Incidence of pheochromocytoma in trauma patients during the management of unrelated illness: a retrospective review.

BACKGROUND: Over the last two decades the rate of detection of asymptomatic adrenal masses has increased as a result of the widespread use of abdominal imaging modalities. Incidental pheochromocytoma discovered during the management of an unrelated illness is a rare presentation of these tumors. They can occur in patients treated for multiple trauma with no history of prior arterial hypertension. METHODS: From January 1995 to December 2005 a total of 45 patients underwent adrenalectomy for incidentaloma. Of these, a pheochromocytoma was detected in 13 patients (29%) seen for an unrelated condition, 3 were in trauma patients. Nine men and 4 women with a mean age 44.5 years (range 21-67) underwent adrenalectomy for incidental pheochromocytoma. RESULTS: Less than half (6 patients, 46%), and one of the trauma patients had a history of arterial hypertension. Preoperative hormonal studies revealed a pheochromocytoma in 11 patients with incidentalomas. One patient had normal preoperative catecholamines levels. Laparoscopic transabdominal adrenalectomy was attempted in 10 patients with one conversion to open surgery in the case of paraganglioma and one for injury to the left renal vein. Three patients underwent open adrenalectomy. Mean surgery time of trauma patients was 167 (range, 130-235) min. Intraoperative instability (systolic pressure >200 mmHg) requiring nitroprusside and/or labetalol, was observed in 7 patients (54%). There was no postoperative morbidity or mortality. Over the last 10 years, 23% of the pheochromocytomas found incidentally were in trauma patients. CONCLUSION: Incidentally discovered adrenal masses need to be investigated for pheochromocytoma. This holds specially true for trauma patients who may be put in serious jeopardy should they need surgery for their injuries.

Use of the embedded peritoneal dialysis catheter: experience and results from a North American Center.

Since 2000, the Ottawa Hospital Home Dialysis Program has used a variation on the embedded peritoneal dialysis catheter technique described by Moncrief et al. In this paper, we describe our approach to placement of peritoneal access and report our experience with 304 embedded catheters placed between January 2000 and December 2003. We review the advantages and disadvantages of this technique and describe factors that have been important to the success of our program.

Antiviral activity and cross-resistance profile of P-1946, a novel human immunodeficiency virus type 1 protease inhibitor.

The HIV protease inhibitor P-1946 is a member of a novel family of l-Lysine derivatives. The compound is a specific HIV-1 protease inhibitor that has potent and selective in vitro antiviral activity (EC50 152 nM) against a range of isolates resistant to commercially available protease inhibitors. The presence of at least four primary and four secondary drug resistance mutations is required to achieve greater than four-fold resistance to P-1946. P-1946's favorable resistance profile makes it a good lead for the development of new agents active against existing PI-resistant virus in treatment-experienced patient.

Lipid-based delivery of combinations of antisense oligodeoxynucleotides for the in vitro inhibition of HIV-1 replication.

We evaluated a new approach to AIDS therapy by using combinations of oligodeoxynucleotides (ODNs), delivered with a lipid-based carrier system, that target different HIV viral genome sites. We identified some of the factors that seem to influence the effectiveness of a combination strategy in cell cultures including ODN concentrations, type of infection (acute vs chronic), backbone modification of the ODN, and the number of sequences. When delivered by the DLS carrier system, some advantages of using a combination of ODNs over treatment with only one ODN could be observed in acute infection assays but not in the chronic infection model. These results suggest that in the acute infection model, the 3 different antisense ODNs in the "cocktail" might block an early step of virus replication by combined inhibitory effects. Various combinations of phosphorothioate-modified (PS) and unmodified oligonucleotides delivered by the DLS system were compared for their antiviral activity in a long-term acute assay using HIV-1 (IIIB strain)-infected MOLT-3 cells. The most effective combination had 3 phosphorothioate antisense ODNs: Srev, SDIS, and SPac (>99% inhibition at 100 pM). However, the additive effect determined when using ODN combinations was rather low, revealing the high level of nonsequence specificity in HIV-1 cell culture models. Data illustrated the high sequence nonspecific activity of ODNs, especially when comparing activity of antisense ODNs with activity of random control sequence ODNs. The latter exhibited an inhibitory effect similar to that of antisense ODNs under our experimental conditions. Nevertheless, we demonstrated that it is possible to achieve high anti-HIV activity by using, in combination, picomolar range concentrations of antisense oligonucleotides complexed to a lipid-based carrier system such as the DLS system, without increasing cell toxicity.

