Peripheral Th17 cells expressing ß7 intestinal homing receptor in recent and chronic HIV infections.

The objective of this study was to conduct an analysis of peripheral blood Th17 cells with the ability to home to gut mucosa (CD4+ Th17+ ß7+ ) during recent or chronic human immunodeficiency virus (HIV) infections. The relationship between HIV load and systemic inflammation markers was studied. Twenty-five patients with recent (n = 10) or chronic (n = 15) untreated HIV infections; 30 treated HIV-infected patients with undetectable HIV load at the time of inclusion and 30 healthy controls were included. Bacterial translocation markers (16S rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+ Th17+ expressing the IL-23 receptor (IL-23R) or ß7] were analysed at baseline and after 6 and 12 months of anti-retroviral therapy (ART). 16S rDNA was detected in all patients. Significantly increased serum levels of sCD14 and IL-6 and a decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+ IL-23R+ and CD4+ Th17+ ß7+ cells were observed in healthy controls and patients at baseline. After 12 months of therapy, patients with a recent HIV infection showed significant increases of CD4+ IL-23R+ and CD4+ Th17+ ß7+ cell percentages and a decrease in IL-6 levels, although 16S rDNA continued to be detectable in all patients. No significant differences were observed in Th17 subpopulations in patients with chronic HIV infection after therapy. Early initiation of ART helps to increase the number of Th17 cells with the ability to home to the intestinal mucosa and to partially restore gut mucosal homeostasis. These results provide a rationale for initiating ART during the acute phase of HIV infection.

[The pineal gland as physical tool of the soul faculties: a persistent historical connection]. / La glándula pineal como instrumento físico de las facultades del alma: una conexión histórica persistente.

INTRODUCTION: The anatomic seat of the human soul has been a controversial matter of discussion in the philosophical, theological and scientific fields throughout history. One of more known hypotheses on this subject was proposed by Descartes, for whom the soul would host in the pineal gland, a brain body with a special location that would adequately address the functionalism of the human body. DEVELOPMENT: In this work, we discuss the historical influences which made possible the Cartesian model of the relationship between spirit (res cogitans) and body-machine (res extensa) and the technical bases of his dualism doctrine. In philosophical terms, Descartes supported Augustine approaches and in physiological and anatomical terms adopted some theories of the classical Antiquity, essentially the proposals of Alexandrian pneumatic school (Herophilos, Erasistratus) in relation to the animal spirits. Descartes might also have known the hypotheses of some contemporary anatomists (Diemerbroeck) which established the location of sensorium commune in the pineal gland. CONCLUSIONS: Although Cartesian theories had strong criticism even in his time, some aspects of these postulates remained up to mid 19th century.

Cartesian theories on the passions, the pineal gland and the pathogenesis of affective disorders: an early forerunner.

The relationship between physical and functional alterations in the pineal gland, the 'passions' (emotions or feelings) and psychopathology has been a constant throughout the history of medicine. One of the most influential authors on this subject was René Descartes, who discussed it in his work The Treatise on the Passions of the Soul (1649). Descartes believed that 'passions' were sensitive movements that the soul, located in the pineal gland, experienced due to its union with the body, by circulating animal spirits. Descartes described sadness as one of the six primitive passions of the soul, which leads to melancholy if not remedied. Cartesian theories had a great deal of influence on the way that mental pathologies were considered throughout the entire 17th century and during much of the 18th century, but the link between the pineal gland and psychiatric disorders it was definitively highlighted in the 20th century, with the discovery of melatonin in 1958. The recent development of a new pharmacological agent acting through melatonergic receptors (agomelatine) has confirmed the close link between the pineal gland and affective disorders.

Zonisamide versus diazepam in the treatment of alcohol withdrawal syndrome.

INTRODUCTION: Anticonvulsant drugs have been used in the treatment of alcohol detoxification. The purpose of the present study was to evaluate the efficacy and safety of zonisamide in a sample of patients presenting alcohol withdrawal syndrome. METHOD: In this 3-week, randomized, flexible-dose trial, 40 inpatients with alcohol dependence disorder received zonisamide or diazepam for detoxification. Zonisamide was started at a dose of 400-600 mg/day (week 1), tapering to a minimum dose of 100-300 mg/day (week 3). Diazepam was administered using a similar regimen (from 130-50 mg/day tapering to 5-15 mg/day). Subjects were treated initially (weeks 1 and 2) in an inpatient unit and for the final week in an outpatient facility. During the inpatient period, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) was used to assess the efficacy of each substance. During the outpatient period the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and a craving scale were used. RESULTS: All subjects completed the study. During the inpatient period both drugs reduced alcohol withdrawal symptoms, but the decrease was more marked in the zonisamide group. At the end of the study (week 3) participants treated with zonisamide showed lower CIWA-Ar scores than subjects receiving diazepam. Also, individuals in the zonisamide group had less craving for alcohol, less anxiety, and less daytime sedation compared with participants treated with diazepam. CONCLUSION: Zonisamide can be a valuable alternative to benzodiazepines in the prevention of alcohol withdrawal syndrome.

