Epiphysial dysplasia: a constant finding in the XXXXY syndrome.

Two patients with the XXXXY syndrome are presented. Both boys are mentally retarded with short stature, muscular hypotonia, and hypogonadism. A constant feature of this syndrome is a varying degree of epiphysial dysplasia probably secondary to hypotonia and growth deceleration.     

Does the impact of intensive lifestyle intervention on cognitive function vary depending baseline level of frailty? An ancillary study to the Action for Health in Diabetes (Look AHEAD) Trial

AimsTo assess whether there is an opportune window when intensive lifestyle intervention (ILI) benefits cognitive function.MethodsStandardized cognitive assessments were collected following ≥8 years of either ILI or a control condition of diabetes support and education (DSE) in 3708 individuals, ages 45-76 years at enrollment, with type 2 diabetes and overweight or obesity. Frailty index (FI) scores were used to group individuals at baseline into tertiles according to their age-related health status. Linear models were used to describe intervention adherence and cognitive function, with interaction terms to examine the consistency of relationships among tertiles.ResultsWorse baseline FI scores were associated with poorer subsequent performance in tests of attention, processing speed, and executive function. No differences in any measure of cognitive function were observed between intervention groups within any FI tertile (all p > 0.10). Among individuals with worse baseline FI scores, weight gain was associated with poorer global cognitive function among participants assigned to DSE. There was no association between weight changes and cognitive function among participants assigned to ILI.ConclusionsAmong adults with type 2 diabetes and overweight/obesity, we found no evidence that there is a window of opportunity based on FI when ILI benefits cognitive function.     

Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a “heterozygote advantage.” Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (≥4) of HLA loci was significantly correlated with a reduction in LP response (P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (Bacillus anthracis LF and EF) than HLA-homozygous subjects.     

Exhaled breath condensate pH assays are not influenced by oral ammonia

BACKGROUND: Measurement of pH in exhaled breath condensate (EBC) is robust and simple. Acidic source fluid (airway lining fluid) traps bases while volatilising acids, leading to EBC acidification in many lung diseases. Lower airway ammonia is one determinant of airway lining fluid pH, raising the concern that addition of the base ammonia by contamination from the mouth might confound EBC pH assays. METHODS: Three discrete methods were used to limit oral ammonia contamination of EBC collections: endotracheal intubation, oral rinsing, and -40 degrees C condenser temperatures. Separately, ammonia was removed from collected EBC samples by lyophilisation and resuspension. Intraweek and intraday variability of ammonia concentration was determined in 76 subjects, and ammonia and pH from a further 235 samples were graphically compared. Ammonia was assayed spectrophotometrically and pH was assessed after deaeration. RESULTS: Data from 1091 samples are presented. Ammonia was reduced in EBC by all methods. Endotracheal intubation decreased EBC ammonia from a mean (SD) of 619 (124) microM to 80 (24) microM (p<0.001, n=32). Oral rinsing before collection also led to a decline in EBC ammonia from 573 (307) microM to 224 (80) microM (p=0.016, n=7). The colder the condensation temperature used, the less ammonia was trapped in the EBC. Lyophilisation removed 99.4 (1.9)% of ammonia. Most importantly, the pH of EBC never decreased after removal of ammonia by any of these methods. Intraweek and intraday coefficients of variation for ammonia were 64 (27)% and 60 (32)%, which is substantially more variable than EBC pH assays. CONCLUSIONS: Although ammonia and pH appear to correlate in EBC, the oral ammonia concentration is not an important determinant of EBC pH. No precautions need to be taken to exclude oral ammonia when EBC pH is of interest. The low pH and low ammonia found in EBC from patients with lung diseases appear to be independent effects of volatile compounds arising from the airway.     

Identification and functional analysis of common human flavin-containing monooxygenase 3 genetic variants

