A practical approach to screening for carbapenemase-producing Enterobacterales- views of a group of multidisciplinary experts from English hospitals.

INTRODUCTION: Carbapenemase-producing Enterobacterales (CPE) are an important public health threat, with costly operational and economic consequences for NHS Integrated Care Systems and NHS Trusts. UK Health Security Agency guidelines recommend that Trusts use locally developed risk assessments to accurately identify high-risk individuals for screening, and implement the most appropriate method of testing, but this presents many challenges. METHODS: A convenience sample of cross-specialty experts from across England met to discuss the barriers and practical solutions to implementing UK Health Security Agency framework into operational and clinical workflows. The group derived responses to six key questions that are frequently asked about screening for CPE. KEY FINDINGS: Four patient groups were identified for CPE screening: high-risk unplanned admissions, high-risk elective admissions, patients in high-risk units, and known positive contacts. Rapid molecular testing is a preferred screening method for some of these settings, offering faster turnaround times and more accurate results than culture-based testing. It is important to stimulate action now, as several lessons can be learnt from screening during the COVID-19 pandemic, as well as from CPE outbreaks. CONCLUSION: Further decisive and instructive information is needed to establish CPE screening protocols based on local epidemiology and risk factors. Local management should continually evaluate local epidemiology, analysing data and undertaking frequent prevalence studies to understand risks, and prepare resources- such as upscaled screening- to prevent increasing prevalence, clusters or outbreaks. Rapid molecular-based methods will be a crucial part of these considerations, as they can reduce unnecessary isolation and opportunity costs.

TB testing in HIV-positive patients prior to antiretroviral treatment.

BACKGROUND: TB diagnosis in patients with HIV is challenging due to the lower sensitivities across tests. Molecular tests are preferred and the Xpert® MTB/RIF assay has limitations in lower-income settings. We evaluated the performance of loop-mediated isothermal amplification (LAMP) and the lipoarabinomannan (LAM) test in HIV-positive, ART-naïve clinic patients.METHODS: A total of 783 eligible patients were enrolled; three spot sputum samples of 646 patients were tested using TB-LAMP, Xpert, smear microscopy and culture, while 649 patients had TB-LAM testing. Sensitivity, specificity, and negative and positive predictive values were estimated with 95% confidence intervals.RESULTS: Sensitivities for smear microscopy, TB-LAMP and Xpert were respectively 50%, 63% and 74% compared to culture, with specificities of respectively 99.2%, 98.5% and 97.5%. An additional eight were positive on TB-LAM alone. Seventy TB patients (9%) were detected using standard-of-care testing, an additional 27 (3%) were detected using study testing. Treatment was initiated in 57/70 (81%) clinic patients, but only in 56% (57/97) of all those with positive TB tests; 4/8 multidrug-resistant samples were detected using Xpert.CONCLUSION: TB diagnostics continue to miss cases in this high-burden setting. TB-LAMP was more sensitive than smear microscopy, and if followed by culture and drug susceptibility testing as required, can diagnose TB in HIV-positive patients. TB-LAM is a useful add-in test and both tests at the point-of-care would maximise yield.

Rictor regulates cell migration by suppressing RhoGDI2.

Rictor and its binding partner Sin1 are indispensable components of mTORC2 (mammalian target of rapamycin complex 2). The mTORC2 signaling complex functions as the regulatory kinase of the distinct members of AGC kinase family known to regulate cell proliferation and survival. In the early chemotaxis studies in Dictyostelium, the rictor's ortholog has been identified as a regulator of cell migration. How rictor regulates cell migration is poorly characterized. Here we show that rictor regulates cell migration by controlling a potent inhibitor of Rho proteins known as the Rho-GDP dissociation inhibitor 2 (RhoGDI2). On the basis of on our proteomics study we identified that the rictor-dependent deficiency in cell migration is caused by upregulation of RhoGDI2 leading to a low activity of Rac and Cdc42. We found that a suppression of RhoGDI2 by rictor is not related to the Sin1 or raptor function that excludes a role of mTORC2 or mTORC1 in regulation of RhoGDI2. Our study reveals that rictor by suppressing RhoGDI2 promotes activity of the Rho proteins and cell migration.

Routinely available cotrimoxazole prophylaxis and occurrence of respiratory and diarrhoeal morbidity in infants born to HIV-infected mothers in South Africa.

