High-throughput nanofluidic real-time PCR to discriminate Pneumococcal Conjugate Vaccine (PCV)-associated serogroups 6, 18, and 22 to serotypes using modified oligonucleotides.

Current real-time high-throughput Polymerase Chain Reaction (qPCR) methods do not distinguish serotypes 6A from 6B, 18C from 18A/B and 22F from 22A. We established a nanofluidic real-time PCR (Fluidigm) for serotyping that included Dual-Priming-Oligonucleotides (DPO), a Locked-Nucleic-Acid (LNA) probe and TaqMan assay-sets for high-throughput serotyping. The designed assay-sets target capsular gene wciP in serogroup 6, wciX and wxcM in serogroup 18, and wcwA in serogroup 22. An algorithm combining results from published assay-sets (6A/B/C/D; 6C/D; 18A/B/C; 22A/F) and designed assay-sets for 6A/C; 18B/C/F; 18C/F, 18F and 22F was validated through blind analysis of 1973 archived clinical samples collected from South African children ≤ 5-years-old (2009-2011), previously serotyped with the culture-based Quellung method. All assay-sets were efficient (92-101%), had low variation between replicates (R2 > 0.98), and were able to detect targets at a limit of detection (LOD) of < 100 Colony-Forming-Units (CFU)/mL of sample. There was high concordance (Kappa = 0.73-0.92); sensitivity (85-100%) and specificity (96-100%) for Fluidigm compared with Quellung for serotyping 6A; 6B; 6C; 18C and 22F. Fluidigm distinguishes vaccine-serotypes 6A, 6B, 18C, next-generation PCV-serotype 22F and non-vaccine-serotypes 6C, 6D, 18A, 18B, 18F and 22A. Discriminating single serotypes is important for assessing serotype replacement and the impact of PCVs on vaccine- and non-vaccine serotypes.

Association between myocardial mechanical dispersion and ventricular arrhythmogenicity in chagas cardiomyopathy.

Chagas disease is a major health concern in Latin America. Ventricular arrhythmia (VA) is a hallmark of Chagas cardiomyopathy (CCM), associated with worse prognosis. The present study aimed to verify the association between myocardial mechanical dispersion (MD) and ventricular arrhythmogenicity in CCM. In a cross-sectional study, 77 patients (55.8 ± 10.4 years) with CCM were evaluated. Global longitudinal strain (GLS) and MD were assessed by echocardiography, derived from the speckle tracking technique. Myocardial MD was measured from the onset of the Q/R wave on electrocardiogram to the peak longitudinal strain in 16 segments of the left ventricle. Frequency and complexity of ventricular extrasystoles (VES) were assessed by dynamic electrocardiography. The density and complexity of VES and the presence of non-sustained ventricular tachycardias (NSVTs) increase as MD increases. In logistic regression, MD was the only variable associated with the presence of paired VES and ventricular bigeminy. In addition, both MD and GLS were associated with the presence of NSVT (both, p < 0.01), and MD was independently associated with NSVT (OR 1.04, 95% CI 1.004-1.201, p = 0.031). In CCM, MD is associated with a higher density and complexity of VES, including NSVT.

Impact of Acorn Flour on Gluten-Free Dough Rheology Properties.

Gluten is a fundamental ingredient in breadmaking, since is responsible for the viscoelastic behaviour of the dough. The lack of gluten has a critical effect on gluten-free dough, leading to less cohesive and less elastic doughs, and its replacement represents a challenge for bakery industry. However, dough rheology can be improved combining different ingredients with structural capacity and taking advantage from their interactions. Although acorn flour was used to bake bread even before Romans, nowadays is an underexploited resource. It presents good nutritional characteristics, particularly high fibre content and is naturally gluten free. The aim of this study was to use acorn flour as a gluten-free ingredient to improve dough rheology, following also market trends of sustainability and fibre-rich ingredients. Doughs were prepared with buckwheat and rice flours, potato starch and hydroxypropylmethylcellulose. Two levels of acorn flour (23% and 35% w/w) were tested and compared with control formulation. Micro-doughLAB was used to study mixing and pasting properties. Doughs were characterised using small amplitude oscillatory measurements (SAOS), with a controlled stress rheometer, and regarding Texture Profile Analysis (TPA) by a texturometer. Dietary fibre content and its soluble and insoluble fractions were also evaluated on the developed breads. Acorn flour showed promising technological properties as food ingredient for gluten-free baking (improved firmness, cohesiveness and viscoelasticity of the fermented dough), being an important fibre source.

