Histopathological and virological features of lung, heart and liver percutaneous tissue core biopsy in patients with COVID-19: A clinicopathological case series.

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.

The silent variants of pituitary tumors: demographic, radiological and molecular characteristics.

INTRODUCTION: Tumors of the anterior pituitary gland (PTs) are mostly benign tumors with a low prevalence, which has nevertheless increased with advances in brain radiology techniques. Nearly half of PTs are not associated with a clinical endocrine syndrome. These tumors have been indistinctly named non-functioning pituitary adenomas (NFPAs) or silent pituitary tumors (SPTs) and the mechanisms of silencing are not fully known. AIM: To study the frequency and characterize the silent variant of PTs in a large local series, and to assess their pituitary adenohypophyseal gene expression. METHODS: This observational, cross-sectional study was performed in a Pituitary Tumor Center of Excellence and involved 268 PTs. After identifying the different subtypes according to the immunohistochemical (IHC) expression of adenohypophyseal hormones, we studied their gene expression by RT-qPCR. RESULTS: We found that silent tumors were larger and more invasive, but not more proliferative than their functional counterparts. The RT-qPCR complements the IHC typification of PTs, reducing the proportion of null-cell subtype. Finally, some silent PT subtype variants showed lower specific adenohypophyseal hormone gene expression than their functional counterparts, which may contribute to the absence of endocrine manifestations. CONCLUSIONS: This paper highlights the importance of identifying the silent variant of the PTs subtypes. As expected, silent tumors were larger and more invasive than their functioning counterparts. However, there was no difference in the proliferation activity between them. Finally, the lower specific gene expression in the silent than in the functioning counterparts of some PTs subtypes gives insights into the silencing mechanisms of PTs.

Determination of policyclic aromatic compounds, (PAH, nitro-PAH and oxy-PAH) in soot collected from a diesel engine operating with different fuels.

A qualitative and quantitative analysis of polycyclic aromatic compounds (PACs; polycyclic aromatic hydrocarbons (PAHs), oxygenated and nitrated polycyclic aromatic hydrocarbons (OPAHs and NPAHs)) present in the soluble organic fraction (SOF) of different soot samples has been carried out to determine the effect of soot-generation conditions on their composition and health effects. The soot samples were generated using a diesel engine bench powered by diesel (DS) and biodiesel (BS) fuels under different combustion conditions. To optimize the procedure, a surrogate soot (Printex-U) and a certified reference material (SRM1650b) were also tested. Different extraction methods were used to extract the PAHs, OPAHs and NPAHs, and the Soxhlet technique using pyridine:acetic acid 1 % was found to be the most suitable procedure to extract the highest concentration (ng mg-1) and more types of PAHs and OPAHs from the soot. The results show that the PACs identified, and their concentrations, depend on the formation and collection conditions. The predominant compounds in all soot samples studied were fluorene (Flo), phenanthrene (Phe), fluoranthene (Fla), pyrene (Pyr), 9-fluorenone (9Flo) and 9,10-anthraquinone (9,10Anq). As such, the presence of these PACs in the atmosphere of urban and rural areas can mainly be attributed to the emissions from diesel vehicles. The percentage of OPAHs with respect to total PACs was highest in the soot generated from a biofuel. These oxidized compounds favor regeneration of the diesel particulate filter (DPF). The results also indicate that the carcinogenicity of the soot depends on the combustion conditions and type of fuel.

Functional phenotypic plasticity mediated by water stress and [CO2] explains differences in drought tolerance of two phylogenetically close conifers.

