A novel immunization method to induce cytotoxic T-lymphocyte responses (CTL) against plasmid-encoded herpes simplex virus type-1 glycoprotein D

DNA molecules complexed with an asialoglycoprotein-polycation conjugate, consisting of asialoorosomucoid (ASOR) coupled to poly-L-lysine, can enter hepatocytes which bear receptors for ASOR. We used this receptor-mediated DNA delivery system to deliver plasmid DNA encoding glycoprotein D (gD) of herpes simplex virus type 1 to ASOR-positive cells. Maximum expression of gD protein was seen at 3 days after injection of this preparation in approximately 13% of cells from BALB/c mice [hepatocytes from mice injected intravenously (i.v.) or peritoneal exudate cells from mice injected intraperitoneally (i.p.)]. In comparison with mice injected with either the plasmid vector alone or the gD-containing plasmid uncomplexed to ASOR, mice immunized with gD-containing plasmid complexed with ASOR-poly-L-lysine induced marked antigen-specific CTL responses. BALB/c mice immunized with gD-DNA developed a T-cell-mediated CTL response against target cells expressing gD and MHC class II glycoproteins, but not against cells expressing only gD and MHC class I molecules. In C3H mice, gD-DNA induced a T-cell-mediated CTL response against target cells expressing gD and class I MHC molecules. Serum anti-gD antibody in low titers were produced in both strains of mice. DNA complexed with ASOR-poly-L-lysine induced CTL responses in mice.     

The psychosocial effects of amblyopia study.

PURPOSE: The purpose of this study was to assess the psychosocial effects of growing up with and living with amblyopia and to determine whether patients with amblyopia but without strabismus encounter psychosocial problems similar to those encountered by individuals with strabismus. METHODS: A 20-question survey focusing on medical background, education, self-image, history of amblyopia, treatment of amblyopia, and effects of amblyopia on work, school, friendships, and self-esteem was provided to patients with amblyopia but not strabismus at Saint Louis University Eye Institute and at the University of Iowa Department of Ophthalmology. In addition, patients were evaluated in terms of somatization, obsession-compulsion, interpersonal sensitivity, depression, and anxiety. Results for patients with amblyopia were compared with those of strabismic, normative, and psychopathologic groups using the Hopkins Symptom Checklist (HSC). RESULTS: Twenty-five patients with amblyopia but without strabismus or previous surgery responded. A significant number of patients felt that amblyopia interfered with school (52%) and work (48%) to some degree and were generally affected in their lifestyle (50%). Fewer were affected in their play of sports (40%) or were influenced as to their job choice (36%). Patients with amblyopia as a whole had a greater degree of somatization, obsessive-compulsive behavior, interpersonal sensitivity, depression, and anxiety than patients with strabismus and HSC control subjects. Differences between patients with amblyopia and those with strabismus were not statistically significant (P > .05), but differences between patients with amblyopia and HSC control subjects were significant (P < .05) in each category. Patients with amblyopia, however, were less symptomatic in these areas than HSC Anxious and HSC Depressed groups. CONCLUSION: Psychosocial difficulties related to amblyopia affect individuals' self-image, work, school, and friendships. Amblyopia has a significant effect on psychosocial functioning and warrants aggressive screening, prevention and treatment during the amblyogenic years.     

In vitro study of the interaction between quinolones and polyvalent cations

The aim of the present study was to evaluate the influence of aluminium and iron on the in vitro dissolution kinetics of ciprofloxacin and ofloxacin as well as the usefulness of this type of in vitro data to predict modifications in in vivo absorption processes as a consequence of different factors, such as the widely documented in vivo interaction between quinolones and cations. Fitting of experimental data to different theoretical in vitro dissolution profiles was performed by non-linear regression methods and the statistical moments were calculated from raw experimental data. Analysis of residuals applied to dissolution curves as well as statistical comparison of the estimated parameters were carried out to evaluate the in vitro interaction. The results reveal significative modifications of the dissolution profiles of these quinolones as a consequence of the presence of cations, especially for Fe2+ which decreases 34.7% the maximum amount dissolved for ciprofloxacin and 29.1% for ofloxacin. Al3+ also produces a decrease of the total amount of quinolone dissolved although less relevant than Fe2+. Analysis of residuals proved to be the best statistical method to evaluate differences between whole dissolution profiles, at least under the experimental conditions used.     

A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion

In this phase I study, terephthalamidine was administered as a 120-hour continuous infusion repeated every 21 days. Thirteen patients received 27 courses of terephthalamidine at four dose levels (14, 28, 46, and 70 mg/m²/day). Dose-limiting toxicity consisted of profound and intractable anorexia, weight loss and prostration in all patients. Toxicity was delayed and accompanied by hyponatremia and hypokalemia. No hematologic or other toxicity was documented. One patient with adenocarcinoma of the lung had a 40% decrease in mediastinal lymph nodes and resolution of a pleural effusion lasting 2 months. Pharmacokinetic analysis by HPLC was performed in all patients during their first course. The harmonic mean terminal half-life for terephthalamidine was 23 hours with a plasma clearance of 1.7 l/hr/m². Both plasma concentrations achieved during infusion (r² = 0.9) and area under the curve (AUC) (r² = 0.8) were proportional to increase in dose (p < 0.002). Renal excretion accounted for 64% of the total cumulative dose, with an average renal clearance of 1.16 l/hr/m². Due to the unacceptable toxicity seen at all doses with this schedule, no further studies are recommended unless the mechanism of toxicity is better understood and can be prevented.     

