Natural prevalence of HCV minority variants that are highly resistant to NS3/4A protease inhibitors.

Minority drug-resistant hepatitis C virus (HCV) variants may go undetected yet be clinically important. NS3/4A protease resistance substitutions V36A and A156S/T/V were selected in patients treated with protease inhibitors. The aim of this study was to investigate whether these substitutions pre-existed in HCV infected patients. An allele-specific PCR protocol that detected the NS3/4A protease resistance substitutions V36A and A156S/T/V was used to determine the prevalence of naturally occurring variants in 45 patients. All patient samples were infected with HCV of genotype 1b and were naïve for pegIFNα/ribavirin treatment. Thirty samples (67%) had at least one HCV PI-resistant variant. A156T (23, 51%) was detected more frequently than A156V (13, 29%) or A156S (1, 2%). V36A was detected in 12 samples (27%). These results demonstrate the high prevalence of minority drug-resistant NS3/4 protease resistance substitutions. Our results also demonstrate that allele-specific PCR can be used to detect minor HCV NS3 protease resistant variants in pretreatment samples and to study in detail the evolution of mutant viruses during targeted antiviral therapy.

[Combined hamartoma of the retina and retinal pigment epithelium. Anti-VEGF treatment of the associated choroidal neovascular membranes]. / Hamartoma combinado de retina y del epitelio pigmentario. Abordaje mediante terapia anti-VEGF de membranas neovasculares asociadas.

CASE REPORT: A 58 year-old female was diagnosed with a juxtapapillary combined hamartoma of the retina and retinal pigment epithelium (CHR-RPE) in her left eye 14 years ago. Her visual acuity in that eye was 20/20. Recently, she came to our department with a sudden visual loss and metamorphopsis in her left eye. After performing funduscopy, angiography and OCT, she was diagnosed with choroidal neovascular membrane (CNVM) at lesion border, and started on antiangiogenic therapy. DISCUSSION: CHR-RPE, despite being a benign condition, may become complicated with severe visual impairment. Antiangiogenic therapy provides a good alternative to photodynamic therapy or laser photocoagulation for treatment of CNVM, avoiding adding iatrogenesis from these treatment to the complications associated with this pathology.

[Effect of various levels of alcohol consumption on plasma lipoproteins and apoproteins]. / Influencia de diversos grados de consumo de alcohol sobre las lipoproteínas y apolipoproteínas plasmáticas.

To assess the abnormalities induced by alcohol on plasma lipids and lipoproteins and their possibly involved mechanisms three basis of the daily intake: social drinkers (less than or equal to 20 g/day; n = 10), moderate drinkers (greater than 20 to less than 70 g/day; n = 11), and severe drinkers (greater than or equal to 70 g/day; n = 15). Eleven nondrinkers were evaluated as control group. Very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL)-2 and HDL-3 were isolated by preparative sequential isopicnic centrifugation, and their apolipoprotein and lipidic composition were measured. In the group of severe drinkers, a marked tendency of HDL-3 cholesterol to be higher than in the remaining groups was found. There was no correlation between this parameter and hepatic enzymes. The HDL-2 cholesterol of severe drinkers was significantly increased (p less than 0.005). The parallel enrichment in apolipoproteins C of the HDL-2 particle in all groups of alcohol users suggests a transfer phenomenon from VLDL. The apoA/C ratio of HDL-2 might be useful as a marker of alcohol intake.

[Drug administration schedules in geriatric patients]. / Análisis de las pautas de dosificación de medicamentos en pacientes geriátricos.

BACKGROUND: In this study the prescription of drugs in an outpatients geriatric population was evaluated in terms of age and body weight. METHODS: From a wide survey carried out on 500 geriatric outpatients, all the prescriptions corresponding to H-2 antagonists, digoxin, theophylline, bromazepam, diazepam, lorazepam and triazolam were analyzed. The patients studied were of 60 or more years of age. For each drug patients were stratified into groups according to intervals of body weight with mean age of the patient being determined in each of the intervals as well as the doses received in mg/kg. RESULTS: Two hundred eighty prescriptions were analyzed with 12% corresponding to the H-2 antagonists, 29% to digoxin, 23% to theophylline and 35% to benzodiazepines. There was no significant correlation between age and the doses received. In general, the lowest body weight corresponded with a higher mean age and a marked increase in the mean dose of cimetidine, ranitidine, theophylline, bromazepam, lorazepam, and triazolam administered. There was a tendency to an adjustment in the doses of digoxin in the most elderly patients. CONCLUSIONS: The data found concerning the prescription of drugs to a geriatric outpatients population indicate that in elderly patients adjustments are not made in the doses of drugs administered according to the age and body weight of the patient. Low body weight of the elderly is a overdosage risk factor.