Measles seroprevalence in pregnant women in Soweto, South Africa: a nested cohort study.

OBJECTIVES: Measles infection causes particularly severe disease in young children who, prior to vaccination, are dependent on maternal antibodies for protection against infection. Measles vaccination was introduced into the South African public immunization programme in 1983 and became widely available in 1992. The aim of this study was to determine measles-specific immunoglobulin G (IgG) levels in pregnant women living with and without HIV born before and after measles vaccine introduction in South Africa. METHODS: Measles IgG antibody level from blood obtained at the time of delivery was compared between women who were born before 1983 (n = 349) and since 1992 (n = 349). Serum samples were tested for measles IgG antibody using an enzyme-linked immunosorbent assay. Geometric mean titres (GMTs) and the proportion with seronegative (<200 mIU/mL) or seropositive titres (≥275 mIU/mL) were compared. RESULTS: Women born since 1992 had lower GMTs [379.7 mIU/mL (95% CI 352.7-448.6)] and fewer were seropositive (55.9%, 195/349) than women born before 1983 [905.8 mIU/mL (95% CI 784.7-1045.5); 76.8%, 268/349], for both comparisons p < 0.001. CONCLUSIONS: We found an association between measles vaccine implementation into the public immunization program in South Africa and peri-partum maternal measles immunity, where women born before vaccine introduction had higher measles IgG antibody titres and were more likely to be seropositive. These findings suggest a need to reconsider the infant measles immunization schedule in settings where women have derived immunity mainly from measles vaccine rather than wild-type virus exposure.

Inflammatory biomarkers in infective endocarditis: machine learning to predict mortality.

Infective endocarditis (IE) is the cardiac disease with the highest rates of mortality. New biomarkers that are able to identify patients at risk for death are required to improve patient management and outcome. This study aims to investigate if cytokines, chemokines and growth factors measured at IE diagnosis can predict mortality. Patients with definite IE, according to the Duke's modified criteria, were included. Using high-performance Luminex assay, 27 different cytokines, chemokines and growth factors were analyzed. Machine learning techniques were used for the prediction of death and subsequently creating a decision tree, in which the cytokines, chemokines and growth factors were analyzed together with C-reactive protein (CRP). Sixty-nine patients were included, 41 (59%) male, median age 54 [interquartile range (IQR) = 41-65 years] and median time between onset of the symptoms and diagnosis was 12 days (IQR = 5-30 days). The in-hospital mortality was 26% (n = 18). Proinflammatory cytokines interkeukin (IL)-15 and C-C motif chemokine ligand (CCL4) were found to predict death, adding value to CRP levels. The decision tree predicted correctly the outcome of 91% of the patients at hospital admission. The high-risk group, defined as CRP ≥ 72 mg/dL, IL-15 ≥ 5·6 fg/ml and CCL4 ≥ 6·35 fg/ml had an 88% in-hospital mortality rate, whereas the patients classified as low-risk had a mortality rate of 8% (P = < 0·001). Cytokines IL-15 and CCL4 were predictors of mortality in IE, adding prognostic value beyond that provided by CRP levels. Assessment of cytokines has potential value for clinical risk stratification and monitoring in IE patients.

Eficiência de óleos essenciais na qualidade sanitária e fisiológica em sementes de feijão-fava (Phaseolus lunatus L. ) / Efficiency of essential oils in the sanitary and physiological quality of lima bean seeds (Phaseolus lunatus L. )

