Combined lung-sound and reflux-monitoring: a pilot study of a novel approach to detect nocturnal respiratory symptoms in gastro-oesophageal reflux disease

Aliment Pharmacol Ther 2011; 33: 592–600

Summary

Background Increased prevalence of respiratory symptoms has been commonly reported in patients with gastro‐oesophageal reflux disease (GERD). Aim To introduce a novel Lung‐Sound‐Monitoring device that allows simultaneous measurement of both nocturnal respiratory symptoms and episodes of acidic and biliary refluxes. Methods Nocturnal respiratory symptoms (coughing and wheezing) were continuously recorded in 20 healthy subjects and 30 reflux patients with respiratory symptoms in parallel to combined pH‐monitoring and Bilitec measurement. Results Analysis could be completed in 20 healthy subjects and in 25 patients with reflux. A clear temporal correlation to reflux phases was detected in 49% of coughing and 41% of wheezing events, respectively. Moreover, 89% of the coughing and 100% of the wheezing events succeeded reflux episodes. Finally, the technique was capable of assessing a statistically significant difference between patients and controls regarding the occurrence of these symptoms. Conclusions Our pilot study establishes the Lung‐Sound‐Monitoring system as a unique tool to measure objectively the temporal correlation between gastroesophageal reflux and the appearance of respiratory symptoms. It represents a useful technique to identify patients with respiratory symptoms due to reflux, and therefore allows one to determine and quantify the impact of therapeutic interventions such as antireflux therapy on respiratory symptoms.     

Molecular dynamics in drug design: new generations of compstatin analogs

We report the computational and rational design of new generations of potential peptide-based inhibitors of the complement protein C3 from the compstatin family. The binding efficacy of the peptides is tested by extensive molecular dynamics-based structural and physicochemical analysis, using 32 atomic detail trajectories in explicit water for 22 peptides bound to human, rat or mouse target protein C3, with a total of 257 ns. The criteria for the new design are: (i) optimization for C3 affinity and for the balance between hydrophobicity and polarity to improve solubility compared to known compstatin analogs; and (ii) development of dual specificity, human-rat/mouse C3 inhibitors, which could be used in animal disease models. Three of the new analogs are analyzed in more detail as they possess strong and novel binding characteristics and are promising candidates for further optimization. This work paves the way for the development of an improved therapeutic for age-related macular degeneration, and other complement system-mediated diseases, compared to known compstatin variants.     

The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells

BACKGROUND: Red cell (RBC) storage can be extended to 9 weeks under anaerobic or alkaline conditions. Simultaneous use of these approaches has not provided additive benefit. Our objective was to determine whether anaerobic storage with acidified additive solution (AS) coupled with metabolic rejuvenation might further improve the benefits of anaerobic storage. STUDY DESIGN AND METHODS: RBC storage in AS with a pH value of 6.5, 7.4, or 8.3 in aerobic or anaerobic conditions was examined using a panel of in vitro biochemical and RBC markers. RBC rejuvenation during cold storage was also evaluated. A randomized crossover radiolabeled recovery study (eight subjects) evaluated anaerobic RBC storage using AS65 with cold rejuvenation for up to 16 weeks of storage. RESULTS: Adenosine triphosphate (ATP) and diphosphoglycerate acid (DPG) were better maintained in anaerobic storage than in aerobic storage. Acidic or neutral AS preserved ATP concentration better, while a neutral or basic pH AS favored maintenance of DPG levels at higher levels for a longer period. AS pH had less of an effect on exposure of phosphatidylserine (PS), vesicle protein release, and hemolysis. Rejuvenation of RBCs during cold, anaerobic storage resulted in increases in ATP and DPG levels and a reversal of PS exposure. Anaerobic storage of RBCs in pH 6.5 AS rejuvenated at 7 weeks of storage yielded RBC 24‐hour recoveries of 77.3 ± 12.5 percent after 10 weeks' storage time. After a second rejuvenation at Week 11, six subjects' units demonstrated a recovery of 75.9 ± 7.3 percent at 12 weeks of storage. CONCLUSION: Extended RBC storage may be achieved using anaerobic conditions combined with low‐pH AS and rejuvenation during storage.     

