Sustained antiretroviral treatment adherence in survivors of the pre-HAART era: attitudes and beliefs.

The objective of this study was to assess adherence of HIV-1-infected patients who started treatment in the pre-HAART era and to determine variables associated with better adherence, including relevant attitudes and beliefs. This is a cross-sectional study enrolling patients who had received antiretroviral therapy for >or=10 years. Adherence was evaluated through self-reporting and plasma drug concentrations. Treatment variables, attitudes and beliefs were collected during structured interviews. The results show that for 87 patients the median (interquartile range) time on therapy was 13 (10-19) years; 80 were on therapy at the time of analysis. Adherence was >or=95% in 54 patients (67.5%), 90-94% in 22 (27.5%) and <90% in 4 (5%). Drug concentrations were below the lower limit of detection in five patients. Younger age (p=0.014), female gender (p=0.005), current substance abuse (p=0.004) and hepatitis C virus co-infection (p<0.001) were related to lower adherence. Adherence did not differ in relation to different drug families or once- or twice-daily regimens. Patients with adherence <95% were more likely to have interrupted treatment without doctor's recommendation (p=0.009). Adherent patients exhibited a higher perception of risk of developing the illness and of benefits of therapy, higher self-efficacy and intention to adhere and were more influenced by events that motivate medication intake. To conclude, adherence was >90% in most patients on antiretroviral therapy for >or=10 years. Adherence was more related to beliefs about health and illness than to the characteristics of medication or level of knowledge about treatment. Care adherence interventions should include assessment of health beliefs.

Enhancement of adriamycin antitumor activity by its binding with an intracellular sustained-release form, polymethacrylate nanospheres, in U-937 cells.

We investigated the antitumor activity of Adriamycin on a monocytic-like cancer cell line U-937 after its binding on polymethacrylate nanospheres (diameter, 270-350 nm). Compared to free Adramycin (F-ADR), nanosphere-bound Adriamycin (B-ADR) exhibits a 3-fold enhancement of cytotoxicity, as determined by cell growth inhibition and DNA synthesis, after continuous exposure to 0.02 and 0.04 microgram/ml. The 90% growth inhibition concentration was 0.051 microgram/ml for F-ADR and was 0.018 microgram/ml for B-ADR (P less than 0.001). Furthermore, the nanosphere densities per cell play an important role since for the same drug concentration the higher the density increases, the better the activity is. Indeed, after 4 days of incubation in a medium containing 160 nanospheres at 0.5 fg/cell, the cell counts were 62.8 +/- 12.8% (SD) of the initial inoculum and they were only 16.1 +/- 0.1% after incubation in a medium containing 800 nanospheres at 0.1 fg/cell (P less than 0.001). A comparable enhancement of activity regarding the nanosphere densities was observed after a 24-h exposure to 0.02 and 0.05 microgram/ml. Short-term uptake studies showed that B-ADR accumulation was higher with B-ADR than with F-ADR. In addition, the efflux kinetics was modified. For cells exposed to F-ADR for 4 h, the efflux half-life was 23.7 +/- 7.7 h and the area to infinity under the efflux curve was 8.6 +/- 2.8 micrograms/mg protein x h-1. For cells exposed to B-ADR, the efflux half-life increased to 85.9 +/- 19.2 h and the area to infinity under the efflux curve to 29.6 +/- 6.6 micrograms/mg protein x h-1 (P less than 0.001). Electron transmission microscopy and previous findings have revealed that B-ADR was well internalized into cells. Our data support the hypothesis that B-ADR acts as an intracellular drug release complex after endocytosis. The findings regarding the number of nanospheres per cell and dose-effect relationships are consistent with mechanisms of drug actions extending to membrane domains.

Psychological impact of structured treatment interruptions in patients with prolonged undetectable HIV-1 viral loads.

Structured treatment interruption strategies may help overcome problems of highly active antiretroviral therapy, but might also represent a cause of stress. We present data that indicate a psychological benefit from structured treatment interruption. Although some disturbances appear at the resumption of therapy, no definitive problems are found that preclude such therapeutic approaches from a psychological perspective. However, a close follow-up of patients during interruption periods is advisable to avoid difficulties reported at treatment resumption presenting a risk to patients' health.

A lactobionate-based extracellular-type solution for donor heart preservation.