RESUMO A espécie Phaseolus lunatus L., conhecida popularmente como feijão-fava constitui uma das alternativas de renda e alimentação para a população da região Nordeste do Brasil. Um dos problemas enfrentados são as doenças que provocam grandes perdas na produção de sementes. O presente trabalho objetivou avaliar a eficiência dos óleos essenciais de copaíba, cravo-da-índia e manjericão na redução da incidência de fungos associados às sementes de feijão-fava, e sua interferência na qualidade fisiológica. Os tratamentos foram constituídos por óleos essenciais de copaíba, cravo-da-índia e manjericão nas concentrações de 0; 1; 1,5 e 2 mL. L-1 e fungicida (Captan®). Foram utilizadas 200 sementes por tratamento. Para análise da qualidade sanitária das sementes foi adotado o método de incubação em placas de Petri contendo dupla camada de papel-filtro umedecida com ADE, sob temperatura de 20 ±2 ºC, por 7 dias. A qualidade fisiológica das sementes foi determinada com base nos testes de germinação, emergência e vigor das sementes. Para o teste germinação foi empregado método de rolo de papel germitest e na emergência osemeio foi realizado em bandejas plásticas contendo areia lavada esterilizada, em condição de casa de vegetação, e após 9 dias da instalação foi determinado o vigor com base nos resultados de índice de velocidade de germinação e emergência; comprimento da parte aérea, raiz primária e plântula; e teor de massa seca da partes aérea, raízes e plântulas de feijão-fava. O delineamento experimental foi interiamente casualizados, em esquama de fatorial simples (3x4)+1 (óleos essenciais x concentrações + fungicida), com quatro repetições de 50 sementes. Os óleos essenciais de copaíba e manjericão reduziram consideravelmente o percentual de incidência dos fungos associados as sementes de feijão-fava. O óleo essencial de cravo-da-índia na concetração de 2 mL. L-1, reduziu a qualidade fisiológica das sementes de feijão-fava.

ABSTRACT The Phaseolus lunatus L. species, popularly known as lima bean, is one of the alternative sources of income and food for the population of Northeast Brazil. One of the problems is the diseases that cause great losses in seed production. This study evaluated the effectiveness of essential oils of copaiba, clove, and basil in reducing the incidence of fungi associated with lima bean seeds, as well as the effect on their physiological quality. The treatments consisted of essential oils of copaiba, clove, and basil at concentrations of 0; 1; 1.5; and 2 mL. L-1 and fungicide (Captan®). A total of 200 seeds were used per treatment. To analyze the sanitary quality of the seeds, the method used was incubation in petri dishes containing a double layer of filter paper moistened with distilled sterilized water at a temperature of 20 ± 2°C, for seven days. The physiological quality of the seeds was determined by testing their germination, emergence, and vigor. For the germination test, the method used was a roll of Germitest paper. For the emergence, the seeds were sown in plastic trays containing washed sterilized sand in greenhouse conditions. After nine days, the vigor was determined based on the results of germination and emergence speed rates; length of the aerial part, primary root, and seedling; and dry matter content of the aerial part, roots, and seedlings of the lima beans. The experimental design was completely randomized in a simple factorial arrangement (3x4)+1 (essential oils x concentrations + fungicide) with four replications of 50 seeds. The essential oils of copaiba and basil considerably reduced the percentage of incidence of the fungi associated with lima bean seeds. The essential clove oil at 2 mL. L-1 reduced the physiological quality of the lima bean seeds.

Reversible dilated cardiomyopathy associated with amphotericin B therapy.

WHAT IS KNOWN AND OBJECTIVE: Amphotericin B (AmB) is commonly used to treat a broad spectrum of fungal infections and leishmaniasis. Its use is limited by numerous adverse effects. Reversible dilated cardiomyopathy associated with AmB is a rare disorder with only four previously reported cases, and all of them referring to patients who presented with a predisposing factor for heart failure. CASE SUMMARY: A previously healthy 45-year-old man with visceral leishmaniasis treated with AmB developed acute dilated cardiomyopathy. Other causes of heart failure as well-known predisposing factors for this condition were ruled out. As with previously reported cases, the cardiac function of our patient returned to normal shortly after. WHAT IS NEW AND CONCLUSION: We describe the first case of dilated cardiomyopathy associated with the administration of AmB in a patient without any known predisposing factor for developing cardiac dysfunction. Available evidence suggests that AmB may induce cardiotoxicity. Further investigations are needed to clarify this issue.

Temporal association of infant immunisation with pneumococcal conjugate vaccine on the ecology of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonisation in a rural South African community.