[The impact of hospitalization on drug prescription]. / Impacto de la hospitalización sobre la prescripción de fármacos.

BACKGROUND: The aim of this study was to investigate the influence of hospitalization on drug prescription and identify the proportion of hospital admissions for "pharmacologic causes" and the incidence of side effects during hospital stay. METHODS: Five hundred four patients admitted to the internal medicine department of a community hospital over a consecutive six-month period were studied. Follow up until hospital discharge was carried out with information being collected according to a protocol established from the characteristics of the treatment administered. RESULTS: Most of the patients admitted were elderly males, with low educational and socioeconomic status, presenting multiple chronic diseases. During hospitalization the number of drugs prescribed doubled (6.0) in relation to the mean (3.3) at the time of admission. Upon discharge the mean number of drugs prescribed (4.1) was significantly higher to that at the time of patient admission. This increase in the number of drugs prescribed upon discharge reflected practically all of the therapeutic groups, specially those of antibiotics, hematologic and digestive drugs, including all the patients regardless of age or sex. The number of drugs prescribed during admission was identified as a variable independently associated to the increase in the number of drugs prescribed on discharge. Hospital admissions for pharmacologic causes were due to therapeutic non compliance (15.4%) and the presentation of side effects (7.8%). The presentation of side effects during hospitalization (8.5%), mostly gastrointestinal, cardiovascular or neurologic was related with age, and the number of drugs administered, and was associated with longer hospital stay. CONCLUSIONS: Contrary to what was expected, hospitalization leads to an increase in the number of drugs prescribed in relation with the therapeutic schedules administered prior to admission.

[The efficacy of universal vaccination against the hepatitis B virus. Simulation with a mathematical model]. / Efectividad de la vacunación universal frente al virus hepatitis B. Simulación con un modelo matemático.

We present a mathematical model of the hepatitis B virus (HBV) infection in a community. The main object is to analyze the effects of two different strategies of mass vaccination: newborns or adolescents. It appears that adolescents mass vaccination produces in the short-term a bigger effect than in the newborns. Mathematically, the model is a system of non linear first order differential equations, in which each function is a related class of individuals (susceptible, infectious, carrier, immune and death by HBV) in the evolution of the HBV. The solution of system is obtained in a numerical way. It should be pointed out that the model explains neatly the herd immunity effect of the vaccine and can be used in the simulation of possible changes in the HBV infection such that generalized use of discarded needles by the drug addicted population, changes in the sexual habits, etc.

[Drug selection in hospitals. A model of reference in self-management of resources]. / Selección de medicamentos en el hospital. Un modelo de autogestión de prestaciones referencial.

The practice of medicine today must balance the optimal use of new pharmaceutical agents with the need for cost containment. Hospital policy regarding therapeutics and its historical perspective are discussed. Various aspects of the operations of Pharmacy and Therapeutics Committees are presented. The potential benefits of a formulary system are therapeutic, economic and educational and it could lead to a uniformity of drug usage throughout a district. The role of Clinical Pharmacology to provide advice to both Institution and physicians in how therapeutic practice may be optimized is also stressed.

Cocaine modulates the expression of transcription factors related to the dopaminergic system in zebrafish.

Nodal-related protein, Ndr2, and transcription factors such as Lmx1b, Otp, Nurr1 and Pitx3 are very important in the differentiation, function and maintenance of mesodiencephalic dopaminergic neurons, and are necessary for the activation of tyrosine hydroxylase (TH) and dopamine (DA) transporter expression. Hence, the aim of the present work was to evaluate the effects of cocaine on the expression of genes related to the embryogenesis development of the dopaminergic system. Zebrafish embryos were exposed to cocaine hydrochloride at 5h post-fertilization (hpf), and collected at two important stages - 24 and 48hpf - to study the effects of cocaine on the expression of ndr2, the lmx1b.1, lmx1b.2, otpa, otpb, nurr1 transcription factors, and their target genes: TH and DA transporter expression. Our results by qPCR showed that cocaine affects the expression of these genes in different ways, depending on the stage of development. Furthermore by in situ hybridization we observed a change in the spatial distribution of lmx1b.1 and lmx1b.2 at both stages (24 and 48hpf) due to exposure to cocaine. We also show the importance of Lmx1b and Otp in th expression through the knockdown of Lmx1b.1 and Lmx1b.2, and of Otpa and Otpb. Additionally, cocaine produced an increase and a decrease in TH levels at 24 and at 48hpf, respectively, possibly due to the change in the expression of the transcription factors and ndr2 expression. We conclude that cocaine alters the correct development of dopaminergic system affecting the expression of transcription factors, during the embryogenesis.

