Steroid 5α-reductase in adult rat brain after neonatal dihydrotestosterone administration.

Testosterone (T) is known to play an important masculinizing role in the developing brain of rat, including the regulation of 5α-reductase (5α-R) isozymes. However, the effects of dihydrotesterone (DHT), a more potent androgen than T, have not been elucidated. In this study, DHT was administered from day 5 through day 20 of postnatal life (period of postnatal sexual differentiation of the central nervous system) at doses of: 12 mg/kg/d on days 5, 6, 7, 8, 19, and 20; 15 mg/kg/d on days 9, 10, 11, 12, 16, 17, and 18; and 18 mg/kg/d on days 13, 14, and 15. In adulthood, quantitative RT-PCR was used to measure mRNA levels of 5α-R1 and 5α-R2 isozymes in the prefrontal cortex (PFC) of male and female rats with varied androgenic status. Under our study conditions, neonatal DHT administration influenced on adult PFC 5α-R isozymes levels and their regulation pattern by androgens, and this pattern was the inverse of that reported in adult neonatally T-treated rats.

Performance of the Sysmex UF1000i system in screening for significant bacteriuria before quantitative culture of aerobic/facultative fast-growth bacteria in a reference hospital.

OBJECTIVE: To evaluate the performance of the Sysmex UF1000i automatic urine screening system in the quantitative culture of fast-growth aerobic/facultative bacteria. METHODS AND RESULTS: A standard procedure was used to recover fast-growth aerobic/facultative micro-organisms in 1225 samples, applying (Sysmex(®)) flow cytometry for parallel bacteria and leucocyte counts. According to the area under the receiver operating characteristic curve, the optimal cut-off values to detect bacteriuria >10(5) colony forming units (CFU) ml(-1) were 690/µl for bacteria and 38/µl for leucocytes (sensitivity, 92%; specificity, 65%; positive predictive value [PPV], 39%; and negative predictive value [NPV], 97%). The use of a single cut-off point of 150 bacteria µl(-1) to detect significant bacteriuria of >10(5) CFU ml(-1) or of ≥10(4) CFU ml(-1) plus leucocyturia obtained similar results (sensitivity, 89%; specificity, 54%; PPV, 31%; and NPV, 96%) and allowed 45.7% of the samples to be rapidly excluded. CONCLUSIONS: The Sysmex UF1000i system can be adapted for bacteriuria screening by the use of an appropriate cut-off point. SIGNIFICANCE AND IMPACT OF THE STUDY: This screening system significantly reduces the workload and produces very few false positives and negatives.

Predicting the onset of major depression in primary care: international validation of a risk prediction algorithm from Spain.

BACKGROUND: The different incidence rates of, and risk factors for, depression in different countries argue for the need to have a specific risk algorithm for each country or a supranational risk algorithm. We aimed to develop and validate a predictD-Spain risk algorithm (PSRA) for the onset of major depression and to compare the performance of the PSRA with the predictD-Europe risk algorithm (PERA) in Spanish primary care. METHOD: A prospective cohort study with evaluations at baseline, 6 and 12 months. We measured 39 known risk factors and used multi-level logistic regression and inverse probability weighting to build the PSRA. In Spain (4574), Chile (2133) and another five European countries (5184), 11 891 non-depressed adult primary care attendees formed our at-risk population. The main outcome was DSM-IV major depression (CIDI). RESULTS: Six variables were patient characteristics or past events (sex, age, sex×age interaction, education, physical child abuse, and lifetime depression) and six were current status [Short Form 12 (SF-12) physical score, SF-12 mental score, dissatisfaction with unpaid work, number of serious problems in very close persons, dissatisfaction with living together at home, and taking medication for stress, anxiety or depression]. The C-index of the PSRA was 0.82 [95% confidence interval (CI) 0.79-0.84]. The Integrated Discrimination Improvement (IDI) was 0.0558 [standard error (s.e.)=0.0071, Zexp=7.88, p<0.0001] mainly due to the increase in sensitivity. Both the IDI and calibration plots showed that the PSRA functioned better than the PERA in Spain. CONCLUSIONS: The PSRA included new variables and afforded an improved performance over the PERA for predicting the onset of major depression in Spain. However, the PERA is still the best option in other European countries.