Relationship between low ultraviolet B irradiance and higher breast cancer risk in 107 countries

Abstract:  Epidemiological data show an inverse relationship between vitamin D levels and breast cancer incidence. This study investigates the relationship of modeled and measured serum 25-hydroxyvitamin D [25(OH)D] levels with age-standardized incidence rates of breast cancer in 107 countries. The hypothesis being tested is that breast cancer incidence is inversely related to geographically-dependent cutaneous sunlight exposure. A multiple regression approach was used to examine the contributions of ultraviolet B (UVB) irradiance to age-standardized incidence rates of breast cancer in the 107 countries with data on these covariates—total column ozone thickness, per capita intake of alcohol and energy from animal and vegetable sources, cigarettes, proportion of female population overweight, and total fertility. Age-standardized incidence rates were substantially higher at latitudes distant from the equator ( R ²  = 0.43, p   <   0.0001). The dose–response gradient between modeled serum 25(OH)D levels and incidence rates of breast cancer followed a standard inverse dose–response curve. Increasing increments in serum 25(OH)D in the range above 22 ng/mL were associated with incrementally lower incidence rates of breast cancer. According to multiple regression, UVB irradiance adjusted for cloud cover was inversely associated with incidence rates (p   =   0.04) after controlling for covariates. Intake of energy from animal sources was also positively associated with incidence rates (p   <   0.01). The overall coefficient of determination, R ², was 0.81 (p   <   0.0001). There was a protective effect of UVB irradiance on risk of breast cancer that was independent of fertility rate, proportion of the population overweight, alcohol intake, animal energy intake, and other covariates.     

Early experience with continuous cervical paravertebral block using a stimulating catheter

Background and Objectives: This study reports our early experience with continuous cervical paravertebral block (CCPVB) using a stimulating catheter for the management of acute pain after shoulder surgery. METHODS: This prospective observational study presents 256 CCPVB for pain relief after 14 different shoulder operations. Surgery was performed under general anesthesia and blocks were placed prior to induction of general anesthesia (n = 81 [32%]), after induction of general anesthesia (n = 116 [45%]), or postoperatively in the recovery room (n = 59 [23%]). A bolus dose of 30 mL of 0.5% ropivacaine was followed by an infusion of 0.1 mL/kg/h of 0.2% ropivacaine. Patient- or nurse-initiated bolus doses of 10 mL of the same drug were used for breakthrough pain and rescue analgesics were available. Postoperative pain, patient satisfaction, and motor function in different parts of the upper limb were evaluated immediately after surgery (time 0), and then 6, 12, 24, 48, 60 hours, and 14 days postoperatively. RESULTS: An average of 2 (range 1-7) attempts were needed to advance the catheter while still stimulating the nerve. Average postoperative pain ranged from 0.27 +/- 1.04 cm to 0.78 +/- 1.56 cm (mean +/- SD) on a visual analog scale (VAS) (0-10 cm) for the first 48 hours and 3.8 +/- 2.1 cm and 3.5 +/- 2.4 cm at 60 hours and 14 days, respectively. Patient satisfaction on a VAS of 0 to 5 was 4.19 +/- 1.1, 4.28 +/- 1.01, and 4.69 +/- 1.05 at times 0, 6 hours, and 14 days, respectively. Motor function returned to normal in the fingers within 24 hours and in the shoulder within 60 hours. Complications included Horner's syndrome (40%), dyspnea (8%), superficial skin infection (5%), posterior neck pain (22%), subclavian artery puncture (1%), contralateral epidural spread (4%), and 8% of the patients complained of an unpleasant "dead feeling" of the arm. Ninety-one percent of patients would request CCPVB again for future shoulder surgery. There was no evidence of nerve damage.     

Decline in human immunodeficiency virus seropositivity and seroconversion in US Navy enlisted personnel: 1986 to 1989. Navy HIV Working Group.

