Transients and tradeoffs of phenotypic switching in a fluctuating limited environment.

Phenotypic variability in a microorganism population is thought to be advantageous in fluctuating environments, however much remains unknown about the precise conditions for this advantage to hold. In particular competition for a growth-limiting resource and the dynamics of that resource in the environment modify the tradeoff between different effects of variability. Here we investigate theoretically a model system for variable populations under competition for a flowing resource that governs growth (chemostat model) and changes with time. This environment generally induces density-dependent selection among competing sub-populations. We characterize quantitatively the transient dynamics in this system, and find that equilibration between total population density and environment can occur separately and with a distinct timescale from equilibration between competing sub-populations. We analyze quantitatively the two opposing effects of heterogeneity--transient response to change, and fitness at equilibrium--and find the optimal strategy in a fluctuating environment. We characterize the phase diagram of the system in term of its optimal strategy and find it to be strongly dependent on the typical timescale of the environment and weakly dependent on the internal parameters of the population.

Dictyostelium discoideum mutants with temperature-sensitive defects in endocytosis.

We have isolated and characterized temperature-sensitive endocytosis mutants in Dictyostelium discoideum. Dictyostelium is an attractive model for genetic studies of endocytosis because of its high rates of endocytosis, its reliance on endocytosis for nutrient uptake, and tractable molecular genetics. Endocytosis-defective mutants were isolated by a fluorescence-activated cell sorting (FACS) as cells unable to take up a fluorescent marker. One temperature-sensitive mutant (indy1) was characterized in detail and found to exhibit a complete block in fluid phase endocytosis at the restrictive temperature, but normal rates of endocytosis at the permissive temperature. Likewise, a potential cell surface receptor that was rapidly internalized in wild-type cells and indy1 cells at the permissive temperature was poorly internalized in indy1 under restrictive conditions. Growth was also completely arrested at the restrictive temperature. The endocytosis block was rapidly induced upon shift to the restrictive temperature and reversed upon return to normal conditions. Inhibition of endocytosis was also specific, as other membrane-trafficking events such as phagocytosis, secretion of lysosomal enzymes, and contractile vacuole function were unaffected at the restrictive temperature. Because recycling and transport to late endocytic compartments were not affected, the site of the defect's action is probably at an early step in the endocytic pathway. Additionally, indy1 cells were unable to proceed through the normal development program at the restrictive temperature. Given the tight functional and growth phenotypes, the indy1 mutant provides an opportunity to isolate genes responsible for endocytosis in Dictyostelium by complementation cloning.

Cloning, expression, and localization of a novel gamma-adaptin-like molecule.

We describe the cloning, expression, and localization of gamma2-adaptin, a novel isoform of gamma-adaptin. The predicted human and mouse gamma2-adaptin proteins are approximately 90 kDa and 64.4% and 61.7%) identical to gamma-adaptin, respectively. gamma2-Adaptin was localized to the Golgi, its localization distinct from gamma-adaptin. The membrane association of gamma- and gamma2-adaptin could further be distinguished by differential sensitivity to the fungal metabolite brefeldin A, gamma2-adaptin binding being insensitive to drug treatment. Together, these results suggest that gamma2-adaptin plays a role in membrane transport distinct from that played by gamma-adaptin.

Open systems: panoramic views of gene expression.

Since their development in the early 1990s, differential gene expression (DGE) technologies have been applied to a multitude of biological challenges, both for the purpose of basic biological research and as a valuable tool for the discovery and development of pharmaceuticals. In this review we survey a class of DGE technologies collectively referred to as 'open' architecture systems. These technologies are distinct from the 'closed' DGE technologies (quantitative PCR, chip technologies), in that no pre-existing biological or sequence information is necessary and they are applicable to any species. Examples of open systems include GeneCalling, SAGE, TOGA, READS, and their progenitor DGE technologies, differential display and cDNA representational difference analysis. We review these technologies and summarize a specific application using GeneCalling for novel gene discovery. Additionally, the significance of data management and experimental design in this new age of expression analysis is discussed.

