Novel, broad-specrum antimycotic agents: the role of echinocandins today

The echinocandins show comparable efficacy in the treatment of candidemia and invasive candidiasis. Caspofungin and micafungin appear to be similarly efficacious in salvage therapy in aspergillosis; anidulafungin has excellent in vitro activity against Aspergillus species but as yet there are no sufficient clinical data for anidulafungin in this disease state. Each drug has minor advantages and disadvantages compared to the others of the same classe; however, there are large differences in the approved indications for the different drugs. The formulary selection process should consider the direct and indirect costs of the single agents; the characteristics of the patient population at risk for invasive mycosis, such as frequent use of interacting drugs and the burden of monitoring plasma drug levels of drugs; and the implications of using products for indications which have not been still approved (off-label indications)

The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern?

After examining the most recent scientific evidences, which assessed the role of some malaria plasmodia that have monkeys as natural reservoirs, the authors focus their attention on Plasmodium knowlesi. The infective foci attributable to this last Plasmodium species have been identified during the last decade in Malaysia, in particular in the states of Sarawak and Sabah (Malaysian Borneo), and in the Pahang region (peninsular Malaysia). The significant relevance of molecular biology assays (polymerase chain reaction, or PCR, performed with specific primers for P. knowlesi), is underlined, since the traditional microscopic examination does not offer distinguishing features, especially when the differential diagnosis with Plasmodium malariae is of concern. Furthermore, Plasmodium knowlesi disease may be responsible of fatal cases, since its clinical presentation and course is more severe compared with those caused by P. malariae, paralleling a more elevated parasitemia. The most effective mosquito vector is represented by Anopheles latens; this mosquito is a parasite of both humans and monkeys. Among primates, the natural hosts are Macaca fascicularis, M. nemestina, M. inus, and Saimiri scirea. When remarking the possible severe evolution of P. knowlesi malaria, we underline the importance of an early recognition and a timely management, especially in patients who have their first onset in Western Hospitals, after journeys in Southeast Asian countries, and eventually participated in trekking excursions in the tropical forest. When malaria-like signs and symptoms are present, a timely diagnosis and treatment become crucial. In the light of its emerging epidemiological features, P. knowlesi may be added to the reknown human malaria parasites, whith includes P. vivax, P. ovale, P. malariae, and P. falciparum, as the fifth potential ethiologic agent of human malaria. Over the next few years, it will be mandatory to support an adequate surveillance and epidemiological network. In parallel with epidemiological and health care policy studies, also an accurate appraisal of the clinical features of P. knowlesi-affected patients will be strongly needed, since some preliminary experiences seem to show an increased disease severity, associated with increased parasitemia, in parallel with the progressive increase of inter-human infectious passages of this emerging Plasmodium.

Severe form of psoriasis occurring after peginterferon plus ribavirin treatment, and frequent resort to filgrastim rescue, in a woman treated for a chronic HCV infection

Associated treatment with pegylated interferon plus specific antiviral compounds significantly improved the prognosis of chronic hepatitis C and B, although antiviral drugs (especially interferon and its derivatives) tend to be myelotoxic and also some rescue treatments, like human recombinant granulocyte colony-stimulating factors (which are extensively administered in order to correct neutropenia induced by antiviral therapy), may alsobe involved in prompting or exacerbating cutaneous psoriasis and its systemic complications. A representative case report of a woman with a chronic, progressive, hepatitis C, who underwent long-term treatment with combined pegylated interferon plus ribavirin, and resorted to multiple cycles of filgrastim to recover a severe, recurring granuloytopenia caused by antiviral therapy itself, and to maintain an effective dosage of anti-HCV antivirals, developed an extensive and severe cutaneous psoriasis, which improved only after specific cyclosporin treatment. From a pathogenetic point of view, in our case it remains extremely difficult to distinguish the role of pegylated interferon from that of the accompanying ribavirin, from that of the frequently administered granulocyte growth factor (filgrastim), since all mentioned drugs were administered concurrently during many months, and according to the existing literature evidences, all of them have a potential to induce psoriasis as a potential untoward effect in subjects suffering from chronic hepatitis. Cyclosporin treatment obtained a stable remission of this last severe cutaneous complication, but the efforts to contain the progression of the underlying evolutive hepatitis C were blunted by the difficult-to-treat genotype 1 HCV infection, and the frequent need to lower drug dosages and/or to interrupt antiviral therapy, because of myelotoxic and later cutaneous complications prompted by anti-HCV therapy itself

Occupational exposure and prevention guidelines in dental and stomatological settings - a literature review

A review of the main infectious pathogens potentially transmissible to health care professionals during Dentistry and Odonto-Stomatological procedures is carried out, with particular attention focused on parenteral exposure in the dental, stomatological, and surgical environment. Epidemiological issues and specific risk factors are treated systematically based on available literature sources, together with all available, recommended chemo-prophylactic and immune-prophylactic strategies, as updated by the state of the art in this field.