Midodrine prevents orthostatic intolerance associated with simulated spaceflight.

Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.

Analysis of the DNA substrate structure and number of the processing sites on the activities of HIV-1 integrase in vitro.

A series of DNA substrates were synthesized to analyze the 3'-processing, integration and disintegration reactions taking place concurrently on the same DNA molecules and to evaluate the potential effects of various structural modifications of these molecules on the activities of HIV-1 integrase (IN). Our results indicate that DNA substrates containing multiple recognition sites for IN can produce efficiently the three activities of the enzyme. The 3'-processing and disintegration sites are recognized and processed by IN, both reactions being carried out in a competitive manner by the enzyme on the same DNA molecule. The presence of the gaps and unpaired nucleotides in the region surrounding the disintegration site had major deleterious effects on enzymes disintegration activity. Analysis of a different conformation at the base of the DNA hairpin has revealed a significant improvement of IN disintegration activity in the presence of double-stranded DNA on the 3' side of the disintegration site, suggesting that this region plays an important role in the stability of the enzyme-substrate complex. Interestingly, the efficiency of disintegration was strongly diminished in the presence of an unpaired nucleotide located immediately at the 3' end of the cleavage site. Overall, our results underline the extreme sensitivity of the HIV-1 IN to its substrates structure and conformation, especially for its disintegration activity, and the considerable importance of the disintegration activity in the reactions carried out in vitro by the purified enzyme.

Orthostatic intolerance and motion sickness after parabolic flight.

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Characterization of mutant HIV-1 integrase carrying amino acid changes in the catalytic domain.

To gain insight into the importance of conserved residues in the core domain of HIV-1 IN, we performed site-directed mutagenesis of the full-length enzyme, overexpressed the mutant proteins in E. coli, purified and analyzed their 3'-processing, integration and disintegration activities in vitro. Change of E152V in the DD(35)E motif abolished all detectable activities of IN. Alteration of two highly conserved residues, P145 and K156, by isoleucine, resulted in a substantial loss or completely abolished the three activities of the enzyme. Mutant P90D weakly reduced the 3'-processing but severely affected the two other IN activities. Results obtained from double and triple mutations, P90D/P1451 and P145I/F185K/C280S, clearly suggest a crucial role of P145 in the catalytic function of IN, whereas the mutants V150E, L158F and L172M had no detectable effect on any of the IN activities. Taken together, these results allowed us to conclude that all the conserved amino acids in the core domain of IN are not equally important for catalytic functions: like D64, D116 and E152, our data suggest that P90, P145 and K156 are also essential for all three enzymatic activities of HIV-1 IN in vitro, whereas V150, L158 and L172 appear to be less critical.

Management of adult splenic injuries in Ontario: a population-based study.

OBJECTIVES: To determine the population-based incidence of splenic injuries in the Province of Ontario, the proportion of splenic injuries treated by observation, splenectomy and splenorrhaphy, changes in management over time and the variation in management of splenic injuries among Ontario hospitals. DESIGN: A retrospective cohort study. PATIENTS: All adults (older than 16 years) admitted with a diagnosis of splenic injury (clinical modification of the International Classification of Diseases, 9th revision) to acute care hospitals in Ontario between 1991 and 1994, identified from the Ontario Trauma Registry. RESULTS: The incidence of splenic injury was 1.7 cases per 1000 trauma admissions per year. Patients with splenic injury were young (median age 32 years) and male (71%), and the death rate was 8%. Observation was the commonest method of treatment (69%), followed by splenectomy (28%) and splenorrhaphy (4%). The use of observation increased over the study period from 59% to 75% (p < 0.001). There was significant variation in the use of observation among hospitals (range 11% to 100%, p < 0.0001). CONCLUSIONS: The majority of splenic injuries are managed by observation with an acceptable hospital death rate. The use of observation has increased over time, confirming the growing adoption of this management approach by most hospitals in the province when feasible. Splenorrhaphy was infrequently performed despite reports to the contrary from many centres in the United States. There was significant variation in splenic injury management, suggesting the need for further refinement and dissemination of practical guidelines for splenic salvage.