Forests are threatened globally by increased recurrence and intensity of hot droughts. Functionally close coexisting species may exhibit differences in drought vulnerability large enough to cause niche differentiation and affect forest dynamics. The effect of rising atmospheric [CO2], which could partly alleviate the negative effects of drought, may also differ between species. We analysed functional plasticity in seedlings of two taxonomically close pine species (Pinus pinaster Ait., Pinus pinea L.) under different [CO2] and water stress levels. The multidimensional functional trait variability was more influenced by water stress (preferentially xylem traits) and [CO2] (mostly leaf traits) than by differences between species. However, we observed differences between species in the strategies followed to coordinate their hydraulic and structural traits under stress. Leaf 13C discrimination decreased with water stress and increased under elevated [CO2]. Under water stress both species increased their sapwood area to leaf area ratios, tracheid density and xylem cavitation, whereas they reduced tracheid lumen area and xylem conductivity. Pinus pinea was more anisohydric than P. pinaster. Pinus pinaster produced larger conduits under well-watered conditions than P. pinea. Pinus pinea was more tolerant to water stress and more resistant to xylem cavitation under low water potentials. The higher xylem plasticity in P. pinea, particularly in tracheid lumen area, expressed a higher capacity of acclimation to water stress than P. pinaster. In contrast, P. pinaster coped with water stress comparatively more by increasing plasticity of leaf hydraulic traits. Despite the small differences observed in the functional response to water stress and drought tolerance between species, these interspecific differences agreed with ongoing substitution of P. pinaster by P. pinea in forests where both species co-occur. Increased [CO2] had little effect on the species-specific relative performance. Thus, a competitive advantage under moderate water stress of P. pinea compared with P. pinaster is expected to continue in the future.

Elucidating the role of genetic drift and natural selection in cork oak differentiation regarding drought tolerance.

Drought is the main selection agent in Mediterranean ecosystems and it has been suggested as an important evolutionary force responsible for population diversification in these types of environments. However, population divergence in quantitative traits can be driven by either natural selection, genetic drift or both. To investigate the roles of these forces on among-population divergence in ecophysiological traits related to drought tolerance (carbon isotope discrimination, specific leaf area, leaf size and leaf nitrogen content), we compared molecular and quantitative genetic differentiation in a common garden experiment including thirteen cork oak (Quercus suber L.) populations across a gradient of rainfall and temperature. Population differentiation for height, specific leaf area, leaf size and nitrogen leaf content measured during a dry year far exceeded the molecular differentiation measured by six nuclear microsatellites. Populations from dry-cool sites showed the lowest nitrogen leaf content and the smallest and thickest leaves contrasting with those from humid-warm sites. These results suggest (i) these traits are subjected to divergence selection and (ii) the genetic differences among populations are partly due to climate adaptation. By contrast, the low among-population divergence found in basal diameter, annual growth and carbon isotopic discrimination (a surrogate for water use efficiency) suggests low or no divergence selection for these traits. Among-population differentiation for neutral markers was not a good predictor for differentiation regarding the quantitative traits studied here, except for leaf size. The correlation observed between the genetic differentiation for leaf size and that for molecular markers was exclusively due to the association between leaf size and the microsatellite QpZAG46, which suggests a possible linkage between QpZAG46 and genes encoding for leaf size.

Mesenchymal stem cells facilitate the derivation of human embryonic stem cells from cryopreserved poor-quality embryos.

BACKGROUND: Human embryonic stem cells (hESCs) have opened up a new area of research in biomedicine. The efficiency of hESC derivation from frozen poor-quality embryos is low and normally achieved by plating embryos on mouse or human foreskin feeders (HFFs). We attempted to optimize embryo survival and hESC derivation. METHODS: Three conditions were tested on frozen poor-quality embryos: (i) embryo treatment with the Rho-associated kinase (ROCK) inhibitor, Y-27632; (ii) use of human mesenchymal stem cells (hMSCs) as feeders; and (iii) laser drilling (LD) for inner cell mass (ICM) isolation. Two hundred and nineteen thawed embryos were randomly treated with (n = 110) or without (n = 109) 10 microM Y-27632. Surviving embryos that developed to blastocyst stage (n = 50) were randomly co-cultured on HFFs (n = 21) or hMSCs (n = 29). ICM isolation was either by whole-blastocyst culture (WBC) or WBC plus LD. RESULTS: Embryo survival was 52% higher with Y-27632. hMSCs appeared to facilitate ICM outgrowth and hESC derivation: three hESC lines were derived on hMSCs (10.3% efficiency) whereas no hESC line was derived on HFFs. ROCK inhibition and ICM isolation method did not affect hESC efficiency. The lines derived on hMSCs (AND-1, -2, -3) were characterized and showed typical hESC morphology, euploidy, surface marker and transcription factor expression and multilineage developmental potential. The hESC lines have been stable for over 38 passages on hMSCs. CONCLUSION: Our data suggest that Y-27632 increases post-thaw embryo survival and that hMSCs may facilitate the efficiency of hESC derivation from frozen poor-quality embryos.