Malaria infection and the anthropological evolution / Infecção por Malária e evolução antropológica

During the evolution of the genus Homo, with regard to species habilis, erectus and sapiens, malaria infection played a key biological role, influencing the anthropological development too. Plasmodia causing malaria developed two kinds of evolution, according to a biological and philogenetical point of view. In particular, Plasmodium vivax, Plasmodium malariae, and Plasmodium ovale, would have either coevolved with human mankind (coevolution), or reached human species during the most ancient phases of genus Homo evolution. On the other hand, Plasmodium falciparum has been transmitted to humans by monkeys in a more recent period, probably between the end of Mesolithic and the beginning of Neolithic age. The authors show both direct and indirect biomolecular evidences of malaria infection, detected in buried subjects, dating to the Ancient World, and brought to light in the course of archeological excavations in some relevant Mediterranean sites. In this literature review the Authors organize present scientific evidences: these confirm the malarial role in affecting the evolution of populations in Mediterranean countries. The people living in several different regions on the Mediterranean Sea sides, the cradle of western civilization, have been progressively influenced by malaria, in the course of the spread of this endemic disease during the last millennia. In addition, populations affected by endemic malaria developed cultural, dietary and behaviour adaptations, contributing to decrease the risk of disease. These habits were not probably fully conscious. Nevertheless it may be thought that both these customs and biological modifications, caused by malarial plasmodia, favoured the emergence of groups of people with a greater resistance against malaria. All these considered factors decreased demographical impact, influencing in a favourable way the general development and growth of civilization.

Durante a evolução do gênero Homo a infecção por malária exerceu papel biológico chave, influenciando até o desenvolvimento antropológico. Os Plasmódios causadores da malária desenvolveram dois tipos de evolução, segundo um ponto de vista biológico, e filogenético. Em particular, os Plasmódios vivax, malariae, e ovale poderiam ter coevoluído com a espécie humana ou ter atingido esta durante as fases mais antigas da evolução do gênero HOMO. Por outro lado, o Plasmódio falciparum teria sido transmitido aos humanos por macacos num período mais recente, provavelmente entre o fim da Idade Mesolítica e o início da Neolítica. Os Autores mostram evidências biomoleculares, tanto diretas como indiretas, de infecção por malária, observada em indivíduos enterrados, reportando ao Mundo Antigo, e trazidas à luz no decorrer de escavações arqueológicas em alguns sítios relevantes Mediterrâneos. Nesta revisão da literatura, os autores organizam evidências modernas. Confirmam o papel da malária ao afetar a evolução das populações no Mediterrâneo. As pessoas que moram nas várias regiões do Mediterrâneo foram progressivamente influenciadas pela malária, ao longo do avanço desta doença. Além disso, as populações afetadas desenvolveram adaptações culturais, alimentares, e de comportamento, contribuindo para uma redução no risco da doença. Entretanto, pode ser que ambas modificações (as biológicas e as dos hábitos) usadas pelos Plasmódios da malária, favoreceram a emergência de grupos de pessoas com maior resistência contra a malária. Todos estes fatores considerados reduziram o impacto demográfico, influenciando de uma maneira favorável o desenvolvimento em geral, e o crescimento da civilização.

