between nylon wool adherence and T cell rosetting in the isolation of B cells.

A comparison was made between two different methods of B cell isolation, nylon wool adherence versus SRBC rosetting in terms of the technical ease of B cell purification and the reproducibility of DR phenotyping. It was found that B cells isolated by either method from 30 randomly selected donors gave equivalent results in the determination of DR phenotypes. Due to its simplicity and reliability, nylon wool adherence may be preferred over the SRBC rosette method for the routine phenotyping of B cells.

High level expression of fms proto-oncogene mRNA is observed in clinically aggressive human endometrial adenocarcinomas.

Six micron paraffin sections of paraformaldehyde-fixed endometrial currettings of 21 benign and neoplastic endometrial specimens were assayed for tumor cell-specific oncogene expression by in situ hybridization with probes for six oncogenes, beta-actin, and the E. coli plasmid pBR322. In the benign hyperplasias and invasive adenocarcinomas, multiple oncogenes, including erbB, fms, c-myc, and Ki-ras were expressed at significant levels. For the adenocarcinomas, statistical analysis demonstrated that high levels of expression of fms-complementary mRNA correlated strongly with clinicopathologic features (high FIGO histologic grade, high FIGO clinical stage, deep myometrial penetration) predictive of aggressive clinical behavior and poor outcome. The authors discuss the role which M-CSF receptor (the fms gene product) and locally-produced M-CSF may play in the development of the observed aggressively-malignant phenotypes. They also propose that pre-hysterectomy assay of fms gene expression in endometrial currettings in FIGO Stage I patients might be clinically useful to help identify preoperatively those patients with deep myometrial penetration or other locoregional spread.

Diffusely infiltrating adenocarcinoma of the endometrium. A subtype with poor prognosis.

We studied cases of stage I endometrial adenocarcinoma encountered at our institution during the period 1970-80. Five out of 164 of these tumors showed a diffusely infiltrating pattern of growth. Two of the five patients died of cancer within 5 years, with a 5-year mortality of 40%. A control group of 15 patients seen over the same period showed a 5-year mortality of 13.3%. Thus, the diffusely infiltrating pattern of growth was indicative of poor prognosis in endometrial carcinoma in stage I disease.