Relation between Epstein-Barr virus and multiple sclerosis: analytic study of scientific production.

Numerous studies have been carried out to determine whether infection by the Epstein-Barr virus (EBV) can be considered as a risk factor for multiple sclerosis (MS). This work is a meta-analysis of case-control observational studies published before January 2009 aimed at assessing the degree of association between EBV and MS infections. A Medline electronic database search was carried out using "Epstein-Barr virus" and "multiple sclerosis" as keywords, from which we selected 30 published studies that met our methodology criteria. We found an association between MS and an exposure to EBV, studied by determining the anti-VCA IgG antibodies (odds ratio [OR] = 5.5; 95% confidence interval [CI] = 3.37-8.81; p < 0.0001), anti-complex EBNA IgG (OR = 5.4; 95% CI = 2.94-9.76; p < 0.0001) and anti-EBNA-1 IgG (OR = 12.1; 95% CI = 3.13-46.89; p < 0.0001). No significant association could be found when studying anti-EA IgG (OR = 1.3; 95% CI = 0.68-2.35; p = 0.457), EBV DNA in serum (OR = 1.8; 95% CI = 0.99-3.36; p = 0.051) and DNA in brain tissues and in cerebrospinal fluid (CSF) (OR = 0.9; 95% CI = 0.38-2.01; p = 0.768). This meta-analysis detected an association between infection by EBV and MS through the investigation of antibodies, mainly anti-EBNA-1, anti-complex EBNA and anti-VCA IgG.

Patient expectations are not always the same.

OBJECTIVE: To validate a scale that measures patients' expectations when seeking advice for health problems of different types. METHODS: 360 patients who had consulted their general practitioner (GP) during the previous 12 months were randomly selected from the lists of 30 GPs. A questionnaire, including a 13-item expectation scale, was administered by interview in the patient's home to assess expectations in relation to five health problems, three biomedical (strong chest pain, genital discharge and the common cold) and two psychosocial (depression/sadness and serious family problem), repeating the expectation scale for each one. The frequency distribution of items was analysed, multi-level factorial analysis was performed and the reliability of the expectation scale was tested for each hypothetical clinical condition. RESULTS: The response rate was 90%. Mean age of patients was 47.3 years (SD 16.5); 51% were women. Expectations were high but varied according to the nature and severity of the condition. The percentage of patients wanting the doctor alone to make decisions ranged from 50% for "family problem" to 68% for "chest pain". The five factorial structures differed and explained 49.3-63.9% of the variance. Similarities were observed depending on the type of problem. "Communication" and "Experience of disease" were thus separate dimensions for the biomedical diseases but mixed for the psychosocial conditions. CONCLUSIONS: The factorial structure of expectations varied, indicating that expectations are not homogeneous in all clinical situations. The desire of the patient to participate in decision-making also differs according to the type of health problem.

Successful kidney transplantation reduces hyperplastic parathyroid gland.

INTRODUCTION: In dialysis patients, the parathyroid glands (PTGs) may increase progressively, producing abnormal bone metabolism. Changes in PTG volume among patients with hyperplastic PTGs are not well known after kidney transplantation. This study investigated PTG volume by ultrasound (US). METHODS: US of PTG was performed immediately (US-0) and 12 months after (US-12) transplantation to identify glands in all recipients. We calculated the percentage reduction in PTG volume (R%PTG). We declared it significant when it was > or =35%. Bone biochemical markers and renal function were recorded sequentially. RESULTS: Among engrafted patients, parathyroid US-0 was performed in 47 and US-0 and US-12 in 36. Some visible gland was observed upon US-0 in 13 recipients, a group that showed higher pretransplantation parathyroid hormone (PTH) levels than the remaining 34 patients with no visible glands (627 +/- 360.0 vs 280 +/- 240.9 pg/mL; P < .05). Of 36 recipients with US-0 and US-12, the baseline study identified PTGs in 12 patients (p+ group), while the remaining 24 had no identified glands (p- group). In the p+ group, no PTG, at US-12 were visible in four patients, and a significant R%PTG was observed in three at this time, representing a reduction in gland volume after transplantation among 58.3% of p+ patients. There was a progressive reduction in PTH among both groups. Patients with glandular volume reduction displayed better renal function: serum creatinine 1.7 +/- .79 versus 2.9 +/- .74 mg/dL (P < .05). CONCLUSIONS: Transplantation reversed hyperparathyroidism and PTG volume among recipients who achieved nearly normal renal function.

