Current legionellosis outbreak with 139 cases in Pamplona, Spain.
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Disease Outbreaks↗
Biomedical subjects
J Castilla
Publications and source records attributed to J Castilla.
Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection.
Transgenic (Tg) mice carrying four extra octapeptide repeats (OR) in the bovine PrP gene (10OR instead of 6) have been generated. In these mice, neuropathological changes were observed depending upon the level of transgene expression. These changes primarily involved a slowly advancing neurological disorder, characterized clinically by ataxia, and neuropathologically, by vacuolization in different brain areas, gliosis, and loss of cerebellar granule cells. Accumulation of insoluble bovine 10OR-PrP (bo10OR-PrP) was observed depending on the level of expression but no infectivity was found associated with this insoluble form. We also compared the behavior of bo6OR-PrP and bo10OR-PrP Tg mouse lines in response to BSE infection. BSE-inoculated bo10ORTg mice showed an altered course of BSE infection, reflected by reduced incubation times when compared to bo6ORTg mice expressing similar levels of the wild type 6OR-PrP. In BSE-inoculated mice, it was possible to detect PrP(res) in 100% of the animals. While insoluble bo10OR-PrP from non-inoculated bo10ORTg mice was non-infectious, brain homogenates from BSE-inoculated bo10ORTg mice were highly infectious in all the Tg mouse lines tested. This Tg mouse model constitutes a new way of understanding the pathobiology of bovine transmissible spongiform encephalopathy. Its potential applications include the assessment of new therapies against prion diseases.
Animals↗
Vertical transmission of bovine spongiform encephalopathy prions evaluated in a transgenic mouse model.
In this work we show evidence of mother-to-offspring transmission in a transgenic mouse line expressing bovine PrP (boTg) experimentally infected by intracerebral administration of bovine spongiform encephalopathy (BSE) prions. PrP(res) was detected in brains of newborns from infected mothers only when mating was allowed near to the clinical stage of disease, when brain PrP(res) deposition could be detected by Western blot analysis. Attempts to detect infectivity in milk after intracerebral inoculation in boTg mice were unsuccessful, suggesting the involvement of other tissues as carriers of prion dissemination. The results shown here prove the ability of BSE prions to spread centrifugally from the central nervous system to peripheral tissues and to offspring in a mouse model. Also, these results may complement previous epidemiological data supporting the occurrence of vertical BSE transmission in cattle.
Animals↗
[Study of immutable variables determining rHuEPO dose requirements on hemodialysis patients].
Patients receiving recombinant human erythropoietin (rHuEPO) therapy show wide variability in their responsiveness to the drug. Variables that affect rHuEPO dose requirements can be broadly divided into modificable and immutable characteristics. Most of the scientific research on rHuEPO hyporesponsiveness has focused on modificable variables (iron status, dialysis adequacy), while immutable variables such as gender, etiology of chronic renal failure (CRF) and age have been insufficiently explored. A cross sectional study was performed in order to evaluate if immutable patient characteristics determine rHuEPO dose requirements among 215 patients (52% males; mean age 66 +/- 14 years) on hemodialysis (HD) for more than twelve months. Data were collected at 10 hemodialysis units in Aragon. Patients were divided into three groups according to their gender, their cause of CRF (diabetic nephropathy, vascular nephropathy, tubulointerstitial nephropathy and primary glomerulonephritis) and their age (younger than 60 years, from 60 to 75 years, older than 75 years). Despite a similar dose of rHuEPO, women had lower mean hemoglobin (11.1 +/- 1.5 versus 11.6 +/- 1.7 g/dl; p = 0.0258) than men. The greater hemoglobin in men than women may be attributed to greater serum albumin in men (3.5 +/- 0.3 versus 3.7 +/- 0.3 mg/dl; p = 0.0001). Requirements of rHuEPO were higher in the patients with etiology of primary glomerulonephritis compared with those with the other etiologies, even those with diabetic nephropathy (p = 0.0374). The rHuE-PO doses required to obtain similar hemoglobin levels were higher in patients younger than 60 years (p = 0.0249). We conclude that women, patients with primary glomerulonephritis as cause of CRF, and patients younger than 60 years showed the highest requirements of rHuEPO doses.
Aged↗
[Women who are partners of a man infected by HIV: description of their characteristics and appraisal of risk].