Validation of a quality of life questionnaire for critically ill patients

Objective Development and validation of quality of life questionnaire for critical care patients.Design Prospective study.Setting Intensive care unit (ICU) of a general hospital and ICUs of 83 Spanish hospitals.Sample Patients admitted to the ICU>18 years of age; close family members.Method A committee of experts designed a questionnaire with characteristics judged essential for intensive care use: easy, quick administration (5–10 min); capable of completion by patient or close family member, by direct or telephone interview. Fifteen items relevant to critical care patients were grouped in three subscales: basic physiological activities, normal daily activities, and emotional state. Reproducibility of interobserver, intraobserver, patient/family member and telephone/direct interviews was analysed and also internal consistency, responsiveness, and main components.Results Internal consistency (578 patients): Cronbach's alpha coefficient=0.85. Reproducibility: intraobserver reproducibility (n=150): Spearman correlation coefficient=0.92. Interobserver (n=85); correlation=0.92. Patient/family member (n=81): correlation=0.92. Telephone/direct interview (n=54): correlation=0.96. Validity: factorial analysis confirmed that the three subscales were fundamental questionnaire components. There was good concordance between questionnaire/subscale and Glasgow Outcome Scale (GOS) results. Responsiveness: quality of life score changes between preadmission and 6 months' postdischarge correlated with GOS findings (weighted kappa index=0.56).Conclusions Questionnaire meets objectives recommended for critical care use, and fulfills essential requirements of validity and reproducibility when applied to critically ill patients.This study forms part of the PAEEC (Project for the Epidemiological Analysis of Critical Care Patients), and was supported by a grant from the Fondo de Investigaciones Sanitarias (F.I.S.-91/0703), and by the Granada University Research Group (Number 3244)     

Blood pressure, physical activity and anthropometry in adolescents]

The relationship of blood pressure with physical activity and anthropometry was studied in 295 adolescents (mean age, 15.3 years) who entered 1. "formación profesional" (a technological training) in 1990 in Puerto Real, a village of Cádiz, Spain. Systolic and diastolic (fifth-phase Korotkoff) blood pressure, and anthropometrics measurements (weight, height and triceps and subscapular skinfolds thickness) were measured with standardized techniques. Habitual and sports physical activity were assessed by a self-reported questionnaire. The results reported in this study suggest that systolic blood pressure is associated with habitual physical activity in girls, and that the systolic blood pressure is associated weakly with sports activity in girls and in boys. The stronger predictor of blood pressure was Quetelet Index (kg/m2).     

Effect of oxodipine on calcium transport in isolated hepatocytes and rat liver mitochondria at different ages

Electron microscopy and biochemical studies were carried out in hepatocytes and mitochondria isolated from livers of young (3-6 month) and old (20-24 month) rats to know under which conditions oxodipine, a calcium antagonist, affects calcium metabolism, the mitochondrial morphology and the differences due to the animals age. Under steady-state conditions, calcium transport through the membrane of isolated hepatocytes was not affected by the presence of the drug in either group of animals studied. By contrast, a clear age-dependent inhibitory effect on the uptake and accumulation of calcium was observed in mitochondria. In the young animals, evidence was observed for a complex mechanism related to cellular respiration and to a possible specific action of the drug. In older animals, this second mechanism appears to be very weak or inexistent. Quantitative morphological studies also point to a deterioration in the mitochondria due to the effect of the drug at the concentrations at which cellular respiration was affected.     

Liposuction in Atypical Cases

Liposuction has become the most frequent aesthetic procedure, and its indications continue to expand to different areas of plastic surgery. In this article the authors present their experience with liposuction in the treatment of nine cases termed ``atypical,' for not being purely aesthetic. Included are four congenital lipodystrophies—occult spinal disraphism, osteogenesis imperfecta, congenital lipomatosis difusa, and Klinefelter syndrome—and five acquired ones—posttraumatic lipoma, posttraumatic asymmetry, insulinic hypertrophic lipodystrophy, adiposis dolorosa, and TRAM flap. Particular features of each lipodystrophy are reviewed and details of fat distribution and density are described. We also review some specific details of the technique. On the other hand, we wish to point out the importance of recognizing and correctly diagnosing some specific lipodystrophies that are part of defined clinical patterns and that require an integral therapeutic approach.     

Inhibition of β‐amyloid toxicity by short peptides containing N‐methyl amino acids

Abstract: Single N‐methyl amino acid‐containing peptides related to the central hydrophobic region β_16–20 (Lys‐Leu‐Val‐Phe‐Phe) of the β‐amyloid protein are able to reduce the cytotoxicity of natural β_1–42 in PC12 cell cultures. N‐methyl phenylalanine analogs yield statistically significant increments in cell viability (Student's t‐test < 0.01%) and are nontoxic in the same assay. These promising results indicate that these peptide molecules could be a starting point for the development of potential therapeutic compounds for the treatment of Alzheimer's disease.