A case of tumour necrosis factor-α inhibitor- and rituximab-induced plantar pustular psoriasis that completely resolved with tocilizumab.

Rituximab, a chimeric B-cell-depleting monoclonal antibody, is a well-established therapy for rheumatoid arthritis. It is emerging that classical psoriatic lesions and plantar pustular psoriasis (PPP) are cutaneous side-effects of this drug. Antitumour necrosis factor (anti-TNF) therapies have multiple documented side-effects including PPP and psoriasis. We report a patient who has rheumatoid arthritis, who failed on anti-TNF therapies and then was commenced on rituximab. Subsequently she developed localized PPP. Due to deterioration of her joint disease she was switched to the interleukin-6 blocker tocilizumab, and the PPP resolved.

Actinomortierella wolfii: Identity and pathology.

Actinomortierella wolfii (Mortierellales), formerly Mortierella wolfii, is a causative agent of bovine systemic infection and abortion. Human infections caused by this species are extremely rare. Here, we present a case of a patient with B-Cell Acute Lymphoblastic Leukemia (B-ALL) who was diagnosed with a rhinocerebral infection caused by this fungus. Amphotericin treatment of the patient proved unsuccessful. This type of disease is otherwise nearly exclusively limited to members of the order Mucorales. The taxonomy of the causative agent is discussed.

Rhinofacial Conidiobolomycosis: A Case Series and Review of the Literature.

Conidiobolomycosis is an uncommon, chronic, localized subcutaneous mycosis primarily affecting rhinofacial region. It is reported mainly from tropical and subtropical countries. The condition is underreported due to the lack of clinical suspicion and usually mismanaged. This rare mycosis is due to the genus Conidiobolus within the order Entomophthorales of class Zygomycetes. Here we present 3 cases of rhinofacial conidiobolomycosis in otherwise healthy adults from different parts of Sri Lanka over 1-year period. All patients had disfiguring subcutaneous lesions in the rhinofacial area. The diagnoses were based on isolation of Conidiobolus coronatus in clinical specimens.

Mycetoma due to Madurella mycetomatis.

Mycetoma is a progressive destructive disease causing severe disability, if untreated, in otherwise healthy people. Susceptible populations are usually adult males and disease is characterized by the triad of tumor formation, presence of grains and draining sinuses. Here, we report a case of mycetoma of a young female, manifested only as a painful swelling over left ankle which was initially suspected as a malignancy. The preliminary diagnosis of mycetoma came with the presence of characteristic "dot in circle" sign in radiological evaluation which was confirmed by the positive fungal culture of 2nd biopsy for M. mycetomatis.

Liposomes as vaccine carriers. Incorporation of soluble and particulate antigens in giant vesicles.

Giant liposomes (mean diameter 5.5 microns) composed of egg phosphatidylcholine or distearoyl phosphatidylcholine, phosphatidyl glycerol, cholesterol and triolein were prepared by a double emulsion technique. They were then mixed with model particulate (killed Bacillus subtilis, and killed Bacille Calmette-Guérin) and soluble (tetanus toxoid) vaccines and freeze-dried. Rehydration of the powder resulted in the generation of vesicles of similar mean diameter and diameter range, containing up to 27% (mean value) of the materials used for entrapment. Separation of entrapped from non-entrapped material was carried out by sucrose gradient centrifugation (B. subtilis and BCG) or centrifugation at 600 x g (toxoid). Light microscopy of liposomes containing B. subtilis labelled with fluorescein isothiocyanate revealed the presence of bacteria in individual vesicles which, in separate studies, were also found to entrap latex particles (0.5 and 1.0 micron diameter). Bacteria-containing liposomes could be freeze-dried in the presence of trehalose with most (83-87%) of the entrapped material recovered within the vesicles on reconstitution with saline. Liposomes were also shown to retain quantitatively their content of B. subtilis and, to a lesser extent, toxoid in the presence of mouse plasma at 37 degrees C and in situ after intramuscular injection into mice, for up to 24 h. Since liposomes are known (Gregoriadis, G. (1990) Immunol. Today 11, 89) to act as immunological adjuvants and vaccine carriers, giant vesicles containing microbes (live or attenuated if needed since the conditions of entrapment are mild) and, when appropriate, soluble antigens, could be used as multiple vaccines to ensure simultaneous presentation of antigens to immunocompetent cells.

Dose resolution in radiotherapy polymer gel dosimetry: effect of echo spacing in MRI pulse sequence.

In polymer gel dosimetry using magnetic resonance imaging, the uncertainty in absorbed dose is dependent on the experimental determination of T2. The concept of dose resolution (Dpdelta) of polymer gel dosimeters is developed and applied to the uncertainty in dose related to the uncertainty in T2 from a range of T4 encountered in polymer gel dosimetry. Dpdelta is defined as the minimal separation between two absorbed doses such that they may be distinguished with a given level of confidence, p. The minimum detectable dose (MDD) is Dpdelta as the dose approaches zero. Dpdelta and the minimum detectable dose both give a quantifiable indication of the likely practical limitations and usefulness of the dosimeter. Dpdelta of a polyacrylamide polymer gel dosimeter is presented for customized 32-echo and standard multiple-spin-echo sequences on a clinical MRI scanner. In evaluating uncertainties in T2, a parameter of particular significance in the pulse sequence is the echo spacing (ES). For optimal results, ES should be selected to minimize Dpdelta over a range of doses of interest in polymer gel dosimetry.