Hepatocyte growth factor and chronic hepatitis C.

OBJECTIVE: The hepatocyte growth factor (HGF) is a pleiotropic cytokine produced by hepatic stellate cells and implicated in liver regeneration and fibrosis. Serum levels of HGF vary in liver diseases, reflecting hepatic damage and hepatocellular dysfunction. In this study, serum levels of HGF and the relationship between HGF and biochemical, histological and virological data, have been analysed in patients suffering from chronic hepatitis C (CHC). PATIENTS AND METHODS: Serum HGF concentration was measured by ELISA in sandwich in 45 patients with CHC. Correlation between HGF levels and histological (necroinflammatory activity and fibrosis score) and biochemical (transaminases, prothrombin activity, albumin, bilirubin), or virological (hepatitis C virus load) parameters was analyzed. Serum HGF concentration was also studied in a subgroup of the original sample treated with interferon and ribavirin. RESULTS: Sserum HGF concentrations of patients with CHC were significantly higher than those detected in healthy controls. Patients with significant fibrosis (F > or = 2) had a significantly older age, lower count of platelets and higher values of AST, GGT and HGF, than those patients with a fibrosis score F < 2. HGF concentration was identified by multivariate analysis as the only independent factor associated with significant fibrosis. Moreover, area under receiver operating curve, using HCG levels, showed similar values to those of previously validated non-invasive indexes of fibrosis. However, levels of HGF did not show a significant decrease in patients with a sustained response to anti-virus C therapy. CONCLUSION: Serum HGF concentration correlates with fibrosis score in patients with CHC, but is insensitive to monitor changes induced by anti-virus C therapy.

The pharmaceutical industry and the German National Socialist Regime: I.G. Farben and pharmacological research.

Before the National Socialist party came to power, the German pharmaceutical industry constituted an international reference as far as the development of new medicines was concerned, having been responsible for synthetic analgesics (phenacetin, phenazones, acetylsalicylic acid), arsphenamine, barbiturates and sulfonamides. The year 1925 saw the founding of I.G. Farben (Interessen-Gemeinschaft Farbenindustrie AG), a conglomerate of companies that would monopolize the country's chemical production and come to own all its major pharmaceutical industries. During the World War II, I.G. Farben participated in numerous operations associated with the criminal activities of the Nazi executive, including the use of slave labour in plants built close to concentration camps, such as that at Auschwitz. With regard to medical and pharmacological research projects, I.G. Farben became involved in experimental programmes using patients from the Nazi regime's euthanasia programmes and healthy subjects recruited without their consent from concentration camps, on whom various pharmacological substances were tested, including sulfamide and arsenical derivatives and other preparations whose composition is not precisely known (B-1012, B-1034, 3382 or Rutenol, 3582 or Acridine), generally in relation to the treatment of infectious diseases, such as typhus, erysipelas, scarlet fever or paratyphoid diarrhoea. Furthermore, I.G. Farben played a decisive role in the German army's chemical warfare programme, contributing to the development of the first two neurotoxic substances, later known as 'nerve agents', tabun and sarin. Some of these activities came to light as a result of the one the famous Nuremberg Trials in 1947, which saw 24 executives and scientists from I.G. Farben brought to justice for, among other offences, the use of slave labour in the concentration camps and forced experimentation with drugs on prisoners.

[Chemotherapy at the end of life: Uncommon clinical practice?] / Quimioterapia al final de la vida: ¿práctica clínica poco frecuente?

