Validation of the Clinical COPD Questionnaire as a psychophysical outcome measure in adult laryngotracheal stenosis

Objectives: To validate the Clinical Chronic Obstructive Pulmonary Disease Questionnaire (CCQ), a patient‐administered instrument developed for bronchopulmonary disease as a disease‐specific psychophysical outcome measure for adult laryngotracheal stenosis. Design: Prospective observational study. Settings: Tertiary/National referral airway reconstruction centre. Participants: Thirty‐three tracheostomy‐free patients undergoing endoscopic laryngotracheoplasty. Main outcome measures: CCQ and the Medical Research Council (MRC) Dyspnoea scale, a previously validated but more limited scale, were administered to patients 2 weeks before surgery, preoperatively, and 2 weeks after endoscopic laryngotracheoplasty. Pulmonary function was assessed preoperatively. Internal consistency was assessed with Cronbach α statistics and test–retest reliability was determined using intraclass correlation. Correlations between CCQ and MRC scale, and pulmonary function were used to assess convergent and divergent validity respectively. Instrument responsiveness was assessed by correlating total and domain‐specific CCQ scores with anatomical disease severity and post‐treatment effect size. Results: There were 12 males and 21 females. Mean age was 44 ± 15 years. Cronbach α coefficient and intraclass correlation coefficient were 0.88 and 0.95 respectively. Total and domain‐specific CCQ scores significantly correlated with the MRC scores (P < 0.001) and significant correlations between CCQ and peak expiratory flow rate and FEV₁ were identified (P < 0.03). There were statistically significant changes in total and domain‐specific CCQ scores when different stenosis severities were compared. Clinical COPD Questionnaire scores also changed significantly and congruently following surgery (P < 0.05 in both cases). Discussion: Clinical COPD Questionnaire is a valid and sensitive instrument for assessing symptom severity and levels of function and well‐being in adult patients with laryngotracheal stenosis and can be used as a patient‐centred disease‐specific outcome measure for this condition.     

The cholinomimetic agent carbachol induces headache in healthy subjects

The parasympathetic nervous system is likely to be involved in migraine pathogenesis. We hypothesized that the cholinomimetic agonist carbachol would induce headache and vasodilation of cephalic and radial arteries. Carbachol (3 µg/kg) or placebo was randomly infused into 12 healthy subjects in a double-blind crossover study. Headache was scored on a verbal rating scale from 0–10. Velocity in the middle cerebral artery (V_MCA) and diameter of the superficial temporal artery (STA) and radial artery (RA) were recorded. Nine participants developed headache after carbachol compared with three after placebo. The area under the curve for headache was increased after carbachol compared with placebo both during infusion (0–30 min) ( P  = 0.042) and in the postinfusion period (30–90 min) ( P  = 0.027). Carbachol infusion caused a drop in V_MCA ( P  = 0.003) and an increase in STA diameter ( P  = 0.006), but no increase in the RA diameter ( P  = 0.200). In conclusion, the study demonstrated that carbachol caused headache and dilation of cephalic arteries in healthy subjects.     

Quantitation of viral DNA in renal allograft tissue from patients with BK virus nephropathy

BACKGROUND: BK virus (BKV) allograft nephropathy (BKVAN) is a complication in renal transplantation recipients. Histopathology is the gold standard for diagnosis. Quantitative polymerase chain reaction (PCR) assay for renal biopsy has not been evaluated as a diagnostic test. Determination of renal BKV load may identify patients at risk for disease before histologic nephropathy. METHODS: Quantitative PCR assay for BKV DNA was performed in 28 biopsies of patients with BKVAN; 50 biopsies were performed before a diagnosis of BKVAN, and 126 control biopsies were from patients without a history of BKVAN. RESULTS: BKV DNA was present in 19 of 50 (38%) biopsies performed 1 to 164 weeks before diagnosis of BKVAN. The viral load (mean 216 copies/cell) was lower than in biopsies of patients with BKVAN (mean 6063 viral copies/cell, <0.05). In 10 of 127 (7.8%) control biopsies, a low level of BKV DNA (mean 3.8 copies/cell) was found in three biopsies from chronic allograft nephropathy patients; two biopsies with acute rejection; four biopsies with borderline change; and one biopsy with cytomegalovirus nephritis. CONCLUSION: BKV load exceeding 59 copies per cell identified all cases of BKVAN. The diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of quantitative PCR were 100%, 92.1%, 73.6%, and 100%, respectively. Lower levels of BKV DNA were identified in biopsies performed before viral nephropathy development. Future research will determine if earlier recognition of at-risk patients allows application of antiviral strategies to improve graft outcome.     