Novel pharmaceutical molecules against emerging resistant gram-positive cocci

INTRODUCTION: methicillin- and also vancomycin (glycopeptide)-resistant Gram-positive organisms have emerged as an increasingly problematic cause of hospital-acquired infections, also spreading into the community. Vancomycin (glycopeptide) resistance has emerged primarily among Enterococci, but the MIC values of vancomycin for the entire Staphylococcus species are also increasing worldwide. MATERIAL AND METHODS: the aim of our review is to evaluate the efficacy and tolerability of newer antibiotics with activity against methicillin-resistant and glycopeptide-resistant Gram-positive cocci, on the ground of our experience at a tertiary care metropolitan Hospital, and the most recent literature evidences in this field. RESULTS: Quinupristin-dalfopristin, linezolid, daptomycin, and tigecycline show an excellent in vitro activity, comparable to the activity of vancomycin and teicoplanin for methicillin-resistant staphylococci, and superior to the one that vancomycin for vancomycin-resistant isolates. Dalbavancin, televancin, and oritavancin are new lipoglycopeptide agents with excellent activity against Gram-positive cocci, and have superior pharmacodynamics properties compared to vancomycin. We review the bacterial spectrum, clinical indications and practical use, pharmacologic properties, and expected adverse events and contraindications associated with each of these novel antimicrobial agents, compared with the present standard of care. DISCUSSION: linezolid activity is substantially comparable to that of vancomycin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, although its penetration into the respiratory tract is exceptionally elevated. Tigecycline has activity against both Enterococus species and MRSA; it is also active against a broad spectrum of Enterobacteriaceae and anaerobes, which allows for use intraabdominal, diabetic foot and surgical infections. Daptomycin has a rapid bactericidal activity for ...

Increasing pathomorphism of pulmonary tuberculosis: an observational study of slow clinical, microbiological and imaging response of lung tuberculosis to specific treatment. Which role for linezolid?

During recent years, a progressive emerging of tuberculosis occurred, related to the overall increased age of general population, primary and secondary (iatrogenic) immunodeficiencies, the availability of invasive procedures, surgical interventions and intensive care supports, bone marrow and solid organ transplantation, and especially the recent immigration flows of people often coming from areas endemic for tuberculosis, and living with evident social-economical disadvantages, and with a reduced access to health care facilities. Since January 2006, at our reference centre we followed 81 consecutive cases of pulmonary tuberculosis, with 65 of them which remained evaluable for the absence of extrapulmonary complications, and a continuative and effective clinical and therapeutic follow-up. The majority of episodes of evaluable pulmonary tuberculosis (49 cases out of 65: 75,4 percent) occurred in patients who immigrated from developing countries. In two patients multiresistant (MDR) Mycobacterium tuberculosis strains were found, while two more subjects (both immigrated from Eastern Europe) suffered from a disease due to extremely resistant (XDR) M. tuberculosis strains. Although enforcing all possible measures to increase patients' adherence to treatment (empowerment, delivery of oral drugs under direct control, use of i.v. formulation whenever possible), over 72 percent of evaluable patients had a very slow clinical, microbiological, and imaging ameliorement (1-6 months), with persistance of sputum and/or bronchoalveolar lavage (BAL) fluid positive for M.tuberculosis microscopy and/or culture for over 1-4 months (mean 9.2±3.2 weeks), during an apparently adequate treatment. When excluding patients suffering from XDR and MDR tuberculosis, in four subjects we observed that off-label linezolid adjunct together with at least three drugs with residual activity against tuberculosis, led to a significantly more rapid clinical-radiological improvement...

Tubercular disease caused by bacillus of Calmette-Guerin administered as a local adjuvant treatment of relapsing bladder carcinoma: Pathogenetic, diagnostic and therapeutic issues, and literature review

Two exemplary case reports of respiratory granulomatous infection caused by bacillus of Calmette-Guérin (BCG) in patients who were repeatedly treated with local, intravesical adjuvant BCG therapy for a relapsing transitional bladder carcinoma, are outlined and discussed, on the ground of the cumbersome diagnostic and differential diagnostic process (especially when a prior tuberculosis and a concurrent chronic obstructive pulmonary disease are of concern), and an updated literature revision. Only four cases of respiratory BCG-itis (pulmonary tuberculosis-like forms), have been reported until now to the best of our knowledge (two of them following bladder instillation of BCG). One episode of ours represents the first described case with a dual, concomitant granulomatous localization of BCG-itis, also involving the genitourinary tract

Severe brain co-infection by Cryptococcus neoformans and Mycobacterium tuberculosis in a patient with non-bacillary lung tuberculosis / Co-infección cerebral grave por Cryptococcus neoformans y Mycobacterium tuberculosis en un paciente con tuberculosis pulmonar no bacilífera

An exceptionally rare case of concurrent central nervous system infection by Cryptococcus neoformans and Mycobacterium tuberculosis in a 25-year-old otherwise healthy Chinese student who very recently joined Italian post-doctoral courses is described, together with diagnostic and therapeutic difficulties encountered in a six-month-long hospitalization period, when only transient and/or negligible immune system impairments were detected. A non-bacillary pulmonary tuberculosis probably preceded both brain complications. This episode of very infrequent concurrent infections, should enforce the need of maintaining an elevated clinical suspicion for opportunistic infections and tuberculosis, even in absence of an obvious immunodeficiency, and related epidemiological clues.