Anesthesia for laparoscopic adrenalectomy (pheochromocytoma) in an anemic adult Jehovah's Witness.

PURPOSE: To report the anesthetic management of an anemic Jehovah's Witness patient presenting for laparoscopic adrenalectomy for pheochromocytoma. CLINICAL FEATURES: A 49-yr-old woman presented with hemodynamic instability progressing to cardiogenic shock and subsequent acute renal failure. Her course was complicated by anemia. An adrenal pheochromocytoma was diagnosed. Preoperatively, alpha- and beta-adrenergic blockade was instituted with phenoxybenzamine and metoprolol therapy and her anemia was treated with erythropoietin. She underwent laparoscopic resection of the adrenal tumour. A cell saver device was employed and attached to the laparoscopic suction-irrigation apparatus to provide salvage capability in the event of a major hemorrhage. The surgical intervention was uneventful and well tolerated. The patient was discharged home and well on follow-up. CONCLUSIONS: Cell salvage is the only mechanism currently acceptable to Jehovah's Witnesses which will allow for perioperative salvage and replacement of blood loss. Its use is encouraged in all situations in which surgical hemorrhage is anticipated.

Use of abdominal computed tomography in blunt trauma: do we scan too much?

OBJECTIVES: To determine what proportion of abdominal computed tomography (CT) scans ordered after blunt trauma are positive and the applicability and accuracy of existing clinical prediction rules for obtaining a CT scan of the abdomen in this setting. SETTING: A leading trauma hospital, affiliated with the University of Ottawa. DESIGN: A retrospective cohort study. PATIENTS AND METHODS: All patients with blunt trauma admitted to hospital over a 1-year period having an Injury Severity Score (ISS) greater than 12 who underwent CT of the abdomen during the initial assessment. Recorded data included age, sex, Glasgow Coma Scale (GCS) score, ISS, type of injuries, number of abdominal CT scans ordered, and scan results. Two clinical prediction rules were found in the literature that identify patients likely to have intra-abdominal injuries. These rules were applied retrospectively to the cohort. The predicted proportion of positive CT scans was compared with the observed proportion, and the sensitivity, specificity, and accuracy were estimated. RESULTS: Of the 297 patients entered in the study, 109 underwent abdominal CT. The median age was 32 years, 71% were male and the median ISS was 24. In only 36.7% (40 of 109) of scans were findings suggestive of intra-abdominal injuries. Application of one of the clinical prediction rules gave a sensitivity of 93.8% and specificity of 25.5% but excluded 23% of patients because of a GCS score less than 11. The second prediction rule tested could be applied to all patients and was highly sensitive (92.5%) and specific (100.0%). CONCLUSIONS: The assessment of the abdomen in blunt trauma remains a challenge. Accuracy in predicting positive scans in equivocal cases is poor. Retrospective application of an existing clinical prediction rule was found to be highly accurate in identifying patients with positive CT findings. Prospective use of such a rule could reduce the number of CT scans ordered without missing significant injuries.

Inflight exercise affects stand test responses after space flight.