BACKGROUND: Immunisation of children with pneumococcal conjugate vaccines (PCV) may affect the bacterial-ecology of the nasopharynx, including colonisation by Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus. The aim of this study was to evaluate the effect of infant PCV-immunisation on the nasopharyngeal ecology of these potentially pathogenic bacteria in a rural African setting. METHODS: Two cross sectional surveys were undertaken from May to October in 2009 (Period-1) which coincided with the introduction of 7-valent PCV (PCV7) and in May-October 2011 (Period-2). Consenting household members, where there was a child <2 years of age in residence, had nasopharyngeal swabs undertaken for culture. RESULTS: From Period-1 to Period-2 in children 0-2 years and 3-12 years, prevalence of overall S. pneumoniae colonisation decreased from 74.9% to 67.0% (p<0.001) and H. influenzae declined among children 3-12 years (55.1-45.3%, p<0.001) but not among those <2 years. The prevalence of S. aureus remained unchanged in all children. Competitive associations were found between S. pneumoniae and S. aureus and between H. influenzae and S. aureus among children. In individuals >12 years, the prevalence of colonisation decreased from 11.2% to 6.8%, 16.7% to 8.8% and 31.2% to 23.7% for S. pneumoniae, H. influenzae and S. aureus, respectively; p<0.001 for all comparions. Synergistic relationships for S. aureus with H. influenzae and S. pneumoniae were observed in both periods among this group.

Foxp3+CD25(high) CD4+ regulatory T cells from indeterminate patients with Chagas disease can suppress the effector cells and cytokines and reveal altered correlations with disease severity.

Immunoregulatory mechanisms are important to control the intense immune activity induced in Chagas disease. We evaluated the phenotypic profile and the mechanisms by which Treg cells function in patients with the indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease. The frequency of Foxp3(+)CD25(high) CD4(+)-T cells is augmented and correlated with the maintenance of a better cardiac function in IND. Treg cells from IND present suppressive activity, although the mechanism is not IL-10 or CTLA-4 dependent and are able to produce augmented levels of IL-17, IL-10 and granzyme B being its frequency correlated with percentage of Annexin V(+) CD4(+)-cells. In contrast, CARD presents higher frequency of IL-6(+), IFN-gamma(+), TNF-alpha(+) and CTLA-4(+) Treg-cells than IND. Thus, our data suggest that Treg cells have an important role in controlling the exacerbated immune response and morbidity in Trypanosoma cruzi infection, probably modulating the cytokine environment and/or killing effector cells.

Influence of low birth weight on microalbuminuria and blood pressure of school children.

UNLABELLED: Low birth weight (LBW) is associated to an increased incidence of hypertension, renal and cardiovascular diseases in adulthood. The objective of this study was to evaluate possible changes in microalbuminuria (MA) and blood pressure (BP) in children with LBW. MATERIAL AND METHODS: The birth weight (BW) of 1,049 children between 8 and 11 years of age, enrolled in schools in the city of Goiânia/Brazil was investigated. Those in the LBW group (BW < or = 2.5 kg) were compared to a similar group with normal birth weight - NBW (BW > or = 3.0 kg). BP and 24-hour urine MA were evaluated. BW and prematurity (gestational age < 37 weeks) were obtained from the information contained in the children's card. RESULTS: There were 34 children with LBW and 34 with NBW. No significant difference was found regarding age, sex, race, weight, height, BMI, and family history of hypertension or diabetes. Children with LBW presented higher systolic BP (p = 0.019) and more albumin in the 24-hour urine then children with NBW (p = 0.024). CONCLUSION: We concluded that school children with LBW present with higher BP and more albumin excretion in the 24-hour urine. These findings can indicate presence of changes in both blood pressure and microalbuminuria in prepubertal children with low birth weight..

Plasmodium falciparum during pregnancy: a puzzling parasite tissue adhesion tropism.

P. falciparum malaria severely affects pregnant women and children. Despite immunity through lifelong exposure to malaria, pregnant women become susceptible to infections causing anaemia, abortions and low birth weight. They experience massive accumulation of infected erythrocytes (IEs) in the placenta. Adhesion of IEs to host endothelial receptors is mediated by members of a large diverse protein family called P. falciparum erythrocyte membrane protein 1 (PfEMP1). Pregnancy malaria is generally associated with the emergence of a distinct subset of parasites expressing a unique PfEMP1 that binds to the host-receptor chondroitin sulfate A (CSA). Resistance to pregnancy malaria is associated with the acquisition of antibodies that block IEs binding to placental CSA. The absence (or rare occurrence) of CSA-binding parasites in malaria patients (children, men and non-pregnant women) suggests that these parasites become virulent only during pregnancy. The molecular mechanisms used by P. falciparum to achieve the timely expression of the Pf-CSA ligand in pregnant women remain puzzling. In this review we will discuss two hypothetical mechanisms by which CSA-binding parasites may arise during pregnancy. The first, a selection process by the placenta of a distinct sub-population of P. falciparum expressing a particular PfEMP1. The second, an induction mechanism that facilitates the expression of a particular PfEMP1 protein by specific host factor(s) present only during pregnancy.