Se describe un caso excepcionalmente raro de una co-infección del sistema nervioso central por Cryptococcus neoformans y Mycobacterium tuberculosis en una estudiante china de 25 años de edad, sin ningún otro tipo de enfermedad, que recientemente participó en un curso post-doctoral en Italia, junto con las dificultades diagnósticas y terapéuticas encontradas durante un período de seis meses de hospitalización, durante el cual se detectaron alteraciones transitorias y/o insignificantes del sistema inmune. Probablemente, ambas complicaciones cerebrales fueron precedidas por una tuberculosis pulmonar no bacilífera. Este episodio de infecciones simultáneas muy poco frecuentes debe reforzar la necesidad de mantener una elevada sospecha clínica de tuberculosis e infecciones oportunistas, aún en ausencia de una evidente inmunodeficiencia e indicios epidemiológicos relacionados.

A prospective microbial surveillance project at a major Italian Hospital: Epidemiological perspectives, and in vitro susceptibility rates

Microbiological surveillance program is currently performed at our tertiary-care teaching Hospital. The temporal trend of microbial isolates from patients admitted during the last four calendar years (2004 to 2007), has been analyzed according to the main bacterial and fungal cultured organisms. The same pathogens isolated more than once from the same patient within one month, have been considered only once. On the whole, the main pathogen group remained that of Enterobacteriaceae (6,608 isolations out of 19,666: 33.6%, with Escherichia coli retrieved in 60-75% of cases), with no significant difference over time. Staphylococci (4,150 isolates), and enterococci (3,276 isolates), were the two largest groups after Enterobacteriaceae, but staphylococci significantly declined during the examined four-year period (p<.001), mainly due to a progressively reduced isolation of coagulase-negative staphylococci. On the other hand, a slight increase of enterococci occurred (p<.05). Based on the frequency of isolation, Gram-negative oxydasepositive organisms accounted for 2,109 episodes, followed by other aerobe Gram-positive organisms other than Staphylococci-Enterococci (613 isolates), and anaerobes (583 isolates): no significant temporal variations occurred over time for these last microbial groups. With regard to Gram-negative oxydase-negative microorganisms (567 isolates), non-betahemolytic streptococci (464 cases), and beta-hemolytic streptococci (260 isolates), a significant trend towards a reduction of frequency occurred from the year 2004 to 2007 (p<.05 to p<.001)

The recent evolution of therapeutic weapons against resistant Gram-positive microorganisms

Multiresistant Gram-positive cocci, including Staphylococcus aureus, the group of coagulase-negative staphylococci, Enterococcus faecalis and Enterococcus faecium, as well as Streptococcus pneumoniae and other streptococci, represent emerging pathogens. This issue is especially concerning in the setting of immunocompromised, hospitalized patients, in particular when surgery, invasive procedures, or prosthetic implants are carried out, patients are admitted in intensive care units, or underlying chronic disorders and immunodeficiency are of concern, and broad-spectrum antibiotics are widely used in the environment; moreover, a community spread of resistant Gram-positive cocci has been recognized during recent years. The spectrum of antimicrobials available for an effective management of these relevant infections is significantly threatened by the emerging of methicillin-resistant and more recently glycopeptide-resistant strains. The streptogramine association represented by quinupristin/dalfopristin, the oxazolidinone derivative linezolid, and the recently licensed daptomycin and tigecycline, together with a number of glycopeptides, fluoroquinolones, cephalosporins, and other experimental compounds, represent an effective response. It is due to the innovative mechanisms of action of these compounds, their maintained or enhanced activity against multiresistant pathogens, their effective pharmacokinetic/pharmacodynamic properties, their frequent possibility of synergistic activity with other compounds effective against Gram-positive pathogens, and a diffuse potential for a safe and easy administration, also to compromised patients.