Confocal mosaicing microscopy in skin excisions: a demonstration of rapid surgical pathology.

Precise micro-surgical removal of tumour with minimal damage to the surrounding normal tissue requires a series of excisions, each guided by an examination of frozen histology of the previous. An example is Mohs surgery for the removal of basal cell carcinomas (BCCs) in skin. The preparation of frozen histology is labour-intensive and slow. Confocal microscopy may enable rapid detection of tumours directly in surgical excisions with minimal need for frozen histology. Mosaicing of images enables observation of nuclear and cellular morphology in large areas of surgically excised tissue. In skin, the use of 10-1% acetic acid as a reflectance contrast agent brightens nuclei in 0.5-5 min and enhances nuclear-to-dermis contrast and detectability of BCCs. A tissue fixture was engineered for precisely mounting surgical excisions to enable mosaicing of 36 x 36 images to create a field of view of 12 x 12 mm. This large field of view displays the excision at 2x magnification, similar to that routinely used by Mohs surgeons when examining frozen histology. Comparison of mosaics to histology demonstrates detectability of BCCs. Confocal mosaicing presently requires 9 min, instead of 20-45 min per excision for preparing frozen histology, and thus may provide a means for rapid pathology-at-the-bedside to expedite and guide surgery.

Nephrotic syndrome as paraneoplastic manifestation of a primary pulmonary lymphoepithelioma-like carcinoma.

We present a case of nephrotic syndrome secondary to a membranous glomerulonephritis (MG), in a nonsmoking female with a solitary pulmonary nodule, which did not show growth during 2 years of followup. A biopsy by videothoracoscopy showed a granulomatous non-neoplastic process with giant multinucleated cells. The appearance of a nephrotic syndrome and its interpretation as paraneoplastic revealed the existence of a primary pulmonary lymphoepithelioma-like carcinoma (LELC), a very rare pulmonary tumor. After resection of tumor there was a complete recovery from the nephrotic syndrome. This case highlights how the investigation of paraneoplastic syndromes can help in the early diagnosis of some malignancies.

Leaf physiological versus morphological acclimation to high-light exposure at different stages of foliar development in oak.

We investigated light acclimation in seedlings of the temperate oak Quercus petraea (Matt.) Liebl. and the co-occurring sub-Mediterranean oak Quercus pyrenaica Willd. Seedlings were raised in a greenhouse for 1 year in either 70 (HL) or 5.3% (LL) of ambient irradiance of full sunlight, and, in the following year, subsets of the LL-grown seedlings were transferred to HL either before leaf flushing (LL-HLBF plants) or after full leaf expansion (LL-HLAF plants). Gas exchange, chlorophyll a fluorescence, nitrogen fractions in photosynthetic components and leaf anatomy were examined in leaves of all seedlings 5 months after plants were moved from LL to HL. Differences between species in the acclimation of LL-grown plants to HL were minor. For LL-grown plants in HL, area-based photosynthetic capacity, maximum rate of carboxylation, maximum rate of electron transport and the effective photochemical quantum yield of photosystem II were comparable to those for plants grown solely in HL. A rapid change in nitrogen distribution among photosynthetic components was observed in LL-HLAF plants, which had the highest photosynthetic nitrogen-use efficiency. Increases in mesophyll thickness and dry mass per unit area governed leaf acclimation in LL-HLBF plants, which tended to have less nitrogen in photosynthetic components and a lower assimilation potential per unit of leaf mass or nitrogen than LL-HLAF plants. The data indicate that the phenological state of seedlings modified the acclimatory response of leaf attributes to increased irradiance. Morphological adaptation of leaves of LL-HLBF plants enhanced photosynthetic capacity per unit leaf area, but not per unit leaf dry mass, whereas substantial redistribution of nitrogen among photosynthetic components in leaves of LL-HLAF plants enhanced both mass- and area-based photosynthetic capacity.

