Bilateral macular hemorrhage after laser in situ keratomileusis

· Background: This is the first report of a bilateral submacular hemorrhage after LASIK surgery in an extreme myo pic patient. A 31-year-old man underwent bilateral surgery for correction of –16.75+0.75×70° and –16.50+0.50×55°. · Methods: Case report. · Results: One day after surgery the patient’s uncorrected visual acuity was in the 20/50 range OU and by 17 days after surgery his visual acuity had declined to 20/200 range. Fundus examination showed multifocal subretinal macular and posterior pole hemorrhages. Fluorescein angiography showed some macular lesions compatible with lacquer cracks. · Conclusions: Preoperative and postoperative fundus examination is important to detect this phenomenon. Patients should be informed of this rare complication. Received: 2 June 1998 Revised version received: 16 November 1998 Accepted: 17 November 1998     

Long-term results of the Spanish trial on treatment and survival of patients with predominantly mild heart failure

A randomized open-label clinical trial was conducted to determine whether mortality, readmission, or quality of life differed between heart failure patients managed with captopril plus diuretics and those with digoxin plus diuretics. A total of 345 heart failure patients in New York Heart Association functional classes 2 and 3 without atrial fibrillation, dyspnea of bronchopulmonary origin, or hypertension not controlled with diuretics was randomized for digoxin (n = 175) or captopril (n = 170) treatment and followed up for a median of 4.5 years. Socioeconomic, demographic, electrocardiographic, echocardiographic, spirometric, and chest radiograph data were obtained at the initial examination. In a random sample of half the patients, ergometric, echocardiographic, and Holter records were obtained at entry and at 3 and 18 months. Patients were followed up for > or = 3 years. The end points were mortality, hospitalization for cardiac events, deterioration in quality of life, worsening of functional class, and need for digoxin or captopril in the captopril and digoxin groups, respectively. The trial had to be terminated prematurely owing to the difficulty in finding candidates free of angiotensin-converting enzyme (ACE)-inhibitor treatment. Baseline patient characteristics were similar in both groups. From the clinical point of view, only the 48-month mortality was relevantly lower (20.9 vs. 31.9%, respectively) among patients treated with captopril than that in those receiving digoxin (log rank test, p = 0.07). No statistically or clinically relevant differences were found in other end points or adverse effects. The results suggest but do not confirm the hypothesis that captopril treatment in mild to moderate heart failure might provide better long-term survival than digoxin.     

Tamoxifen aziridine binding to cytosolic proteins from human breast specimens is negatively associated with estrogen receptors, progesterone receptors, pS2, and cathepsin-D

[³H]Tamoxifen Aziridine ([³H]TAZ) is a derivative of the antiestrogen tamoxifen that covalently labels the Estrogen Receptor (ER), and perhaps other uncharacterized proteins. In a previous article we described that [³H]TAZ binds to a cytosolic protein from human uterine tissues that shares some, but not all, the ER properties. Here we have extended these studies to [³H]TAZ binding to cytosol proteins from human breast cancer specimens, and studied its quantitative association with other molecular markers and clinico-pathological variables. Cytosols were obtained in hypotonic buffer containing 20 mM molybdate and protease inhibitors, incubated with [³H]TAZ, and subjected to Sucrose Gradient Analysis (SGA). A [³H]TAZ labeled peak that consistently migrated with the 4S fractions was found in most of the assayed cytosols (range of 0 to 1278 fmol/mg p.). The 4S peak of [³H]TAZ was partially inhibited by both estrogens and antiestrogens. When [³H]E₂ was used instead of [³H]TAZ, only an 8S peak was detected. [³H]TAZ was covalently bound to a protein with an apparent MW of 65 kDa, as determined by SDS-PAGE and fluorography. The mean of [³H]TAZ binding was significantly higher in the subgroups of samples classified as ER-, PR-, pS2- or cathepsin D-, than in the respective positive subgroups (P < 0.01 in all the cases). [³H]TAZ binding was not associated with clinico-pathological variables, except that its mean was significantly larger in tumors larger than 5 cm than in smaller tumors. These results, and those previously reported, suggest that: 1) [³H]TAZ labels a cytosolic protein present in human breast cancers and uterine tissues that does not share all the ER properties, and 2) the [³H]TAZ binding by breast cancer cytosols is negatively associated with markers of estrogenic dependency, and its quantification may provide valuable information on antiestrogen responsiveness of a given tumor.     