The University of Wisconsin solution, which contains the impermeant lactobionate and has an intracellular-type electrolyte composition, has been shown to improve donor heart preservation. Because a deleterious effect of the intracellular-type solutions has been reported, we evaluated a new lactobionate-based extracellular-type solution, by comparing it with University of Wisconsin solution and a crystalloid cardioplegic solution in 45 rabbit hearts. Hearts were arrested by infusion of these solutions and immersed in the same solution (lactobionate-based extracellular-type solution, University of Wisconsin solution) or in the lactated Ringer's solution (crystalloid cardioplegic solution) for 6 hours at 4 degrees C. A Langendorff circuit was used for reperfusion. Left ventricular compliance was better preserved with both lactobionate-based solutions than with the crystalloid cardioplegic solution. Adenosine triphosphate was best preserved with the lactobionate-based extracellular-type solution after arrest and after reperfusion, whereas reperfusion arrhythmias were less marked with the University of Wisconsin solution. These results suggest that lactobionate plays an important role in the preservation of ventricular compliance and that the lactobionate-based extracellular-type solution is preferable for adenosine triphosphate preservation. Further study will be required to assess the factors predisposing to reperfusion arrhythmias.

Thermodynamic parameters of the interaction between Co(II) bovine carbonic anhydrase and anionic inhibitors.

The pH dependence of the apparent affinity constants of perchlorate for cobalt(II)bovine carbonic anhydrase II has been measured by electronic absorption spectroscopy. The obtained data have been analyzed in terms of the ionization of two acidic groups of CoBCAII, and the affinity of perchlorate for the two water-containing species of the enzyme have been estimated. Furthermore, the affinity constants of nitrate, perchlorate, and azide for CoBCAII in the temperature range 5 degrees C-30 degrees C have been determined by spectrophotometric titrations at pH 7. The affinity constants for these ligands decrease with increasing temperatures. The temperature dependence of binding was used to estimate the enthalpy and entropy parameters for the formation of the corresponding 1:1 adducts. The obtained results indicate that binding of these anions to the cobalt enzyme is an enthalpy driven process which is opposed by a moderate entropy change.

Interaction of sulphate and chloride with cobalt(II)-carbonic anhydrase.

The interaction between Cobalt(II)-Bovine Carbonic Anhydrase II and the inhibitors sulphate and chloride have been investigated through 1H NMR and electronic absorption spectroscopies. Both inhibitors bind to the metal ion forming a 1:1 adduct and the corresponding affinity constants have been determined. These inhibitors interact weakly with CoBCA II and this interaction only occurs at low pH values. The T1 values of the meta-like protons of the coordinated histidines have been measured. The coordination number of the metal ion in the adducts is discussed on the basis of temperature dependence of the isotropic shifts, T1, and molar absorbance values.

1H NMR and UV-Vis spectroscopic characterization of sulfonamide complexes of nickel(II)-carbonic anhydrase. Resonance assignments based on NOE effects.

The binding of acetazolamide, p-fluorobenzensulfonamide, p-toluenesulfonamide, and sulfanilamide to nickel(II)-substituted carbonic anhydrase II has been studied by 1H NMR and electronic absorption spectroscopies. These inhibitors bind to the metal ion forming 1:1 complexes and their affinity constants were determined. The 1H NMR spectra of the formed complexes show a number of isotropically shifted signals corresponding to the histidine ligands. The complexes with benzene-sulfonamides gave rise to very similar 1H NMR spectra. The NMR data suggest that these aromatic sulfonamides bind to the metal ion altering its coordination sphere. In addition, from the temperature dependence of 1H NMR spectra of the p-fluorobenzenesulfonamide adduct, a conformational change is suggested. The T1 values of the meta-like protons of the coordinated histidines have been measured and resonance assignments based on NOE experiments were performed.

Intrathecal morphine for postoperative analgesia following repair of frontal encephaloceles in children: comparison with intermittent, on-demand dosing of nalbuphine.

STUDY OBJECTIVE: To determine the efficacy of lumbar intrathecal (i.t.) morphine in a dose of 0.02 mg/kg in providing analgesia following repair of frontal encephaloceles. DESIGN: Prospective, open-label investigation of i.t. morphine with secondary comparison to a retrospective cohort. SETTING: Metropolitan hospital in the Philippines. PATIENTS: 24 ASA physical status I and II children undergoing frontal encephalocele repair. INTERVENTIONS: Following induction of general anesthesia. I.t. morphine (Group 1) was administered via single-shot technique or through a lumbar i.t. drain placed for cerebrospinal fluid drainage during the surgical procedure. Postoperative analgesia was assessed by visual analog score in patients greater than 5 years of age or a behavioral score in patients less than 5 years of age. The retrospective cohort received postoperative analgesia with intermittent doses of intravenous nalbuphine (Group 2). MEASUREMENTS AND MAIN RESULTS: Group 1 had decreased postoperative analgesic requirements, decreased intraoperative inhalational anesthetic requirements, and a longer time to the first request for postoperative analgesia than Group 2. The time to the first request for postoperative analgesia was 16.0 +/- 9.1 hours in Group 1 and 1.6 +/- 1.2 hours in Group 2 (p < 0.0001). Six of 12 patients in Group 1 required no analgesic drugs during the first 24 postoperative hours while all 12 patients in Group 2 (p = 0.02) did require analgesic drugs during this period. The patients in Group 1 who did not require supplemental analgesic drugs maintained pain scores of 2 or less throughout the first 24 postoperative hours. CONCLUSION: Lumbar IT morphine provides effective analgesia following repair of frontal encephaloceles in children and adolescents.