Ionic dependence of the velocity of release of ATP from permeabilized cholinergic synaptic vesicles.

Evidence is provided to show that synaptic vesicles have an internal matrix. Suspensions of cholinergic synaptic vesicles isolated from the electric organ of Torpedo marmorata fish were permeabilized in solutions containing low concentrations of Na(+) or Ca(2+). The release of ATP from the vesicular matrix was 10 times more effective with Ca(2+) than with Na(+). We ascertained whether these two cations induced a different velocity of release of ATP from the matrix. The release of ATP was monitored with the chemiluminescent reaction of luciferin-luciferase. The light signal generated was the result of the kinetics of ATP release of the enzymatic reaction. To overcome the kinetics of the enzymatic reaction, the light records were deconvoluted. The actual kinetics of ATP release of vesicles containing Na(+) or Ca(2+) were coincident. To validate this result, comparison was made with ATP release from intact nerve terminals which were already deconvoluted. The results show that the real time course of release is longer than that obtained from synaptic vesicles. This was as expected given that the release of neurotransmitters is due to successive molecular steps of synaptic vesicle exocytosis.

Histological differences in the adrenal glands and cortisol levels of suckling dairy goat kids in enriched and non-enriched environments.

Intensive production systems can negatively affect the welfare of goats. Environmental enrichment techniques can be used to reduce stress. The aim of this study was analyze the effect of environmental enrichment on the histological characteristics of adrenal glands, cortisol levels and weekly weight gain of suckling Alpine French male kids under confinement. A randomised design was used to test the effect of the treatment. The animals (n=20) were randomly assigned to two treatments (enriched and non-enriched) with two replicates each. Enrichment elements included elevated sacks of henequen, trunks, tires and coconuts. The cortisol levels were measured weekly. Male kids were euthanized when their weight reached 10kg, and immediately after euthanasia, samples of the adrenal glands were collected. The adrenal glands were weighed and measured, and histological sections were taken and fixed. Four hundred cells were measured from each animal, with two blind measurements taken from each sample. There were no significant differences between experimental groups (P>0.05) in the weigh, size, the area of cells from the glomerulosa and fasciculata areas of the adrenal glands, the cortisol levels and weekly weight gain. However, there were histological differences between the glomerular and fascicular zones of the left and right adrenal glands of the different groups (P<0.05). These findings suggest that adrenal glands of animals in non-enriched environment, contained histological changes, suggestive of increased activity. We suggest testing adrenal histology as an indicator of stress and recommend the use of environmental enrichment as a means to reduce stress.

Molluscum contagiosum in a patient with no risk factors.

PURPOSE: To report a case of molluscum contagiosum in a patient with no risk factors. METHODS: A 38-year-old patient with a tumor located in the lower eyelid that appeared 5 months previously was seen in the authors' hospital. The lesion had grown slowly and appeared as a crateriform mass with elevated edges. It was surgically excised and the histopathology study confirmed the diagnosis of molluscum contagiosum. Risk factors were absent. RESULTS: The histopathologic study confirms the presence of eosinophilic inclusion bodies in the keratinocytes cytoplasm. CONCLUSIONS: External evaluation of the lower lid lesion did not show the morphologic configuration of a molluscum contagiosum. A virus can be suspected if attention is paid to the margin of the eyelid and the patient's age.

Inhibition of ATP-diphosphohydrolase(apyrase) of Torpedo electric organ by 5'-p-fluorosulfonylbenzoyladenosine.

It has been shown previously that ATP is released into extracellular space from pre- and postsynaptic sources in peripheral synapses. The extracellular metabolism of ATP is likely to affect nucleotide- and nucleoside-mediated regulation of neurotransmission. The enzymes responsible for ATP breakdown are nucleotidases whose active site faces the extracellular space. ATPase and ADPase Ca(2+)-dependent activities were characterized in presynaptic plasma membrane preparation from the electric organ of Torpedo. Features described were in accordance with the presence of an ATP-diphosphohydrolase (apyrase EC 3.6.1.5) in this fraction. Active site studies using the affinity label 5'-fluorosulfonylbenzoyladenosine were performed on Torpedo apyrase. ATPase and ADPase Ca(2+)-dependent activities were inhibited with 5'-fluorosulfonylbenzoyladenosine. From this study it is concluded: (1) 5'-fluorosulfonylbenzoyladenosine binds specifically to the active site of apyrase. (2) Divalent cations accelerate the apyrase inactivation rate. (3) Divalent cations are not required for the binding of either the substrate or the inhibitor to the active site. (4) The apyrase active site is more specific for highly phosphorylated nucleotides. The results presented may be extrapolated to apyrases from other sources. The importance of this enzyme and its regulation are discussed.