Urinary tract infections and lupus erythematosus.

BACKGROUND: Infections are one of the main causes of morbidity and mortality in patients with systemic lupus erythematosus. OBJECTIVE: To analyse urinary tract infection (UTI) risk factors in lupus patients; the influence of these factors on disease activity, organ damage, and disease development; the type and prevalence of UTI; and the micro-organisms involved. METHOD: 86 control subjects and 81 lupus patients were studied prospectively over a 12 month period and examined on five occasions. Epidemiological data and information on urinary symptoms, disease activity (SLEDAI), and organ damage (SLICC/ACR) data were collected. Autoantibodies, complement levels, urine culture, and antibiogram were determined; urological studies were also carried out. SPPS 10.0 and STATA 6.0. were used for statistical analysis. RESULTS: The prevalence of UTI in lupus patients was 36%. Lupus influences the onset of UTI (p = 0.001), regardless of other variables. UTI risk factors in lupus patients were age (p = 0.002), previous cases of UTI (p = 0.0001), antinuclear antibodies (ANA) >1/80 IU/ml (p = 0.022), thrombocytopenia (p = 0.02), and admission to hospital due to UTI (p = 0.002). Leucopenia (p = 0.09) and the weekly administration of methotrexate (p = 0.06) had a bearing on the onset of UTI; disease development (p = 0.99), lupus activity (p = 0.32), and organ damage (p = 0.36) do not. The uropathogen most frequently isolated was E coli (60%). CONCLUSIONS: Lupus patients are likely to have UTI, usually manifesting in the lower tract. They are community acquired, basically caused by E coli, and favoured by age, previous UTI, admissions to hospital due to UTI, thrombopenia, ANA, leucopenia, and methotrexate treatments.

Performance of quantitative ultrasound in the discrimination of prevalent osteoporotic fractures in a bone metabolic unit.

There is a growing interest in ultrasound evaluation of bone status as an alternative to the measurement with dual X-ray absorptiometry (DXA), due to its low cost, portability, and nonionizing radiation. The aim of our study was to investigate the relation among DXA, QUS, clinical, anthropometric, and lifestyle factors, and to determine QUS cutoff values in order to discriminate fractures in patients referred to the Bone Metabolic Unit at an Endocrinology Service. We studied 300 patients (281 females and 19 males; age 58 +/- 11 years) referred for evaluation of osteoporosis. In all cases we determined basic anthropometric parameters, a clinical history including previous osteoporotic fractures and risk factors for osteoporosis, and QUS parameters in calcaneus (Hologic Sahara), and BMD in lumbar spine (LS) and femoral neck (FN), by DXA (Hologic QDR 1000). Using the WHO densitometric criteria, 37, 46.7, and 16.3% of our population were osteoporotic, osteopenic, and normal, respectively. A QUI T-score

Performance of COLIA1 polymorphism and bone turnover markers to identify postmenopausal women with prevalent vertebral fractures.

Some studies have suggested that bone turnover markers (BTM) and collagen type I alpha 1 gene (COLIA1) may be useful in the prediction of rates of future bone loss, and may therefore provide information about fracture risk. Our study aimed to examine the association of the COLIA1 genotype with the risk of vertebral fracture and to investigate the predictive value of this genetic factor in comparison with bone mineral density (BMD) and BTM, in ambulatory postmenopausal Spanish women. We determined the COLIA1 polymorphism by polymerase chain reaction, BMD by dual-energy X-ray absorptiometry and BTM in 43 postmenopausal women with prevalent vertebral fracture and a control group of 101 postmenopausal women without fracture. There was a significant overrepresentation of the 'T' allele in fractured women ( p = 0.029). BTM exhibited no differences between women with or without fractures or COLIA1 genotype groups. After adjusting for all other variables, the osteoporosis densitometric criteria variable was the most strongly associated with fracture (OR = 5 [1.8-13.3]) followed by COLIA1 (OR = 2.1 [1-4.3] per copy of the 'T' allele). Our study shows that COLIA1 is associated with prevalent vertebral fracture independently of bone mass, and the performance of this genetic factor to assess prevalent vertebral fracture is better than bone turnover markers.