Evaluation of gastric biopsies for neoplasia: differences between Japanese and Western pathologists.

Cited variations in the evaluation of gastric endoscopic biopsies for neoplasms between pathologists in Japan and those in the United States and Europe (the West) may have stemmed from several causes. The five-tiered group classification of the Japanese Research Society for Gastric Cancer (JRSGC) for interpretation of biopsies is not used in the West. Some differences may also exist in the morphologic criteria to reach a diagnosis of dysplasia or carcinoma. The goals of this study were to test the Western and Japanese classifications of gastric dysplasia and adenocarcinoma and to assess the differences between four Japanese and seven Western pathologists. One hundred biopsies, 20 from each of the five categories of the JRSGC scheme as determined by one observer, were collected. The Japanese observers used the JRSGC system, expressed in Roman numerals, whereas Western pathologists used a five- or six-tiered scheme expressed in diagnostic terms. Pairwise agreement was evaluated using k statistics within both groups. Consensus diagnosis on each biopsy was accepted as the opinion of the majority. The sensitivity and specificity of each reviewer for a certain diagnosis were also assessed. The intragroup agreements were moderate for both the Japanese (mean k = 0.663) and the Westerners (mean k = 0.652). The pairwise agreements between Japanese and Western observers were low (mean k = 0.542). Overall, the sensitivity was low for all Japanese observers for the diagnosis of dysplasia (38.7% vs 92.5%), and the sensitivity for the diagnosis of adenocarcinoma was high in both groups but higher among the Japanese observers (93.9% and 85.2%, respectively). Overall, the Japanese-Western interobserver agreement was moderate. The JRSCG scheme did not translate into higher interobserver agreement among Japanese observers. The sensitivity for the diagnosis of gastric adenocarcinoma was high for both groups, but the specificity was low among the Japanese. The cause seemed to be centered around the diagnosis of dysplasia in the Western system, which was a lesion frequently interpreted as carcinoma in Japan because of the different definitions of carcinoma in each system. Such a discrepancy might be important because it may explain some of the differences in the prevalence and prognosis of early gastric cancer between Japan and the West. An international effort is needed to harmonize morphologic criteria and analyze whether therapeutic consequences may stem from such discrepancies.

Interferon inhibits PWM induced B cell differentiation but not onset of proliferation.

The dependence of B lymphocyte differentiation into plasmacytes on anteceding B and T cell proliferation was studied using interferon as a probe. Possible correlations of the effect of interferon on PWM induced T and B cell proliferation and B cell differentiation into either kappa or lambda light chain immunoglobulin synthesizing plasmacytes have been investigated. The hypothesis that the observed inhibition of the PWM induced formation of plasmacytes by interferon is due to putative enhanced suppressor cell activity resulting from increased T cell proliferation is tested. Human, peripheral blood lymphocytes were exposed to PWM in the presence or absence of human leukocyte interferon. Proliferation was assayed by pulse cytophotometric analysis of cell kinetics, as well as [3H]TdR labelling of S-phase cells. Incidence of plasmacytes was detected by immunofluorescence using kappa or lambda light chain specific antibody. During continuous [3H]TdR labelling of stimulated cells, interferon inhibited incorporation of precipitable label by 40% at 96 and 144 h, indicating reduced net DNA synthesis by interferon treated cells. The relative fraction of cells in S-phase as well as G1- and G2 + M- was similar for treated and untreated cells. The fraction of cells rosetting SRBC remained stable for both treated and untreated cells. The size of the interferon treated population was persistently smaller once proliferation began. The time of initiation of proliferation was comparable for treated and untreated cells. Consistent with the findings of others using cell lines, interferon apparently induces a dilation of all cell cycle phases, thereby reducing the rate of proliferation. The same reduction occurred for both T and B cells. Time of initiation of DNA synthesis was, in contrast, not delayed by interferon, suggesting it is specific for events during the proliferative cell cycle. The occurrence of both kappa and lambda light chain immunoglobulin secreting plasmacytes was inhibited by interferon. The degree of inhibition was comparable for both kinds of plasmacytes detected. While not delaying the onset of DNA synthesis, interferon apparently retards subsequent cell proliferation and inhibits the differentiation of B cells to plasmacytes. The data indicate that active cellular proliferation and B cell differentiation require interferon sensitive events which cells initially recruited from quiescence by PWM do not. The inhibition of the incidence of plasmacytes cannot be attributed to an imbalance of T cell proliferation relative to non-T cells.

