Respiratory disease in common variable immunodeficiency and other primary immunodeficiency disorders.

Respiratory disease is a significant cause of morbidity and mortality amongst patients with primary immunodeficiency disorders. Computed tomography (CT) plays an important role in the multidisciplinary approach to these conditions, in detecting, characterizing, and quantifying the extent of lung damage and in directing treatment. The aim of this review is to classify the primary immunodeficiency disorders and describe the thoracic complications and the associated CT findings whilst discussing the role of radiology in diagnosis and surveillance.

The surgical management of obesity with emphasis on the role of post operative imaging.

The role of surgery in the morbidly obese is becoming more prominent. There are a variety of surgical approaches which can be used and radiology plays a crucial role in post operative follow up, particularly in the management of complications. Many general radiologists remain unfamiliar with both the normal and abnormal appearances after bariatric surgery and this pictorial review aims to bridge this gap.

Imaging the lungs in patients treated for lymphoma.

The lymphomas are a heterogeneous group of malignancies, which exhibit a range of different molecular features, genetics, and clinical presentations. Consequently, therapeutic approaches and clinical outcomes differ greatly. Following therapy, the thorax may be a site of disease recurrence, but infection, drug reactions, and radiation pneumonitis are commonly encountered. We present a comprehensive review of these conditions, focussing on their radiological appearances, in order that radiologists may better engage their colleagues in haemato-oncology.

The role of a consultant radiologist--are patients still in the dark?

Little is known regarding public awareness of the roles and responsibilities of a consultant radiologist. Between 1 April and 20 May 2008, 916 outpatients attending our radiology department completed a questionnaire addressing this issue. We found public perception variable. Thirty-six percent of respondents thought we were responsible for choosing appropriate imaging; only 65% perceived that we reported studies. Another 38% felt that we did not play an important role in their treatment, and 38% considered that we were not part of their medical team. Thirty-two percent of respondents preferred their hospital consultant to give them their imaging results, with 17% preferring this to come from the radiologist. There is significant under-appreciation of the roles and responsibilities of a consultant radiologist. It is important that we educate the public to ensure that future health policy reflects the increasingly central role imaging plays in health-care delivery.

Computed tomography after radical pancreaticoduodenectomy (Whipple's procedure).

Whipple's procedure (radical pancreaticoduodenectomy) is currently the only curative option for patients with periampullary malignancy. The surgery is highly complex and involves multiple anastomoses. Complications are common and can lead to significant postoperative morbidity. Early detection and treatment of complications is vital, and high-quality multidetector computed tomography (MDCT) is currently the best method of investigation. This review outlines the surgical technique and illustrates the range of normal postoperative appearances together with the common complications.

Response assessment in lymphoma.

The lymphomas are a heterogeneous group of malignant diseases. They are divided into two broad groups: Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Patients suffering from HD and NHL can be cured by appropriate chemotherapy and/or radiotherapy. Accurate staging and response assessment is essential to guide management decisions. The International Workshop Group (IWG) criteria, published in 1999, have become the widely accepted standard for response assessment in NHL. Although the IWG criteria have proved extremely useful in the standardization of treatment response, they do have a number of limitations. As a consequence of this, together with advances in functional imaging, revised criteria have been published recently. The aim of this review is to describe the evidence supporting the available imaging techniques, the limitations of each technique, and how these should be applied in clinical practice. We briefly review the corresponding response criteria for central nervous system (CNS) lymphomas, and take a look at novel imaging techniques that may play a role in the future.

The suppression of gastro-oesophageal reflux by alginates.

AIMS: The aim of this study was to compare alginate products with the same amount of active ingredients but different dosage forms, in the suppression of reflux provoked by a standard meal in healthy human volunteers, using ambulatory oesophageal pH monitoring. METHODS: This was a single centre, randomised, open, three-period crossover, controlled study comparing Gaviscon Advance (10 ml) with a control (10 ml water) and with a new tablet product containing the same active ingredients as Gaviscon Advance. Volunteers who had oesophageal pH < 4 for at least 2% of the 4-h period after ingestion of a test meal followed by control at a reflux screening visit were included in the study. RESULTS: The difference between Gaviscon Advance and control in the mean angular transformed percentage of time for which oesophageal pH fell below four was statistically significant (p < 0.0001) demonstrating the sensitivity of the method. No significant difference between the two alginate products was found based on the least squares adjusted mean angular transformed percentage of time for which pH fell below four. There were also no significant differences between the two alginate dosage forms in the angular transformed percentage of time for which oesophageal pH fell below five and in the log-transformed number of occasions on which oesophageal pH fell below four and five. DISCUSSION AND CONCLUSION: The study shows that alginate reflux suppressants containing a low amount of antacid are effective in suppressing acid reflux and that suspension and tablet forms are able to give equivalent acid suppression.

Administration of an alginate based gastric reflux suppressant on the bioavailability of omeprazole.