The contribution of IGF-I to skeletal integrity in postmenopausal women.

OBJECTIVES: The pathogenic role of the decline in serum concentrations of IGF-I in postmenopausal osteoporosis is not fully elucidated. We investigated the associations among IGF-I, bone mineral density (BMD), ultrasound parameters and prevalence of vertebral fractures in postmenopausal women. DESIGN: A cross-sectional study. PATIENTS: One hundred and fifty-four ambulatory postmenopausal women (61 +/- 7 years) referred for osteoporosis screening. MEASUREMENTS: IGF-I was measured by radioimmunoassay and BMD using dual-energy X-ray absorptiometry. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at calcaneus were measured by a quantitative ultrasound system. RESULTS: IGF-I was significantly lower in osteoporotic subjects and correlated positively with BMD, BUA and SOS. After adjusting for age, years since menopause and body mass index, IGF-I accounted for 8.5% of the variance at lumbar spine BMD, 4.6% at femoral neck and 7.1% at calcaneal BUA. BUA was associated with IGF-I independently of BMD. IGF-I was lower in women with vertebral fractures (91 +/- 39 microg/l vs. 114 +/- 44 microg/l; P = 0.003). The osteoporosis densitometric criteria (t-score < or = -2.5 SD) was the most strongly independent associated variable with prevalent vertebral fractures [odds ratio (OR): 3.3 (1.4-7.6)], followed by IGF-I levels below 75th percentile [OR: 3 (1-8.8)]. CONCLUSIONS: Our study shows that IGF-I is strongly associated with bone mineral density and reflects aspects of bone quality. The contribution of IGF-I to skeletal integrity in postmenopausal women is clinically relevant.

[Factors associated with the occurrence of adverse reactions to drugs in patients who went to the emergency service of a general hospital: a case-control study]. / Factores asociados con la presentación de reacciones adversas a medicamentos en pacientes que acuden al servicio de urgencia de un hospital general: estudio de casos y controles.

OBJECTIVE: To describe adverse reactions to medicine (ARM) and analyse the factors associated with their presenting in patients attending a general hospital's emergency service. DESIGN: Case-control epidemiological study. SETTING: Emergency service of the San Cecilio University Hospital in Granada. PATIENTS: 654 patients over 15, men and women, who attended the emergency service between October and December 1997. 354 of them had an ARM (cases) and 300 did not (controls). MEASUREMENTS AND RESULTS: 60% of the cases were women, with an average age of 53 +/- 20. 68% of the ARM were type-A (expected). The most affected organs and systems were: digestive tract (41.8%) and skin (31.6%). Drug groups most associated with presentation of ARM were hypnosedatives and salicylates used as analgesics--antithermic drugs (28.2%), and beta-lactams and macrolides (22.6%). Most ARM were classified as probable (52%) and moderate (62%). Family practitioners were the main prescribers (49%) of medicines. 13% of patients were admitted to hospital because of a serious ARM and two people died (0.5%). According to the odds ratio, treatment with cytostatics, psychiatric drugs, NSAIDs, amoxycillin, digoxin, ACEIs and calcium antagonists, being a woman, self-medication, being under 65 and history of ARM were all associated with the presence of an ARM in our patients (cases). CONCLUSIONS: The type of medicine, being a woman, history of ARM, self-medication, and presenting digestive and dermatological symptoms were factors strongly linked to an ARM in patients attending the emergency service.

Design and validation of a new image analysis method for automatic quantification of interstitial fibrosis and glomerular morphometry.