Transtracheal high frequency jet ventilation and iatrogenic injury

Editor—We read with interest the article by Bourgain andcolleagues,¹ who reported an 8.4% incidence of subcutaneousemphysema and 1% incidence of pneumothoraces with jet ventilationvia the transtracheal route. Transtracheal catheter placementis an extremely useful technique for patients with significantglottic pathologies such as obstructing glottic tumours, andcan be lifesaving. We do, however, have concerns over its usein     

Hb Leiden-beta (0) thalassemia in a Chinese with severe hemolytic anemia

The first case of Hb Leiden (alpha2beta2 6 or 7 Glu---O)-beta (0) thalassemia in a young patient with chronic severe hemolytic anemia, which improved after splenectomy, is described. His parents were Chinese. The patient's blood showed no Hb A or normal beta chains when no blood transfusion was given. His mother was heterozygous for beta(0) thalassemia, and his father and brother had a trait for the unstable Hb Leiden. The Hb Leiden level of the father was 22.6% and that of the brother was 19.3%. It is probable that the abnormal hemoglobin in this Chinese family resulted from an independent gene mutation, unrelated to the one found in 2 Caucasian families reported earlier.     

Effect of leflunomide and cidofovir on replication of BK virus in an in vitro culture system

BACKGROUND: Cidofovir and Leflunomide are used empirically in the treatment of BK virus nephropathy. The aim of this study is to quantify the antiviral activity of these drugs. METHODS: BK virus was grown in a cell-culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed using a quantitative polymerase chain reaction assay. RESULTS: The inhibitory concentration, effective concentration, and selectivity index for Leflunomide are 39.7+/-6.9, 11.3+/-2.8, and 3.8+/-0.8 microg/mL, respectively. For Cidofovir, these indices were, respectively, 63.9+/-17.2, 36.3+/-11.7, and 2.3+/-0.8 microg/mL. CONCLUSIONS: The in vitro activity of Cidofovir and Leflunomide is modest, and the selectivity index is low. There is a need to develop more effective and less toxic anti-BK virus drugs for clinical use.     

Steroid-free tacrolimus monotherapy after pretransplantation thymoglobulin or Campath and laparoscopy in living donor renal transplantation

Living donor renal transplantation was performed under a regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. From October 9, 2002, to December 31, 2004, 196 consecutive, unselected laparoscopic live donor nephrectomies resulting in 196 living donor renal transplantations were performed. Recipients were pretreated with rabbit antithymocyte globulin (thymoglobulin; 24 patients or [12%]) or Campath 1H (alemtuzumab; 166 patients [85%]), or were not in protocol (6 patients [3%]), and were given postoperative steroid-free low-dose tacrolimus immunosuppressive monotherapy with subsequent weaning. There was no donor mortality. Major and minor donor morbidities were 2.6% and 4.2%, respectively. Laparoscopic live donor nephrectomy recipient outcomes with a mean follow-up of 401 days included (1) recipient and graft survival of 99.0% and 97.4%, respectively; (2) no ureteral stenosis; (3) 0.5% delayed graft function, from recurrent focal segmental glomerulosclinosis; and (4) no vascular thrombosis. The incidence of acute rejection at 30, 90, and 401 days was 1.5%, 3.8%, and 11.2% (all 196 recipients), 0%, 25%, and 29.2% (thymoglobulin recipients), and 1.8%, 3.9%, and 8.4% (Campath 1H recipients), respectively. Sixty-six patients (33.7%) are receiving spaced-dose immunosuppressive monotherapy. The mean creatinine concentration in all recipients was 1.5 +/- 1.1 mg/dL. There were no instances of cytomegalovirus tissue invasive disease or posttransplantation lymphoproliferative disease. The incidence of new-onset posttransplantation insulin-dependent diabetes was 0.5%. At current follow-up, the use of Campath 1H rather than thymoglobulin for pretreatment seems to have significantly improved the efficacy of our regimen.     

Obesity-related Differential Gene Expression in the Visceral Adipose Tissue

Background:This study investigates the expression patterns in human adipose tissue, and identifies genes that may be involved in the abnormal energy homeostasis. Methods: Subjects were prospectively recruited from morbidly obese patients undergoing bariatric surgery and from non-obese organ donors. Extensive clinical data and visceral fat specimens were obtained from each subject at the time of surgery. A group of 50 obese patients and 9 non-obese controls were selected for further study. Two custom two-color cDNA microarrays were produced with 40,173 human individual cDNA clones. Microarray experiments were performed for each sample, and a selected group of gene expression values were confirmed with real-time RT-PCR. Results: A comparison of gene expression profiles from obese and non-obese patients identified 1,208 genes with statistically significant differential expression between the 2 groups. Most prominent among these genes are multiple glycolysis enzyme encoding genes; others are involved in oxysterol biosynthesis and signaling, or are ATP-binding transporters and solute carriers. Conclusion: Differential gene expression in the adipose tissue of morbidly obese patients includes genes related to lipid and glucose metabolism, membrane transport, and genes promoting the cell cycle. These findings are a first step toward clarifying the molecular pathogenesis of obesity and identifying potential targets for therapeutic intervention.