BACKGROUND: In view of the apparent increase in the aggressiveness of palliative chemotherapy, the purpose of this study was to find out and analyse the characteristics of cancer patients treated in our hospital, and who received chemotherapy near the end of life. PATIENTS AND METHODS: Retrospective, observational study in oncology-haematological patients who received chemotherapy between January 2016 and May 2017, and who died in that same period. Data on sociodemographic and clinical variables were collected. In order to determine the risk factors for receiving chemotherapy in the last month of life, a multivariate logistic regression model was developed and subsequently validated using "bootstrap" re-sampling techniques. RESULTS: A total of 293 patients who received chemotherapy during the study period died. The median time between the last cycle of chemotherapy and death was 52 (0-459) days. Chemotherapy was received in their last month of life in 98 (33.4% of patients. the multivariate analysis indicated that the low chemo-sensitivity of the tumour, the particular medical oncologist, and the fact of dying in the hospital setting, were associated with an increased risk of receiving chemotherapy in the last month of life. CONCLUSIONS: A worrying percentage of patients receive chemotherapy near the end of life. This makes it difficult to receive high-quality palliative care, as well as to die in a familiar environment. It is necessary to review the decision-making process in advanced cancer patients.

A bibliometric study of the use of the classification and diagnostic systems in psychiatry over the last 25 years.

BACKGROUND: Our purpose was to examine the use of classification and diagnostic systems in the field of psychiatry (CDSP) from a bibliometric perspective, over the period 1980-2005. METHODS: We selected (in EMBASE and MEDLINE databases) documents that contained, in any of their sections, the descriptors 'psychiatr*', 'DSM*', 'ICD*', or 'diagnostic criteria',as well as other more specific descriptors. As a bibliometric indicator of production we applied Price's law. We also calculated the national participation index (PI) and correlated it with overall PI in biomedical and health sciences, and with PI in the discipline of psychiatry. RESULTS: We obtained 20,564 original documents; 15,743 referred to the Diagnostic and Statistical Manual of Mental Disorders (DSM) and 3,106 to the International Classification of Diseases (ICD). Our results indicate non-fulfilment of Price's law, since scientific production on CDSP does not undergo exponential growth (correlation coefficient r = 0.9651, vs. r = 0.9927 after linear adjustment). Of the 10 journals with the highest impact factor in the field of psychiatry, the Journal of Clinical Psychiatry has the highest PI in the DSM subgroup (PI = 14.77), and the British Journal of Psychiatry in the ICD subgroup (PI = 1.54). The principal producer country is the United States (PI = 37.9), though in proportion to its production in the psychiatric field the ranking is headed by Finland. Only 10 countries, of the 20 major producers in health sciences, surpass their own PI in the field of psychiatry (Brazil, Italy, Japan, Austria, Spain, Germany, France, India, Switzerland, and China). CONCLUSIONS: Over recent years, the use of CDSP (basically the DSM or ICD) in the scientific literature has increased. Nevertheless, the abstracts to these studies, included in the principal databases, should always specify the diagnostic criteria employed, with a view to increasing information levels and reliability for the reader.

[A protocol of assessment, follow-up and nutritional action at a nursing home]. / Protocolo de valoración, seguimiento y actuación nutricional en un centro residencial para personas mayores.

OBJECTIVE: 1) To assess the nutritional status of able elderly, institutionalized at a nursing home; 2) To propose the required nutritional interventions; 3) To establish a consensus protocol for nutritional assessment and follow-up at the Center. METHOD: Cross-sectional study on all able residents, carrying out: 1) Mini Nutritional Assessment Test; 2) Anthropometrical assessment; 3) Biochemical assessment; and 4) an additional questionnaire (gathering information on dental prostheses, swallowing difficulties, and special diets or oral supplements). Analysis of these data to implement appropriate recommendations and elaborating a nutritional protocol. RESULTS: The mean age of the 50 residents assessed was 84 years [66-97], mean weight 62 kg [35-87], mean height 154 cm [140-175], mean body mass index 26 [15.6-36], mean tricipital fold 18.1 mm [4-36], and mean muscle arm circumference 20.6 cm [14.7-27.1]. By using the Mini Nutritional Assessment Test we identified 3/50 (6% [95% CI: 1-16]) malnourished residents, and 6/50 (12% [95% CI: 4-24]) residents at risk for malnourishment. The body mass index allowed to identify 11/50 (22% [95% CI: 11-35]) overweighed residents-body mass index 27-29-, 10/50 (20% [95% CI: 10-33]) with grade I obesity -body mass index 30-35 and 1/50 (2% [95% CI: 0-10]) with grade II obesity-body mass index > 35-. None of them presented values below the 5th percentile for both the tricipital fold and the muscle arm circumference. Values above the 95th percentile were found in 10/50 (20% [95% CI: 10-33]) residents for the tricipital fold and in 7/50 (14% [95% CI: 5-26]) for the muscle arm circumference, both criteria being present in 3 residents. In all of them the body mass index mayor was > 27. When analyzing the biochemical parameters, the results were not concordant, since laboratory workups analyzed were not always done at the same time as the interview. After analyzing the data obtained, a nutritional assessment and follow-up protocol was elaborated in collaboration with the physicians in charge of the Center, in which five categories were defined according to the nutritional status. CONCLUSIONS: 1) 3/50 malnourished residents were identified, 6/50 at risk for malnourishment, and 22/50 with overweight. 2) We proposed the performance of a whole laboratory work-up in these residents, reviewed their dietary habits in order to correct them or prescribe oral supplements, and recommended adapted physical exercise. 3) A nutritional assessment and follow-up protocol was elaborated.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Effect of lamotrigine on sexual function in patients with epilepsy.