Impact of triplicate testing on HIV genotypic tropism prediction in routine clinical practice.

Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be assessed phenotypically or genotypically. Preliminary clinical trial data suggest that genotypic analysis in triplicate is associated with improved prediction of virological response by increasing the detection of X4-tropic variants. Our objective was to evaluate the impact of triplicate genotypic analysis on prediction of co-receptor usage in routine clinical practice. Samples from therapy-naive and therapy-experienced patients were collected for routine tropism testing at three European clinical centres. Viral RNA was isolated from plasma and proviral DNA from peripheral blood mononuclear cells. Gp120-V3 was amplified in a triplicate nested RT-PCR procedure and sequenced. Co-receptor usage was predicted using the Geno2Pheno([coreceptor]) algorithm and analysed with a false-positive rate (FPR) of 5.75%, 10%, or an FPR of 20% and according to the current European guidelines on the clinical management of HIV-1 tropism testing. A total of 266 sequences were obtained from 101 patient samples. Discordance in tropism prediction for the triplicates was observed in ten samples using an FPR of 10%. Triplicate testing resulted in a 16.7% increase in X4-predicted samples and to reclassification from R5 to X4 tropism for four cases rendering these patients ineligible for Maraviroc treatment. In conclusion, triplicate genotypic tropism testing increases X4 tropism detection in individual cases, which may prove to be pivotal when CCR5-inhibitor therapy is applied.

[Analysis of the efficiency of the screening of anti-HVA IgG antibodies before active or passive immunization]. / Analisis de la eficiencia de la detección de anticuerpos anti-hepatitis A IgG previa a la inmunización activa o pasiva.

BACKGROUND: The epidemiological patron of hepatitis A has changed in the last few years and a decrease of the anti-hepatitis A antibodies IgG (Anti-HVA) have been observed at early ages, which will accompany in the future an increase of symptomatic hepatitis. The prevention of hepatitis A requires a strict application of the norms of personal and environmental hygiene and the administration of vaccines or immunoglobulins. In order to determine the convenience of immunization actively or passively with or without the previous detection of Anti-HVA, requires the knowledge of with strategy is more efficient. METHODS: An analysis is carried out to determine the threshold of prevalence, where the reason of efficiency is established by comparing the unit cost of immunization either actively or passively of the population, with a cost of immunizing only the negative Anti-HVA by previous screening, with the formula: the unit cost of the active or passive immunization (unit cost of screening + cost of active or passive (in specific immunoglobuline) immunization in the negative Anti-HVA). The results correlate with the prevalence of Anti-HVA in age group founded in sero-epidemiological studies published by Salleras (1992 and Pérez-Trallero (1994). RESULTS: The threshold of prevalence, the reason of efficiency equals 1, it's situated in 18% and 65% respectively for the active and passive immunization, which corresponds to the age group of 10-19 years and 20-29 years based on sero-epidemiological studies used. CONCLUSIONS: With prevalence of Anti-HVA equal to or above 18% of the population the most efficient strategy is to determine the Anti-HVA before the active immunization; This threshold of prevalence move to up to 65% with passive immunization. Beneath these prevalence it's more efficient to immunize actively or passively without prior screening.

[Drug use pattern in an ambulatory geriatric population]. / Patrón de utilización de medicamentos en una población geriátrica ambulatoria.

AIM: To provide an update of drug utilization patterns of 500 ambulatory subjects over 60 years of age. METHODS: Subjects were asked about their prescribed and nonprescribed medications an a detailed questionnaire was fulfilled. The case records and prescription sheets, when available, were examined. RESULTS: Drug histories were obtained on 313 women and 187 men. the mean age was 71 years (range 60-96). Of these participants 1.8% were taking no medications. The average number of drugs used was 4.8 (range from 0-16) nevertheless, the mean number of pharmacological active ingredients was much higher (7.3). The mean number of nonprescribed medications was 0.11, the majority with only an active ingredient. 87% had been used for longer than three months, and were taken daily (84%). The most commonly prescribed medications in this population were paracetamol, digoxin, hydrochlorothiazide, amiloride, nifedipine and captopril. CONCLUSIONS: The elderly are, in fact, receiving an increasing number of medications with a narrow therapeutic index and chronically.