OBJECTIVE: To describe the situations of risk and the prevalence of HIV in women with a heterosexual partner infected by HIV. DESIGN: Cross-sectional descriptive study. SETTING: Out-patient HIV diagnosis centre in Madrid. PATIENTS: 229 women seen for the first time between 1993 and 2002 because they had a stable heterosexual partner diagnosed with HIV, and who were exposed to no other risk. MAIN MEASUREMENTS: Social and personal details, reproduction history, sexual conduct, clinical, and analytic data of both partners. RESULTS: 66% of couples had maintained sexual relations for over a year. Women were on average younger (29.6 years old) than the men. 29% of the women had children and 5.2% were pregnant. 82% of men had injected drugs, but only 13% still did. 73% had been diagnosed with HIV for over 6 months, 16% had AIDS criteria, and 35% were taking retroviral treatment. 60% of the men who knew of their infection had systematically avoided sex without condoms, against 33% of those who did not know they were infected (P<.001). 19% had had accidents in use of the condom. HIV seroprevalence in the women was 6.1% (95% CI, 3.5%-10.3%). CONCLUSIONS: Health care of people with HIV must include care of their sexual partner, involving information, psychological support, preventive and reproductive advice, as well as diagnosis of HIV or other sexually transmitted diseases.
Adult↗
[Prevalence of the HIV infection in patients seen at specialized diagnosis centers in 9 cities in Spain from 1992 to 2001].
OBJECTIVE: To describe the prevalence of HIV infection in persons tested between 1992 and 2001. DESIGN: Descriptive, cross-sectional epidemiological study. SETTING: 10 ambulatory centers specialized in diagnosing HIV, located in 9 cities in Spain. PARTICIPANTS: 53,183 persons older than 12 years, tested for the first time for HIV. MAIN MEASURES: Number of persons tested per year, number of persons diagnosed as seropositive for HIV according to sex, age group and category of exposure. RESULTS: The number of persons tested increased from 4401 in 1992 to 6407 in 2001. Approximately half reported heterosexual risk exposure/exposure through high-risk heterosexual behaviors, excluding prostitution. Intravenous drug users (IVDU) increased from 15.3% in 1992-1993 to 1.4% in 2000-2001, and women prostitutes/female sex workers increased from 6.7% to 25.1%. A total of 2898 persons were diagnosed as having HIV infection; 78% of them were men. The number of diagnoses decreased from a high of 1058 in 1992-1993 to 304 in 2000-2001, and this trend was seen for all categories of exposure except female prostitutes and men with heterosexual risk factors. The prevalence decreased from 14% in 1992 to 2% in 2001. There were decreases in all categories of exposure, especially during the first years of the study, with a tendency to level off. In 2001 the prevalence figures were 23.8% for IVDU, 7.9% for homosexual men and women, 0.8% for female sex workers and 1% for other heterosexual men and women. CONCLUSIONS: The specialized diagnostic centers play an important role in diagnosing HIV, and this service complements primary care services. Greater efforts are needed in the prevention of HIV infection.
Adult↗
Different behavior toward bovine spongiform encephalopathy infection of bovine prion protein transgenic mice with one extra repeat octapeptide insert mutation.
In humans, insert mutations within the repetitive octapeptide region of the prion protein gene (Prnp) are often associated with familial spongiform encephalopathies. In this study, transgenic mice expressing bovine PrP (boTg mice) bearing an additional octapeptide insertion to the wild type (seven octapeptide repeats instead of six) showed an altered course of bovine spongiform encephalopathy (BSE) infection, reflected as reduced incubation times when compared with boTg mice expressing similar levels of the wild-type six-octapeptide protein. In both boTg mouse lines (bo6ORTg and bo7ORTg), incubation times were affected drastically depending on transgene expression levels and the inoculum used. In accordance with the lack of an interspecies barrier to BSE infection, we detected the typical signs of CNS spongiform degeneration by histopathological analysis and the presence of the bovine prion PrP(res) by Western blot or immunohistochemical analyses. When 7OR-PrP(res) was propagated in bo7ORTg mice, a similar earlier onset of clinical signs was observed compared with bo6ORTg mice. Proteins PrP(C) and PrP(res) containing seven octapeptides (7OR-PrP(C) and 7OR-PrP(res)) showed similar protease sensitivity and insolubility in nondenaturing detergents to homologous 6OR-PrP(C) and 6OR-PrP(res). In addition, bo7ORTg mice showed a higher sensitivity than bo6ORTg mice for detecting prion infection in specimens previously diagnosed as negative by conventional biochemical techniques. In the absence of clinical signs of disease, 7OR-PrP(res) could be detected as early as 120 d after inoculation by immunohistochemical and Western blot analyses. These findings may help us improve the current mouse bioassays and understand the role of the octapeptide repeat region in susceptibility to disease.
