Interactions of doxorubicin with organized interfacial assemblies. 1. Electrochemical characterization.

Doxorubicin is an anthracycline that has found wide use as a chemotherapeutic agent, with the primary target of its action being nuclear DNA. Despite the large body of knowledge on this family of compounds, the mechanism of doxorubicin penetration through the cellular or nuclear membrane remains understood to a limited extent. The plasma membrane acts as a barrier to the permeation of polar molecules, and this effect is mainly due to the hydrophobicity of membrane interior. The partitioning of DOX molecules into the lipid bilayer must thus be the basis for its passive transport across the biological membrane and therefore a key area of research activity lies in understanding how the structure of the anthracycline influences its interactions with amphiphilic interfaces. We have studied interactions between doxorubicin and Langmuir/Langmuir-Blodgett monomolecular films of octadecylamine (C18NH2), dihexadecylphosphate (DHP) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and DMPC bilayer films (Langmuir-Schaeffer) on a polycrystalline gold surface using ellipsometry, cyclic voltammetry, electrochemical impedance spectroscopy, and quartz crystal microbalance measurements. For all biomimetic films there is a substantial interaction between doxorubicin and the interface, and the extent of this interaction depends on the hydrophobic/hydrophilic properties of the film formed and its organization.

Interactions of doxorubicin with organized interfacial assemblies. 2. Spectroscopic characterization.

Doxorubicin is an anthracycline that has found wide use as a chemotherapeutic agent, with the primary limitation to its use being cardiotoxicity. Depending on the identity and location of pendent side groups, the anthracyclines exhibit varying degrees of chemotherapeutic activity and toxicity, and a key area of research activity lies in understanding how the structure of the anthracycline influences its interactions with amphiphilic interfaces. We have studied interactions between doxorubicin and interfacial adlayers of octadecylamine (C18NH2), dihexadecylphosphate (DHP), and both monolayers and bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) on mica using time- and frequency-resolved spectroscopic measurements. We report surface-enhanced resonance Raman data and fluorescence lifetime and anisotropy imaging data for doxorubicin at these interfaces. For all monolayers, there is a substantial interaction between doxorubicin and the interface. For DMPC bilayers, the extent of the interaction between doxorubicin and the interface depends on how the interface was formed.

[Usefulness of systematic brain magnetic resonance imaging in children with neurofibromatosis type 1]. / La réalisation systématique de l'imagerie par résonance magnétique cérébrale a-t-elle un intérêt chez l'enfant atteint de neurofibromatose de type 1?

BACKGROUND AND AIM: The aim of this study was to evaluate the usefulness of systematic screening of asymptomatic neurofibromatosis type 1 (NF1) children with magnetic resonance imaging (MRI). PATIENTS AND METHODS: We retrospectively reviewed the MRIs of children diagnosed with NF1 disease according to the National Institutes of Health criteria, who had been followed for at least 1 year by the department of pediatric neurology (Lyon, France). Brain MRI was systematically performed in asymptomatic patients under 6 years of age. RESULTS: One hundred patients with a median follow-up of 3.7 years (range, 1-8.6 years) were reviewed. Brain MRI was performed in a total of 94 children. Nine optic pathway gliomas were detected in symptomatic patients. Six children had symptoms caused by the tumor. Gliomas remained stable in 10 patients; 1 symptomatic glioma in an 8-year-old girl required treatment. Spontaneous regression was seen in 1 patient. CONCLUSION: Our results suggest that MRI screening of asymptomatic children to detect optic pathway gliomas does not improve the therapeutic decision and should not be performed systematically. We suggest further investigation in collaboration with the French NF Network.

Dynamics of 4-benzylamino-7-nitrobenzofurazan in the 1-propanol/water binary solvent system. Evidence for composition-dependent solvent organization.

We report on the fluorescence lifetime and rotational diffusion dynamics of 4-benzylamino-7-nitrobenzofurazan (BBD) in a series of 1-propanol/water binary solvent systems. The fluorescence lifetime of BBD increases monotonically with increasing 1-propanol concentration. The rotational diffusion dynamics of BBD also vary with solution 1-propanol content, but this variation is not monotonic. Comparison of the BBD rotational diffusion time constant to solution viscosity and 1-propanol composition reveals the presence of a solution composition dependence of solvent-solute interactions, with a relative decrease in solvent-solute interaction strength for solvent system compositions where the 1-propanol/water azeotrope is known to exist. These data point collectively to the existence of microscopic heterogeneity in these binary solvent systems.

