Comparison of the internal state scale to clinician-administered scales in asthma patients receiving corticosteroid therapy

Mood symptoms are reported frequently in asthma patients, particularly during corticosteroid therapy. This investigation compared the Internal State Scale (ISS), a self-report measure of symptoms of mania and depression, to the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS) in a group of asthma patients (n=60 at baseline) before, during, and after a 1-2 week burst of prednisone. The depression and well being subscales of the ISS correlated well with HDRS scores. The perceived conflict subscale correlated with the BPRS scores. However, none of the ISS subscales correlated consistently and specifically with the YMRS in this population. Possible explanations for differences observed in bipolar versus asthma patients given the ISS are discussed. These data suggest the ISS may be a useful tool for depression symptoms and overall psychopathology in asthma patients and in patients receiving corticosteroid therapy. However, its ability may be attenuated outside of the population for which it was designed.     

Paediatric acid-base disorders: A case-based review of procedures and pitfalls

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided.Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance.     

Nephron number and its determinants in early life: a primer

Although there is wide variation, humans possess on average 900,000 nephrons per kidney. So far as is known, nephrons cannot regenerate; therefore, an individual’s nephron endowment has profound implications in determining his or her long-term risk of developing chronic kidney disease. Most of the variability in human nephron number is determined early in life. Nephrogenesis is a complex and carefully orchestrated process that occurs during a narrow time window until 36 weeks gestation in humans, and disruption of any part of this sequence may lead to reduced nephron number. In utero, genetic abnormalities, toxic insults, and nutritional deficiencies can each alter final nephron number. Infants born prematurely must continue nephrogenesis in an ex utero environment where there may be multiple threats to successful nephrogenesis. Once the nephron endowment is determined, postnatal factors (such as acute kidney injury or chronic illnesses) can only decrease nephron number. Current techniques for estimating nephron number require an invasive procedure or complete destruction of the tissue, making noninvasive means for counting nephron surgently needed. A better understanding of nephron number and its determinants, particularly during growth and maturation, could allow the development of therapies to support, prolong, or resume nephrogenesis.     

Inhaled corticosteroid use in HIV‐positive individuals taking protease inhibitors: a review of pharmacokinetics,case reports and clinical management

As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids.     

Anomalous origin of the left circumflex coronary artery from the right aortic sinus: A familial clustering

Origin of the left circumflex coronary artery from the right sinus of Valsalva or the right coronary artery is a well-described anomaly. We report 3 cases which suggest a familial association of this anomaly. The familial clustering that we report has not been previously demonstrated. © 1993 Wiley-Liss, Inc.     

Bcl‐3 deficiency protects against dextran‐sodium sulphate‐induced colitis in the mouse

Bcl-3 is a member of the IκB family of proteins and is an essential negative regulator of Toll-like receptor-induced responses. Recently, a single nucleotide polymorphism associated with reduced Bcl-3 gene expression has been identified as a potential risk factor for Crohn''s disease. Here we report that in contrast to the predictions of single nucleotide polymorphism (SNP) analysis, patients with Crohn''s disease and ulcerative colitis demonstrate elevated Bcl-3 mRNA expression relative to healthy individuals. To explore further the potential role of Bcl-3 in inflammatory bowel disease (IBD), we used the dextran-sodium sulphate (DSS)-induced model of colitis in Bcl-3^−/− mice. We found that Bcl-3^−/− mice were less sensitive to DSS-induced colitis compared to wild-type controls and demonstrated no significant weight loss following treatment. Histological analysis revealed similar levels of oedema and leucocyte infiltration between DSS-treated wild-type and Bcl-3^−/− mice, but showed that Bcl-3^−/− mice retained colonic tissue architecture which was absent in wild-type mice following DSS treatment. Analysis of the expression of the proinflammatory cytokines interleukin (IL)-1β, tumour necrosis factor (TNF)-α and IL-6 revealed no significant differences between DSS-treated Bcl-3^−/− and wild-type mice. Analysis of intestinal epithelial cell proliferation revealed enhanced proliferation in Bcl-3^−/− mice, which correlated with preserved tissue architecture. Our results reveal that Bcl-3 has an important role in regulating intestinal epithelial cell proliferation and sensitivity to DSS-induced colitis which is distinct from its role as a negative regulator of inflammation.     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Decade-long bacterial community dynamics in cystic fibrosis airways

The structure and dynamics of bacterial communities in the airways of persons with cystic fibrosis (CF) remain largely unknown. We characterized the bacterial communities in 126 sputum samples representing serial collections spanning 8-9 y from six age-matched male CF patients. Sputum DNA was analyzed by bar-coded pyrosequencing of the V3-V5 hypervariable region of the 16S rRNA gene, defining 662 operational taxonomic units (OTUs) from >633,000 sequences. Bacterial community diversity decreased significantly over time in patients with typically progressive lung disease but remained relatively stable in patients with a mild lung disease phenotype. Antibiotic use, rather than patient age or lung function, was the primary driver of decreasing diversity. Interpatient variability in community structure exceeded intrapatient variability in serial samples. Antibiotic treatment was associated with pronounced shifts in community structure, but communities showed both short- and long-term resilience after antibiotic perturbation. There was a positive correlation between OTU occurrence and relative abundance, with a small number of persistent OTUs accounting for the greatest abundance. Significant changes in community structure, diversity, or total bacterial density at the time of pulmonary exacerbation were not observed. Despite decreasing community diversity in patients with progressive disease, total bacterial density remained relatively stable over time. These findings show the critical relationship between airway bacterial community structure, disease stage, and clinical state at the time of sample collection. These features are the key parameters with which to assess the complex ecology of the CF airway.