In vivo nuclear magnetic resonance studies of glycolytic kinetics in Lactococcus lactis.

The metabolism of glucose by nongrowing cells of L. lactis strain MG5267 was studied under controlled conditions of pH, temperature, and gas atmosphere (anaerobic and aerobic) using a circulating system coupled to nuclear magnetic resonance (NMR) detection that allowed a noninvasive determination of intracellular pools of intermediate metabolites by 13C-NMR with a time resolution of 30 seconds. In addition, intracellular parameters, such as pH, NTP levels, and concentration of inorganic phosphate in the cytoplasm, could be monitored on-line by 31P-NMR with a time resolution of approx. 3 min. The time course for the concentrations of intracellular fructose 1,6-bisphosphate (FBP), 3-phosphoglycerate (3-PGA), and phosphoenolpyruvate (PEP), together with kinetic measurements of substrate consumption and endproducts formation, were used as a basis for the construction of a mechanistic model for glycolysis. In vivo measurements were complemented with determinations of phosphorylated metabolites in perchloric acid extracts. A top-down model was developed by simplifying the metabolism to the resolution allowed by the experimental data collected by in vivo NMR (grouped in seven metabolic steps). This simplified mechanistic model was adjusted to the metabolite concentrations determined by in vivo NMR. The results obtained led to the rationalization of the dynamics of glucose metabolism as being driven largely by ATP surplus. This excess causes accumulation of FBP due to NAD+ limitation, whose regeneration is dependent on downstream pyruvate reduction. The model was capable of predicting qualitative shifts in the metabolism of glucose when changing from anaerobic to aerobic conditions.

An interlaboratory study to find an alternative to the MPN technique for enumerating Escherichia coli in shellfish.

Nine laboratories in eight countries tested 16 batches of common mussels (Mytilus edulis) over a 32 week period in order to find an alternative to the Most Probable Number (MPN) technique to enumerate E. coli. The alternatives investigated included the 3M Petrifilm system, the Merck Chromocult agar method and a Malthus conductance technique. The Petrifilm was found to be unsuitable and was subsequently dropped from the trial. After 669 analyses, a correlation of 0.83 was observed for log E. coli counts between the MPN and Chromocult methods and there was no significant evidence that either method tended to give higher readings than the other. The MPN was slightly better than the Chromocult method for repeatability but the Chromocult was slightly better for reproducibility. However, the observed differences are probably too small to be of practical importance. On the basis of these data therefore, the two methods appear equally suitable for E. coli enumeration in shellfish. There were poor correlations between these methods and the Malthus technique. A small but significant number of samples tested positive on the Malthus instrument but were recorded negative on the MPN and Chromocult tests. Subsequent analysis positively identified E. coli from these Malthus assays. After statistical analysis, errors were noted in both the MPN and Chromocult methods but it was found that there would be no statistical differences if the Chromocult agar were used as an alternative to the MPN technique.

A novel pathway for the conversion of homocysteine to methionine in eukaryotes.

Activation of amino acid homocysteine was compared with that of methionine in rabbit crude liver extracts and purified multi-enzyme complex of aminoacyl-tRNA synthetases. Activation was studied by measuring the incorporation of radioactive amino acid into unlabelled trichloroacetic-acid insoluble materials in the absence of protein synthesis. Homocysteine synthetase activity was found in the crude extract and in the purified multi-enzyme complex of aminoacyl-tRNA synthetases. On a molar basis, the activation of methionine by the crude extract was five times higher than the activation of homocysteine. There was a partial loss of Hcy-tRNA synthetase activity in the purified multi-enzyme complex. Preliminary reconstitution experiments indicated a requirement for an additional factor for Hcy-tRNA synthetase activity. TLC of the amino acid released from tRNA charged with [14C]homocysteine, revealed radioactivity in homocysteine, methionine and homocysteine thiolactone, indicating a conversion of tRNA-attached homocysteine to methionine. Total tRNA was separated on a benzoylated cellulose column into a fraction enriched in initiator tRNA and a methionine-accepting, but initiator tRNA-deficient, fraction. Homocysteine-accepting activity was present only in the initiator tRNA-enriched fraction. Based on the above data we propose that homocysteine activation in reticulocyte lysates, reported previously, also occurs in liver. Activated homocysteine is attached to initiator tRNA and then converted to methionine by a methylating enzyme. In the absence of methylation, tRNA-attached homocysteine is hydrolysed to produce homocysteine thiolactone.