Recurring Candida albicans esophagitis in a HIV-infected patient undergoing long-Term antiretroviral therapy, and with absent-negligible immunodeficiency

A patient with HIV infection developed the first episode of AIDS-defining opportunism (severe Candida albicans esophagitis) with an underlying CD4+ lymphocyte count of 1,025 cells/µL. After treatment with a highly active antiretroviral therapy (HAART), taken with insufficient compliance and leaving a residual viral load, our patient suffered from two relapses of esophageal candidiasis, which occurred three months and seven years later, when his CD4+ lymphocyte count was 930 and 439 cells/µL, respectively, and a viral load slightly above 10(4) copies/mL was still present. Also in the HAART era, Candida esophagitis remains one of the most common AIDS-defining diseases, but a presentation with a concurrent CD4+ count above 1,000 cells/µL remains a rare exception, as well as the two isolated, subsequent relapses, occurred with a CD4+ count ranging from 439 to 930 cells/µL, and a residual HIV viremia due to insufficient adherence to the prescribed HAART regimens. Our case report represents the opportunity to revisit the epidemiology and, especially, the pathogenesis of this opportunistic fungal complication in HIV-infected patients and in other subjects at risk, on the ground of an extensive literature review, and to explore possible alternative supporting factors other than the crude absolute CD4+ lymphocyte count, with emphasis on the possible role of a persisting HIV viremia, and other potential contributing factors. Clinicians engaged with immunocompromised patients and subjects with HIV disease, should be aware that a Candida esophagitis may occur and relapse also when the cell-mediated immunity, as measured by a simple CD4+ cell count, do not show relevant abnormalities.

Causes of hospitalization among extra-European Union children in a large hospital of Northern Italy, in a five-year observation period

The hospitalizations of 1,239 patients aged 14 years or less and immigrated from extra-European Union countries in Italy were assessed in the 6-year period, from 1999 to 2004. The main demographic and clinical features were analyzed according to several variables, also distiguishing patients aged less than one year, from those aged 1-14 years. The introduction of a deed of indemnity law in 2001 profoundly changed the pattern of admissions and health care needs and exploitation during subsequent years, leading to a massive regularization of clandestine immigrants.

Bartonellosis: suggestive case reports in adult and pediatric patients and therapeutic issues

Cat-scratch disease warrants extensive investigation, from an epidemiological, a diagnostic, but especially a therapeutic point of view. Two suggestive episodes of Bartonella henselae-caused cat-scratch disease are reported, and discussed in the light of the most recent literature evidence. The first case occurred in a 60-year-old man, thus suggesting that it is important to maintain an elevated level of suspicion for this disease in adults as well. Both episodes were characterized by a very prolonged and complicated disease course (with the involvement of three lymph node sets in the first case), a need for lymph-node drainage, and apparently negligible activity of many antimicrobial courses, with a very slow local cure. While specific culture and molecular biology techniques proved negative (probably due to late availability of appropriate clinical specimens), indirect immunofluorescence antibody assay was positive since the first weeks of disease, and elevated levels were also fond many months after disease onset. When clinicians face patients with prominent swelling of lymph nodes draining from the upper limbs, cat-scratch disease may be suspected on the grounds of epidemiological and clinical features, with a limited systemic involvement contrasting with a prominent local disease. The significance of specific antibody temporal kinetics in the subacute disease course is still unknown. Although biomolecular assays are now available, the time elapsed from disease onset to clinical diagnosis usually hampers diagnosis, while the roles of surgical debridement and of the unpredictable activity of antimicrobial chemotherapy warrant careful investigation.

Combined pegylated interferon and ribavirin for the management of chronic hepatitis C in a prison setting

The elevated frequency of chronic hepatitis C virus (HCV) infection found among prison inmates, and the availability of improved pharmacological cure for this potentially life-threatening disorder, make investigations conducted in this somewhat neglected area very relevant, since only a few, open-label experiences have been reported till now. In the metropolitan prison of Bologna (Italy), HCV seroprevalence was found to be over 31 percent in 2003, so that a pilot feasibility study based on treatment with pegylated interferon plus ribavirin was initiated, after careful counseling carried out by a joint commission of health care personnel of the correctional facility and infectious diseases consultants. Thirty-nine patients were enrolled, and despite expected dropouts due to difficulty in maintaining the same level of counseling pressure over time, and the particularly unfavorable climatic conditions during Summer 2003, a sustained virological response was obtained for 8 out of the 21 patients who remained evaluable after the first three month follow-up, although we need to take into account that a high percentage of subjects (67 percent) were selected for therapy due to their favorable HCV genotypes (types 2 and 3). Our preliminary experience shows that an intrinsically complicated therapy, such as the administration of pegylated interferon plus ribavirin, can attain a relatively high success rate, even in a very unfavorable and uncomfortable context, such as a prison, where only enforced counseling, active participation of institutional health care operators, and patient's willingness to maintain an elevated level of co-operation and adherence, can overcome most structural and relational difficulties.

