An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

Evidence of a long QT founder gene with varying phenotypic expression in South African families.

We report five South African families of northern European descent (pedigrees 161, 162, 163, 164, and 166) in whom Romano-Ward long QT syndrome (LQT) segregates. The disease mapped to a group of linked markers on chromosome 11p15.5, with maximum combined two point lod scores, all generated at theta = 0, of 15.43 for the D11S922, 10.51 for the D11S1318, and 14.29 for the tyrosine hydroxylase (TH) loci. Recent studies have shown that LQT is caused by an Ala212Val mutation in a potassium channel gene (KVLQT1) in pedigrees 161 to 164. We report that the same mutation is responsible for the disease in pedigree 166. Haplotype construction showed that all the families shared a common haplotype, suggesting a founder gene effect. DNA based identification of gene carriers allowed assessment of the clinical spectrum of LQT. The QTc interval was significantly shorter in both carriers and non-carriers in pedigree 161 (0.48 s and 0.39 s, respectively) than the same two groups in pedigree 161 (0.52 s and 0.42 s, respectively). The spectrum of clinical symptoms appeared more severe in pedigree 162. The possible influence of modulating genetic factors, such as HLA status and sex of family members, on the expression of an LQT founder gene is discussed.     

Wrist arthrodesis following ulnar bar excision in Fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva is a rare disorder characterized by the progressive development of heterotopic bone in the connective tissues of skeletal muscle, ligaments and tendons. Surgical trauma is one of the most potent stimuli for ossification and surgical treatment is generally considered to be contraindicated in this condition. We report a good functional result in a patient with severe hand disability secondary to an ulna-carpal bar in fibrodysplasia ossificans progressiva.     

Increased expression of α2-6 linked sialic acids by nasal mucins in allergic rhinitis

Mucins have a polypeptide backbone, oligosaccharide side-chains and peripheral structures that include sialic acids. Several pathogens have specific receptors for sialic acids, including human strains of influenza A virus which preferentially recognise and bind α2-6 linked rather than α2-3 linked sialic acids.¹ 1 NElson J., COuceiro S.S., PAulson J.C. & BAum L. (1993) Influenza virus strains selectively recognise sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of haemagglutinin receptor specificity. The aim of this study was to identify possible disease-related changes in the expression of sialic acids in nasal mucins. Nasal mucosal samples were placed in organ culture. Metabolically-labelled mucins were purified by gel filtration, blotted on to nitrocellulose membranes and probed with the sialic acid-binding lectins Sambucus nigra and Maackia amurensis. Ninety-five mucosal samples were collected (49 turbinates, 31 nasal polyps, 15 samples from FESS). Lectin binding, expressed as optical density, showed significantly increased binding of S. nigra to cellular (P = 0.02; Kruskal–Wallis) and secreted (P = 0.045) mucin from allergic mucosa compared to non-allergic mucosa. No significant differences were found in the binding patterns of M. amurensis. This study has demonstrated increased expression of α2-6 linked sialic acids in the mucins synthesised and secreted by allergic compared to non-allergic nasal mucosa. This may cause a change in the way mucins and pathogens interact in allergic rhinitis, leading to altered susceptibility to upper respiratory tract infection.     

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

Re-assessing accumulated oxygen deficit in middle-distance runners

The purpose of this study was to re-assess the accumulated oxygen deficit (AOD), incorporating recent methodological improvements i.e., 4 min submaximal tests spread above and below the lactate threshold (LT). We Investigated the Influence of the VO2 -speed regression, on the precision of the estimated total energy demand and AOD. utilising different numbers of regression points and including measurement errors. Seven trained middle-distance runners (mean +/- SD age: 25.3 +/- 5.4y, mass: 73.7 +/- 4.3kg. VO2max 64.4 +/- 6.1 mL x kg(-1) x min(-1)) completed a VO2max, LT, 10 x 4 min exercise tests (above and below LT) and high-intensity exhaustive tests. The VO2 -speed regression was developed using 10 submaximal points and a forced y-intercept value. The average precision (measured as the width of 95% confidence Interval) for the estimated total energy demand using this regression was 7.8mL O2 Eq x kg(-1) x min(-1). There was a two-fold decrease in precision of estimated total energy demand with the Inclusion of measurement errors from the metabolic system. The mean AOD value was 43.3 mL O2 Eq x kg(-1) (upper and lower 95% CI 32.1 and 54.5mL o2 Eq x kg(-1) respectively). Converting the 95% CI for estimated total energy demand to AOD or including maximum possible measurement errors amplified the error associated with the estimated total energy demand. No significant difference in AOD variables were found, using 10,4 or 2 regression points with a forced y-intercept. For practical purposes we recommend the use of 4 submaximal values with a y-intercept. Using 95% CIs and calculating error highlighted possible error in estimating AOD. Without accurate data collection, increased variability could decrease the accuracy of the AOD as shown by a 95% CI of the AOD.     

Abnormalities in myelopoietic regulatory interactions with acidic isoferritins and lactoferrin in mice infected with Friend virus complex: association with altered expression of Ia antigens on effector and responding cells

The regulation of myelopoiesis was evaluated in B6D2F1 mice inoculated with Friend virus complex (spleen focus-forming virus plus helper virus) or helper virus alone by analyzing acidic isoferritin (AIF) and lactoferrin (LF) interactions with target cells. Under normal conditions, AIF suppresses colony and cluster formation by an Ia- antigen-positive cycling subpopulation of mouse granulocyte-macrophage progenitor cells (CFU-GM). Under the same conditions, the release of AIF-inhibitory activity and granulocyte-macrophage colony stimulatory factors (GM-CSF) from an Ia-antigen-positive subpopulation of monocytes and macrophages is suppressed by LF. Within one to two days after inoculation in vivo with Friend virus complex or helper virus, mouse CFU-GM become insensitive in vitro to suppression by purified human AIF as well as crude mouse AIF, and by four days, bone marrow, spleen, and thymus cells of these mice release much greater quantities of AIF- inhibitory activity than the cells from mice injected with control medium. The Friend virus complex itself has no influence in vitro on CFU-GM from normal mice. In addition, the release of AIF-inhibitory activity from bone marrow, spleen, and resident peritoneal cells and the release of GM-CSF from resident peritoneal cells of mice infected with Friend virus complex are not suppressed by LF. The inability of AIF to suppress colony formation by bone marrow and spleen CFU-GM from mice infected with Friend virus complex is associated with the loss of Ia (I-A subregion) antigens from CFU-GM, even though CFU-GM are in cycle. The nonresponsiveness of bone marrow, spleen, and peritoneal cells from these mice to LF suppression of AIF release and the inability of LF to influence GM-CSF release from peritoneal cells is associated with loss of Ia antigens from these cells. The above abnormalities are similar to the defects noted using cells from patients with leukemia. These results suggest that mice infected with Friend virus complex can serve as a model for investigating abnormalities in cell regulation and their relationships to disease progression.     

Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.