BACKGROUND & OBJECTIVE: Omeprazole treats gastro-oesophageal reflux disease (GORD) by inhibition of acid secretion whereas alginate based reflux suppressants work by forming a low density raft of near neutral pH which floats on the stomach contents and physically impedes gastro-oesophageal reflux. There is limited pharmacokinetic information regarding possible drug interaction between these two types of products, although these may be frequently co-prescribed to improve symptom control in GORD patients. This study was designed to determine whether the administration of a 10 per cent w/v liquid alginate suspension affected the pharmacokinetic profile of omeprazole. METHODS: This was a randomized, two-treatment, two-sequence, two-period crossover study in 26 volunteers. Each treatment was dosed for 3 consecutive days with a washout period of 7 days between dosing periods. Blood samples for pharmacokinetic analysis were taken over the 24 h period following the final dose of omeprazole. RESULTS: Geometric means and ratios were as follows: C(max) was 555 for omeprazole/alginate and 558 for omeprazole alone (ratio 99.55%, 90% confidence interval 82.75-119.75%; AUC(0-t) was 2050 for omeprazole/alginate and 2094 for omeprazole alone (ratio 97.90%, 90% confidence interval 87.83-109.12%); AUC(0-a) was 2247 for omeprazole/alginate and 2231 for omeprazole alone (ratio 100.74%, 90% confidence interval 90.05-112.70%). Mean values for T(max), K(el) and T(1/2) were also similar for the two treatment regimens. INTERPRETATION & CONCLUSION: As the 90 per cent confidence intervals for the geometric mean ratios for C(max), AUC(0-t), and AUC(0-alpha) are all contained within the bioequivalence interval of 80-125 per cent, it can be concluded that the administration of this liquid alginate suspension does not affect the pharmacokinetic profile of omeprazole.

A fatal case of disseminated zygomycosis associated with the use of blood glucose self-monitoring equipment.

We report a fatal case of disseminated zygomycosis due to Cunninghamella bertholletiae in a 68-year-old man with myelodysplasia and type II diabetes mellitus, receiving desferrioxamine therapy for iron overload secondary to multiple transfusions. It is thought that he acquired the infection through the use of blood glucose self-monitoring equipment.

Alginate rafts and their characterisation.

Alginate/antacid anti-reflux preparations are designed to provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study tested the in vitro effectiveness of a range of liquid products in forming rafts that were cohesive, buoyant, voluminous, resistant to reflux and durable under conditions of movement (resilient). The products tested had a wide range of acid neutralising capacities (ANCs). It was found that products with a high ANC and no calcium ion source formed rafts of low strength, weight and volume, which appeared more as floating precipitates than coherent gels. Products with a high ANC and a calcium ion source formed medium strength, weight and volume rafts. Products with a low ANC formed strong coherent rafts with medium to large weight and volume, and those with low ANC and a calcium ion source formed the strongest rafts. Products with stronger rafts were found to be more resilient and more resistant to reflux in an in vitro reflux model. Significant overall differences in raft buoyancy were found between products forming coherent rafts but these could not be related to the product formulation or amount of available carbon dioxide.

Feasibility of a bioadhesive drug delivery system targeted to oesophageal tissue.

This contribution examines the feasibility of utilising an oesophageal-adhesive alginate layer to support model drug particles. Such a bioadhesive system offers the prospect of local drug delivery to the oesophagus, which in turn has applications in the treatment of conditions including gastro-oesophageal reflux disease and oesophageal cancer. Surface-modified (amine, carboxylate and sulfate) as well as neutral fluorescent beads were investigated as model drug particles. A fluorescence assay technique was utilised to quantify the extent and duration of adhesion of a fixed dose of these particles to excised porcine oesophageal tissue. Retention of the particles was investigated both from aqueous systems and within an adhesive alginate solution. After 30 min significantly higher adhesion of neutral beads was recorded from the alginate solution as compared to the aqueous suspension (n = 6, P < 0.05). The beads that possessed a negative charge showed significantly greater retention within the alginate carrier (n = 6, P < 0.05). However, the amine-modified beads showed retention profiles that were similar both within the alginate carrier and within the aqueous suspension (n = 6, P > 0.05).

A simple, high throughput method for the quantification of sodium alginates on oesophageal mucosa.

Sodium alginate is a potential bioadhesive, but the lack of a convenient and suitable method for its quantification on the mucosal surface complicates the evaluation of its mucosal retentive properties. This paper develops and evaluates a spectrophotometric method for the rapid quantification of a range of sodium alginates differing in chemical composition, and investigates how quantification was influenced by the presence of oesophageal mucosa. The method, based on dye complexation with 1,9-dimethyl methylene blue (DMMB) was sensitive to alginate molecular weight and uronic acid composition, however, no significant correlations between assay performance and alginate molecular characteristics were demonstrated. The assay was also influenced by complexation time, calcium ions and mucin, but was unaffected by the presence of oesophageal tissue scrapings. The assay proved to be capable of quantifying sodium alginate with excellent linearity (r = 0.999), reproducibility (CV < 3%) and sensitivity (0.3 g l(-1)) and proved to be a precise, high-throughput method that may be used for quantifying the retention of sodium alginate on oesophageal mucosa.

An in vitro mucosal model for prediction of the bioadhesion of alginate solutions to the oesophagus.