Age of Onset↗
Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.
Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.
Anti-HIV Agents↗
[Dialysis and Transplant Registry of the Spanish Society of Nephrology and regional registries. Rapport 2001].
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Adolescent↗
Sentinel surveillance of HIV infection in HIV test clinics, Spain 1992-2002.
HIV infection in Spain was monitored in persons undergoing voluntary HIV testing in ten sentinel clinics between 1992 and 2002. Only patients on their first visit were considered for inclusion, and their numbers rose from 4426 in 1992 to 6649 in 2002. Most of them recognised their risk exposure as heterosexual. The proportion of injecting drug users decreased from 19% to 2% of the study population, and the proportion of female sex workers increased from 6% to 26%. The number of patients diagnosed with HIV infection declined from 604 in 1992 to 153 in 2002, and HIV prevalence fell from 13.6% to 2.3% in the same period. In all risk exposure categories, a decrease in HIV prevalence was observed, more pronounced during the first few years and stabilised in the later years. In 2002, the highest HIV prevalence was found in injecting drug users (IDUs) (14.2%), homo/bisexual men (7.5%) and individuals who had an HIV infected heterosexual partner (10.2%).
Adult↗
Early detection of PrPres in BSE-infected bovine PrP transgenic mice.
Transgenic mouse lines expressing different levels of the bovine prion protein gene (boPrP(C)) were generated. Upon infection with BSE prions, all transgenic lines tested exhibited characteristics of the bovine disease. Typical CNS spongiform degeneration was observed by histopathology and presence of PrP(res) could be detected both by Western blot and immunohistochemistry (IHC) assays, confirming for this model the absence of an interspecies barrier to BSE infection. Differences in incubation times post-inoculation depend upon the expression level of boPrP(C) and the amount of prions in the inoculum. In the absence of clinical signs, pathognomonic markers of disease could be detected as early as 150 or 196 days post-inoculation by IHC and Western blot analysis, respectively. This result indicates that prion infectivity in experimental mouse bioassays can be measured earlier by assessing immunologically the presence of PrP(res) in brains from inoculated animals. Although these transgenic mice were also susceptible to sheep scrapie prion infection, the extent of incubation times was considerably longer and PrP(res) was detected in only 70 % of inoculated mice. Interestingly, transgenic mice-propagated sheep scrapie prions displayed distinct biochemical properties when compared to both the original sheep scrapie and transgenic mouse-propagated BSE inoculum.
Animals↗
Absence of hepatitis C virus transmission in a prospective cohort of heterosexual serodiscordant couples.
OBJECTIVE: To analyse hepatitis C virus (HCV) transmission in a cohort of heterosexual couples who are discordant both for HIV and for HCV. METHODS: We followed an open cohort of 171 people, 152 women and 19 men, who were not initially infected by either HIV or HCV, and whose steady heterosexual partner presented antibodies to both viruses (index case). Other risk exposures were excluded. Every 6 months clinical, epidemiological, and risk behaviour information was collected, and antibodies to both viruses were determined. RESULTS: During 529 person years of follow up more than 40 000 vaginal or anal penetrations were recorded. 74 partners (43.3%) had vaginal and/or anal intercourse without condoms with the index case; another 15.8%, who always used condoms, declared breaking or slipping episodes during intercourse; and another 22.2% had unprotected orogenital exposures. During the follow up, over 5800 unprotected vaginal and anal contacts with the index case were estimated, as well as more than 25 000 unprotected orogenital contacts. 31 women became pregnant (two were index cases), and seroconversion to HIV occurred for one woman (1.7 per 10 000 unprotected contacts; 95% CI, 0 to 9.5), but there was no seroconversion to HCV (95% CI, 0-6.3 per 10 000 unprotected contacts). CONCLUSION: These results are consistent with a low or null transmissibility of HCV in heterosexual relations, even when the index case is HIV co-infected.