The US Navy administered 1,795,578 enzyme-linked immunosorbent assay (ELISA) tests to 848,632 active-duty Navy enlisted personnel during 1986 to 1989. This study identified 2438 human immunodeficiency virus (HIV)-seropositive active-duty enlisted Navy personnel, including 778 seroconverters. Three types of quarterly rates of HIV seropositivity and seroconversion were determined. All three rates declined. This decline could not be explained by changes in the population tested according to age, race, sex, occupation, or geographic location of home port.     

Comparison of red blood cell survival in sheep determined using red blood cells labeled with either biotin at multiple densities or [14C]cyanate: validation of a model to study human physiology and disease

BACKGROUND: Measurement of red blood cell (RBC) survival (RCS) is important for investigating pathophysiology and treatment of anemia. Our objective was to validate the multidensity biotin method for RCS determination in sheep, a commonly used model of RBC physiology. [¹⁴C]Cyanate served as the reference method for long‐term RCS because the ⁵¹Cr method (the reference method for humans) is not reliable in sheep. STUDY DESIGN AND METHODS: Aliquots of autologous RBCs from eight adult sheep were labeled with [¹⁴C]cyanate and four separate densities of biotin (BioRBCs) and reinfused. Short‐term RCS was assessed by posttransfusion recovery at 24 hours (PTR₂₄); long‐term RCS was assessed by the time to 50% survival (T₅₀) and mean potential life span (MPL). RESULTS: Values for PTR₂₄ of the four BioRBC densities were not different. Values for RCS as reflected by T₅₀ and MPL were nearly identical for [¹⁴C]cyanate and the two intermediate‐density BioRBC populations. In contrast, the lowest‐density BioRBC population survived slightly longer (p < 0.01), but with a difference of no clinical significance. The highest‐density BioRBC population importantly shortened RCS (p < 0.01 compared to the two intermediate densities). CONCLUSION: This study provides evidence that BioRBCs labeled at four biotin densities can be used to independently and simultaneously measure short‐term RCS and that BioRBCs labeled at the three lowest biotin densities can be used to accurately and simultaneously measure long‐term RCS. Because the sheep RBC model is comparable to humans, this nonradioactive method has promise for use in RBC kinetic studies in neonates and pregnant women.     

Validating the International Classification of Functioning, Disability and Health Comprehensive Core Set for Rheumatoid Arthritis from the patient perspective: a qualitative study

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for Rheumatoid Arthritis (RA) from the patient perspective. METHODS: Patients with RA were interviewed about their problems in daily functioning. Interviews were tape recorded and transcribed verbatim. Interview texts were divided into meaning units. The concepts contained in these meaning units were linked to the ICF according to 10 established linking rules. Of the transcribed data, 15% were analyzed and linked by a second health professional. The degree of agreement was calculated using the kappa statistic. RESULTS: Twenty-one patients were interviewed. Two hundred twenty different concepts contained in 367 meaning units were identified in the qualitative analysis of the interviews and linked to 109 second-level ICF categories. Of the 76 second-level categories from the ICF RA Core Set, 63 (83%) were also found in the interviews. Twenty-five second-level categories, which are not part of the current ICF RA Core Set, were identified in the interviews. The result of the kappa statistic for agreement was 0.62 (95% boot-strapped confidence interval 0.59-0.66). CONCLUSION: The validity of the ICF RA Core Set was supported by the perspective of individual patients. However, some additional issues raised in this study but not covered in the current ICF RA Core Set need to be investigated.     

Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients

The development of cytomegalovirus (CMV) disease and subsequent emergence of drug-resistant strains was examined in a large group of solid organ transplant recipients; drug-resistant CMV was detected in a total of 30 transplant recipients (20 lung, 5 kidney, 4 heart, and 1 liver). Drug resistance was confirmed both phenotypically and genotypically. The sequences of drug-resistant CMV strains from the same patient differed from drug-susceptible baseline sequences only at single sites previously confirmed to confer drug resistance. At least 1 isolate from each patient had a mutation in the UL97 phosphotransferase coding sequence. Mutations in the DNA polymerase gene were found in 6 of 38 sequenced strains. Lung transplant recipients had the highest incidence of drug-resistant virus: of the 30 patients, 28 were CMV-seronegative transplant recipients of CMV-seropositive organs, which strongly supports the premise that drug resistance is most prevalent in that transplant population.