Immunohistochemical evaluation of K-ras, p53, and HER-2/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: evidence for multistep carcinogenesis.

The pathobiology of precursor lesions leading to invasive pancreatic adenocarcinoma remains a controversial area, but knowledge of the mechanisms of tumorigenesis may lead to possibly earlier detection, prevention, and treatment in the future. We hypothesize that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions and are part of a continuous developmental spectrum evolving into ductal adenocarcinoma of the pancreas. To further define this sequence, we studied the immunohistochemical markers HER-2/neu, K-ras, and p53 in 15 adenocarcinomas and 15 nonmalignant specimens of the pancreas. The 15 nonmalignant specimens of the pancreas included both normal pancreas and chronic pancreatitis. Overall, HER-2/neu was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 30, 11 of 20 (55%), 10 of 15 (67%), and 12 of 15 (80%), respectively, with progressive increase in the intensity of staining; p53 was positive in 1 of 30 (3%), 0 of 20, 3 of 15 (20%), and 13 of 15 (80%), respectively, and K-ras was positive in 1 of 30 (3%), 6 of 20 (30%), 11 of 15 (73%), and 8 of 15% (53%), respectively. These data support the hypothesis that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions, and, in a fashion similar to that in colorectal tumorigenesis, pancreatic cancer seems to accumulate progressive genetic alterations.

Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study.

The objective of endoscopic surveillance in Barrett esophagus (BE) is to assess the risk of subsequent development of invasive carcinoma. Criteria for morphologic evaluation of dysplasia, the presumed precursor lesion, have been established, although there are surprisingly few data in the literature correlating biopsy diagnosis of dysplasia with outcome. We collected follow-up information on 138 patients with BE whose initial endoscopic biopsy specimens had been selected for submission in an interobserver variability study performed by 12 pathologists with special interest in gastrointestinal pathology and reviewed blindly twice each by all the participants. Cases were scored as BE with no dysplasia, atypia indefinite for dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma, and frankly invasive carcinoma, thus generating 24 scores on each biopsy specimen. Clinical follow-up was obtained and correlated with both the submitting diagnoses and majority diagnoses. Kaplan-Meier statistics were used to compare both the submitting and majority diagnoses with outcome using detection or documentation of invasive carcinoma as the endpoint. Using the submitting diagnoses, no invasive carcinomas were detected in 44 cases diagnosed as BE (median follow-up, 38.5 months). Carcinomas were detected in 4 of 22 (18%) cases submitted as IND (median progression-free survival of 62 months), in 4 of 25 (15%) cases of LGD (median progression-free survival of 60 months), in 20 of 33 cases of HGD (median progression-free survival, 8 months), and all 13 (100%) cases submitted as adenocarcinoma. Grade on initial biopsy correlated significantly with progression to invasive carcinoma (log-rank P =.0001). Majority diagnosis was achieved in 99 of the cases. Using the majority diagnoses, no invasive carcinomas were found in 50 cases of BE (median follow-up, 48 months), and carcinomas were detected in 1 of 7 (14%) IND cases (80% progression-free survival at 2 months), 3 of 15 (20%) LGD (median progression-free survival, 60 months), 9 of 15 (60%) HGD (median progression-free survival, 7 months), and all 12 (100%) carcinoma. Initial grading again correlated significantly with progression to invasive carcinoma (log-rank P =.0001). However, there were 39 cases without a majority diagnosis. Among these, no carcinomas developed in 8 cases with an average score between BE and IND. Carcinomas were detected in 9 of 21 (43%) cases with an average score between IND and LGD, and 7 of 10 (70%) cases with an average score between LGD and HGD. There were ulcers in 8 of 39 cases (20%) of the "no-majority" group and in 13 of 99 (13%) of the majority cases. Of 21 total ulcerated cases, cancer was demonstrated in 15 (71%) of these on follow-up. These data support combining the IND and LGD categories for surveillance purposes. Cases without dysplasia may be followed up conservatively. The data obtained from submitted diagnoses as opposed to those from blind review suggest that knowledge of the clinical findings aids in diagnosis. The data also support the assertion that HGD is strongly associated with invasive carcinoma. Rebiopsy of ulcerated areas should be considered because they may harbor malignancy. Histologic grading of dysplasia using established criteria is a powerful prognosticator in BE. HUM PATHOL 32:379-388.

Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.

Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by kappa statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set was then reviewed twice by each of the same 12 pathologists, and follow-up kappa statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean kappa = 0.82 and 0.80). Interobserver agreement was substantial (kappa = 0.66) and improved after the consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver kappa improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver kappa was 0.60 (substantial agreement), improving to 0.65 after the meeting (P <.05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged (kappa = 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma (kappa = 0.65), moderate to substantial for BE (kappa = 0.58), fair for LGD (kappa = 0.32), and slight for IND (kappa = 0.15). The intraobserver reproducibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. HUM PATHOL 32:368-978.

Pathologist-gastroenterologist interaction. The changing role of the pathologist.

The importance of interaction between clinicians and pathologists is examined in the setting of gastroenterology and gastrointestinal disease, and the importance of communication is emphasized. The endoscopist must provide the pathologist with information about the patient, including results of the gross examination, biopsy location, relevant clinical history, bowel preparation, and current medications. The pathologist must provide a reproducible and useful report that answers the clinical questions posed by the endoscopist. This consultation between the gastroenterologist and pathologist provides the framework for proper patient care.

Hypersensitivity myocarditis: Findings in native and transplanted hearts.

Seven explanted hearts from a total of 288 heart transplants performed at UCLA Medical Center had histologic evidence of hypersensitivity myocarditis (prevalence = 2.4%). Three patients had a clinical history of drug allergy, and two had a clinically documented drug reaction prior to transplant. Three patients had peripheral eosinophilia prior to transplant. Five patients with hypersensitivity myocarditis had dilated cardiomyopathy, one had congenital abnormalities, and one had ischemic heart disease. In the period up to 3 weeks posttransplant, four patients had episodes of acute rejection (ISHLT grade 2 to 4) with eosinophils histologically. Results suggest that hypersensitivity myocarditis may have an increasing prevalence in the native heart before transplant and in the newly transplanted heart.

Treatment of Pseudomonas endophthalmitis associated with prosthetic intraocular lens implantation.

Eight patients were treated for Pseudomonas endophthalmitis associated with the implantation of contaminated intraocular lenses. All patients showed clinical signs of infection (loss of red reflex, diminished visual acuity, and intraocular lens coagulum) and P. aeruginosa was isolated from vitreous aspirates and unused lenses of the same lot. Antibiotic treatment was initiated with systemic penicillin G, cephalothin, and chloramphenicol as well as subtenon-injected gentamicin. After identification of the organism, treatment was continued with systemic carbenicillin and gentamicin and subtenon-injected gentamicin. The intraocular lens was left in place for the first 48 hours of treatment in all eight patients. Five patients were successfully treated without removal of the intraocular lens and attained visual acuity of 6/6 (20/20) to 6/15 (20/50). Three patients (the two most seriously infected and one in whom antibiotics were discontinued) eventually lost their infected eye. Vitreous concentrations of gentamicin were good in one patient (1.7 micrograms/ml) and undetectable in another. Carbenicillin concentrations in vitreous (96 and 140 micrograms/ml) were high in two patients sampled. Endophthalmitis in the presence of a prosthetic intraocular lens can be successfully treated in some patients without removal of the prosthesis.

