Selective tumor kill of cerebral glioma by photodynamic therapy using a boronated porphyrin photosensitizer

The prognosis for patients with the high-grade cerebral glioma glioblastoma multiforme is poor. The median survival for primary tumors is < 12 months, with most recurring at the site of the original tumor, indicating that a more aggressive local therapy is required to eradicate the unresectable "nests" of tumor cells invading into adjacent brain. Two adjuvant therapies with the potential to destroy these cells are porphyrin-sensitized photodynamic therapy (PDT) and boron-sensitized boron neutron capture therapy (BNCT). The ability of a boronated porphyrin, 2,4-(alpha, beta-dihydroxyethyl) deuteroporphyrin IX tetrakiscarborane carboxylate ester (BOPP), to act as a photosensitizing agent was investigated in vitro with the C6 rat glioma cell line and in vivo with C6 cells grown as an intracerebral tumor after implantation into Wistar rats. These studies determined the doses of BOPP and light required to achieve maximal cell kill in vitro and selective tumor kill in vivo. The data show that BOPP is more dose effective in vivo by a factor of 10 than the current clinically used photosensitizer hematoporphyrin derivative and suggest that BOPP may have potential as a dual PDT/BNCT sensitizer.     

Euphorigenic doses of cocaine reduce [123I]beta-CIT SPECT measures of dopamine transporter availability in human cocaine addicts

The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [123I]beta-CIT ([123I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) binding to striatal dopamine transporters (DAT) was assessed in human cocaine addicts using single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n = 6) were injected with [123I]beta-CIT and imaged 24 h later under equilibrium conditions. Sequential cocaine infusions (0.28 +/- 0.03 and 0.56 +/- 0.07 mg/kg) produced significant (P < 0.0005) reductions in the specific to non-specific equilibrium partition coefficient, V3" (6 +/- 6 and 17 +/- 3%), a measure proportional to DAT binding potential. Regression analysis of the logit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED50) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces behavioral effects in humans at measurable levels of DAT occupancy.     

Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses

Sinus cavities are often a major obstacle to the placement of dental implants in the posterior maxilla, especially when early tooth loss has occurred. Several grafting procedures aimed at reducing the expanded volume of these pneumatic cavities have been routinely utilized since 1979. Essentially, these techniques have consisted of recreating the necessary viable bone volume at the floor of sinus cavities by placing different bone substitute materials to allow for the insertion of endosseous implant devices. The progress achieved in the refinement of the surgical procedures and the knowledge acquired in the field of patient screening and selection, choice of biomaterials, management of complications, etc., have made sinus graft surgery highly codified and predictable. A comprehensive statistical study by multifactorial procedures was carried out to establish a Burt Contingency Chart. This chart visualizes the frequencies of all the "modality combinations" among the selected "qualitative parameters" and, by a " factorial analysis", the "multiple correlations", so that the "statistical affinities" that may exist among the same variables can be determined. This critical study endeavors to search for and reveal the favorable clinical, biologic and scientific parameters necessary for the success of sinus graft surgery on short-, medium-, and long-term bases (more than nine years). It is a particularly homogenous study, since all the operative procedures have been carried out exclusively by the author under standardized conditions. The wide variety of biomaterials utilized by the author since 1979 shows the development of bone substitute biomaterials as they have been introduced into the market during the past 15 years. The large number of patients treated, the variety of grafting materials, the important success rate obtained, and the long duration of patient follow-up have been instrumental in enabling us to establish scientifically significant results. Autogenous bone and its combinations with calcium- and phosphorus-containing biomaterials remain undoubtedly the best all-purpose biomaterials. The synthetic biomaterials have their own specific indications according to their stable (non-resorbable) or unstable (resorbable) nature and their rates of metabolic "turnover". Differently treated bones from the tissue bank (if not contaminated or immunologically questionable) behave in a fashion not unlike autogenous bone. Root-form implants are by far the best implants in the reconstructed sinus sites, while other implant types (subperiosteal implants, etc.) inserted beneath the reinforced osseous sinus floor, buccal wall, and pyramidal process, also have their indications.     

