Organ specific apoptosis following polymicrobial intraperitoneal infection.

BACKGROUND: Leukocyte apoptosis allows safe removal of potentially harmful cells and facilitates resolution of inflammation. We hypothesized that the number of apoptotic cells changes in a disproportionate fashion in parenchymal organs in response to intra-abdominal infection. MATERIALS AND METHODS: The percentage of apoptotic cells in the liver, spleen, lung, and peripheral blood was evaluated following cecal ligation and puncture (CLP) in mice. Tissue myeloperoxidase (MPO) levels were measured as an index of neutrophil extravasation. RESULTS: Liver & spleen MPO continually increased, while lung MPO remained low after CLP. In parallel to the increase in MPO, liver & spleen apoptosis continually increased throughout the 9-day follow-up period, whereas lung apoptosis remained unchanged. CONCLUSIONS: The distribution of apoptotic cells during intraperitoneal infection occurs in an organ specific manner, with significant increases in the spleen and liver. This distribution likely reflected the clearance of apoptotic cells as the inflammatory focus became contained.

A multicenter evaluation of whether gender dimorphism affects survival after trauma.

BACKGROUND: The frequency of women who have sustained severe injuries has increased over the past 30 years. The purpose of this study was to evaluate whether severely injured women have a survival advantage over men. To address this issue, we undertook a multicenter evaluation of the effects of gender dimorphism on survival in trauma patients. METHODS: Patient information was collected from the databases of three level I trauma centers. We included all consecutive patients who were admitted to these centers over a 4-year period. We evaluated the effects of age, gender, mechanism of injury, pattern of injury, Abbreviated Injury Score (AIS), and Injury Severity Score (ISS) on survival. RESULTS: A total of 20,261 patients were admitted to the three trauma centers. Women who were younger than 50 years of age (mortality rate 5%) experienced a survival advantage over men (mortality rate 7%) of equal age (odds ratio 1.27, P <0.002). This advantage was most notably found in the more severely injured (ISS >25) group (mortality rate 28% in women versus 33% in men). This difference was not attributable to mechanism of injury, severity of injury, or pattern of injury. CONCLUSIONS: Severely injured women younger than 50 years of age have a survival advantage when compared with men of equal age and injury severity. Young men have a 27% greater chance of dying than women after trauma. We conclude that gender dimorphism affects the survival of patients after trauma.

Impact of recent trends of noninvasive trauma evaluation and nonoperative management in surgical resident education.

BACKGROUND: The use of ultrasonography and nonoperative management of solid organ injury has become standard practice in many trauma centers. Little is known about the effects of these changes on resident educational experience. METHODS: We retrospectively reviewed resident evaluation of abdominal trauma and trauma operative experience as reported to the residency review committee between 1994 and 1999. RESULTS: A total of 4,052 patients underwent one or more of three diagnostic modalities. The nontherapeutic laparotomy rate as a result of positive diagnostic peritoneal lavages decreased from 35% to 14%. Although resident operative trauma experience was stable because of increases in operative burns and nonabdominal trauma, the number of abdominal procedures declined. CONCLUSION: Noninvasive diagnostic tests have allowed more rapid trauma evaluation and fewer nontherapeutic laparotomies. As nonoperative experience grows, the opportunity for operative experience decreases. These trends may adversely affect the education of residents and suggest that novel approaches are needed to ensure adequate operative experience in trauma.

Immediate and delayed leukocyte apoptosis in two models of peritonitis.

Leukocyte apoptosis is an energy-dependent process that facilitates resolution of the cellular inflammatory response. Levels of apoptosis can be accelerated or inhibited after exposure to various stimuli. To compare apoptosis in transmigrated leukocytes, two models of peritonitis in mice were used that both cause leukocyte influx into the peritoneal cavity: (1) intraperitoneal thioglycollate administration producing a sterile peritonitis and (2) cecal ligation and puncture (CLP) producing a polymicrobial bacterial peritonitis. Samples of blood and peritoneal exudate cells (PEC) were collected at multiple time points after induction of peritonitis. Leukocytes were either fixed immediately to determine an immediate apoptosis level or cultured for 24 h to determine a delayed apoptosis level. Apoptosis was assessed using terminal uridine-triphosphate nick-end labeling (TUNEL) assay, flow cytometry, and confocal microscopy. Leukocyte influx into the peritoneal cavity was confirmed in both models. At all time points, and in both models, there was increased immediate apoptosis in PEC compared with unmanipulated controls and this increase was maximal in CLP after 18 h, although it appeared to remain at a stable level in the sterile peritonitis model by 3 h. There was also an increase in PEC delayed apoptosis at early time points in both models, again maximal at 18 h for CLP, with the levels being significantly higher than the thioglycollate model at 6 h and 18 h. The mice had a relative peripheral neutropenia at 6 h after CLP, but not post thioglycollate injection, and this persisted until 42 h. Lung and liver MPO levels were elevated in CLP but did not increase after thioglycollate. There was no increase in immediate peripheral leukocyte apoptosis in either model, but an increase in delayed peripheral leukocyte apoptosis was observed by 18 h in both models. Peripheral leukocyte CD1lb expression, which is a marker of activation, was also persistently elevated in the CLP model, but not in sterile peritonitis. In conclusion, CLP is a more potent stimulus for apoptosis of leukocytes than their migration to the site of inflammation alone, as occurs in the thioglycollate model. Blood leukocyte apoptosis also appears not to be dependent on CD11b expression, and therefore activation status.