OBJECTIVES: To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower respiratory tract infections (LRTIs) and diarrhoea. DESIGN: A prospective observational cohort study. Morbidity and feeding data on infants born to HIV-infected mothers were collected routinely at clinic visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status. SETTING: Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIV infected mothers received CTM prophylaxis and in the other (McCord Hospital) infants did not receive CTM prophylaxis. SUBJECTS: Infants born to HIV-infected mothers. Outcome measures. Incidence of LRTI and diarrhoea. RESULTS: In multivariate analysis controlling for breast-feeding status, number of clinic visits and HIV infection status, HIV infected infants with access to CTM prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case. CTM prophylaxis was associated with a non-significant increased risk for diarrhea in both infected (odds ratio (OR) 1.58, p = 0.45) and uninfected infants (OR 1.52, p = 0.10). CONCLUSIONS: This observational study confirms current thinking that CTM prophylaxis is protective against LRTIs in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent unnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects of CTM prophylaxis are undertaken.

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

AIM: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at I wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. RESULTS: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1. 17-3.13, p = 0.006). CONCLUSION: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.

Method of feeding and transmission of HIV-1 from mothers to children by 15 months of age: prospective cohort study from Durban, South Africa.

OBJECTIVE: To determine the risk of HIV transmission by infant feeding modality. DESIGN AND SETTING: A prospective study in two hospitals in Durban, South Africa. PARTICIPANTS: A total of 551 HIV-infected pregnant women enrolled in a randomized trial of vitamin A. INTERVENTIONS: Women self-selected to breastfeed or formula feed after being counselled. Breastfeeders were encouraged to practice exclusive breastfeeding for 3-6 months. MAIN OUTCOME MEASURES: Cumulative probabilities of detecting HIV over time were estimated using Kaplan-Meier methods and were compared in three groups: 157 formula-fed (never breastfed); 118 exclusively breastfed for 3 months or more; and 276 mixed breastfed. RESULTS: The three feeding groups did not differ in any risk factors for transmission, and the probability of detecting HIV at birth was similar. Cumulative probabilities of HIV detection remained similar among never and exclusive breastfeeders up to 6 months: 0.194 (95% CI 0.136-0.260) and 0.194 (95% CI 0.125-0.274), respectively, whereas the probabilities among mixed breastfeeders soon surpassed both groups reaching 0.261 (95% CI 0.205-0.319) by 6 months. By 15 months, the cumulative probability of HIV infection remained lower among those who exclusively breastfed for 3 months or more than among other breastfeeders (0.247 versus 0.359). CONCLUSION: Infants exclusively breastfed for 3 months or more had no excess risk of HIV infection over 6 months than those never breastfed. These findings, if confirmed elsewhere, can influence public health policies on feeding choices available to HIV-infected mothers in developing countries.

Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease.

Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated proteins can induce antigen-specific anti-inflammatory immune responses in mucosal lymphoid tissue which then act systemically. We hypothesized that chronic mucosal administration of Abeta peptide might induce an anti-inflammatory process in AD brain tissue that could beneficially affect the neuropathological findings. To test this hypothesis, we treated PDAPP mice, a transgenic line displaying numerous neuropathological features of AD, between the ages of approximately 5 and approximately 12 months with human Abeta synthetic peptide mucosally each week. We found significant decreases in the cerebral Abeta plaque burden and Abeta42 levels in mice treated intranasally with Abeta peptide versus controls treated with myelin basic protein or left untreated. This lower Abeta burden was associated with decreased local microglial and astrocytic activation, decreased neuritic dystrophy, serum anti-Abeta antibodies of the IgG1 and IgG2b classes, and mononuclear cells in the brain expressing the anti-inflammatory cytokines interleukin-4, interleukin-10, and tumor growth factor-beta. Our results demonstrate that chronic nasal administration of Abeta peptide can induce an immune response to Abeta that decreases cerebral Abeta deposition, suggesting a novel mucosal immunological approach for the treatment and prevention of AD.

Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group.

OBJECTIVE: Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome. We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1. DESIGN AND METHODS: In Durban, South Africa 728 pregnant HIV infected women received either vitamin A (368) or placebo (360) in a randomized, double-blind trial. The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery. HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis. Results are reported on mother-to-child transmission rates up to 3 months of age. RESULTS: There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [20.3%; 95% confidence interval (CI), 15.7-24.9] and placebo groups (22.3%; 95% CI, 17.5-27.1), nor were there differences in foetal or infant mortality rates between the two groups. Women receiving vitamin A supplement were, however, less likely to have a preterm delivery (11.4% in the vitamin A and 17.4% in the placebo group; P = 0.03) and among the 80 preterm deliveries, those assigned to the vitamin A group were less likely to be infected (17.9%; 95% CI, 3.5-32.2) than those assigned to the placebo group (33.8%; 95% CI, 19.8-47.8). CONCLUSION: Vitamin A supplementation, a low-cost intervention, does not appear to be effective in reducing overall mother-to-child transmission of HIV; however, its potential for reducing the incidence of preterm births, and the risk of mother-to-child transmission of HIV in these infants needs further investigation.

Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study. South African Vitamin A Study Group.

BACKGROUND: The observation that mother-to-child transmission of HIV-1 can occur through breastfeeding has resulted in policies that recommend avoidance of breastfeeding by HIV-1-infected women in the developed world and under specific circumstances in developing countries. We compared transmission rates in exclusively breastfed, mixed-fed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV-1. METHODS: We prospectively assessed infant-feeding practices of 549 HIV-1-infected women who were part of a vitamin A intervention trial in Durban, South Africa. The proportions of HIV-1-infected infants at 3 months (estimated by use of Kaplan-Meier life tables) were compared in the three different feeding groups. HIV-1 infection was defined by a positive RNA-PCR test. FINDINGS: At 3 months, 18.8% (95% CI 12.6-24.9) of 156 never-breastfed children were estimated to be HIV-1 infected compared with 21.3% (17.2-25.5) of 393 breastfed children (p=0.5). The estimated proportion (Kaplan-Meier) of infants HIV-1 infected by 3 months was significantly lower for those exclusively breastfed to 3 months than in those who received mixed feeding before 3 months (14.6% [7.7-21.4] vs 24.1% [19.0-29.2], p=0.03). After adjustment for potential confounders (maternal CD4-cell/CD8-cell ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV-1 transmission than mixed feeding (hazard ratio 0.52 [0.28-0.98]) and a similar risk to no breastfeeding (0.85 [0.51-1.42]). INTERPRETATIONS: Our findings have important implications for prevention of HIV-1 infection and infant-feeding policies in developing countries and further research is essential. In the meantime, breastfeeding policies for HIV-1-infected women require urgent review. If our findings are confirmed, exclusive breastfeeding may offer HIV-1-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV-1 while maintaining the overwhelming benefits of breastfeeding.

Immunocytochemistry of formalin-fixed human brain tissues: microwave irradiation of free-floating sections.

Formalin fixation, the chemical process in which formaldehyde binds to cells and tissues, is widely used to preserve human brain specimens from autolytic decomposition. Ultrastructure of cellular and mitochondrial membranes is markedly altered by vesiculation, but this does not interfere with diagnostic evaluation of neurohistology by light microscopy. Serious difficulties are encountered, however, when immunocytochemical staining is attempted. Antigens that are immunoreactive in unfixed frozen sections and protein extracts appear to be concealed or destroyed in formalin-fixed tissues. In dilute aqueous solution, formaldehyde is in equilibrium with methylene glycol and its polymeric hydrates, the balance by far in favor of methylene glyco. Carbonylic formaldehyde is a reactive electrophilic species well known for crosslinking functional groups in tissue proteins, nucleic acids, and polysaccharides. Some of its methylene crosslinks are readily hydrolyzed. Others are stable and irreversible. During immunostaining reactions, intra- and inter-molecular links between macromolecules limit antibody permeation of tissue sections, alter protein secondary structure, and reduce accessibility of antigenic determinants . Accordingly, immunoreactivity is diminished for many antigens. Tissues are rapidly penetrated by methylene glycol, but formaldehyde binding to cellular constituents is relatively slow, increasing progressively until equilibrium is reached. In addition, prolonged storage in formalin may result in acidification of human brain specimens. Low pH favors dissociation of methylene glycol into formaldehyde, further reducing both classical staining and antigen detectability. Various procedures have been devised to counter the antigen masking effects of formaldehyde. Examples include pretreatment of tissue sections with proteases, formic acid, or ultrasound. Recently, heating of mounted sections in ionic salt solution by microwave energy was found to restore many antigens. Theory and practice of microwave antigen retrieval are covered extensively in the handbook Microwave Cookbook for Microscopists. A concise overview of microwave methods in the neurosciences has been published, and clinical applications have been reviewed. In this context, it should be noted that fresh tissues may be stabilized for immunocytochemistry by reversible, non-chemical binding processes such as cryosectioning after microwave treatment and freeze-drying. Thus, it may be possible to enhance immunostaining for some antigens by microwave irradiation of unfixed as well as fixed specimens. Parameters to be optimized for microwave retrieval of specific antigens include temperature, irradiation time, tissue buffer composition, salt concentration, and pH. Temperature, irradiation time, and pH are key variables. With this in mind, an optimal method was developed for retrieval of a wide variety of antigens in human brain tissues. Typical microwave protocols employ elevated temperatures that may reach 100 degrees C, where denaturation causes irreversible uncoiling and disruption of protein secondary and tertiary structures. Under these conditions, stable covalent bonds securing methylene crosslinks between polypeptides remain intact, but more reactive links formed by Schiff bases may be hydrolyzed. Resultant conformational changes presumably expose buried loops of continuous amino acids and protruding regions, increasing accessibility of their epitopes. Protein denaturation seems to be a reasonable explanation for the effects of microwaves on antigen retrieval. This idea is supported by the observation that denaturing solutions such as 6 M urea increase immunoreactivity of some antigens. Still, the molecular basis of these effects remains unresolved, in part due to the complex chemistry of formaldehyde reactions with tissue constituents. Indeed, some methylene bridges between similar groups such as NH2 and NH may be hydrolyzed by washing fixed tissues in distilled wa

