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.     

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.     

Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients.

PURPOSE: To evaluate safety and preliminary efficacy of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy (RT) in unresectable head and neck cancer patients. Secondary end points were the measurement of h-R3 serum levels and the assessment of the potential mechanisms of antitumor effect on patient biopsies. Anti-idiotypic response to h-R3 was assessed. To predict pharmacologic effect, a mathematical model for antibodies recognizing antigens expressed in tumors and normal tissues was built. PATIENTS AND METHODS: Twenty-four patients with advanced carcinomas of the head and neck received six once-weekly infusions of h-R3 at four dose levels in combination with RT. Pretreatment tumor biopsies were obtained to evaluate epidermal growth factor receptor expression as an enrollment criterion. Second biopsies were taken to evaluate the proliferative activity and angiogenesis in comparison with the pretreatment samples. Patient serum samples were collected to measure h-R3 levels and anti-idiotypic response. RESULTS: The combination of h-R3 and RT was well tolerated. Antibody-related adverse events consisted in infusion reactions. No skin or allergic toxicity appeared. Overall survival significantly increased after the use of the higher antibody doses. Immunohistochemistry studies of tumor specimens before and after treatment revealed that antitumor response correlated with antiproliferative and antiangiogenic effect. One patient developed antibodies to h-R3. The mathematical model predicted that the maximum difference between the area under the curve in tumors and normal tissues is reached when the antibody has intermediate affinity. CONCLUSION: h-R3 is a well-tolerated drug that may enhance radiocurability of unresectable head and neck neoplasms.     

Clinical presentation of a group of NF2 patients to a tertiary referral skull base unit

The objective of the investigation was to document the clinical presentations of a group of patients with neurofibromatosis type two syndrome (NF2), and took the form of a retrospective case note review. The investigation took place in the tertiary referral skull base unit. The dominant presentation of patients with NF2 is with auditory/vestibular symptoms (56%), with a smaller proportion of presentations being due to non-acoustic intracranial and spinal tumours (44%). At the time of presentation the majority of clinically significant tumours could be demonstrated in each patient with MRI of the head and spine, with few new tumours arising during the subsequent follow-up period. The range of presentation of patients with NF2 results in their management being fragmented into a variety of clinical setting, diluting the experience amassed in any one centre.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.