[Mechanical ventilation-associated pneumonia and the prevention of stress ulcer. A randomized clinical trial of antacids and ranitidine versus sucralfate]. / Neumonía asociada a ventilación mecánica y profilaxis del ulcus de estrés. Ensayo clínico aleatorizado de antiácidos y ranitidina frente a sucralfato.

BACKGROUND: To study two groups of patients intubated with different prophylaxis of stress gastric ulcer in a prospective randomized trial. The differential effect on gastric pH, gastric colonization and the incidence of pneumonia associated to mechanical ventilation (PMV) were analyzed. METHODS: A prospective randomized study was carried out in two groups of patients: 1) prophylaxis with antacids and H2 blockers (AA+H2) and 2) prophylaxis with sucralfate. Intubated patients without initial respiratory infection were included in the protocol. Periodically gastric aspirations were collected measuring gastric pH and performing semi-quantitative cultures. When pneumonia was suspected bronchial brushing was carried out with telescoped catheter (BBTC) and quantitative culture. RESULTS: Fifty-one patients were studied (n = 51), distributed into 25 in the AA+H2 group and 26 in the sucralfate group. In the first group mean pH was higher (5.3 +/- 1.7) than in the sucralfate group (3.2 +/- 2.1) (p = 0.006). Nosocomial pneumonia (NP) was suspected on 25 occasions: 20 patients were positive for NP, 11 in the AA+H2 group and nine in the sucralfate group with no significant differences being observed. S. aureus, S. pneumoniae and H. influenzae (n = 14) were the etiology of predominant PMV. The global mortality of the group was of 22%. CONCLUSIONS: The prophylaxis of stress ulcers in intubated patients treated with antacids and ranitidine provoked higher gastric pH and an increase in gastric colonization in comparison to that observed with sucralfate. No significant differences were observed in the frequency of pneumonia by PMV diagnosed by BBTC.

Bilateral infraorbital block with 0.5% bupivacaine as post-operative analgesia following cheiloplasty in children.

Various studies have shown that bupivacaine nerve blocks provide prolonged post-operative analgesia. We studied the efficacy of a 0.5% bupivacaine infraorbital nerve block as post-operative analgesia in a random, prospective, double blind manner in children undergoing cleft lip repair. Following the induction of anesthesia with ketamine 2-4 mg/kg im, 60 patients, aged 2-13 years, ASA I and II were equally divided: Group A received 1-1.5 ml bupivacaine, 0.5% with 1:200,000 epinephrine; Group B received 1-1.5 ml saline injected into the vicinity of the infraorbital foramina. In every patient, the surgeon infiltrated the lip with 4-7 ml of 1% lidocaine with 1:100,000 epinephrine for both anesthesia and hemostasis. Post-operative evaluations were completed after 4, 8, and 12 to 24 hours and were based on a visual analogue scale for pain. Similarly, the nurses and the parents also evaluated post-operative discomfort using specific criteria. All the observers were kept unaware of the solutions used for the block. The results showed that Group A was pain free for a mean duration of 19.4 +/- 5.06 (SD) hours in contrast to 11.7 +/- 6.19 hours for Group B, (p less than 0.001). Group A required no other analgesic whereas a total of 17 patients in Group B required analgesic medication starting at four hours post-operatively, (p less than 0.001). Both the nurses and the parents confirmed that those who received infraorbital block were more comfortable than those who did not. One-way analysis of variance indicates that the mean scores for both groups differs significantly at all levels of comparison, (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Efficacy of topical povidone-iodine applied the day before cataract surgery to reduce conjunctival flora]. / Eficacia de la povidona yodada tópica administrada el día previo a la cirugía de catarata para reducir la flora conjuntival.