Immunocytochemistry of tau phosphoserine 413 and tau protein kinase I in Alzheimer pathology.

One unique phosphorylation site consistently found in paired helical filament tau, serine 413, is modified by tau protein kinase I/glycogen synthase kinase-3 beta but no other known tau kinase. Here we present immunocytochemistry from Alzheimer's disease brains showing that focal subpopulations of hippocampal CA1 pyramidal neurons and neuritic plaques are strongly reactive for tau protein kinase I/glycogen synthase kinase-3 beta and tau phosphoserine 413 in early stages of pathology. Colocalization of these epitopes suggests that tau protein kinase I/glycogen synthase kinase-3 beta abnormally phosphorylates tau and is in a position to disrupt neuronal metabolism in anatomical areas vulnerable to Alzheimer's disease.

Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily.

BACKGROUND: Reactive oxygen species, ionizing radiation, and other free radical generators initiate the conversion of guanine (G) residues in DNA to 8-oxoguanine (OG), which is highly mutagenic as it preferentially mispairs with adenine (A) during replication. Bacteria counter this threat with a multicomponent system that excises the lesion, corrects OG:A mispairs and cleanses the nucleotide precursor pool of dOGTP. Although biochemical evidence has suggested the existence of base-excision DNA repair proteins specific for OG in eukaryotes, little is known about these proteins. RESULTS: Using substrate-mimetic affinity chromatography followed by a mechanism-based covalent trapping procedure, we have isolated a base-excision DNA repair protein from Saccharomyces cerevisiae that processes OG opposite cytosine (OG:C) but acts only weakly on OG:A. A search of the yeast genome database using peptide sequences from the protein identified a gene, OGG1, encoding a predicted 43 kDa (376 amino acid) protein, identical to one identified independently by complementation cloning. Ogg1 has OG:C-specific base-excision DNA repair activity and also intrinsic beta-lyase activity, which proceeds through a Schiff base intermediate. Targeted disruption of the OGG1 gene in yeast revealed a second OG glycosylase/lyase protein, tentatively named Ogg2, which differs from Ogg1 in that it preferentially acts on OG:G. CONCLUSIONS: S. cerevisiae has two OG-specific glycosylase/lyases, which differ significantly in their preference for the base opposite the lesion. We suggest that one of these, Ogg1, is closely related in overall three-dimensional structure to Escherichia coli endonuclease III (endo III), a glycosylase/lyase that acts on fragmented and oxidatively damaged pyrimidines. We have recently shown that AlkA, a monofunctional DNA glycosylase that acts on alkylated bases, is structurally homologous to endo III. We have now identified a shared active site motif amongst these three proteins. Using this motif as a protein database searching tool, we find that it is present in a number of other base-excision DNA repair proteins that process diverse lesions. Thus, we propose the existence of a DNA glycosylase superfamily, members of which possess a common fold yet act upon remarkably diverse lesions, ranging from UV photoadducts to mismatches to alkylated or oxidized bases.

Evaluation of a temporal increase in ventricular septal defects: estimated prevalence and severity in northeastern New York, 1970-1983.

A marked increase or "epidemic" in ventricular septal defects (VSD) in recent years has been reported by the Center for Disease Control. Many pediatric cardiologists believe that this increase is simply a reflection of more intensive diagnosis and evaluation of infants throughout the country. Yet to our knowledge there has been no objective evidence for this explanation. We evaluated this possibility by considering records on live births occurring in 1970-1983 in the counties surrounding Albany, New York. In that period a single group of pediatric cardiologists has been evaluating all infants with suspected or confirmed cardiac defects in this area. We limited this analysis to ventricular septal defects unassociated with any cardiac syndrome complex. Thus, VSDs occurring as part of cyanotic heart disease or other complex cardiac "syndromes" were excluded. Consistent with the reported national trend, the estimated prevalence rate of ventricular septal defects diagnosed under 1 year of age in this period has increased from 1.0 per 1,000 live births in 1970 to 4.0 per 1,000 in 1983.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac rhabdomyoma in the neonate: surgical management.