OBJECTIVE: To assess the course of sexual function in epilepsy patients treated with lamotrigine. MATERIAL AND METHODS: This open study included 141 patients treated with lamotrigine for a period of 8 months: 79 patients initiated treatment with lamotrigine monotherapy, and 62 were switched to lamotrigine because of lack of efficacy or adverse events to a previous antiepileptic drug (AED). Patients were assessed at baseline and after 4 and 8 months of treatment. In the baseline and final visits the Changes in Sexual Functioning Questionnaire (CSFQ) was applied. Analysis was performed in an intent-to-treat population. RESULTS: In women who started treatment with lamotrigine, a significant improvement was observed, both in total CSFQ score (increase of 5.39 +/- 6.95 points; p < 0.05), and in the five dimensions of the scale (desire/frequency, desire/interest, pleasure, arousal/excitement and orgasm). In men, a significant improvement was only observed in the pleasure dimension. In the group of patients in whom a previous AED was substituted by lamotrigine, significant improvement was recorded in the dimensions of pleasure and orgasm in men and desire/frequency in women, whilst in women the desire/interest dimension showed a decrease. CONCLUSIONS: In this observational study, an improvement in sexual dysfunction was observed in association with lamotrigine. This could have been the result of improvement of the epilepsy, changes in quality of life, elimination of side effects from other AEDs, or a mood-stabilizing effect of lamotrigine.

Absence of favourable changes in circulating levels of interleukin-16 or beta-chemokine concentration following structured intermittent interruption treatment of chronic human immunodeficiency virus infection.

Changes in virological and immunological parameters were analysed following structured intermittent interruption of highly active anti-retroviral therapy (HAART) of patients with chronic human immunodeficiency virus (HIV) infection. Parameters analysed were serum levels of the CD8+ T-cell-derived inhibitory molecules interleukin-16 (IL-16), monocyte inhibitory protein-1beta (MIP-1beta) and RANTES ('regulated upon activation, normal T-cell expressed and presumably secreted'), and the enhancer of HIV replication, monocyte chemotactic protein-1 (MCP-1). Twenty-five patients with chronic HIV infection were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off) in comparison with 20 healthy sex- and age-matched controls. At enrolment, HIV-infected patients showed significantly higher serum concentrations of IL-16 and RANTES, and significantly lower concentrations of MCP-1, than did healthy controls. Levels of MIP-1beta were similar in both groups. Only the serum levels of IL-16 increased significantly in HIV-infected patients after every treatment interruption. However, differences between the CD4+ or CD8+ T-cell counts/microL, HIV loads and serum concentrations of each cytokine at baseline and at the end of the three cycles of intermittent interruptions of therapy were not significant. It was concluded that structured intermittent interruption of HAART for patients with chronic HIV infection did not modify the immunological parameters, including serum levels of CD8+ T-cell-derived inhibitory molecules, or the virus parameters studied. Thus, the findings do not support the use of this treatment modality for the management of HIV-infected patients.

Acute Q fever and the risk of developing endocarditis. / Fiebre Q aguda: riesgo de desarrollo de endocarditis.