Interstitial fibrosis and morphologic changes in kidney glomeruli, the structural effects of many diseases, lead to significant pathologic alterations. A reliable and objective method to accurately quantify the extent of interstitial fibrosis and the degree of alteration in glomerular morphology is needed for both clinical practice and experimental work. The morphometric methods of quantification described to date are time-consuming and require trained personnel. This article describes the design and validation of an image analysis-based application (Fibrosis HR) for automatically and rapidly quantifying interstitial fibrosis and glomerular morphology in the same tissue section stained with Sirius red. The image processing algorithms described herein automatically segment interstitial fibrosis and mesangial matrix using automatic thresholding and morphologic filtering. The glomerular region is extracted by a simple interactive step and an automatic mathematical morphology algorithm, whereas the glomerular tuft is automatically segmented with automatic thresholding and a sequence of Boolean and mathematical morphology operations. All extracted areas are automatically quantified in absolute (microm2) and relative (%) values. For validation of this method, interstitial fibrosis, mesangial matrix, and glomerular and glomerular tuft areas were manually segmented and their quantifications statistically compared with those obtained automatically. Statistical analyses showed significant intra- and interoperator variability in manual segmentation of interstitial fibrosis, mesangial matrix, and glomerular tuft areas. Automatic quantifications of the same areas did not differ significantly from their mean manual evaluations. There was no significant intra- or interoperator variability in the interactive identification of the glomerular region. In conclusion, Fibrosis HR produces robust, fully reproducible, accurate, objective, and reliable quantifications, which facilitate the evaluation of in vivo experimental models of renal interstitial and glomerular pathologies and improve the accuracy of clinicopathologic analyses of renal diseases in human biopsies.

School setting and teaching experience as risk factors for depressive symptoms in teachers.

A representative sample of teachers working at the primary or secondary grade level in both public and private schools answered an anonymous questionnaire on sociodemographic information and completed the Center for Epidemiologic Studies Rating Scale for Depression (CES-D). The teachers were classified as depressed when they scored 16 on the CES-D; 27.5% of the subjects were above this cut-off score. Logistic regression was used to calculate a multivariate model with the variables school ownership, grade level and teaching experience. Working in a public school, teaching at the primary level and longer teaching experience all increased the risk of depressive symptomatology.

Role of the renin-angiotensin system in the development of thyroxine-induced hypertension.

OBJECTIVE: We evaluated the influence of chronic blockade of the renin-angiotensin system on hypertension induced by long-term thyroxin (T4) administration. To this end, we determined the effects of chronic treatment with captopril on blood pressure, cardiac hypertrophy and other renal and metabolic variables of hypertensive hyperthyroid rats. METHODS: T4 was administered s.c. at 0.38 mumol/kg per day and captopril was given in the drinking water (1.38 mmol/l). Both treatments were maintained for 6 weeks. Control rats received tap water. After the treatment period, the rats were placed in metabolic cages. Later, blood pressure was measured in conscious rats by intra-arterial determination. RESULTS: T4-treated rats showed an increased mean arterial pressure (MAP) whereas, in rats treated with T4 plus captopril, MAP was similar to that of the control group. Captopril did not affect the increased heart rate or ventricular weight/body weight ratio of hyperthyroid rats, but it improved the reduced creatinine clearance of these animals. CONCLUSIONS: The elevation in blood pressure produced by long-term T4 administration was prevented by chronic blockade of the renin-angiotensin system. Captopril improved the renal function of hyperthyroid rats, but did not affect the relative cardiac hypertrophy of these animals.

Reclassification after delivery of diabetes in pregnancy.

Gestational diabetes mellitus (GDM) constitutes a risk factor for the development of non insulin-dependent diabetes mellitus (NIDDM). The search for parameters to provide discrimination between a high risk and a low risk for future development of NIDDM is today the aim of many investigations. The absence or presence of several factors such as glycemia during pregnancy and post partum, the need for insulin treatment, disorders of the pancreatic insulin secretion, the number of pregnancies, maternal obesity, the early diagnosis of GDM, the family history of diabetes mellitus, the race and immune disorders give rise to a very high relative risk (RR) of developing NIDDM. To know the degree of risk will allow a future appropriate clinical intervention to reduce the incidence of NIDDM and its economic cost.

Subcellular distribution of soluble and membrane-bound Arg-beta-naphthylamide hydrolyzing activities in the developing and aged rat brain.

The subcellular distribution of soluble and membrane-bound Arg-beta-naphthylamide-hydrolyzing activities was studied in the left and right rat brain during development and aging. During development, the soluble activity was heterogeneous, whereas adult animals showed the highest activity in the synaptosomal fraction. However, except in fetuses, membrane-bound activity was greatest in the microsomal fraction. Except in microsomal and myelin fractions, soluble and membrane-bound activities showed a decrease in 1-wk-old rats compared with fetuses and a subsequent increase to adult levels in 1-mo-old rats. This profile differed in the microsomal fraction, which increased steadily throughout development. In the synaptosomal fraction, both activities were lower in 24-mo-old rats than in 5-mo-old animals. No differences between the hemispheres were observed in soluble or membrane-bound fractions at any age tested.