Evolution in the management of hepatic trauma: a 25-year perspective.

OBJECTIVE: To define the changes in demographics of liver injury during the past 25 years and to document the impact of treatment changes on death rates. SUMMARY BACKGROUND DATA: No study has presented a long-term review of a large series of hepatic injuries, documenting the effect of treatment changes on outcome. A 25-year review from a concurrently collected database of liver injuries documented changes in treatment and outcome. METHODS: A database of hepatic injuries from 1975 to 1999 was studied for changes in demographics, treatment patterns, and outcome. Factors potentially responsible for outcome differences were examined. RESULTS: A total of 1,842 liver injuries were treated. Blunt injuries have dramatically increased; the proportion of major injuries is approximately 16% annually. Nonsurgical therapy is now used in more than 80% of blunt injuries. The death rates from both blunt and penetrating trauma have improved significantly through each successive decade of the study. The improved death rates are due to decreased death from hemorrhage. Factors responsible include fewer major venous injuries requiring surgery, improved outcome with vein injuries, better results with packing, and effective arterial hemorrhage control with arteriographic embolization. CONCLUSIONS: The treatment and outcome of liver injuries have changed dramatically in 25 years. Multiple modes of therapy are available for hemorrhage control, which has improved outcome.

Prehospital hypotension as a valid indicator of trauma team activation.

BACKGROUND: Criteria for trauma team activation are continually being evaluated to ensure proper utilization of resources. We examined the impact of prehospital (PH) hypotension (systolic blood pressure < or = 90) on outcome (operative intervention and mortality) and its usefulness as an indicator for trauma team activation. METHODS: A database was created by using the trauma registry for all nonburned, injured patients from July of 1993 through October of 1998 at our Level I trauma center. RESULTS: Of 6,976 patients (83% blunt injury) in the database, 4,437 had a PH blood pressure recorded. Documented PH hypotension was present in 791 patients. Hypotension persisted in the emergency department (ED) in 299 patients, but 193 of them showed minimal or no signs of life on arrival. Four hundred ninety-two patients had PH hypotension but normal ED systolic blood pressure, and 130 patients developed ED hypotension after normal PH systolic blood pressure. Nearly half of the patients with hypotension were taken from the ED directly to the operating room primarily for hemorrhage control procedures. The early and late mortality rates of patients with PH and ED hypotension were 12% and 32%, respectively. Other PH interventions had minimal effect on mortality in the hypotensive patient. CONCLUSION: Prehospital hypotension remains a valid indicator for trauma team activation. Even though most of the non-DOA patients (492 of 598) were stable on arrival to the ED, nearly 50% required operative intervention, and an additional 25% required intensive care unit admission. The trauma team should be activated and involved with these patients early.

Cerebral vascular response to hemorrhagic hypotension in newborn lambs: the influence of developing anemia.

The ability of newborn animals to autoregulate cerebral blood flow (CBF) has been documented. Most studies of the cerebral vascular response to hypotension utilize hemorrhage, generally confounded with anemia. We studied the cerebral blood flow and metabolic response of chloralose and urethane anesthetized newborn lambs to regulated hypotension. Lambs (< or = 7 days old) were catheterized for radioactive microsphere determinations of CBF. The dorsal sagittal sinus was catheterized to obtain cerebral blood samples for the calculation of oxygen uptake. Cerebral perfusion pressure was reduced in a step-wise fashion with hemorrhagic hypotension. Animals spontaneously became anemic with hypotension (AH; n = 8). In a group of animals (NH; n = 6), anemia was prevented by infusion of autologous red blood cells. Arterial pressure was reduced from control to 50, 40, and 30 mm Hg. In the AH group hematocrit fell 37% but was not different from control in the NH group. Total CBF was maintained in all groups. The lowest perfusion pressures studied were 25 +/- 1 and 22 +/- 1 mm Hg in AH and NH groups respectively. Oxygen delivery decreased (37%) only in the AH group, secondary to anemia. Calculated oxygen consumption was maintained in the AH group but increased (approximately 50%) in the NH group at 50 and 40 mm Hg. The ratio of oxygen uptake to oxygen delivery (fractional oxygen extraction) increased linearly in both groups as arterial pressure decreased. The major findings of these experiments are (i) The anesthetized newborn lamb can maintain CBF when perfusion pressure falls to 25 mm Hg and this autoregulatory capacity (classically defined) is not dependent on a change in hematocrit and, presumably, viscosity; (ii) Cerebral hypotension, anemic or not, appears to be accompanied by an increase in fractional extraction of oxygen.

Microvascular complications of NIDDM in Hispanics and non-Hispanic whites. San Luis Valley Diabetes Study.

The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case-control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20-74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4-63.7) than in Hispanics (41.8 per 100, 95% CI 34.8-48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people.