OBJECTIVES: Assess clinical and serological data as parameters indicative of a possible evolution to endocarditis after an episode of acute Q fever. PATIENTS AND METHODS: Retrospective cohort study of evolution to endocarditis after an acute Q fever episode, analyzing the clinical and serological evolution and the antibiotic treatment administered. RESULTS: Eighty patients were recruited, 20% of whom had phase i IgG antibody levels ≥ 1:1024 in the first 3 months. Only 44% of the patients underwent antibiotherapy in the acute phase; only 2 patients underwent extended antibiotherapy. Fifteen percent of the patients underwent an echocardiogram. None of the patients had symptoms suggestive of chronic infection or progressed to endocarditis after a median follow-up of 100 months, regardless of the early increase in phase i IgG antibodies. CONCLUSIONS: The early increase in phase i IgG antibodies in asymptomatic patients is not associated with progression to endocarditis despite not undergoing prolonged antibiotic treatment.

Contrast media algogenic potential in peripheral arteriography. Potentiation of bradykinin-induced pain in the rat.

RATIONALE AND OBJECTIVES: Contrast media (CM) with minimal algogenic (pain causing) potential in animal models of peripheral arteriography are still able to produce vascular pain in humans; the poor predictive value of preclinical evaluation led us to develop a more sensitive method based on CM potentiation of bradykinin effects in the rat. METHODS: Behavioral pain responses and histologic alterations of the arteries were determined after intrafemoral injection of bradykinin to saline- or CM-pretreated rats. Pain reactions were compared with those elicited by single and repeated CM injections. RESULTS: Contrast media enhanced bradykinin-induced pain was dose dependent with the following potency order: iopamidol > iopromide > ZK 139129 > ZK 119095. Vasodilation and alterations of the arterial internal layer also were seen. Iopromide produced this sensitization at doses that did not elicit evident pain reactions per se. CONCLUSION: The method proved to be a highly sensitive preclinical discriminant of CM algogenic potential.

Effects of yohimbine on morphine analgesia and physical dependence in the rat.

The effects of yohimbine on morphine analgesia and on the development of opiate physical dependence were studied to find out more about the involvement of alpha 2-adrenergic mechanisms in opioid actions. Male Sprague-Dawley rats (250-300 g) were used. The acute effect of morphine (5 mg/kg i.p.) in the tail-flick test was reduced significantly by pretreatment with a single dose of yohimbine (2 mg/kg i.p.). Alone yohimbine, produced a slight hyperalgesia. Animals treated with a sustained-release preparation of morphine (300 mg/kg s.c.) showed the same sensitivity to opiate analgesia 72 h later whether they were treated concomitantly with yohimbine or not, but they exhibited fewer withdrawal symptoms upon naloxone injection after yohimbine (2 or 4 mg/kg i.p. 24, 28, 48 and 52 h after the start of systemic morphine treatment). The results obtained confirm previous data on the effects of yohimbine on morphine analgesia and reveal the importance of alpha 2-adrenergic activation in the development of opioid physical dependence.

Relapse to opiate use provokes biphasic changes of blood pressure in heroin-withdrawn addicts treated with clonidine.

The effect of relapse to opiate use on blood pressure and heart rate has been studied in heroin-withdrawn addicts treated with clonidine in an outpatient detoxification procedure. The daily dose of clonidine was established according to body weight and amount of heroin usually consumed at the onset of treatment. Patients who returned to heroin use were detected by increased urinary levels of opiates. Clonidine elicited significant reductions of blood pressure and heart rate reaching a plateau in the second day of treatment. Heroin consumption was found to provoke a further decrease of both systolic and diastolic pressure when the time interval between the relapse and the cardiovascular determinations was about 3 h as estimated by the patients. At longer intervals (16 h) this effect was reversed and both the hypotensive and the bradycardiac actions of clonidine seemed to be impaired. The possible impact of endogenous opioids and alpha-2 receptor sensitivity on these biphasic alterations is discussed.

Yohimbine reduces morphine tolerance in guinea-pig ileum.

Opiates are known to inhibit electrically-evoked twitches of longitudinal muscle-myenteric plexus strips from guinea-pig ileum. When this preparation was incubated with morphine for 1 h tolerance developed to the inhibitory effect, since dose-response curves were shifted to the right. In the present study, the effects of alpha-2 adrenergic agents on the tolerance induced by morphine in this preparation was investigated. Addition of yohimbine 10 microM (but not 0.1 or 1 microM) to the incubating medium reduced the magnitude of opiate tolerance. This effect did not appear in the presence of the alpha-2 agonists clonidine or guanfacine (10 microM). Our results provide evidence of the longitudinal muscle-myenteric plexus as a useful model for the study of the relationship between morphine tolerance and alpha-2 adrenergic mechanisms.

