Scaling of heat transfer and temperature distribution in granular flows in rotating drums.

Accurate prediction of the time required to heat up granular materials to a target temperature is crucial for several processes. However, we do not have quantitative models to predict the average temperature or the temperature distribution of the particles. Here, we computationally investigate the scaling of heat transfer in granular flows in rotating drums. Based on our simulations, which include a wide range of system and material properties, we identify the appropriate characteristic time that is used to derive equations that predict the particles' average temperature and the particles' temperature distribution.

The effect of the drying temperature on the properties of wet-extruded calcium stearate pellets: pellet microstructure, drug distribution, solid state and drug dissolution.

Although drying is widely applied during the manufacturing of solid dosage forms, its potential effect on the product's (key) properties is often underestimated. Hence, the present study addresses drying related modifications of wet-extruded pellets comprising calcium stearate (CaSt, matrix former) and ibuprofen (model drug). After spheronization, the pellets were tray dried at different temperatures. The dried pellets were evaluated regarding their microstructure, the ibuprofen distribution, solid state modifications and the resulting in-vitro dissolution profiles. The ibuprofen distribution profiles along the pellets' cross-sections varied for the different drying conditions. The profiles turned from inhomogeneous to uniform with increasing drying temperature. Temperatures above 20°C yielded solid state modifications, including ibuprofen transition into the amorphous state and the formation of eutectic compositions. As none of the batches exhibited a high specific surface area associated with an open, well-interconnected pore system, the dissolution profiles were a function of the ibuprofen distribution. Differences in the solid state did not contribute to the dissolution behavior, since the CaSt matrix did not swell or dissolve in the dissolution medium. These findings show that drying may considerably affect the final product properties even for moderate drying conditions.

Impact of drying on solid state modifications and drug distribution in ibuprofen-loaded calcium stearate pellets.

Drying is a common pharmaceutical process, whose potential to alter the final drug properties-even at relatively low temperatures-is often neglected. The present study addresses the impact of drying at 20 and 50 °C on wet-extruded calcium stearate (CaSt) pellets. Drying at 20 °C caused the majority of ibuprofen to accumulate at the pellet surface due to a strong convective flow from the pellet's center to the surface. In contrast, pellets dried at 50 °C still contained ibuprofen in the pellet's interior due to the higher drying rate and the associated film breakage during drying. Moreover, the higher drying temperature caused CaSt to form a second lamellar phase and ibuprofen to convert (partly) into its amorphous state. Overall, the drying process affected the solid state and the spatial ibuprofen distribution within the pellet. Knowledge of these effects can aid in tailoring advanced multipellet formulations.

Stuck in traffic: Patterns of powder adhesion.

The adhesion of fine particles to surfaces is important for applications ranging from drug delivery to fouling of solar cells. In this letter, we show that powder adhesion can occur in unexpected patterns, concentrating particular grain types in some locations and clearing them from others, and we propose a straightforward traffic model that appears to reproduce many of the behaviors seen. The model predicts different patterns depending on inter-particle cohesion, and we find in both experiment and model that adhesion occurs in three distinct stages.

The effect of agitated drying on the morphology of L-threonine (needle-like) crystals.

Experiments have been carried out to study the behavior of L-threonine (needle-like) crystals during agitated drying. For an L-threonine/water system the morphology of the crystals was monitored using light microscopy and image analysis. Analysis of the transient behavior of the crystal size and shape distribution showed that attrition and agglomeration took place simultaneously during the process. The variation of the operating conditions (temperature, agitation and vacuum) revealed that attrition dominated the drying process when the drying rate was low and/or the shear rate was high. For high drying rates and low shear rates, agglomeration became dominant. This study suggests that crystal redissolution had no significant impact on crystal morphology. It was also found that due to their needle-like shape, large L-threonine crystals were very sensitive to attrition. When attrition controlled the drying process, most of the particle size reduction took place below a critical moisture content of 4%. When agglomeration controlled the drying process, most of the crystal size enlargement occurred below a moisture content of 6%.

Anxiety levels in women attending colposcopy clinics for treatment for cervical intraepithelial neoplasia: a randomised trial of written and video information.

OBJECTIVE: To assess the effectiveness of video information in reducing the level of anxiety in women attending Colposcopy clinics. DESIGN: An observational study followed by a randomised trial. SETTING: Colposcopy Clinic, Royal Free Hospital, London. PARTICIPANTS: Between April and December 1999, all new referrals to the clinic with a cervical smear showing moderate or severe dyskaryosis. MAIN OUTCOME MEASURE: The level of anxiety measured by the Spielberger State Anxiety Inventory. CONCLUSION: Women attending colposcopy clinics for either diagnosis or treatment, experience a high level of anxiety. The highest levels occur in women attending a one-stop see and treat clinic. The introduction of visual information in the form of an explanatory video prior to attendance significantly reduced anxiety.

From Kafka to Casualty: doctors and medicine in popular culture and the arts-- a special studies module.