This paper discusses the development of an in vitro model utilised to assess the adhesion of alginate solutions to porcine oesophageal tissue. The methodology involved the construction of retention apparatus onto which sections of tissue were mounted. Fluorescently labelled alginate solutions of known rheological profile were dispensed onto the tissue at a concentration of 2% w/v. A washing solution was applied at a specified rate to mimic saliva flow and the eluted material collected. Fluorimetric analysis allowed dose retention to be assessed as a function of time. The effect of the nature of the washing solution and the choice of alginate were investigated. It was found that after 30 min up to 20% of the applied alginate dose remained associated with the tissue, regardless of the alginate selected from the range examined. The nature of the washing medium did not have a significant effect on retention, irrespective of the inherent mucin concentration. Overall this study indicated that the technique presented offers a viable means of studying bioadhesion of liquids and also demonstrates that alginate solutions may have an application as bioadhesive agents for localisation within the oesophagus.

The effect of chitin and chitosan on the proliferation of human skin fibroblasts and keratinocytes in vitro.

The effects of chitin [(1 --> 4)-2-acetamido-2-deoxy-beta-D-glucan] and its partially deacetylated derivatives, chitosans, on the proliferation of human dermal fibroblasts and keratinocytes were examined in vitro. Chitosans with relatively high degrees of deacetylation strongly stimulated fibroblast proliferation while samples with lower levels of deacetylation showed less activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chitosan chloride was further evaluated using cultures of fibroblasts derived from a range of human donors. Some fibroblast cultures produced a positive mitogenic response to CL313A treatment with proliferation rates being increased by approximately 50% over the control level at an initial concentration of 50 microg/ml, whilst others showed no stimulation of proliferation or even a slight inhibition (< 10%). The stimulatory effect on fibroblast proliferation required the presence of serum in the culture medium suggesting that the chitosan may be interacting with growth factors present in the serum and potentiating their effect. In contrast to the stimulatory effects on fibroblasts, fraction CL313A inhibited human keratinocyte mitogenesis with up to 40% inhibition of proliferation being observed at 50 microg/ml. In general highly deacetylated chitosans were more active than those with a lower degree of deacetylation. These data demonstrate that highly deacetylated chitosans can modulate human skin cell mitogenesis in vitro. Analysis of their effects on cells in culture may be useful as a screen for their potential activity in vivo as wound healing agents, although in the case of fibroblasts it is important to select appropriate strains of cells for use in the screen.

A novel application of NMR microscopy: measurement of water diffusion inside bioadhesive bonds.

The self-diffusion coefficient of water (D) inside bioadhesive bonds formed by dry and prehydrated hydrophilic matrices has been spatially resolved using nuclear magnetic resonance (NMR) microscopy. One-dimensional profiles showing the variation of D inside bioadhesive bonds were calculated from nine diffusion-weighted profiles obtained immediately after bond formation and every 5 min for 30 min. The resulting data indicated that the hydration state of a hydrophilic matrix can significantly and dramatically influence the dynamics of water movement inside a bioadhesive bond.

The gastrointestinal transit profile of 14C-labelled poly(acrylic acids): an in vivo study.

The gastrointestinal distribution profiles for three 14C-labelled poly(acrylic acid)s of different average molecular weights and degrees of cross-linking have been established using the rat model. Despite initial differences in transit times and retention characteristics, these structural features were found to be of little influence to the overall gastrointestinal transit of the materials under consideration. No evidence for the systemic absorption of any of the polymers could be identified.

An investigation of mucus/polymer rheological synergism using synthesised and characterised poly(acrylic acid)s.

A range of poly(acrylic acid)s with different average degrees of polymerisation and cross-linking densities were synthesised using a solution polymerisation process. The rheological characteristics of aqueous dispersions of these materials and those of mixtures with homogenised pigs gastric mucus were investigated using dynamic oscillatory rheology, and compared to the known mucoadhesive Carbopol 934P. From the storage moduli, the rheological synergy and relative rheological synergy were calculated, and the effects of concentration and pH on this considered. Generally, the larger the molecular weight (and degree of cross-linking), the greater the rheological synergy, with Carbopol 934P giving the most pronounced effect. Rheological synergy was seen to be concentration-dependent, and a maximum concentration to produce an optimum effect was evident. Acid pHs were seen to favour synergy, although in marked contrast to previous literature reports, the optimum mucus-polymer interaction was not observed at the half ionised value (pH = pKa) but at pH regimes that were unique to each polymer type. This could be influenced by the structural constrains imposed on potential hydrogen bonded interactions. It was concluded that synthesising poly(acrylic acid)s with better defined physicochemical properties than commercially available polymers will advance the study of the phenomenon of rheological synergy.

Synthesis of radiolabeled congeners of the carbomers: (14)C-labeled poly(acrylic acid)s.

A general method for the synthesis of (14)C-acrylic acid is described in detail. The material is used for the synthesis of a range of radiolabeled poly(acrylic acid)s in which the (14)C-label forms an integral part of the polymer backbone. The chemical structure of the synthesized polymers is examined in the light of spectroscopic data, molecular weight determinations, and rheological studies.