High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer

The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.     

The effect of verbal elaborations on memory in young and older adults

The Stein paradigm was used to examine the circumstances under which verbal elaborations enhance memory in young and older adults. Subjects studied target adjectives that were embedded in one of three sentence contexts that varied in elaboration of the subject-adjective relationship: (1) nonelaborated base sentences; (2) base sentences with semantically consistent, but arbitrary verbal, elaborations; and (3) base sentences with explanatory verbal elaborations that clarified the significance of the subject-adjective relationship. The presence of the elaborations was varied at encoding and retrieval, and cued recall of the target adjectives was tested with incidental and intentional learning procedures. In Experiments 1A and 1B, explanatory elaborations at encoding and retrieval yielded the largest memorial facilitation for both young and older adults, and the benefit was comparable for the incidental and intentional learning measures. In Experiment 2, age-related differences in recall were minimal with explanatory elaborations at encoding and retrieval, but larger age differences occurred in the nonelaborated comparison conditions. In Experiment 3, explanatory elaborations present at encoding but not at retrieval enhanced recall when the original Stein stimuli were used, but not with the present stimuli. The implications of these results with regard to the mnemonic efficacy of verbal elaborations for young and older adults are discussed.     

Evidence for a non-thermal microwave effect in the sintering of partially stabilized zirconia

A hybrid furnace, which allows the simultaneous application of microwave and radiant energy, has been used to investigate the sintering of partially stabilized zirconia (doped with 3 mol % yttria). Microwave-enhanced sintering is clearly demonstrated with densification occurring at a lower temperature when a high-frequency electric field is applied. By considering the variation of electric field strength with furnace temperature, this enhancement is shown to be non-thermal in nature, being dependent on the electric field strength and not the power density (heating) of the microwaves. This dependence on electric field is consistent with an additional driving force term in the equation which describes the diffusion of vacancies through the material during sintering.     

Physical and chemical characterization of thermosoftened bases for molten filled hard gelatin capsule formulations

Dynafill, Dynasan-114, Lutrol-F68, PEG-10000 and PEG-20000 have been examined as potential bases for the preparation of fusion formed solid dispersions for molten filling into hard gelatin capsules. Investigations included, an examination of thermal effects on crystal structure by DSC and XRD, a theological study to evaluate capsule filling characteristics, dissolution studies on drug/base formulations, chemical analysis for free fatty acid impurities in Dynafill and Dynasan-114, and detailed studies on selected drug/base formulations. PEG-20000 and Dynasan-114 were not examined in detail, after preliminary investigations had shown high viscosity and poor filling characteristics for PEG-20000 and poor dissolution characteristics for Dynasan-114. Dynafill provided good release profiles when formulated with a variety of model drugs (Acetohexamide, Ibuprofen, Indomethacin, Quinidine sulphate and Theophylline). Results from hot stage photomicrography supported by DSC and XRD were used to construct a phase diagram of the Ibuprofen/Lutrol-F68 system. The evidence from the phase diagram indicated the formulation of a simple eutectic system with no solid solubility and a eutectic composition at approximately 35% w/w Ibuprofen.     

An experimental investigation of triboelectrification in cohesive and non-cohesive pharmaceutical powders

A detailed experimental investigation has been undertaken of the triboelectrification process of the pharmaceutical excipient alpha-lactose monohydrate and selected drugs. Particle charge studies involved the design and construction of an apparatus to incorporate pneumatic powder feed, triboelectric charging via a cyclone separator and simultaneous powder charge (Q) and mass (M) measurements using a modified Faraday well. Preliminary studies showed the charging of the selected materials to be unaffected by relative humidity up to 84%, due to the very low hygroscopicity of the powders. Experiments using lactose size fractions with brass, steel and cellulose contact charging surfaces conducted at different feeder gas pressures, gave net electronegative specific charge values (Q/M) for the metal surfaces, and electropositive values for cellulose. Specific charge increased linearly with gas pressure for the metals, and non-linearly for cellulose. Samples of micronised lactose and beclomethasone dipropionate (BDP) showed more tendency than unmicronised samples to adhere to the contact surface which resulted in more complex charging processes. A novel system to analyse the charge and mass data in further detail was developed, giving relative Q/M values at unit time intervals. It is proposed that this will overcome the limitations of reliance on the final net specific charge value. Preliminary results indicated differences in the charging mechanism for lactose in contact with the two metal surfaces.     

Meniscal regeneration in the long-term after total meniscectomy?

A cohort of 39 patients (28 male, 11 female) that had undergone total meniscectomy as adolescents (mean age 16 years) underwent FISP 3D Magnetic Resonance Imaging at a mean follow up of 30 years. The presence of meniscal tissue was assessed by two independent observers blinded to the operation details. The volume of any meniscal tissue present was calculated. A posterior horn remnant was seen in 57% of medial and 45% of lateral meniscectomy cases. The mean volume of an operated medial meniscal remnant was 0.29 mL compared with a mean volume of 1.15 mL for an intact medial meniscus. The mean volume of an operated lateral meniscal remnant was 0.30 mL compared with 1.07 mL for an intact lateral meniscus. We have shown that the incidence of incomplete excision of the posterior horn is more common after total medial meniscectomy, and that at a mean follow up of 30 years there is no convincing in vivo MRI evidence of long-term meniscal regeneration.     

Protein-lipid interactions in concentrated infant formula

Radiolabeled milk proteins ([carbon-14] beta-lactoglobulin or [carbon-14] kappa-casein) were added to raw skim milk used to prepare concentrated humanized infant formula. Ultracentrifugation of the sterilized product allowed separation of three fractions: lipids and the proteins associated with them; free casein micelles and other dense particles; and the fluid phase. Distribution of radiolabeled tracer proteins or of protein measured by chemical methods among these three phases varied significantly with differences in processing conditions (time and temperature of sterilization) or amount of certain additives (potassium hydroxide or urea). In the range of 0 to 8 meq/L of potassium hydroxide added to the formula after homogenization but before sterilization, the lipid layer content of carbon-14 from [carbon-14] kappa-casein in the sterilized product decreased by 4.7% for each 1 meq/L of added potassium hydroxide. Lipid layer content of protein decreased by 2 g/L (of a total of 32 g/L) for each 1 meq/L potassium hydroxide. Such differences in the structure of the product, related to interactions of protein with lipid, protein, or calcium phosphate, may correlate with physical properties and stability of milk-based lipid-rich products.     

Radical radiotherapy for squamous cell carcinoma of the larynx, oropharynx and hypopharynx: patterns of recurrence, treatment and survival

The present study investigates 1085 previously untreated patients with squamous cell carcinoma of the head and neck for factors that influence recurrence following treatment with definitive radiotherapy. In the second part of this study, those diagnosed with recurrence were studied with regard to treatment and were further analysed with regard to identification of prognostic factors which may affect outcome in the patient who actually develops a recurrence.