Oxygen delivery and consumption in head-injured and multiple trauma patients

Critically ill patients often demonstrate that whole body oxygen consumption (VO2) is dependent on oxygen delivery (DO2). In this retrospective study, the relationship of VO2 to DO2 in patients with isolated head injury (HI, n = 18) was compared to that in patients with multiple trauma (MT, n = 60) without serious head injury. Mean pulmonary capillary wedge pressure, central venous pressure, arterial PCO2, cardiac index, and oxygen delivery were significantly lower in HI, but oxygen consumption was not different in the groups. In both groups, changes in DO2 (delta DO2) within each patient were significantly correlated with changes in VO2 (delta VO2) in that same patient. This relationship was not different between the HI patients, (delta VO2 = (0.20 +/- 0.02) delta DO2), and the MT patients (delta VO2 = (0.17 +/- 0.01) delta DO2). When these groups were further divided into those with high hematocrit (greater than 32%) and low hematocrit (less than 32%), HI patients with a low hematocrit demonstrated a steeper regression slope, with 26 +/- 3% of the DO2 change being reflected in the VO2 change. This was significantly greater than the slope in HI patients with high hematocrit (13 +/- 3%) and the MT patients at high (19 +/- 2%) or low (16 +/- 2%) hematocrits. These data show a correlation between changes in oxygen delivery and consumption that is similar in both head-injury patients and multiple trauma patients without serious head injury. This relationship was greatest in head-injured patients at low hematocrit. This relationship of VO2 and DO2 in both groups suggests an influence of neurohumoral factors rather than local tissue phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)     

A pediatric trauma center without a pediatric surgeon: a four-year outcome analysis.

Approximately 25% of all injury victims are in the pediatric age group, and one in four injured children will require a pediatric trauma center. According to the American College of Surgeons as well as many state guidelines, a level I pediatric trauma team should be directed by a pediatric surgeon. In 1986, the pediatric surgeon left our pediatric trauma center, but the center remained open under a cooperative effort by the adult trauma surgeons and pediatric intensivists. We have retrospectively reviewed the charts of all pediatric trauma patients (age less than or equal to 15 years) for the subsequent 4 years to determine the outcome of treatment without a pediatric surgeon. During this period, we treated 303 pediatric patients with multiple or serious single-system injuries. The mean age was 6.9 +/- 0.3 (SEM) years and 66% were boys. Falls were the cause of injury in 31% of the patients, with pedestrian/bicycle, motor vehicle crashes, and penetrating injuries resulting in 26%, 19%, and 3% of the injuries, respectively. The mean ISS was 15.6 +/- 0.8, and 73% of the patients had at least one AIS greater than or equal to 3. Surgical procedures were required in 48% of the patients. There were 27 deaths in this group, most commonly related to head injury (89%). The mean Pediatric Trauma Score of the patients who died was 1.6 +/- 0.8 and no patient with a Pediatric Trauma Score greater than 7 died.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of α-integrin subunits in fetal polycystic kidney diseases

An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by β1-integrins, a subfamily of integrin receptors, formed by the association of the β1-chain with different α-subunits. To date, no study on α-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of α-integrin subunits (α1, α2, α3, α5, and α6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in α1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits α2, α3, and α6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the α1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of α2, α3, and α6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases. Received May 28, 1996; received in revised form October 2, 1996; accepted October 25, 1996     

Mapping the Von Hippel -- Lindau disease tumour suppressor gene: identification of germline deletions by pulsed field gel electrophoresis

Von Hlppel—Lindau (VHL) disease is a dominantly Inheritedfamillal cancer syndrome In which affected individuals havea greatly increased predisposition to the development of haemangloblastomasof the central nervous system and retina, renal cell carcinomaand phaeochromocytoma. The VHL gene has been mapped to chromosome3p25 -p26 by genetic linkage studies and we have previouslydemonstrated that the VHL gene is tightly linked to the D3S601locus (Zmax = 18.86 at     

Western equine encephalomyelitis virus infection affects the life table characteristics of Culex tarsalis (Diptera: Culicidae)

The life table attributes of Culex tarsalis Coquillett females infected experimentally by feeding on 4 and 6 log10 plaque-forming units (PFU) of western equine encephalomyelitis virus (WEEV) per milliliter of heparinized chicken blood were compared with an uninfected control group. Females continually were offered 10% sucrose and an oviposition substrate and daily a blood meal through a biomembrane feeder. Mortality (dead females) and fecundity (female eggs per female) were monitored daily until all females died. Overall, 94% of 198 females in the two virus-infected groups were positive for WEEV at death when tested by plaque assay; the average body virus titer at death did not differ between groups. WEEV infection significantly altered the life table characteristics of Cx. tarsalis. Life expectancy at infection in days (ex), reproductive effort in female eggs per female per generation (Ro), and generation time (T) in days for the infected cohorts were significantly lower than for the uninfected controls, whereas the reproductive rate (rc) in female eggs per female per day was higher for infected than uninfected cohorts. In agreement with the WEEV infection data that showed similar body titers, there were few differences between the life table parameters for the 4 and 6 log10 PFU treatment groups. Greatest differences were observed for survivorship between days 17-40 when virus titers in infected dying females were greatest. Our data extend recent studies that indicate mosquito infection with encephalitis viruses has a cost of reduced life expectancy and fitness.     