Correlation of cross-linked fibrin degradation products (D-dimer) with coronary angiographic lesion morphology.

We tested the hypothesis that complex irregular coronary lesions are "active" lesions and thus associated with ongoing fibrinolysis by measuring the degradation products of cross-linked fibrin (D-dimer) in 136 patients undergoing coronary arteriography. Blood samples obtained before catheterization were assayed by an enzyme linked immunosorbent assay (ELISA) using specific monoclonal antibodies for D-dimer particles. In the four groups with complex coronary morphologies (filling defects, extrinsic lesions with irregular borders and total occlusions with or without staining) the majority of patients (64%) had normal D-dimer levels. The incidence of abnormal D-dimer levels was not significantly higher in any of these four groups than in the two groups with normal coronaries or with smooth lesions. In the same patients, however, the clinical diagnosis was predictive of the presence of elevated D-dimer levels. These findings suggest that complex coronary lesions are often not associated with ongoing fibrinolysis and that endogenous fibrinolysis frequently ceases in the presence of persistent clot.

Early regeneration of Calluna heathland under various fertilization treatments.

A sod-cutting and fertilization experiment was performed on a Calluna-dominated heathland in The Netherlands to determine appropriate management regimes for Calluna regeneration, and to further understand the nutrient responses of heathland species. Replicated permanent plots were analysed by multivariate techniques. Sod-cutting alone caused Calluna regeneration from its soil seed bank. A single fertilization at the start of the experiment caused initial vegetation differences which disappeared after a few years as the nutrients were lost from the system, except that one application of nitrogen enhanced the rate of Calluna regeneration. Repeated fertilization caused large differences in the vegetation: repeated nitrogen enhanced several bryophyte species while greatly inhibiting Calluna, repeated phosphate partly inhibited Calluna while greatly favouring several lichen species, and the most striking result of repeated calcium was also an increase in bryophytes, but the species were different from those favoured by nitrogen. Treatments which inhibited Calluna tended to increase species diversity because of the lessened Calluna dominance.

Dopaminergic therapy in children with restless legs/periodic limb movements in sleep and ADHD. Dopaminergic Therapy Study Group.

The long-term effects of monotherapy with levodopa or the dopamine agonist pergolide on the motor/sensory, behavioral, and cognitive variables in seven children with restless legs syndrome/periodic limb movements in sleep (RLS/PLMS) and attention-deficit-hyperactivity disorder (ADHD) were investigated. Five of the seven children had previously been treated with stimulants that had either been determined to be ineffective or to have intolerable side effects. Dopaminergic therapy improved the symptoms of RLS and reduced the number of PLMS per hour of sleep (P = 0.018) and associated arousals (P = 0.042) for the entire group. After treatment, three children no longer met the criteria for ADHD, and three reverted to normal on the Test of Variable Attention. ADHD improved in all seven as measured by the Connors parent rating scale (P<0.04) and the Child Behavior Checklist (P<0.05). A significant improvement also occurred in the visual, but not verbal, memory scores on the Wide Range Assessment of Memory and Learning (P<0.001). Five of seven children continue on dopaminergic therapy 3 years after treatment initiation, with good response. We postulate that the improvement in ADHD may be the result of the amelioration of RLS/PLMS and its associated sleep disturbance. Alternatively, ADHD and RLS/PLMS may share a common dopaminergic deficit.

Primary hepatic B-cell lymphoma of mucosa-associated lymphoid tissue.