Influence of the behaviorally active peptides ACTH1-10 and ACTH4-10 on the melatonin modulation of 3H-flunitrazepam receptor binding in the rat cerebral cortex.

Possible interactions of ACTH-like peptides with melatonin regulation of central-type benzodiazepine (BNZ) receptors have been studied by means of high-affinity 3H-flunitrazepam binding to rat cerebral cortex membrane preparations. Intracerebroventricular injections of melatonin produce a dose-dependent increase in Bmax in pinealectomized rats, without changes in KD. Analogous effects were obtained after intracerebroventricular injection of melatonin in adrenalectomized and in adrenalectomized plus pinealectomized rats, which indicated the lack of participation of adrenal steroids in this response. Moreover, intracerebroventricular injection of ACTH1-10 induced a similar dose-dependent increased Bmax in sham-operated animals, whereas pinealectomy, but not adrenalectomy, partially counteracted this effect of ACTH1-10 administration. Besides, simultaneous injection of ACTh1-10 plus melatonin reverses the effects of pinealectomy, resulting in an additive effect of both compounds on Bmax. The response obtained when using ACTh4-10 was somewhat different, because no dose response was obtained in any experiment. Although lack of endogenous melatonin partially reduced the increasing effect of ACTH4-10 on Bmax, there were no additive effects at the different doses used. The results strongly suggest that ACTH-like peptides, in addition to melatonin, play a role in regulating central-type rat BNZ receptors.

Influence of socioeconomic and health care development on infant and perinatal mortality in Spain 1975-86.

STUDY OBJECTIVE: This study aimed to analyse the influence of social, economic, and health development on infant and perinatal mortality in Spain between 1975 and 1986, and to identify possible changes in these relationships over time. DESIGN: Study of the association between mortality and a range of variables. SETTING: 50 Spanish provinces. MEASUREMENTS AND MAIN RESULTS: Mean infant and perinatal mortality were estimated for two periods--1975-8 and 1983-6. Social, economic, and health care indicators were collected as independent variables for these two periods. The rates of variation between periods were estimated for each variable. Multiple linear regression models were used to define the association between infant and perinatal mortality and their respective rate of variation with the former indicators. Mean familial income was the main predictive factor for infant and perinatal mortality in the first period but in the second period health care indicators were more relevant. CONCLUSIONS: The reduction in Spanish infant and perinatal mortality over the period can be attributed mainly to the improvement in prenatal and neonatal health care in Spain in recent years, while economic factors seem less important.

[Validation of a functional social support scale for use in the family doctor's office]. / Validación de una escala de apoyo social funcional para su uso en la consulta del médico de familia.

OBJECTIVE: The present work seeks to validate the Duke-UNC questionnaire as modified by Broadhead, which is used to measure social support in its qualitative dimension. DESIGN: It is a transversal, prospective and observational study. LOCATION: The study has been done at the primary care level, corresponding to the basic health area of Cartuja (Granada). PATIENTS: The questionnaire was administered to 139 patients seen in the offices of the Cartuja Health Centre. 25 of them were male and 114 female, of an age ranging from 18 to 84. The subjects were selected on a systematic base of three by three with a random starting-point from among people over 18 years old visiting the office. INTERVENTIONS: To check the reliability and validity of the questionnaire, Pearson's, Edward's and Cronbach's alpha techniques were used. The factorial analysis was verified by the varimax rotation method. MEASUREMENTS AND MAIN RESULTS: We have observed that the questionnaire correctly measures qualitative social support, it being appreciated that the correlation coefficients are high, as is the internal consistency of the scale. After the factorial analysis we also confirmed the existence of two components: Factor 1 which measures the confidential social support and Factor 2 which measures the affective social support. CONCLUSIONS: The Duke-UNC questionnaire reduced to 11 items is a fast and simple instrument for detecting the level of social support in its affective and confidential dimensions. Its use will allow us to discover situations of high social risk; permitting us in these cases to carry out the relevant support interventions.