Admission of foreign citizens to the general teaching hospital of bologna, northeastern Italy: an epidemiological and clinical survey

BACKGROUND: The emergency regarding recent immigration waves into Italy makes continued healthcare monitoring of these populations necessary. METHODS: Through a survey of hospital admissions carried out during the last five years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission of these subjects were evaluated, together with their correlates. Subsequently, we focused on admissions due to infectious diseases. All available data regarding foreign citizens admitted as inpatients or in Day-Hospital settings of our teaching hospital from January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) features, and single discharge diagnoses, were also evaluated, and a further assessment of infectious diseases was subsequently made. RESULTS: Within a comprehensive pool of 339,051 hospitalized patients, foreign citizen discharges numbered 7,312 (2.15 percent), including 2,542 males (34.8 percent) and 4,769 females (65.2 percent). Males had a mean age of 36.8±14.7 years, while females were aged 30.8±12.2 years. In the assessment of the areas of origin, 34.6 percent of hospitalizations were attributed to patients coming from Eastern Europe, 15.3 percent from Northern Africa, 7.3 percent (comprehensively) from Western Europe and United States, 6.9 percent from the Indian subcontinent, 5.9 percent from sub-Saharan Africa, 5.7 percent from Latin America, 4.1 percent from China, 2.5 percent from the Philippines, and 1.1 percent from the Middle East. Among women, most hospitalizations (58.8 percent) were due to obstetrical-gynecological procedures or diseases, including assistance with delivery (27.1 percent), and pregnancy complications (18.7 percent), followed by psycho-social disturbances (5.9 percent), malignancies (5.1 percent), gastrointestinal diseases (4.7 percent), and voluntary pregnancy interruption (4.4 percent). Among men, the most frequent causes of admissions were related to trauma (15.9 percent), followed by gastroenteric disorders (12 percent), heart-vascular diseases (8.9 percent), psycho-social disorders (8.4 percent), respiratory (7.1 percent), kidney (6.1 percent), liver (5.2 percent), and metabolic (4.9 percent) diseases, and alcohol or substance abuse (4.2 percent). Infectious diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, representing 12.1 percent of the 7,312 DRGs attributed to foreign patients.

Factores psicogenéticos en el síndrome de galactorrea-amenorrea / Psychogenetic factors in the galactorrhea-amenorrhea syndrome

Este trabajo intenta corroborar las etapas etiopatogénicas del adenoma prolactínico a partir de una personalidad premórbida que, ante factores desencadenantes psicogenéticos desajustarian el sistema límbico-hipotálamo-hipofisario con sobreestimulación crónica del lactotropo. Se presenta una paciente de 45 años (1983) con un síndrome de galactorrea-amenorrea (GA) de 8 años de data, sin patología orgánica demostrable tratada con psicoterapia y en ciertos períodos agregando BEC, con controle seriados clínicos, bioquimicos, por imágenes y psicológicas. Examen físico: galactorrea bilateral a la expresión (+++). La Rx selar simple, la tomografía lineal y la TAC fueron normales. El eje PRL mostró basales normales con hiperrespuesta a la THR (15/210/85 ng/ml), MCP (26/250/210 ng/ml) e insulina (14/28/105 ng/ml). El eje gonadotrófico reveló LH y FSH bajas, hiperrespondientes a la LH-RH (FSH: 2/26/14; LH: 5/16/23 mU/ml). Los otros ejes fueron normales. El informe psicológico senaló personalidad patológica con neurosis de angustia, rasgos fóbico-histéricos y fuertes defensas obsesivas. Se administró BEC 7,5 mg/día y al año comenzó simultáneamente psicoterapia. Reaparecieron las menstruaciones y desapareció la galactorrea. Al elaborar la presión relacionada con el abandono que padeció toda su vida, el control clínico y de laboratorio se mostraron normales, salvo la respuesta de la PRL al TRH bajo BEC. Suspendida la BEC reaparece la galactorrea con una metrorragia dishormonal que obligó al legrado uterino, coincidendo con la tumultuosa compresión de los motivos de su soledad. Se administró neuvamente BEC 2,5 mg/día por 9 meses. En este período se elabora su necesaria jubilación por invalidez, desapareciendo la galactorrea y las metrorragias...