Rhabdomyoma is the most common cardiac neoplasm in neonates. Tuberous sclerosis is found in half of the patients with rhabdomyomas. We maintain a surgical policy of accepting for operation only neonates in whom it has been demonstrated that the primary cause for hemodynamic compromise is obstructing, intracavitary neoplasms. Only the intracavitary portions of the rhabdomyoma are excised; no effort is made to completely remove all intramural tumors. Rhabdomyomas demonstrate benign pathological characteristics and may regress. Neonates with rhabdomyomas but no hemodynamic impairment, or those in whom only intramural masses can be demonstrated, are not considered surgical candidates. Tuberous sclerosis by itself should not be judged a contraindication to operation. The results of our surgical policy regarding rhabdomyomas in neonates are reported in two case presentations.

Right heart reconstruction following repair of tetralogy of fallot.

Ten patients in whom tetralogy of Fallot had been repaired underwent late reconstruction of the outflow tract of the right ventricle because of poor hemodynamic results. The major hemodynamic problems that necessitated right ventricular (RV) outflow tract reconstruction were severe pulmonary insufficiency in 9 patients and pulmonary stenosis in 1. Impaired RV contractility and RV aneurysm were the most important factors prompting valve replacement for severe pulmonary insufficiency. Seven patients received a Hancock prosthesis and 3, an aortic homograft. Among the 7 patients who underwent postoperative cardiac catheterization, the surgical results were hemodynamically excellent in 2, good in 3, and unsatisfactory in 2. The management of pulmonary insufficiency in such patients is discussed.

Ventricular diastolic pressure-volume relations after the intra-atrial baffle operation for transposition of the great arteries.

Right and left ventricular diastolic pressure-volume (P-V) relations were assessed in 30 patients approximately 2 years after the Mustard operation. The overall distensibility index (delta V/ delta P), the compliance index at end-diastole (dv/dp), and the modulus of ventricular stiffness (Kp) were calculated in all, as well as the half-time of early diastolic pressure fall (T) in 10 cases. Transducer-tipped catheters were used in 15 patients and biplane cineangiography was employed in all. Values for the above indices equal to 2 standard deviations below the mean, obtained from five postoperative Mustard patients with no residual defects, were used as "normals." Seven patients with pulmonary hypertension (PH) and six with pulmonic stenosis (PS) were found to have impaired P-V relations. The impairment was more profound in the PH group. Delta v/delta p and dv/dp were abnormal in six of seven patients for both ventricles and T was abnormal in two of five. Kp was abnormal for the LV, and the RV ejection fraction was diminished. In the PS group (nine patients) the impairment was milder, affecting more than LV and end-diastole (dv/dp). Compliance studies might be useful in patients with LV afterload problems following the Mustard operation.

Left ventricular function and compliance in pulmonary atresia with intact ventricular septum.

Left ventricular systolic function and compliance were assessed in 15 cases of pulmonary atresia with intact ventricular septum. The left ventricular ejection fraction measured from cineangiography was used for the evaluation of the systolic function. The end-diastolic pressure (EDP), left ventricular compliance index at end-diastole (dv/dp), and left ventricular stiffness constant K were used as compliance indices. The mean left ventricular ejection fraction was slightly diminished. The right ventricular end diastolic pressures (RVEDPs) correlated significantly (r = 0.90) with the left ventricular end diastolic pressure (LVEDP). On the basis of left ventricular compliance, two distinctive groups of patients could be identified: Group I consisted of Patients 1 to 7, all with impaired left ventricular compliance. A shunt operation was the basic palliation in this group. None of these patients survived infancy. Group II consisted of Patients 8 to 15, all with normal left ventricular compliance. Pulmonary valvotomy as well as aortopulmonary shunts were the basic palliative procedures in this group. Six of eight patients in this group are long-term survivors. No difference was found in right ventricular size, tricuspid valve size, presence of tricuspid insufficiency, presence of a patent ductus arteriosus, postoperative oxygen saturations, and atrial pressure gradients between the two groups. Evaluation of the left ventricular compliance in patients with pulmonary atresia and intact ventricular septum might be of significant prognostic valve for their early survival.