HIV-1 genetic diversity in Galicia Spain: BG intersubtype recombinant viruses circulating among injecting drug users.

BACKGROUND: The HIV-1 epidemics in Western Europe are dominated by B subtype viruses. Non-B subtype is largely restricted to individuals infected outside of Europe and to their direct contacts and is generally acquired by the heterosexual route. METHODS: Protease and a segment of reverse transcriptase were amplified and sequenced from plasma RNA in 451 individuals from seven cities of Galicia, north-western Spain. Subtype sequence homologies were determined using the BLAST algorithm. Non-B sequences were examined by phylogenetic analysis and intersubtype recombination by bootscanning. The env V3 region was analysed in all non-B and in 38 B subtype viruses. RESULTS: Ten different non-B genetic forms were identified in 20 (4.4%) individuals. Subtypes were concordant between pol and V3 in five viruses; 14 (70%) infections were with intersubtype recombinant viruses, and one individual had a dual B+G infection. Seven recombinant viruses were phylogenetically related to five reported recombinant forms. Three non-recombinant G and six recombinant BG viruses formed a monophyletic cluster for pol. All but three individuals with non-B infections were native Spanish. Only 6 of 16 individuals referred to sexual contacts with sub-Saharan Africans. Twelve (60%) non-B subtype infections, including all with G and BG viruses, were in injecting drug users (IDU). CONCLUSIONS: Non-B subtype viruses were identified in 4.4%, with a high diversity of genetic forms, including 70% infections with intersubtype recombinant viruses. The majority of individuals with non-B infections were IDU, most of them without known contacts with non-European sources, and among whom BG recombinant viruses are circulating.

Real time monitoring and analysis via the medical information bus, Part I.

Because of the complexity of monitored data in modern intensive care units (ICUs), and the risk of information being overlooked if medical staff have to pay attention to a multiplicity of monitoring apparatuses and alarm signals, the data for each patient may well be best presented on a single bedside screen after digestion by expert system techniques. Such central units should be able to deal with data from any monitoring apparatus, not just a predefined set. Furthermore, relay of the information from each bed to a central control station (one per ICU) is desirable for the purposes of permanent storage and for in-depth analysis. The paper describes a comprehensive system for ICU monitoring management and patient data analysis that integrates multiple expert systems and computers. The basic difficulties in applying expert system techniques to monitoring are overcome with the shell OPS/83, which allows calls to sequential C routines and allows time-driven reasoning through appropriate design of the inference engine and rules. Flexibility as regards connectable monitoring apparatus is afforded by basing data acquisition mainly, though not exclusively, on the IEEE Medical Information Bus.

Real time monitoring and analysis via the medical information bus, Part II.

The complexity of the monitored data available in modern intensive care units suggests that they may be best processed, for presentation to medical staff, by expert system techniques. However, standard expert system shells are ill-fitted to either the basic sequential monitoring tasks of data acquisition and storage, or to handling the temporal considerations inherent in monitoring and in the recognition and processing of sporadic alarm signals. A solution to this dilemma is described: an expert system that has an appropriately designed inference engine and manages data acquisition via a medical information bus (MIB). Use of this MIB standard allows great flexibility as regards the monitoring apparatuses employed; in particular, the connection or disconnection of any apparatus is recognised and triggers the automatic reconfiguration of the network.

[Analysis of the management of the vaccination campaign in 1996-1997 against meningococcus C in Galicia]. / Análisis de la gestión de la campaña de vacunación 1996-1997 frente al meningococo C en Galicia.

This paper describes the process to design and plan a vaccination campaign against group C N. Meningitidis developed in the Autonomous Community of Galicia between December 9, 1996 and January 31, 1997. We also analyse the results of this process in terms of management results, vaccine coverage and preliminary estimates of effectiveness. A Work group was established, made up of professionals in charge of different intervention areas. A person was designated in charge of the whole campaign and a follow-up and information system was created. The work plan consisted of daily meetings for follow-up, co-ordination and task distribution; and periodical meetings with primary health care and peripheral public health coordinators. Strategies of implantation--in order to make sure the campaign accessibility and acceptability; of budget and of communication with health workers, inhabitants and mass media were developed. Up to 100 tasks were identified to develop the technical information and logistic activities: mailings, meetings, leaflets, ...; purchasing of 584.980 doses of vaccine, supplying to 715 vaccination points (1040 deliveries); problem solving and intervention recording. A vaccination coverage of 85% was achieved, with notification of 8 adverse reactions and 6 errors in the administration of the vaccine (34 children affected). The strategy chosen for the design and planning of the campaign has proven to be effective and valid and sufficient to achieve the final goals, in due time and without problems of misinformation, shortage of vaccine or lack of participation of professionals or people. Mistakes due to incorrect administration of the vaccine, management problems, rupture of the cold chain or recording failures were minimal and accidental.