The genetic effects in the somatic cells of persons working under chronic irradiation of different intensities after the accident at the Chernobyl Atomic Electric Power Station

A complex genetic study of two groups from of Chernobyl NPP personnel (from "Shelter" unit and 3rd Block) has been carried out using classical cytogenetic and GPA methods. The first group was the most vulnerable from the viewpoint of accumulated dose (exceeding 25 cGy for the moment of study). Positive correlation between individual and group frequencies of cytogenetic markers of irradiation (stable and unstable chromosomes aberrations) and NO mutations in the GPA locus was found.     

A medico-legal evaluation of the use of assisted reproductive technologies in Turkey

In Turkey, as possibly in the case of several or even many other countries, infertility is generally regarded as a negative phenomenon in women. Assisted Reproductive Technologies (ARTs), which provide certain childless couples with the possibility of having a baby, are being applied more and more frequently in this country, apparently as has been the case in the world at large. From a medicolegal point of view, the related applications in Turkey can only be realized in the case of married couples. Other forms of application in this area, on the other hand, such as sperm banks or surrogate motherhood, are not allowed legally. A text which was called "Guidelines Regarding the Centers of In Vitro Fertilization and Embryo Transfer" was prepared in 1987 by the Ministry of Health. The aim of these Guidelines is to find solutions to the medico-legal problems created by the application of ARTs in this country.     

Meningeal carcinomatosis in patient with esophagus adenocarcinoma

We assessed the practicality of using the Short Michigan Alcoholism Screening Test (SMAST) and the Alcohol Use Disorders Identification Test (AUDIT) in screening adolescents for alcoholism in a primary care setting. In addition, we sought to determine the prevalence of alcohol use among adolescents, 16-21 years of age, presenting to a private Family Medicine practice for medical care. A consecutive sample of 67 subjects presenting for medical care were asked to complete the SMAST and AUDIT questionnaires. Overall, 52 (78%) of the questionnaires were returned with complete data. Of the 52 patients, 25 (48%) admitted to drinking. Using a "positive" score on either the SMAST or AUDIT as a positive test for alcohol use yielded a sensitivity of 40% and a predictive value positive of 100%. Using a "negative" score on both the SMAST and AUDIT as a negative test for alcohol use yielded a specificity of 100% and a predictive value negative of 64%. Although alcohol use was relatively common considering the age group, using the SMAST and AUDIT to screen for alcoholism is labor intensive and is not practical in this situation. Because patients appeared to misinterpret some questions and were often accompanied to the office by their parents, their answers may not be valid. History of alcoholism taken upon typical office examination and relevant advice appears to be a better alternative to the use of questionnaires in determining the prevalence of alcohol use in this age group.     

Biphasic testosterone delivery profile observed with two different transdermal formulations

PURPOSE: Our long-term goal is to develop formulations for pulsatile testosterone (T) delivery. T has been reported earlier to show biphasic pharmacokinetics in humans by Mazer et al, as well as biphasic permeation across excised rat skin by our group. We examined two kinds of formulations to evaluate their delivery profiles and to assess whether differences in the formulation approach affect pharmacokinetics in animal models. METHODS: One formulation consisted of T and a polymer blend dissolved in isopropanol; administered by dispensing the solution on the skin to cast a film in situ. The other was an adhesive-dispersion patch. In vitro release from the patch was evaluated using a flow-through cell interfaced with an HPLC pump and UV detector. Single dose pharmacokinetics were evaluated in castrated Wistar rats and bonnet monkeys immunized against gonadotropin-releasing hormone to deplete endogenous T. RESULTS: Two maximas were observed in the T release profile from the patch and in serum concentration versus time profiles in both animal models on application of either formulation. The relative magnitudes of the two maximas and the time interval separating them were different in the case of each formulation. CONCLUSIONS: Both formulations result in biphasic pharmacokinetics of T in the animal models studied. Discrete maximas presumably correlate with "burst" and "sustained" phases of drug release.