Hyperprolactinemia in women with paternal deprivation during childhood.

It was reported that most females with prolactinoma, idiopathic hyperprolactinemia, or euprolactinemic galactorrhea were reared either without their father or with an alcoholic, violent father. To gain further insight into this association, a group of sisters of patients with prolactinoma (generally exposed to the same environment as the patients') and a control group were studied. Women with paternal deprivation during childhood differed from the women who had normal childhoods in that they had: 1) higher mean serum prolactin concentration (14.7 versus 9.4 ng/mL; P less than .001); 2) higher incidence of hyperprolactinemia (12 of 50 versus three of 59; P less than .005); and 3) higher incidence of galactorrhea (14 of 50 versus seven of 59: P less than .03). These observations support the contention that paternal deprivation during childhood is associated, in a minority of women, with a predisposition to develop hyperprolactinemia and presumably, prolactinoma later in life. A hypothesis on the possible mechanisms of a casual relationship is presented.

Hyperprolactinaemia and breast disease as evaluated by xeromammography.

This report compares the xeromammographic patterns of 35 patients with hyperprolactinaemia and 70 (age-matched) normoprolactinaemic controls. It is shown that nulliparous patients have less frequent mammary dysplasia and more patterns of involution than the nulliparous controls. The groups of parous patients and parous controls were similar to each other and both had more involutions and less dysplasia than the nulliparous controls. Hyperprolactinaemia in parous women is not associated with any changes in the xeromammographic breast patterns as compared to parous controls. The changes described in hyperprolactinaemic patients can be understood in terms of their low oestrogenic activity.

Effect of treatment with bromocriptine on the size and activity of prolactin producing pituitary tumours.

Eleven consecutive patients with large prolactinomas were treated for 6 months with bromocriptine, (7.5 mg/day). Nine had invasion of the sphenoidal sinus, one a visual field defect and one a secondary trigeminal neuralgia. At the end of the treatment period 8 of the first 9 patients showed radiographical signs of bone remodelling and/or actual reduction of the tumour size. The last 2 patients had complete disappearance of their symptoms. The remissions could be observed as early as 3 weeks after the start of the treatment. Two patients suffered acute, reversible (partial in one case) episodes of loss of vision during the study. During the treatment the prolactin values decreased in all patients to an average of 1.7% of the baseline levels. There was a steep rise in the serum prolactin concentrations after withdrawal of the drug. After one month there was a plateauing at a high level, although lower than basal level. Libido and potency were restored in all 3 males studied. Two of the females experienced orgasm for the first time in their lives after some years of primary frigidity. It is concluded that bromocriptine reproducibly reduces the size of prolactinomas. This effect can be observed shortly after the beginning of the treatment and is at least partially reversible. Episodes of pituitary apoplexy may occur during the treatment of large tumours despite an otherwise favourable response.

Psychosomatic factors in patients with hyperprolactinemia and/or galactorrhea.

A biographic and clinical investigation of 101 patients with hyperprolactinemia and/or galactorrhea is reported. Fifty-one patients were reared without their fathers and 18 with an alcoholic, violent one. These situations were uncommon in the control population, and the differences were statistically significant. There was a high frequency of complaints of obesity, headaches, frigidity, lightheadedness, and fullness of the abdomen, limbs, or face. There was a significant temporal correlation of external events in the natural history with onset or worsening of the symptoms. It is concluded that exposure during childhood to an environment characterized by an absent or alcoholic, violent father conditions some women to develop hyperprolactinemia and/or galactorrhea later in life as a response to specific environmental changes. These conclusions apply similarly to patients with prolactinoma, idiopathic hyperprolactinemia, and euprolactinemic galactorrhea, suggesting a close relationship among the 3 entities.