[Intraoperative control of mean arterial pressure and heart rate with alfentanyl with fuzzy logic]. / Control intraoperatorio de la presión arterial media y frecuencia cardíaca por alfentanilo por medio de un controlador borroso.

OBJECTIVES: To describe a fuzzy logic controller that adjust alfentanil infusion during surgery based on changes in mean arterial pressure (MAP) and heart rate (HR). MATERIAL AND METHODS: We designed a fuzzy logic controller using if ... then ... conditions written in C language, to be executed by a 486 PC with a 66 Mhz CPU. The controller was used with eight ASA I-II patients undergoing gynecological surgery under anesthesia with propofol, alfentanil and ventilated with oxygen/air. MAP and HR were input every three minutes, after which the controller generated an infusion based on those figures. We performed a statistical study of alfentanil consumption time until extubation and time of hemodynamic stability. Relative error of MAP was calculated. RESULTS: The controller was used for a total of 373 min with the eight patients. MAP was 15% below the desired level for 2.14% (18 min) of that time and was 15% over the desired level for 5.6% (21 min) of the time. MAP held steady within the range of stability for the remaining 92.26% (334 min) of the time the controller was used. The relative error of MAP was 7.8 +/- 1.5%. Mean time until extubation was 7 min and 2 s. CONCLUSIONS: We believe the controller can be used to automate taks executed by experts. The controller was useful for stabilizing HR and MAP.

A quarter of a century with AIDS.

In Northwestern Spain (NWS), the annual incidence of AIDS diagnoses increased from 1984 (when the first case was diagnosed) until 1996. However, since 1996, this incidence has reduced considerably, including a notable 40% reduction between 1997 and 1998. The Galician Register of AIDS supplies information on the evolution of AIDS pathology in NWS. This report compiles data on patients who were diagnosed with AIDS in NWS between 1984 and 2008. From 1981, when the first case of AIDS was described, until December 31, 2008, a total of 3,766 AIDS cases were registered in NWS. Of these, 2,085 cases (55.4%) resulted in death. Examining data from individual provinces revealed that the highest number of cases was in A Coruña (1,548 cases) followed by Pontevedra (1,485 cases).For almost half of the new cases of AIDS diagnosed between 2003 and 2008 (44%), less than six months passed between the diagnosis of infection and manifestations of the disease. Thus, the number of patients that do not receive early diagnosis of HIV infection has remained high.With regard to the transmission mechanism, 64% of the cases occurring during these years resulted from needle-sharing among injected drug users (IDUs). Unprotected heterosexual and homosexual practices were responsible for 20% and 17% of the cases, respectively.

Long-term monitoring of genotypic and phenotypic resistance to T20 in treated patients infected with HIV-1.

The aim of this study was to investigate the susceptibility to T20 and the dynamics of amino acid changes in HR1 and HR2 of gp41 of HIV-1 obtained from plasma, peripheral blood mononuclear cells (PBMC), and primary isolates (PI) in four highly antiretroviral-experienced patients. These patients received T20 plus an antiretroviral regimen and were followed-up over a period of 40-72 weeks. In one non-responder patient, N43D substitution was detected at 12 weeks of treatment, in association with a value of T20-IC50 of 10 microg/ml (10-fold increase). Double mutations N42T + N43D were observed in plasma RNA at 32 weeks and remained detectable up to 16 weeks after the withdrawal of the drug. The S138A substitution in HR2 was observed in plasma RNA at 32 weeks, and both in plasma RNA and in PI DNA at 40 weeks, associated with an increase of the T20-IC50 to 25 microg/ml (25-fold increase). Mutations V101G and E137K, not reported previously, were also observed in the HR2 region. Whether these new substitutions play a role in T20 resistance needs to be examined. In three temporary responders, coinciding with viral load rebound, G36D, and N42T substitutions were observed at 12, 24, and 40 weeks. G36D mutation was associated with a value of T20-IC50 of 5 microg/ml. The HR2 S138A mutation was detected after the detection of HR1 substitutions and was associated with an increase in the level of T20-IC50 to 125 microg/ml (125-fold increase) All these data reinforce the role of gp41 amino acids 36-45 and the potential influence of the HR2 S138A mutation in the genotypic/phenotypic resistance to T20.

Refining the priming principle for vecuronium during rapid-sequence induction of anesthesia.

