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)     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.      

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.