Effect of adjuvant-induced arthritis on bone mass in rats and its prevention by non-steroid anti-inflammatory drugs (NSAIDs).

The effect of two propionic acid derived drugs, ketoprofene and butibufene, on the prevention of osteopenia due to adjuvant-induced anti-inflammatory arthritis, was studied in groups composed of 10 rats each. Another group of 10 rats was treated with a placebo and 20 non-treated rats served as controls. Once arthritis was evoked, propionic acid derived drugs were administered at equivalent doses, in the form of a local cream applied on the foot where arthritis was induced. The placebo group was treated with the cream without propionic acid derivatives. Rats were sacrificed at the end of the study and the femurs where arthritis was induced were dissected. Bone densitometry studies were conducted with double energy X-ray on these bones to calculate the bone mass. Bone mass was higher in the group treated with ketoprofene (p < 0.025) than in the butibufene and placebo-treated groups, and these 3 groups showed lower values than the control (p < 0.001). These results suggest that propionic acid derivatives can prevent the osteopenia induced by inflammation and the subsequent lack of limb use, an effect which may be related to its analgesic and/or anti-inflammatory effects. In addition, this may serve as a good model for the indirect measurement of the effectiveness of analgesic and/or non-steroid anti-inflammatory drugs in experimental animals.

Effect of morphine and acetylcholine on contractile activity and cyclic AMP in guinea-pig ileum.

Neither acute nor prolonged exposure to morphine altered cAMP content or spontaneous movements of longitudinal muscle-myenteric plexus strips of the guinea-pig ileum. By contrast, exogenous acetylcholine or electrical stimulation of the strips elicited both a decrease of cAMP concentration and a twitch response. Atropine blocked the effects of stimulation on these parameters. Addition of morphine to electrically stimulated strips inhibited the twitch response but did not affect cAMP levels. Incubation with morphine led to the development of tolerance to the inhibitory effect on twitch activity and prevented the fall in cAMP normally elicited by electrical stimulation. These results suggest that muscarinic activation is associated with a reduction of cAMP content, an effect which would be impaired in opiate-tolerant tissues.

Evolution of the management of depression in Spain from the psychiatrist's perspective. A comparative analysis: 1997 vs 1982.

The main problem of depression is not only the high prevalence of the disorder but also its serious consequences on the patient's quality of life and the associated social costs in terms of health care resource utilization and productivity losses. In recent years, there has been a considerable improvement in the knowledge of depression from the pathogenic, clinical and therapeutic perspectives. The present study analyzes whether such advances are reflected in a positive evolution of the treatment of depression in Spain. To this effect we have contrasted the results of two socio-sanitary studies published in this country: the White Book editions of 1982 and 1997 (WB82 and WB97, respectively). From the methodological perspective, the physician selection criteria employed were very uniform (structured questionnaires delivered to 128 (WB82) and 300 (WB97) randomly selected psychiatrists). The origin of patients consulting for specialized care has varied over this 15-year period. In effect, WB82 patients were essentially referred by friends (87.5%) and from the primary care setting (44.5%), whereas in the WB97 study referral from primary care predominated (50.1%), followed by the patient's personal decision (24.8%). In turn, 40.7% and 51.7% of the psychiatrists in WB97 respectively considered the diagnostic and therapeutic means available in primary care to be insufficient. The priorities for improving patient quality of life, as reflected by both editions of the study, were the training of primary care physicians and the adequate provision of means in the mental health care centers. On the other hand, fewer problems for establishing a correct diagnosis were referred in the 1997 edition of the study (28.7%) than in 1982 (48.4%). In this sense, the main problem reported in WB82 was the lack of specialized training, whereas the masking of depression by some other disease process or symptoms was the main problem in WB97 (67.6% vs 21.1% according to WB82). The main symptoms upon which the diagnosis of depression are based do not seem to have evolved much in the past 15 years. The most frequently cited manifestations were a worsening of mood, loss of interest and leisure capacity, sleep alterations and diminished vitality. A comparative analysis of the therapeutic resources used was not possible, for prior to 1982 the only drugs available to physicians were the classical tricyclic agents and some MAO inhibitors; the selective serotonin reuptake inhibitors (SSRIs) - possibly the greatest advance in the treatment of depression in these 15 years - had not yet been introduced. Nevertheless, it should be pointed out that 98% of the psychiatrists consulted in WB97 considered pharmacologic treatment to be the most widely adopted form of management once depression has been diagnosed.