Low temperature during winter elicits differential responses among populations of the Mediterranean evergreen cork oak (Quercus suber).

Populations of cork oak (Quercus suber L.) were assessed for seasonal and inter-population variability in, and temperature responses of, the ratio between light-induced variable and maximum fluorescence of chlorophyll, Fv/Fm, considered a surrogate for the maximum photochemical efficiency of photosystem II (PSII). Seedlings from 10 populations throughout the distribution range of Q. suber in the Mediterranean basin were grown in a common garden in central Spain. The Fv/Fm ratio of dark-adapted leaves was measured at dawn every month for 2 years. Air temperature was recorded at a nearby climatic station. During the summer, when maximum air temperatures reached 40 degrees C, there were no significant differences in Fv/Fm among populations, but significant differences were seen during the winter. In colder months, Fv/Fm ranged in all populations between 0.5-0.6 and 0.2-0.3 in 2001 and 2002, respectively. The variance explained by the population effect was greatest during winter months, especially in 2002, reaching a peak value of 10% when minimum air temperature was below -10 degrees C. Populations originating from warmer sites showed the largest decline in Fv/Fm between the end of 2001 and the beginning of 2002. Thus, a negative linear relationship was established between mean annual temperature at the population source and population mean Fv/Fm recorded in the coldest month in 2002 and normalized by the Fv/Fm spring measurement.

[Use of optical coherence tomography to study variations of normal parameters with age]. / Estudio de parámetros de normalidad en relación a la edad con el tomógrafo óptico de coherencia.

PURPOSE: To determine by Optical Coherence Tomography (OCT) the variation of a variety of measurable parameters (macular thickness, retinal parapapillary fiber layer thickness and optic disc morphology) with age. METHOD: We carried out OCT in 40 normal subjects (80 eyes) aged between 20 and 60 years, divided into 4 groups according to the age decades. RESULTS: Statistically significant differences were found in the macular thickness in the comparative study groups but the differences varied according to the sector assessed; the superior outer sector (p=0.00), temporal outer sector (p=0.01), temporal inner sector (p=0.04), nasal inner sector (p=0.03) and inferior inner sector (p=0.00). In the study of retinal parapapillary fiber layer thickness, statistically significant differences were found between groups in the inferior sector only (p=0.04). No statistically significant differences were found between groups in the study of optic disc morphology. CONCLUSIONS: Both the macular thickness and the nerve fiber layer in the inferior sector decrease with age. These differences in thickness are statistically significant between the extremes of age decades.

Selective early induction of synaptosomal-associated protein (molecular weight 25,000) following systemic administration of kainate at convulsant doses in the rat.

SNAP-25 (synaptosomal-associated protein of mol. wt 25,000) is an essential component for neurotransmitter release, and its expression has been related to the plastic responses that follow CNS injury. In the present study, transient induction of SNAP-25 in selected brain areas is shown by immunohistochemistry at short times after a single intraperitoneal injection of kainate at convulsant doses. Six hours after kainate injection, SNAP-25 immunoreactivity was noticed in the perikarya of certain neurons of the perirhinal and lateral cortices, polymorphic layer of the dentate gyrus, CA3 pyramidal area of the hippocampus, and thalamus. In the same areas, a strong increase in SNAP-25 immunorectivity was detected at 12 and 24 h after kainate injection in cell bodies and fibers. Four days after kainate administration, the immunostaining pattern was similar to that observed in control animals. Intraperitoneal injection of cycloheximide blocked the expression of SNAP-25, thus suggesting de novo SNAP-25 protein synthesis following kainate administration. Kainate-dependent induction of SNAP-25a messenger RNA synthesis was observed by in situ hybridization in the mentioned brain areas. Heat shock protein of mol. wt 72,000 (HSP70/72) is a chaperone whose expression is induced early under stress conditions. Its expression and distribution were compared to that of SNAP-25 after the excitotoxic insult. Brain areas overexpressing SNAP-25 and HSP70/72 overlapped. In addition, partial co-localization of both antigens was observed by double-labeling immunohistochemistry. These results provide evidence of an involvement of SNAP-25 in the reactive response that follows kainate administration, and support the role of this protein in the plastic events that take place after kainate excitotoxicity.