OBJECTIVE: To evaluate the efficacy of the topical use of periocular and conjunctival povidone-iodine solution applied the day before cataract surgery to reduce conjunctival flora. PATIENTS AND METHODS: Randomized and prospective clinical trial with 82 patients. The treatment group (41 patients) received an application of topical 10% povidone-iodine solution on the periocular skin and instillation of topical 5% povidone-iodine solution on the forniceal conjunctiva the day before and one hour before surgery. The control group (41 patients) only received the usual perioperative disinfectant. Conjunctival smears were obtained from in all patients at the end of the surgery and these were sent to the Microbiology Laboratory for culture. RESULTS: In the treatment group 1 positive culture was found in the 41 eyes (2.4%). In the control group, there were positive cultures in 6 out of 41 eyes (14.6%). The difference is statistically significant (p<0.05). CONCLUSIONS: The disinfecting of the periocular skin with 10% povidone-iodine solution and of the conjunctiva with 5% povidone-iodine solution the day before and one hour before cataract surgery is effective in reducing conjunctival bacterial colonization compared with perioperative disinfection alone.

Obstructive sleep apnea is associated with cancer mortality in younger patients.

OBJECTIVE: The association between obstructive sleep apnea (OSA) and cancer mortality has scarcely been studied. The objective of this study was to investigate whether OSA is associated with increased cancer mortality in a large cohort of patients with OSA suspicion. METHODS: This was a multicenter study in consecutive patients investigated for suspected OSA. OSA severity was measured by the apnea-hypopnea index (AHI) and the hypoxemia index (% night-time spent with oxygen saturation <90%, TSat90). The association between OSA severity and cancer mortality was assessed using Cox's proportional regression analyses after adjusting for relevant confounders. RESULTS: In all, 5427 patients with median follow-up of 4.5 years were included. Of these, 527 (9.7%) were diagnosed with cancer. Log-transformed TSat90 was independently associated with increased cancer mortality in the entire cohort (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.42), as well as in the group of patients with cancer (HR, 1.19; 95% CI, 1.02-1.41). The closest association was shown in patients <65years in both the AHI (continuous log-transformed AHI: HR, 1.87; 95% CI, 1.1-3.2; upper vs lower AHI tertile: HR, 3.98; 95% CI, 1.14-3.64) and the TSat90 (continuous log-transformed TSat90: HR, 1.73; 95% CI, 1.23-2.4; upper vs. lower TSat90 tertile: HR, 14.4; 95% CI, 1.85-111.6). CONCLUSIONS: OSA severity was associated with increased cancer mortality, particularly in patients aged <65 years.

Influence of the type of pegylated interferon on the onset of depressive and neuropsychiatric symptoms in HIV-HCV coinfected patients.

This is a prospective observational comparative 48-week study to assess the impact of the different types of Peg-IFN on depressive and neuropsychiatric symptoms during treatment in HIV-HCV coinfected patients. Thirty-one patients treated with Peg-IFN alpha-2b 1.5 microg/kg/w plus ribavirine (RBV) (Peg-IFN alpha-2b Group) and 32 patients receiving Peg-IFN alpha-2a 180 microg/w plus RBV (Peg-IFN alpha-2a Group) were included. Depressive and neuropsychiatric symptoms, quality of life and adherence were assessed. Fifteen subjects (23%) discontinued therapy (p = 0.3, between groups). Overall, 37 patients presented mild to moderate depressive symptoms, 9 moderate to severe and 3 severe, without differences between groups. Patients in Peg-IFN alpha-2b reported higher fatigue and dizziness at weeks 12 (p < 0.05) and 24 (p < 0.05), and irritability and memory loss at week 24 (p < 0.05) with respect to Peg-IFN alpha-2a Group. At week 12, role functioning, general health perception, vitality, emotional role, mental health and the summary areas of physical health and mental health were lower in Peg-IFN alpha-2b Group (p < 0.05). The same was observed in physical functioning (p = 0.05) and role functioning, general health perception, emotional role and mental health (p < 0.001) at week 24. Three months after finishing treatment, no patient had depressive or neuropsychiatric symptoms, and quality of life improved. Antiretroviral adherence was low but adherence to anti-HCV therapy remained high in both groups. According to our data, Peg-IFN alpha-2a and Peg-IFN alpha-2b exert a similar impact on the overall rate of depressive symptoms, although patients treated with Peg-IFN alpha-2a experience less fatigue and fewer neuropsychiatric symptoms and a lower impairment in their physical and mental quality of life.

Papillary squamous cell carcinoma of the oropharynx.