A new class of drug for the management of type 2 diabetes: sodium glucose co-transporter inhibitors: 'glucuretics'.

BACKGROUND: Type 2 diabetes is a common, chronic disease with a prevalence that is increasing at epidemic proportions. Management involves advice on lifestyle changes, oral anti-hyperglycaemic agents and/or insulin. The kidneys play a major role in the regulation of glucose, re-absorbing 99% of the plasma glucose filtered through the renal glomeruli tubules. The glucose transporter, SGLT2, which is found primarily in the S1 segment of the proximal renal tubule accounts for 90% of glucose re-absorption. Competitive inhibition of SGLT2 induces glucosuria in a dose dependent manner and appears to have beneficial effects on glucose regulation in individuals with type 2 diabetes. O-glucoside phlorozin is the model substance for SGLT2 inhibitors: various O-, C-, N- and S-glucosides with varying affinity and specificity have been synthesised. AIMS: The aim of this review is to describe the background, the mechanism of action and the possible role for sodium glucose co-transporter inhibitors in the treatment of diabetes. MATERIALS AND METHODS: Databases, including MEDLINE, COCHRANE, EMBASE and EBM reviews were searched for literature relating to sodium glucose transport inhibitors and improvements in glycaemic control in patients with diabetes. RESULTS: The data suggest that sodium glucose transport inhibitors significantly improve glycaemic control by increasing glucosuria. Some studies described significant reductions in weight and improvement in blood pressure. The most common side effect was infection involving the urinary and genital tracts. CONCLUSIONS: Sodium glucose co-transport inhibitors appear to be an effective line of treatment, well tolerated and could be a further drug class in the armamentarium available for the management of type 2 diabetes.

Simple methods for the correction of T2 maps of phantoms.

Two simple methodologies for correcting the errors in T2 maps for phantom measurements are presented; they both give accurate MRI maps with a low coefficient of variation (CV). The rate correction method is based on an equation relating the true T2 (T2,t) and that determined experimentally (T2,exp) for homogenous phantoms. The response matrix method is a phenomenological analysis of the difference between T2,exp and T2,t, from which correction factors are computed for a range of T2 values and for every pixel of an image. The factors were obtained from phantoms filled with a homogeneous gelatin gel and having different T2,t values. The CV in homogeneous phantom measurements were reduced from 2.5-4.0% to approximately 0.6-2.0% for T2,t values ranging from 180-600 ms. Examples are shown for the correction of T2 maps of phantoms filled with polymer dosimeter gel irradiated with photon beams from a linear accelerator. The methodologies presented can easily be implemented on a clinical MRI scanner.

Liposomally-encapsulated ricin toxoid vaccine delivered intratracheally elicits a good immune response and protects against a lethal pulmonary dose of ricin toxin.

A small study was performed to examine whether the instillation of ricin toxoid vaccine into the lungs of Porton rats offered protection from lethal effects of subsequent intratracheal challenge with ricin toxin. Further the immune response to liposomally-encapsulated vaccine and the protection offered was compared with vaccine either adsorbed to Alhydrogel adjuvant or as a simple aqueous solution. The formaldehyde-treated ricin toxin vaccine (RTV) was administered at two dose levels, 500 and 100 micrograms kg-1 body weight to groups of rats, on two occasions by intratracheal instillation. Liposomally-encapsulated vaccine (LRTV) produced a higher titre of ricin-specific antibodies than Alhydrogel-vaccine (ARTV) and vaccine solution. When challenged with 3 LD50 of ricin by intratracheal instillation 7 weeks after the second vaccine instillation, all rats in both LRTV dose groups survived with minimal signs of incapacitation. Analysis of antibody secretion by spleen cells, 14 days post challenge, showed that the IgG isotype in the LRTV group was significantly higher than that in the ARTV and RTV groups and also that the proportion of specific IgA in lung fluid was higher in the LRTV group than in the ARTV and RTV groups. The results of this study indicate that effective vaccinations against inhaled ricin could be achieved with liposomally-encapsulated ricin toxoid, via the lung and should be investigated further.

Differences in the carboxy-terminal (Putative phospholipid binding) domains of Clostridium perfringens and Clostridium bifermentans phospholipases C influence the hemolytic and lethal properties of these enzymes.

The phospholipases C of C. perfringens (alpha-toxin) and C. bifermentans (Cbp) show >50% amino acid homology but differ in their hemolytic and toxic properties. We report here the purification and characterisation of alpha-toxin and Cbp. The phospholipase C activity of alpha-toxin and Cbp was similar when tested with phosphatidylcholine in egg yolk or in liposomes. However, the hemolytic activity of alpha-toxin was more than 100-fold that of Cbp. To investigate whether differences in the carboxy-terminal domains of these proteins were responsible for differences in the hemolytic and toxic properties, a hybrid protein (NbiCalpha) was constructed comprising the N domain of Cbp and the C domain of alpha-toxin. The hemolytic activity of NbiCalpha was 10-fold that of Cbp, and the hybrid enzyme was toxic. These results confirm that the C-terminal domain of these proteins confers different properties on the enzymatically active N-terminal domain of these proteins.