Adolescent↗
Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways.
Although cisplatin, cis-diamminedichloroplatinum(II), has been successfully used in the chemotherapy of cancer for more than 25 years, its biochemical mechanism of action is still unclear. The current accepted paradigm about cisplatin mechanism of action is that the drug induces its cytotoxic properties through binding to nuclear DNA and subsequent interference with normal transcription, and/or DNA replication mechanisms. If cisplatin-DNA adducts are not efficiently processed by cell machinery, cytotoxic processes eventually end up in cell death. However, before cisplatin enters the cell it may bind to phospholipids and phosphatidylserine in the cell membrane. In addition, in the cytoplasm many potential platinum-binding sites are also available, including RNA and sulfur-containing biomolecules. Moreover, there is much evidence suggesting that the cytotoxic effects induced by binding of cisplatin to non-DNA targets (especially proteins) may contribute to its biochemical mechanism of action. On the other hand, it has been found that several factors such as the dose of drug as well as the metabolic condition of the cell subjected to cisplatin aggression, may determine that cancer cells die through apoptosis or necrosis. In fact, it has recently been reported that both mechanisms of cell demise work in concert so that within a population of tumour cells there is a continuum of possible modes of cell death.
Animals↗
[HIV prevalence among homosexual and bisexual men in Spain, 1992-2000].
BACKGROUND: Our purpose was to describe the time trend in HIV seroprevalence among homo/ bisexual men. SUBJECTS AND METHOD: We analyzed 9,383 homo/ bisexual men who had a first voluntary test for HIV in 10 Spanish clinics from 1992 to 2000. RESULTS: HIV prevalence decreased from 20.3% in 1992 to 8.4% in 2000. In the multivariate analysis this decline appeared independently associated with the testing year and the birth cohort. CONCLUSIONS: New generations of voluntarily tested homo/bisexual men are less infected by HIV, but it is yet necessary to intensify the prevention programs.
Adolescent↗
[Are we diagnosing people infected with HIV in time?].
OBJECTIVE: To describe the number of AIDS cases who did not know of their HIV infection until they developed AIDS, and the factors relating to this situation. DESIGN: Descriptive study of data of the National AIDS Register.Setting. Spain.Patients. Cases of AIDS in the over-14s diagnosed between 1997 and 1999. RESULTS: Of the 6910 cases of AIDS studied, 35% (n = 2421) knew that they were HIV-positive at the same time as they were diagnosed with AIDS (in the same month or the previous one). The multi-variate analysis showed that this situation occurred less commonly in women (OR = 0.61; 95% CI, 0.53-0.71), in cases diagnosed in prison (OR = 0.19; 95% CI, 0.13-0.27), in cases diagnosed early (OR = 0.49; 95% CI, 0.41-0.60) and among residents in provinces with AIDS rates higher than the Spanish average (OR = 0.88; 95% CI, 0.78-0.99). Ignorance of HIV infection until the AIDS diagnosis was associated to ages of under 25 and over 34, homo/bisexual transmission (OR = 3.20; 95% CI, 2.69-3.80) and heterosexual transmission (OR = 4.88; 95% CI, 4.21-5.65) compared with intravenous drug users, and to the person coming from countries other than Spain, both developed (OR = 2.78; 95% CI, 1.89-4.08) and under-developed (OR = 1.85; 95% CI, 1.26-2.72) countries. CONCLUSIONS: A considerable number of people diagnosed with AIDS were unaware of their HIV infection, especially among people who had never injected drugs. HIV needs to be diagnosed earlier so as to improve prevention and treatments.
Adolescent↗
Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV-infected patients.
