RESUMO
JM216 [bis-acetato-ammine-dichloro-cyclo-hexylamine-platinum (IV)] is an oral platinum complex with in vivo activity against murine and human tumor models and a lack of nephro- and neurotoxicity in rodents. During a phase I study of a single-dose schedule, JM216 was given in dry-filled hard gelatin capsules by mouth without hydration or diuresis. In all, 37 patients were given a total of 88 courses at doses ranging from 60 to 700 mg/m2. The study was stopped before the MTD was reached because of nonlinear pharmacokinetics. Myelosuppression was manifest by leucopenia or thrombocytopenia and showed marked variability at 420-700 mg/m2. Vomiting was mild and controllable by antiemetics in approximately 50% of courses. The onset of vomiting was delayed to 4 h after during ingestion. There was no nephro-, oto- or neuro-toxicity. A partial response was recorded in a patient with recurrent ovarian cancer, and significant falls in plasma tumour markers (CA125) were seen in two further cases. Plasma pharmacokinetics were linear and showed moderate interpatient variability at dose levels of < or = 120 mg/m2. At dose levels of > or = 200 mg/m2, Cmax and AUC increased less than proportionally to dose. This was associated with greater interpatient pharmacokinetic variability and reduced urinary platinum recovery. A significant sigmoidal relationship existed between ultrafilterable plasma AUC and the percentage of reduction in platelet count (r2 = 0.78). Nonlinear absorption was a limitation to this single-dose schedule of oral NM216; however, little non-haematological toxicity was seen at doses associated with myelosuppression and antitumour activity. Clinical studies of divided dose schedules using doses within the range of pharmacokinetic linearity (< or = 120 mg/m2) are now being investigated.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Administração Oral , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Feminino , Humanos , Absorção Intestinal , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/farmacocinéticaRESUMO
This retrospective study analysed the accuracy and reliability of predictions generated in patients treated with orthognathic surgery by comparing Quick Ceph Image software (Quick Ceph Image Pro version 3.0) predictions with post-surgical lateral cephalographs. Pre- and post-surgical lateral cephalographs of 28 adult patients (12 males and 16 females) were scanned into the computer and 28 landmarks were identified and digitized. Digitization error was assessed from repeated digitization. Fourteen measurements of the predicted and actual postsurgical hard tissue landmarks were compared using Student's t-test. Results showed a good correlation between repeated digitization for all measurements. Student's t-test indicated that 10 of the 14 measurements showed no statistically significant differences. Only the ANB (P=0.008), FMA (P=0.001), SN-Mxl (P=0.03) and Wit's (P=0.0001) showed statistically significant differences between the predicted and actual measurements. However only the Wit's showed clinical significant differences between the two measurements. Caution still must remain as the surgeon may not achieve his planned position in an individual patient. In some cultures there may also be medico-legal implications of these predictions.
Assuntos
Cefalometria , Diagnóstico por Computador/métodos , Procedimentos Cirúrgicos Bucais , Procedimentos Cirúrgicos Ortognáticos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adolescente , Adulto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Má Oclusão/cirurgia , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , SoftwareRESUMO
The preliminary results in a prospective study to evaluate the effects of secondary alveolar bone grafting in adults and children with cleft lip and palate is presented. Bone grafting was performed in 67 patients using two different surgical approaches. Autogenous cancellous bone from the iliac crest was used in all the cases. The patients were divided into three groups according to the state of eruption of the canine and the age group, whether adult or children. The minimum period for observation of the cases following the bone grafting is three months, the maximum one and a half years. The initial findings indicated that better results were obtained when the bone grafting was done in younger patients prior to the eruption of the canine.
Assuntos
Processo Alveolar/cirurgia , Transplante Ósseo , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Adolescente , Adulto , Reabsorção Óssea/etiologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/etiologiaRESUMO
The objective of this study was to measure the force applied to attach crimpable hooks securely to rectangular stainless steel archwires, both inside and outside the mouth. A specially designed strain gauge was utilized to measure the force applied by each operator. In vitro testing of the attached hooks was carried out using an Instron Universal Testing Machine. Two operators crimped a total of 80 TP Orthodontic crimpable hooks to 0.019 x 0.025-inch stainless steel archwires. For one operator there was a significant difference between the intra- and extra-oral forces used to produce firmly attached crimpable hooks (P = 0.03). However, in vitro testing demonstrated no statistically significant difference between the force levels required to displace the crimped hooks for either operator. The clinical significance of these findings is also discussed. Better reliability of crimpable hooks may be achieved by placing them out of the mouth.
Assuntos
Análise do Estresse Dentário , Aparelhos Ortodônticos , Feminino , Força da Mão , Humanos , Masculino , Boca , Fios OrtodônticosRESUMO
Desmin is a muscle-specific protein and a constitutive subunit of the intermediate filaments (IF) in skeletal, cardiac and smooth muscles. It is an early marker of skeletal muscle myogenesis. We have characterized a clone of desmin cDNA from an embryonic zebrafish (Danio rerio) cDNA library. The full-length cDNA comprised 1798 nucleotides, encoding a protein of 473 amino acids. The predicted amino acid sequence of the zebrafish desmin shares a high degree of similarity to other vertebrate desmins, but also contains a sequence at the carboxyl terminal of the tail domain that is unique to the zebrafish. It carries many features which are distinctive of IF subunit proteins. These include the T/SSYRRXF/Y motif in the head domain, and the intermediate filament signature consensus, [I/V]-X-[T/A/C/I]-Y-[R/K/H]-X-[L/M]-L-[D/E], located in the carboxyl terminus of the central helical rod. Unlike other 3' UTR sequences, the 3' UTR of the zebrafish cDNA sequence has two CAYUG elements flanking a single polyadenylation site. The temporal and spatial expression patterns of desmin mRNA during early zebrafish development were studied. The onset of desmin expression occurred at the 1-3 somite stage (11 hpf). It increased throughout somitogenesis, with maximum expression at the Prim-6 stage (25 hpf), and decreasing expression towards the protruding-mouth stage (72 hpf). Desmin mRNA was initially localised exclusively to the somites, but was subsequently also detected in other musculature in the developing heart and fins. The onset of expression and the spatial localization of desmin mRNA in the zebrafish coincides with that reported for MyoD and myogenin.