Epidemiology of ankle arthritis: report of a consecutive series of 639 patients from a tertiary orthopaedic center.

The purpose of our study was to identify the cause of symptomatic ankle arthritis in a consecutive series of patients presenting in a tertiary care setting. Between 1991 and 2004, 639 patients with Kellgren grade 3 or 4 ankle arthritis presented to the University of Iowa Orthopaedic Foot and Ankle Surgery service. The cause of the arthritis was determined based on medical history, physical examination, and imaging studies. To get a sense of the relative prevalence of the etiologies of lower extremity arthritis in our setting, we evaluated the cause of arthritis of all new patients presenting to the University of Iowa Orthopaedic Department from 1999-2004 with arthritis of the ankle, to those with arthritis of the hip or knee during one year. Of the 639 arthritic ankles, 445 (70%) were post-traumatic, 76 (12%) were rheumatoid disease and 46 (7%) were idiopathic (primary osteoarthritis). The post-traumatic ankle arthritis patients were most commonly associated with past rotational ankle fractures. The majority of ankle arthritis is associated with previous trauma, whereas the primary cause of knee or hip arthritis is idiopathic. Unique strategies to prevent or treat post-traumatic ankle arthritis are needed.

Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.

Clinical and biological impact of antiretroviral therapy with protease inhibitors on HIV-related Kaposi's sarcoma.

OBJECTIVE: To evaluate the clinical and biological impact of protease inhibitors on HIV-associated Kaposi's sarcoma. DESIGN AND SETTING: A cohort of 10 patients included prospectively from April 1996 to June 1997 were studied in one institutional centre after initiation of protease inhibitors. PATIENTS AND METHODS: All patients but one (stable disease) had progressive Kaposi's sarcoma. Three out of 10 patients had stopped specific chemotherapy for Kaposi's sarcoma for more than 4 weeks, three were still under chemotherapy, and four had never received specific treatment of Kaposi's sarcoma. Plasma HIV viral load, human herpesvirus (HHV)-8 viraemia in peripheral blood mononuclear cells (PBMC), and CD4 cell count were sequentially assessed from the beginning of therapy. For six patients, a semiquantitative evaluation of HHV-8 viral load in the Kaposi's sarcoma lesions was performed during treatment using polymerase chain reaction. RESULTS: After initiation of HIV triple therapy with protease inhibitors, we observed six complete responses, two partial responses, and two patients with progressive disease. All patients had undetectable plasma HIV viral load within 2 months of treatment. Undetectable HHV-8 viraemia in PBMC occurred in seven out of eight patients with partial or complete response and in none of the progressive patients. A decrease or negation of HHV-8 viral load in Kaposi's sarcoma lesions was observed in two complete responders. CONCLUSION: Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposi's sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.

Detailed deletion mapping of chromosome 6q in borderline epithelial ovarian tumors.

We have used PCR amplification of tandem repeats and Southern blot analysis to study the pattern of allelic loss at chromosome 6q in borderline ovarian tumors and compared that with invasive ovarian carcinomas. DNA from 46 borderline ovarian tissues, 20 invasive ovarian tumor tissues, together with corresponding uninvolved (control) tissues was used. The invasive tumors demonstrated the highest percentage of loss of heterozygosity (13 of 45 informative cases, 29%) at the 6q25-27 locus site. In contrast, the borderline ovarian tumors showed only an 11% frequency of loss of heterozygosity (3 of 26). Our results display a sharp contrast in the pattern of loss of heterozygosity between invasive and borderline ovarian tumors and suggest that allelic loss at chromosome 6q may not be involved in the development of borderline ovarian tumors.

[The thoracic outlet: true syndromes, disputed syndrome (TOS, thoracic outlet syndrome). Current status 1991]. / Le défilé thoracique: syndromes vrais, syndrome controversé ("TOS"). Mise à jour 1991.