Invariant aphthovirus consensus nucleotide sequence in the transition to error catastrophe

RNA viruses replicate as complex distributions of non-identical but closely related variant genomes termed viral quasispecies. When the error rate during genome replication exceeds a threshold value, the genetic information cannot be maintained and the system enters error catastrophe. This violation of the error threshold results in virus extinction and it is currently being investigated as a new antiviral strategy, based on antiviral activity of some mutagenic agents. Previous studies with the important animal pathogen foot-and-mouth disease virus (FMDV) have shown that FMDV entry into error catastrophe is associated with an increase of complexity (mutation frequency and Shannon entropy) of the mutant spectrum of the quasispecies and that mutated, pre-extinction RNA interferes with the infectivity of standard RNA. Here, we report that despite the increase of complexity, the genomic consensus nucleotide sequence of pre-extinction FMDV RNA remains invariant, and that the fitness of pre-extinction FMDV is at least six-fold lower than the fitness of the parental viral clone, prior to mutagenic treatments. Thus, a low fitness genome ensemble can suppress replication of high fitness virus. Furthermore, the results show that profound genetic modifications associated with fitness decrease of a virus population can take place without any manifestation in the consensus genomic sequence. Thus, increase in mutant spectrum complexity and invariance of the consensus sequence characterizes FMDV extinction through error catastrophe.     

Interobserver agreement in the diagnosis of pulmonary embolism with helical CT

PURPOSE: Our objective was to asses the interobserver agreement in the detection of pulmonary embolism (PE) with contrast-enhanced helical CT at the main pulmonary, lobar and segmental arteries. A prospective study was carried out in 51 patients with suspected PE. Finally, 29 patients were diagnosed of PE. SUBJECTS AND METHODS: All patients were studied with helical CT. Images (5 mm collimation, 1.5 pitch factor, 3 mm reconstruction interval) were obtained after bolus contrast injection (120 ml, 4 ml/s, 15 s delay time). All cases were blinded and independently interpreted in three ways: two radiologists with different level of expertise and two expert radiologists reading by consensus. Agreement was evaluated by means of the kappa test. RESULTS: Kappa values for thrombi detection expressed an excellent agreement at the main (between 0.802 and 0. 946), lobar (between 0.915 and 0.958) and segmental (between 0.879 and 0.718) levels. For all vessels, mean kappa values were similar and excellent for all three combinations of readers. Arteries with more discrepancies were located mainly at the anterior and posterior areas of the upper lobes. CONCLUSIONS: The high degree of agreement shown in this study indicates that helical CT is a reproducible test in the diagnosis of PE to the segmental level. Isolated readings and levels of expertise do not influence agreement.     

Immune responses of a meningococcal A + W outer membrane vesicle (OMV) vaccine with and without aluminium hydroxide adjuvant in two different mouse strains

Meningococci (Neisseria meningiditis) of serogroups A and W have caused large epidemics of meningitis in sub‐Saharan Africa for decades, and affordable and multivalent vaccines, effective in all age groups, are needed. A bivalent serogroup A and W (A + W) meningococcal vaccine candidate consisting of deoxycholate‐extracted outer membrane vesicles (OMV) from representative African disease isolates was previously found to be highly immunogenic in outbred mice when formulated with the adjuvant aluminium hydroxide (AH). OMV has been shown to have inherent adjuvant properties. In order to study the importance of AH and genetical differences between mice strains on immune responses, we compared the immunogenicity of the A + W OMV vaccine when formulated with or without AH in inbred C57BL/6J and BALB/cJ mice (Th1 and Th2 dominant strains, respectively). The immunogenicity of the vaccine was found to be comparable in the two mice strains despite their different immune profiles. Adsorption to AH increased anti‐OMV IgG levels and serum bactericidal activity (SBA). The immune responses were increased by each dose for the adsorbed vaccine, but the third dose did not significantly improve the immunogenicity further. Thus, a vaccine formulation with the A and W OMV will likely benefit from including AH as adjuvant.