Flavin-containing monooxygenases (FMOs) are important for the disposition of many therapeutics, environmental toxicants, and nutrients. FMO3, the major adult hepatic FMO enzyme, exhibits significant interindividual variation. Eighteen FMO3 single-nucleotide polymorphism (SNP) frequencies were determined in 202 Hispanics (Mexican descent), 201 African Americans, and 200 non-Latino whites. Using expressed recombinant enzyme with methimazole, trimethylamine, sulindac, and ethylenethiourea, the novel structural variants FMO3 E24D and K416N were shown to cause modest changes in catalytic efficiency, whereas a third novel variant, FMO3 N61K, was essentially devoid of activity. The latter variant was present at an allelic frequency of 5.2% in non-Latino whites and 3.5% in African Americans, but it was absent in Hispanics. Inferring haplotypes using PHASE, version 2.1, the greatest haplotype diversity was observed in African Americans followed by non-Latino whites and Hispanics. Haplotype 2A and 2B, consisting of a hypermorphic promoter SNP cluster (-2650C>G, -2543T>A, and -2177G>C) in linkage with synonymous structural variants was inferred at a frequency of 27% in the Hispanic population, but only 5% in non-Latino whites and African Americans. This same promoter SNP cluster in linkage with one or more hypomorphic structural variant also was inferred in multiple haplotypes at a total frequency of 5.6% in the African-American study group but less than 1% in the other two groups. The sum frequencies of the hypomorphic haplotypes H3 [15,167G>A (E158K)], H5B [-2650C>G, 15,167G>A (E158K), 21,375C>T (N285N), 21,443A>G (E308G)], and H6 [15,167G>A (E158K), 21,375C>T (N285N)] was 28% in Hispanics, 23% in non-Latino whites, and 24% in African Americans.     

Current approach on spinal cord monitoring: the point of view of the neurologist,the anesthesiologist and the spine surgeon

Optimal outcome in spine surgery is dependent of the coordination of efforts by the surgeon, anesthesiologist, and neurophysiologist. This is perhaps best illustrated by the rising use of intraoperative spinal cord monitoring for complex spine surgery. The challenges presented by neurophysiologic monitoring, in particular the use of somatosensory and motor evoked potentials, requires an understanding by each member for the team of the proposed operative procedure as well as an ability to help differentiate clinically important signal changes from false positive changes. Surgical, anesthetic, and monitoring issues need to be addressed when relying on this form of monitoring to reduce the potential of negative outcomes in spine surgery. This article provides a practical overview from the perspective of the neurophysiologist, the anesthesiologist, and the surgeon on the requirements which must be understood by these participants in order to successfully contribute to a positive outcome when a patient is undergoing complex spine surgery.

     

Unusual features in familial asphyxiating thoracic dysplasia (Jeune''s disease)

Asphyxiating thoracic dysplasia or Jeune's disease is a hereditary condition characterized by typical roentgenologic changes of the ribs, pelvis and extremities. Affected infants have very narrow chests and suffer from respiratory insufficiency which often leads to early death.
A large family of Arabic and Greek origin is described. Two siblings were dwarfed, had narrow chests and skeletal changes similar to those seen in Jeune's disease. In both infants widening and shortening of the left lower ribs and a trident appearance of the pelvis was demonstrated. One child who was severely mentally retarded died in infancy from bronchopneumonia and the other suffers from respiratory difficulties. Other members of the family had roentgenologic changes of the pelvis, spine and skull and mental retardation, features which have not previously been described in this disease.     

Exhaled-breath condensate pH can be safely and continuously monitored in mechanically ventilated patients

BACKGROUND: Airway inflammation in acute and chronic respiratory diseases is characterized in part by abnormal pH in airway-lining fluid. The pH of exhaled-breath condensate (EBC) is low (acidic) in various pulmonary inflammatory diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, pneumonia, and acute respiratory distress syndrome. Because the time course of pH changes in the airway is not yet clear, we aimed to develop a method for frequent and intensive EBC pH data collection in mechanically ventilated patients. METHODS: We examined the collection, gas-standardizing (CO2 removal), and continuous monitoring of pH of EBC from the expiratory port of a Servo-i ventilator with mechanically ventilated patients. We developed a condensing device that attaches to the exhaust port and is chilled by an electric cooling system. We built a 2-chamber gas-standardization and pH-measuring device that attaches to the condensing system and records pH every 6 s. After safety testing, we enrolled mechanically ventilated patients (with diverse reasons for requiring ventilatory support) for up to 96 h of continuous EBC pH condensimetry. RESULTS: The pressure, volume, and flow of the ventilator attached to a test lung were unchanged by application of the condensimeter, at various flows (2-120 L/min) and ventilator settings. We monitored 19 pediatric patients for 6-96 h. The pH of the accumulated EBC in the storage container correlated with the geometric mean of all the pH data points from the condensimeter during the recording period (r2 = -0.95, p < 0.001), which internally validated that the condensimetry system provides accurate, well gas-standardized readings for up to 96 h. The EBC pH values were similar to published reports of single samples. The EBC pH became more acidic during clinical deterioration and normalized with recovery. CONCLUSION: Continuous monitoring of EBC pH from the ventilator exhaust port is safely achievable and reliably provides data that may become useful in monitoring critically ill patients.