Administration of a subparalyzing dose of a nondepolarizing muscle relaxant (priming dose) prior to its intubating dose hastens the onset time (time from muscle relaxant administration to 100% depression of twitch tension) of neuromuscular blockade. This study was undertaken to determine the optimal priming and intubating doses and time interval between these doses (priming interval) of vecuronium during rapid-sequence induction of anesthesia. The authors measured single-twitch tension in 79 healthy, awake, premedicated (fentanyl, 50-150 mu iv, and/or diazepam, 5-10 mg iv) patients. In Part A of the study, the priming dose was varied (0.0, 0.005, 0.01, 0.0015, or 0.02 mg/kg iv). Decrement of twitch tension and symptoms were recorded 3 min later. Four minutes after the priming dose, thiopental, 4-6 mg/kg iv, and vecuronium, 0.1 mg/kg iv, were given. Onset times for the 0.01, 0.015, and 0.02 mg/kg groups were significantly shorter than for 0.005 and 0.0 mg/kg groups. No breathing difficulties were encountered in any of the groups. Decrement of twitch tension greater than 25% of control only occurred in the 0.02 mg/kg group (4 of 11 patients). In Part B, the priming interval was varied (2, 4, or 6 min) after giving the optimal priming dose (0.01 mg/kg). Anesthesia was induced as in Part A. Onset times for the 4-min group were significantly faster than the 2- or 6-min groups. In Part C, the intubating dose was varied (0.07, 0.1, or 0.15 mg/kg iv) after the optimal priming dose and optimal priming interval (4 min). Onset times for the 0.1 mg/kg and 0.15 mg/kg groups were significantly faster than the 0.07 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)

Neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium.

To compare the time course of neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium, the authors studied 98 patients anesthetized with nitrous oxide (60%) and halothane or enflurane. Neuromuscular blockade, as monitored by single stimulus-induced twitch tension (TT), was antagonized at varying degrees of spontaneous recovery (2-80% of control TT). Time to antagonism (time from injection of neostigmine or edrophonium to 90% recovery of control TT) was not different between edrophonium, 0.5 mg/kg, and neostigmine, 0.04 mg/kg, when spontaneous recovery had been allowed to occur to at least 11% of control TT prior to antagonist administration (P greater than 0.05). For profound neuromuscular blockade (TT less than or equal to 10% of control) induced by pancuronium or vecuronium, time (mean +/- SD) to antagonism with neostigmine, 0.04 mg/kg, was 7.0 +/- 2.2 min and 5.6 +/- 1.7 min, respectively, while the same for edrophonium, 0.5 mg/kg, was 20.0 +/- 8.0 min and 15.0 +/- 12.5 min, respectively (P less than 0.05). Time to antagonism of profound atracurium-induced neuromuscular blockade was 8.5 +/- 3.3 min for neostigmine, 0.04 mg/kg, and 9.8 +/- 7.0 min for edrophonium, 0.5 mg/kg, (P less than 0.05). For profound vecuronium-and pancuronium-induced neuromuscular blockade, time to antagonism by edrophonium, 1.0 mg/kg, was 4.6 +/- 3.0 min and 3.9 +/- 1.6 min respectively. The authors conclude that neostigmine, 0.04 mg/kg, antagonizes neuromuscular blockade within 12 min when TT is greater than 2% of control at time of reversal. When TT is greater than 10% of control, edrophonium, 0.5 mg/kg, produces similar time to antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Single- and multidrug resistance mutations to reverse transcriptase and protease inhibitors: human immunodeficiency virus type 1-infected patients from two geographical areas in Spain. Spanish Groups for Antiretroviral Resistance Studies.

OBJECTIVES: To describe the prevalence of genotypic resistance mutations, including single and multidrug resistance (MDR) to reverse transcriptase (RT) and protease (PR) inhibitors in treated and untreated patients from two geographical areas in Spain (Madrid and Galicia). STUDY DESIGN/METHODS: Resistance mutations to RT inhibitors were studied by line probe assay (LiPA) or by automated sequencing in 468 patients (Madrid, 268; Galicia, 200), and resistance mutations to PR inhibitors were studied by automated sequencing in 295 patients (Madrid, 85; Galicia, 210). RESULTS: The proportion of resistance mutations in treated and untreated patients results were higher by the LiPA method than by sequencing. By sequencing, we detected resistance mutations to nucleoside analogue RT (NRT) inhibitors and NRT inhibitors plus nonnucleoside RT (NNRT) inhibitors in 35.4% and 17.2% of treated patients, respectively. We also detected MDR to zidovudine plus lamivudine in 13.9% of treated patients from Galicia, in 1.7% from Madrid (p < 0.001), and in 1.5% of untreated patients from Galicia. Also, we detected MDR to NRT inhibitors in 3.8% and to NNRT inhibitors in 9.1%. We found resistance mutations to PR inhibitors in 38.1% of treated patients and in 0.9% of untreated patients. CONCLUSIONS: These findings reinforce the usefulness of testing for resistance mutations in some cases to evaluate their prevalence in a given population and in the follow-up of treated patients.