This paper describes and reflects on the content and teaching methods of a two-week medical humanities special studies module (SSM) taken by third-year students at the Royal Free & University College Medical School. It aims to add to the common pool of knowledge, and will be of use to people who are considering setting up something similar.

Encouraging out-patients to make the most of their first hospital appointment: to what extent can a written prompt help patients get the information they want?

A randomised controlled study in which a written prompt was sent to new patients to help them make the most of their consultation was conducted amongst patients referred to the dermatology, gynaecology and orthopaedic out-patients clinics at the Royal Free Hospital, London. The impact of the help card on patients' expectations, preparation for and experience of their out-patient consultation are discussed. A help card and letter were sent to a random sample of patients before their appointment to encourage them to prepare and prioritize questions to ask the doctor at the consultation. After their consultation, patients were sent a postal questionnaire to complete at home. Analysis of the questionnaires provided quantitative and qualitative data about patients' information requirements and whether they were fulfilled. The results highlight the difficulties out-patients have in asking questions and discussing topics fully at their initial consultation, even when they have thought of questions in advance. Half the patients who were sent a help card said they got more out of their consultation as a result, yet few statistically significant differences between the help card group and the other patients were found.

Batch uptake of lysozyme: effect of solution viscosity and mass transfer on adsorption.

In this study, solid-phase adsorption by macroporous and hyper-diffusive resins was investigated in a batch uptake adsorption system to quantify solid-phase diffusion rates as a function of bulk phase viscosity. The performance of chromatographic resins used for adsorption of proteins is dependent on several factors including solid and liquid-phase diffusivity, boundary layer mass transfer, and intraparticle mass transfer effects. Understanding these effects is critical to process development and optimization of both packed and fluidized bed adsorption systems. The macroporous resin used here was Streamline SP, and the hyper-diffusive resin was S-HyperD LS. Both have been frequently used in fluidized bed adsorption of proteins; however, factors that affect uptake rates of these media are not well quantified. Adsorption isotherms were well represented by an empirical fit of a Langmuir isotherm. Solid-phase diffusion coefficients obtained from simulations were in agreement with other models for macroporous and hyper-diffusive particles. S-HyperD LS in the buffer system had the highest uptake rate, but increased bulk phase viscosity decreased the rate by approximately 50%. Increases in bulk phase viscosity increased film mass transfer effects, and uptake was observed to be a strong function of the film mass transfer coefficient. Uptake by Streamline SP particles was slower than S-HyperD in buffer, due to a greater degree of intraparticle mass transfer resistance. The effect of increased film mass transfer resistance coupled with intraparticle mass transfer resistances at an increased bulk phase viscosity resulted in a decrease of 80% in the uptake rate by Streamline SP relative to S-HyperD.

Hyperthyroidism due to inappropriate TSH secretion with associated hyperprolactinaemia--a case report and review of the literature.

A patient with inappropriate thyrotrophin (TSH) secretion is described. She initially presented with classical hyperthyroidism during pregnancy, responded to propylthiouracil and, subsequently, had a normal delivery. Hyperthyroidism persisted and 7.5 months later a subtotal thyroidectomy was performed. After a further 16 months, mild symptoms of hyperthyroidism recurred. She again responded to propylthiouracil, but developed galactorrhoea. At that stage, it was noted that she had persistently elevated circulating TSH in the presence of elevated T4 and T3 levels. Her symptomatology was mild, although objective indices of thyroid activity, including pulse rate, BMR, sex hormone binding globulin and cholesterol, were indicative of hyperthyroidism. CT scan and tomography of the sella were normal. She had a markedly exaggerated TSH response to thyrotrophin releasing hormone (TRH). Basal TSH and responsiveness to TRH was suppressed by high dose dexamethasone. The TSH response to TRH was partially suppressed by exogenous T3, but there was no effect on basal TSH levels. TSH also decreased slightly with L-dopa and bromocriptine. Circulating TSH rose markedly during methimazole administration. TSH alpha and beta subunits were elevated and appropriate for the high TSH. In addition, both subunits increased following TRH. The patient had basal hyperprolactinaemia with an impaired prolactin (PRL) response to TRH and metoclopramide. PRL suppressed with L-dopa and bromocriptine. The remaining anterior pituitary function was intact. Most of the laboratory findings argue against the presence of a TSH producing pituitary tumour and the most likely cause for inappropriate TSH secretion in this patient is selective resistance of the thyrotroph to thyroid hormones. A mild element of peripheral resistance might also be present. The hyperprolactinaemia could be related to lactotroph resistance to thyroid hormone. The complexities of treatment in this patient are stressed. Therapy was initially attempted with low dose dexamethasone, but this had no effect. T3 treatment produced an exacerbation of her symptomatology and did not influence basal TSH, thyroid hormones, or 131I uptake. Bromocriptine administration for 11 months partially suppressed basal TSH without influencing T3 and there was an increase in T4. Methimazole did decrease her T4 and T3, but TSH and PRL rose to even greater levels. Her hyperthyroidism was eventually controlled with an ablative dose of 131I. Thyroid hormone will be given in an attempt to suppress her TSH.