BACKGROUND: High viral load is currently considered to be one of the main indicators of the progression of HIV-induced immunodepression, but few studies have analysed its relationship to the presence of oral candidiasis (OC). The aim of this cross-sectional study is to analyse the relationship between viral load, total CD4 lymphocyte count, and percentage of CD4 lymphocytes to the occurrence of OC. METHODS: The present cross-sectional study included 156 HIV-infected patients seen at a clinic for sexually transmitted diseases and HIV. We assessed the presence or absence of OC, and microbiological samples were obtained from the palatine mucosa and dorsal tongue for a smear stained with KOH (potassium hydroxide) and culture on Sabouraud's dextrose agar in all patients. Viral load was determined by quantification of viral RNA in peripheral blood with a minimum detectable level of 500 RNA copies/ml. CD4+ counts/CD4+ percentage were categorized as <200/<14%, 200-499/14-28%, and >500/>29%, and HIV viral loads were categorized as <500, 500-10,000, >10,000 copies/ml. RESULTS: Thirty-eight percent (37.8%) of the patients had OC. Patients with CD4+ lymphocyte counts below 200 x 10(6)/l and CD4+ percentages below 14% showed a significantly higher frequency of OC (57.9% and 48.0%, respectively). Patients with a viral load over 10,000 copies/ml also had OC more frequently (44.8%). In the multiple logistic regression analysis, OC showed a statistically significant association with high viral load [>10,000 vs <500, odds ratio (OR)=11.4], low percentage of CD4+ lymphocytes (<14% vs >28%, OR=5), and injection drug use (IDU vs heterosexual transmission, OR=10.2). In HIV-infected patients, high viral load was associated with more frequent OC, regardless of CD4+ lymphocyte level. CONCLUSIONS: These findings suggest that oral candidiasis could be a useful clinical marker of patients with high viral load. In view of these results, emphasis should be placed on the importance of systematic examination of the oral cavity in all medical follow-up examinations of HIV-infected patients.
AIDS-Related Opportunistic Infections↗
Factors influencing HIV progression in a seroconverter cohort in Madrid from 1985 to 1999.
OBJECTIVE: To study HIV progression from seroconversion over a 15 year period and measure the population effectiveness of highly active antiretroviral therapy (HAART). METHODS: A cohort study of people with well documented dates of seroconversion. Cumulative risk of AIDS and death were calculated by extended Kaplan-Meier allowing for late entry. Cox proportional hazards models were used to study variables associated with HIV progression. To assess the impact of HAART, calendar time was divided in three periods; before 1992, 1992-6, and 1997-9. RESULTS: From January 1985 to May 2000, 226 seroconverters were identified. The median seroconversion interval was 11 months, median seroconversion date was March 1993. 202 (89%) were men, 76% of whom were homo/bisexual. A 66% reduction in progression to AIDS was observed in 1997-9 compared to 1992-96 (HR 0.34 95% CI: 0.16 to 0.70). People with primary education appeared to have faster progression to AIDS compared to those with university studies (HR 2.69 95%CI: 1.17 to 6.16). An 82% reduction in mortality from HIV seroconversion was observed in 1997-9 (HR 0.18 95% CI: 0.05 to 0.68) compared to 1992-6. Progression to death for people with primary education was twice as fast as for those with university education (p 0.0007). People without confirmation of an HIV negative test had faster progression (HR 4.47 95% CI: 1.18 to 16.92). CONCLUSIONS: The reduction in progression to AIDS and death from seroconversion from 1992-6 to 1997-9 in Madrid is likely to be attributable to HAART. HIV progression was faster in subjects with primary education; better educational level may be associated with better adherence to medication.
Acquired Immunodeficiency Syndrome↗
Novel concepts in the development of platinum antitumor drugs.
The limitations of cisplatin as an anticancer drug have stimulated the search for other antitumor-active platinum complexes with improved pharmacological properties. The two main goals in the search for new platinum anti-cancer agents are the reduction of the dose-limiting toxicities of cisplatin and the circumvention of cisplatin resistance. However, it should be pointed out that this has proven to be a difficult task. In fact, less than 1% of the thousand of platinum complexes tested for pre-clinical antitumor activity have entered clinical trials in the past 30 years. Nonetheless, right now, several new platinum complexes are in clinical trials, a proof of the continued belief that platinum complexes may still fulfil the needs for novel antitumor drugs. This review will focus on the three main innovative approaches found in the platinum anticancer-field, namely, (1) compounds with decreased reactivity against nucleophiles, (2) compounds with carrier ligands, and (3) compounds which bind differently to DNA as compared to cisplatin. In the latter class, special attention is paid to dinuclear and polinuclear platinum complexes.
Animals↗