Host recombination is dependent on the degree of parasitism.

Parasites and hosts are involved in a continuous coevolutionary process leading to genetic changes in both counterparts. To understand this process, it is necessary to track host responses, one of which could be an increase in sex and recombination, such as is proposed by the Red Queen hypothesis. In this theoretical framework, the inducible recombination hypothesis states that B-chromosomes (genome parasites that prosper in natural populations of many living beings) elicit an increase in host chiasma frequency that is favoured by natural selection because it increases the proportion of recombinant progeny, some of which could be resistant to both B-chromosome effects and B-accumulation in the germline. We have found a clear parallelism between host recombination and the evolutionary status of the B-chromosome polymorphism, which provides explicit evidence for inducible recombination and strong support for the Red Queen hypothesis.

Action of suramin upon ecto-apyrase activity and synaptic depression of Torpedo electric organ.

1. The role of ATP, which is co-released with acetylcholine in synaptic contacts of Torpedo electric organ, was investigated by use of suramin. Suramin [8-(3-benzamido-4-methylbenzamido)naphthalene-1,3,5-trisulphoni c acid], a P2 purinoceptor antagonist, potently inhibited in a non-competitive manner the ecto-apyrase activity associated with plasma membrane isolated from cholinergic nerve terminals of Torpedo electric organ. The Ki was 30 microM and 43 microM for Ca(2+)-ADPase and Ca(2+)-ATPase respectively. 2. In Torpedo electric organ, repetitive stimulation decreased the evoked synaptic current by 51%. However, when fragments of electric organ were incubated with suramin the evoked synaptic current declined by only 14%. Fragments incubated with the selective A1 purinoceptor antagonist, DPCPX, showed 5% synaptic depression. 3. The effects of suramin and DPCPX on synaptic depression were not addictive. Synaptic depression may thus be linked to endogenous adenosine formed by dephosphorylation of released ATP by an ecto-apyrase. The final effector in synaptic depression, adenosine, acts via the A1 purinoceptor. 4. ATP hydrolysis is prevented in the presence of suramin. It slightly increased (20%) the mean amplitude of spontaneous miniature endplate currents. The frequency distribution of the amplitude of spontaneous events was shifted to the right, indicating that ATP, when not degraded, may modulate the activation of nicotinic acetylcholine receptors activated by the quantal secretion of acetycholine.

Malignant lymphoma in a patient with relapsing bronchiolitis obliterans organizing pneumonia.

A case of relapsing bronchiolitis obliterans organizing pneumonia complicated by malignant lymphoma (four years after the diagnosis) is reported in a 58-year-old woman. To our knowledge, such an association has not been described previously in detail in the literature.

Hormonal content of plasma and endometrium of women taking oral contraceptives.

A total of 134 women were studied, 75 of whom were using cyclic steroid contraception (ethinyl estradiol, 0.05 mg plus norgestrel, 0.5 mg) and 59 of whom had normal ovaulatory cycles. By radioimmunoassay techniques simultaneous determinations were made of total estrogens (TE) and progesterone (P) in both plasma and endometrium and of FSH and LH in plasma, covering all days of the pseudomenstrual and true menstrual cycles. As expected, the ovulating women showed a midcycle peak of plasma TE and an increase in plasma P thereafter, while no cyclic variations were observed in the treated group. Correlations of endometrial concentrations of TE and P with plasma FSH and LH levels are discussed. In 13 of the 75 treated women elevations of endometrial P concentrations were present, presumably demonstrating the "escape phenomenon." The possible future value of endometrial hormone determinations is suggested.