There are 5 syndromes involving the thoracic outlet. The first four, although not well known, especially the first two, are authentic; they are: 1) arterial, due to a well formed cervical rib or to an incompletely formed first rib; 2) neurological, related to the fibrous band associated with a rudimentary cervical rib or a giant transverse process of C7; 3) venous, namely "effort thrombosis"; 4) late post-traumatic, secondary to a fracture of the clavicle. The study of these four syndromes prepares the reader to that of the controversial fifth syndrome, which is entirely subjective, made only of symptoms. The fifth syndrome, by very far the most frequent in the literature, called "scalenus anticus syndrome" in the past, now called "thoracic outlet syndrome" or "TOS" by North-American authors, has two varieties, one where hypotonic shoulder muscles, mostly in women, respond well to specific and simple exercises, and one where there is an accident in the background, a whiplash type of injury in most cases. Despite the fact that TOS is made only of symptoms, "diagnosing" it has led to scores of operations, scalenotomy in the past, now mostly resection of the first rib, sometimes scalenectomy. Huge surgical statistics, that deal mostly with resection of the first rib, have not proven the authenticity of this second variety of the 5th syndrome. Surgeons report only early surgical results, and the results claimed are invariably impressive. Never is there a statistic about return to work after surgery. First rib resection can be dangerous and it can be complicated by tardy permanent brachial plexopathy. One very recent European study proves the discrepancy between the early appreciation of the results by the surgeon and the late appreciation by independent observers.

Identification of HIV-1 envelope glycoprotein in the serum of AIDS and ARC patients.

Binding of the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein (gp120) has been reported to alter the function and surface antigen expression of lymphocytes and monocytes in vitro. To determine whether these in vitro findings could be relevant in vivo, we searched for the presence of this antigen in the serum of patients with AIDS and the AIDS-related complex (ARC). Using an antigen capture enzyme-linked immunosorbent assay (ELISA) with polyclonal anti-gp120 antibody, we detected envelope antigens (gp160/120) in serum of 22 of 32 AIDS patients. In contrast, an ELISA using solid-phase recombinant CD4 to capture gp160/120 failed to detect any positives. A modification of the anti-gp120-based ELISA identified gp160/120-IgG immune complexes in all of 11 AIDS patients tested and in 4 ARC patients who were negative for gp160/120 antigen. We conclude that gp160/120, predominantly in the form of immune complexes, can be identified as circulating antigen in patients with AIDS. The potential pathogenic consequences of this antigenemia, its relation to soluble CD4 therapy, and its application as a clinical marker of disease merit further study.

Anterior uveal melanoma, with secondary keratitis, cataract, and glaucoma, in a horse.

Intraocular melanoma was diagnosed in a 13-year-old horse. Secondary clinical findings included keratitis, cataract, and glaucoma. The eye was enucleated. Follow-up information did not give an indication of metastatic disease.

Periorbital epidermoid cyst in the medial canthus of three dogs.

Periorbital epidermoid cyst in the medial canthus was identified ultrasonographically and confirmed histologically in 3 dogs. Surgical resection of the cysts, with reconstruction of the lacrimal canaliculi, was curative in all 3 cases.

Cryosurgery for treatment of recurrent proliferative keratoconjunctivitis in five dogs.

Cryosurgery was used for treatment of recurrent proliferative keratoconjunctivitis in 5 dogs that had been treated with combined medical and surgical procedures without success. Four dogs recovered completely after one application of cryosurgery. The fifth dog did not respond to cryosurgery until after oral administration of corticosteroids was stopped, indicating a possible immune-mediated mechanism of action of cryosurgery on proliferative keratoconjunctivitis.

Tumor regression and temporary restoration of immune response after plasmapheresis in a patient with recurrent oral cancer.

A major response to plasmapheresis is reported in a patient with advanced, recurrent squamous cell cancer of the oral cavity, similar to that previously reported in three of six comparable patients. Tumor regression followed temporary reduction of inhibition of normal lymphocyte response to phytohemagglutinin (PHA) by the patient's serum (from 99% to zero) and partial restoration of the patient's lymphocyte response (from 2% to 38% of control). The IgE level rose both overall and during some exchanges; this correlate of tumor response had been noted earlier. The tumor showed extensive necrosis, but the clinical effects were relatively short-lived and the patient died 11 weeks later. Biopsy specimens taken early in apheresis showed intense new infiltration of tumor by lymphocytes and monocytes; later biopsy specimens showed predominantly plasma cells with trapping and lysis of tumor cells. No other anti-cancer therapies had been used for 16 months before this trial, and no replacements were given other than saline and albumin.

A microcomputer system for the practising cardiac surgeon.

The authors present a computer program designed for the practising cardiac surgeon who wishes to computerize patient data. The program is efficient, versatile and can be adapted to individual needs. It can be used with any IBM PC-compatible machine and requires little knowledge of computer science. More than 250 items on 30 000 patients can be stored and all this information analysed simultaneously. The program can chart a patient's profile and tabulate the information of the entire registry. It can generate lists of patients with their surgeons, cardiologists, diagnoses, operations and dates of intervention. It can also be used for mailing purposes.