Mucosa-associated lymphoid tissue (MALT) lymphomas are low-grade B-cell lymphomas that occur in a variety of extranodal sites but rarely as a primary hepatic lymphoma. We describe the histological findings, immunophenotype, and immunohistochemistry of one such lymphoma found incidentally in a 69-year-old woman. The lymphoid infiltrate invaded the liver in a serpiginous configuration with entrapment of nodules of normal liver. Reactive follicles were surrounded by intermediate-sized lymphoid cells with slightly irregular nuclei and pale cytoplasm. Only a few scattered lymphoepithelial lesions were identified since most of the bile ducts were destroyed. The immunophenotype determined by flow cytometry identified the lymphoid cells as being CD19, CD20 positive and exhibiting lambda light chain restriction. CD5, CD10, and CD23 were negative. Immunohistochemistry showed the neoplastic cells to be positive for CD20 (L-26) and bcl-2. The reactive follicles were negative for bcl-2. CD3 showed only a few scattered T cells. Cyclin D1 did not stain the neoplastic cells. Cytokeratin (AE1/AE3) highlighted the lymphoepithelial lesions and residual bile ducts. MALT lymphomas need to be recognized and distinguished from other B-cell lymphomas, particularly mantle cell lymphomas, because of the difference in behavior and treatment.

Simultaneous measurements of intrauterine pressure, including the head-to-cervix pressure, by an open-end catheter and a strain gauge.

An open-end catheter and a small strain gauge were tied and introduced into the uterine fundus during the labor of 8 parturients. As the tied probes were progressively withdrawn, the pressures given by each were simultaneously recorded. Normally the measurements are identical, but when the free ends of the probes are located between the head and the cervix, striking differences appear, the strain gauge giving much higher figures. Conversely, two intrauterine open-end catheters give the same results even if one is located in the fundus and the other is between the head and the cervix. It is suggested that the strain gauge measures a pressure which is not reliable enough because the area of application of the stress cannot be known accurately.

Measuring the height of a cephalic presentation: an objective assessment of station.

The authors have previously described a method of objectively assessing the height of the presentation, an ultrasonic echograph measuring the distance from the head to the sacral tip. They have now obtained 453 measurements made before and during labor; norms are given according to the clinical evaluation of the station. The usefulness of the method is discussed. It may make the Bishop's score more precise, permit a more accurate check of trial of labor and help to recognize a low station correctly before an application of forceps.

Importance of sleep in the management of pediatric pain.

This article outlines several aspects of sleep regulation relevant to pediatric pain management. A broad range of connections between sleep and pain are described: (1) pain can interfere with the quality and quantity of children's sleep; (2) insufficient sleep (quality or quantity) can cause daytime sequelae (behavioral and emotional changes) that interfere with the coping skills necessary for effective pain management; (3) fear and anxiety often have a negative impact on both pain and sleep; (4) feelings of safety and control frequently have a positive effect on both sleep and pain symptoms; (5) adequate sleep seems to promote both physiological (tissue repair) and psychological (transient cessation of the perception of pain signals) processes relevant to recovery from pain, injury, and illness; and (6) treatment approaches to pediatric sleep and pain problems show considerable overlap with respect to many pharmacological as well as cognitive-behavioral interventions. Given these multiple links, a better understanding of sleep--and its importance in physical and mental health--is likely to be of value to clinicians and researchers working in areas of pediatric pain management. One specific hypothesis to be addressed is the possible contribution of sleep disruption as a step in the progression to some chronic pain syndromes.

Vaginal ligature of uterine arteries during postpartum hemorrhage.

Immediate postpartum hemorrhage due to uterine inertia is usually treated by injection of oxytocics. In some situations, bleeding continues and distends the uterine cavity, in turn disturbing the hemostasis that accompanies uterine retraction. Uterine bleeding must be rapidly reduced while the coagulation defect is corrected. The authors propose the vaginal ligature of uterine arteries, which can be performed in the delivery room, as an alternative to hysterectomy.