The expression of γΔ T cell receptor and the prevalence of primed,activated and IgA-bound T cells in Behçet's syndrome

Mucosal ulceration of the oral, and to a lesser extent genital tissues is an essential feature of Behçet''s syndrome and is associated with changes in the IgA class of immune responses. Indeed, a significant increase in the proportion of cytophilic IgA1 was found in circulating CD8 and CD4 cells (P less than 0.01), with a corresponding decrease in IgA-Fc receptors on these T cells. Furthermore, 30-40% of the cytophilic IgA1 on T cells may have been of the polymeric secretory type and the rest of the monomeric variety. IgA isotype of B cells was also significantly increased (P less than 0.001), without an overall change in circulating B cells. However, a surprising finding was the significant up-regulation of gamma delta T cell receptor in the CD8 (P less than 0.01) in the absence of a change in the proportion of alpha beta T cell receptor. The results suggest that some common microbial antigen might initiate at the mucosal surface an immune defence reaction characterized by T cells with gamma delta receptors and IgA-specific B cells. However, IgA1 bound to circulating T cells may down-regulate the central T cell function.     

Partial androgen insensitivity with phenotypic variation caused by androgen receptor mutations that disrupt activation function 2 and the NH(2)- and carboxyl-terminal interaction

Partial androgen insensitivity with sex phenotype variation in two unrelated families was associated with missense mutations in the androgen receptor (AR) gene that disrupted the AR NH(2)-terminal/carboxy terminal interaction. Each mutation caused a single amino acid change within the region of the ligand-binding domain that forms activation function 2 (AF2). In one family, the mutation I737T was in alpha helix 4 and in the other F725L was between helices 3 and 4. Neither mutation altered androgen binding as determined by assays of mutant AR in the patient's cultured genital skin fibroblasts or of recombinant mutant receptors transfected into COS cells. In transient cotransfection assays in CV1 cells, transactivation with the AR mutants at low concentrations of DHT was reduced several fold compared with wild-type AR but increased at higher concentrations. Defects in NH(2)-terminal/carboxy terminal interactions were identified in mammalian two hybrid assays. In similar assays, there was reduced binding of the p160 coactivators TIF2/SRC2 and SRC1 to the mutant AR ligand binding domains (LBD). In the family with AR I737T, sex phenotype varied from severely defective masculinization in the proband to a maternal great uncle whose only manifestation of AIS was severe gynecomastia. He was fertile and passed the mutation to two daughters. The proband of the F725L family was also incompletely masculinized but was raised as a male while his half-sibling by a different father was affected more severely and reared as a female. These studies indicate that the function of an AR AF2 mutant in male development can vary greatly depending on the genetic background.     

The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro alpha 1 (I) chain of type I procollagen.

The features of three babies with perinatal lethal osteogenesis imperfecta (OI II) resulting from substitutions of glycine by valine in the triple helical domain of the alpha 1(I) chain of type I collagen were studied. The babies were heterozygous for this substitution at residue 1006 in case 1 (OI35), 973 in case 2 (OI59), and 256 in case 3 (OI7B). OI35 had the most severe clinical form, OI IIC, with premature rupture of membranes, severe antepartum haemorrhage, stillbirth, severe short limbed dwarfism, and extreme osteoporosis. OI59 was a better formed baby but was also born prematurely as a result of premature rupture of membranes and severe antepartum haemorrhage. She had the radiographic features of OI IIA. OI7B was born at term and also had the radiographic features of OI IIA. Pathological examination of the skeletons of OI35 and OI59 showed grossly deficient intramembranous and endochondral ossification. Trabecular bone was sparse in the long bones and vertebrae. The trabeculae contained a cartilage core and an overlying layer of woven bone or osteoid. The diaphyses lacked cortical bone. The periosteal fibroblasts of OI35 contained grossly distended rough endoplasmic reticulum consistent with the 53% reduction in collagen secretion by cultured dermal fibroblasts. The aorta, skin, and lungs were hypoplastic in OI35 and OI59. The findings in this study show that glycine substitutions by valine in Gly-X-Y triplets, from glycine 256 to glycine 1006, of the triple helical domain of alpha 1(I) chains produce the OI II phenotype. The phenotype was most severe in the baby with the most carboxy-terminal substitution.     

Loneliness,social support,social isolation and wellbeing among working age adults with and without disability: Cross-sectional study

BackgroundLoneliness is significantly related to health and wellbeing. However, there is little information on the prevalence of loneliness among people with disability or the association between disability, loneliness and wellbeing.Objective/hypothesisFor a nationally representative sample of adults (age 16–64) with/without disability, to examine exposure to three indicators of low social connectedness (loneliness, low perceived social support, social isolation), and to evaluate the association between low social connectedness and wellbeing. To test whether disability status moderated the relationship between low social connectedness and wellbeing.MethodsSecondary analysis of data from three annual rounds of the cross-sectional English Community Life Survey (CLS) 2016–19.ResultsPeople with disability experienced loneliness, low perceived social support and social isolation at significantly higher rates than people without disability. Effect sizes were significantly greater for loneliness. Disability was associated with lower wellbeing. With one exception, low social connectedness was associated with lower wellbeing. Again, effect sizes were significantly greater for loneliness. The prevalence of loneliness was highest among adults with disability who were younger, economically inactive, living in rented or other accommodation, living alone and with low levels of access to environmental assets. There was no evidence that disability status moderated the association between exposure to low social connectedness and low wellbeing.ConclusionsLoneliness was a particularly significant driver of poor wellbeing among people with disability. The relative independence between different indicators of social connectedness suggests that interventions to reduce loneliness will need to do more than simply increase rates of social contact or social support.