A case of papillary squamous cell carcinoma of the oropharynx is reported. The lesion was located in the base of the tongue and grossly presented a characteristic finger-like pattern of growth. The clinicopathological profile of the neoplasm is presented and the differential diagnosis with other exophytic squamous cell carcinomas is discussed.

[Radio-immunometric determination of the ferritin for evaluation of the iron storage pool (author's transl)]. / Dosage radio-immunométrique de la ferritine pour l'appréciation des réserves martiales.

Seventy-three patients with several haematological diseases have been studied with radio-iron-kinetic, cyto-chemical measurement of iron in the bone marrow, and radio-immunometric determination of the ferritin in the serum. This method gives results which correlate significantly with other methods which evaluate the iron storage pool, in normal or iron-deficient patients. In some cases, an excess of serum ferritin, contrasting with normal serum iron, is confirmed by cytochemical and/or Fe-kinetic studies. In myeloproliferative diseases however, secretion of ferritin by immature cells may induce an excess of serum ferritin. In such cases, the dosage of ferritinaemia cannot be considered as an index of the iron storage pool. Future development of specific dosage of isoferritins could enable to measure the true iron stores, as well as to give an index estimating the evolution of the abnormal cell population.

Prospective randomized two-Arm controlled study to determine the efficacy of a specific intervention to improve long-term adherence to highly active antiretroviral therapy.

BACKGROUND: Nearly perfect compliance seems to be indispensable to obtain the maximum benefit from highly active antiretroviral therapy (HAART). Interventions to ensure a high level of adherence during a relatively long-term period of therapy are necessary. METHODS: This is a prospective, randomized, two-arm controlled study including patients starting their first-or second-line HAART who were randomized to receive psychoeducative intervention to implement adherence (experimental group [EG]) or a usual medical follow-up (control group [CG]). We aimed to study the efficacy of a psychoeducative intervention to ensure long-term adherence to HAART, its relation with the virologic efficacy of treatment, and to determine the variables related to long-term adherence. Visits were made at weeks 0, 4, 24, and 48 for data collection. Self-reported adherence was registered at each visit and its veracity was tested by randomized blood analyses performed without previous warning to 40% of patients. Appropriate adherence was defined as the consumption of >/=95% of medication prescribed. Statistical analyses were performed both by the as treated (AT) and the intention to treat missing = failure (ITT) methods. RESULTS: In all, 116 patients were included. At week 48, 94% of patients in the EG versus 69% controls achieved adherence >/=95% (p =.008); 89% of patients in the EG versus 66% controls had HIV-1 RNA levels <400 copies/ml (p =.026). Overall, 85% of patients with adherence >/=95% but only 45% of those with adherence <95% had viral load (VL) <400 copies/ml (p =. 008). In multivariate analysis, variables significantly related to adherence were having received a psychoeducative intervention (odds ratio [OR], 6.58; p =.04), poor effort to take medication (OR, 5.38; p =.03), and high self-perceived capacity to follow the regimen (OR, 13.76; p =.04). Self-reported adherence and drug plasma levels coincided in 93% of cases. However, differences in adherence did not reach statistical significance in the ITT analysis although a clear tendency toward benefit was observed in EG. CONCLUSIONS: Specific and maintained psychoeducative interventions based on excellence on clinical practice are useful to keep high levels of adherence as well as high levels of viral suppression. There is a clear relation between high adherence levels and virologic success. Assessment of certain specific variables related to adherence may be helpful to monitor patient's compliance in the clinical setting.

Colgajo miofacial del músculo temporal: presentación de casos clínicos / Myofacial flat of the temporal muscle: presentation of a clinical cases

El tratamiento quirúrgico de los tumores de cavidad oral y seno maxilar precisa una reconstrucción del defecto. Es preferible realizarla en un solo tiempo quirúrgico para disminuir la morbilidad del paciente y el costo sanitario. Presentamos nuestros resultados tras la reconstrucción de defectos después demaxilectomía total o parcial con el colgajo miofascial del músculo temporal en 22 pacientes. Discutimos sobre las ventajas de este colgajo frente a otros actualmente utilizados

Valoración estadística de las actividades realizadas en el Centro de Información del Medicamento de Granada durante el último año

El Centro de Información del Medicamento (CIM) es un servicio en el que se realiza la selección, análisis y evaluación de las fuentes de información sobre medicamentos para elaborar y comunicar la información encaminada a facilitar el uso racional de los fármacos (1). Este trabajo es un informe de las actividades desarrolladas en el Centro de Información del Medicamento del Colegio Oficial de Farmacéuticos de Granada durante el año 2001 (AU)