PURPOSE: The purpose of this study was to determine whether exercise performed by Space Shuttle crew members during short-duration space flights (9-16 d) affects the heart rate (HR) and blood pressure (BP) responses to standing within 2-4 h of landing. METHODS: Thirty crew members performed self-selected inflight exercise and maintained exercise logs to monitor their exercise intensity and duration. Two subjects participated in this investigation during two different flights. A 10-min stand test, preceded by at least 6 min of quiet supine rest, was completed 10-15 d before launch (PRE) and within 4 h of landing (POST). Based upon their inflight exercise records, subjects were grouped as either high (HIex: > or = 3 times/week, HR > or = 70% HRmax, > or = 20 min/session, N = 11), medium (MEDex: > or = 3 times/week, HR < 70% HRmax, > or = 20 min/session, N = 10), or low (LOex: < or = 3 times/week, HR and duration variable, N = 11) exercisers. HR and BP responses to standing were compared between groups (ANOVA, P < or = 0.05). RESULTS: There were no PRE differences between the groups in supine or standing HR and BP. Although POST supine HR was similar to PRE, all groups had an increased standing HR compared with PRE. The increase in HR upon standing was significantly greater after flight in the LOex group (36 +/- 5 bpm) compared with HIex or MEDex groups (25 +/- 1 bpm; 22 +/- 2 bpm). Similarly, the decrease in pulse pressure (PP) from supine to standing was unchanged after space flight in the MEDex and HIex groups but was significantly greater in the LOex group (PRE: -9 +/- 3; POST: -19 +/- 4 mm Hg). CONCLUSIONS: Thus, moderate to high levels of inflight exercise attenuated HR and PP responses to standing after space flight.

Acute manipulations of plasma volume alter arterial pressure responses during Valsalva maneuvers.

The effects of changes in blood volume on arterial pressure patterns during the Valsalva maneuver are incompletely understood. In the present study we measured beat-to-beat arterial pressure and heart rate responses to supine Valsalva maneuvers during normovolemia, hypovolemia induced with intravenous furosemide, and hypervolemia induced with ingestion of isotonic saline. Valsalva responses were analyzed according to the four phases as previously described (W. F. Hamilton, R. A. Woodbury, and H. T. Harper, Jr. JAMA 107: 853-856, 1936; W. F. Hamilton, R. A. Woodbury, and H. T. Harper, Jr. Am. J. Physiol. 141: 42-50, 1944). Phase I is the initial onset of straining, which elicits a rise in arterial pressure; phase II is the period of straining, during which venous return is impeded and pressure falls (early) and then partially recovers (late); phase III is the initial release of straining; and phase IV consists of a rapid "overshoot" of arterial pressure after the release. During hypervolemia, early phase II arterial pressure decreases were significantly less than those during hypovolemia, thus making the response more "square." Systolic pressure hypervolemic vs. hypovolemic falls were -7.4 +/- 2.1 vs. -30.7 +/- 7 mmHg (P = 0.005). Diastolic pressure hypervolemic vs. hypovolemic falls were -2.4 +/- 1.6 vs. -15.2 +/- 2.6 mmHg (P = 0.05). A significant direct correlation was found between plasma volume and phase II systolic pressure falls, and a significant inverse correlation was found between plasma volume and phase III-IV systolic pressure overshoots. Heart rate responses to systolic pressure falls during phase II were significantly less during hypovolemia than during hypervolemia (0.7 +/- 0.2 vs. 2.82 +/- 0.2 beats. min-1. mmHg-1; P = 0.05) but were not different during phase III-IV overshoots. We conclude that acute changes in intravascular volume from hypovolemia to hypervolemia affect cardiovascular responses, particularly arterial pressure changes, to the Valsalva maneuver and should be considered in both clinical and research applications of this maneuver.

Sleep-wake differences in scaling behavior of the human heartbeat: analysis of terrestrial and long-term space flight data.

We compare scaling properties of the cardiac dynamics during sleep and wake periods for healthy individuals, cosmonauts during orbital flight, and subjects with severe heart disease. For all three groups, we find a greater degree of anticorrelation in the heartbeat fluctuations during sleep compared to wake periods. The sleep-wake difference in the scaling exponents for the three groups is comparable to the difference between healthy and diseased individuals. The observed scaling differences are not accounted for simply by different levels of activity, but appear related to intrinsic changes in the neuroautonomic control of the heartbeat.

An episode of ventricular tachycardia during long-duration spaceflight.

An episode of nonsustained ventricular tachycardia was recorded from a crew member during the second month aboard the MIR space station. Although asymptomatic, this cardiac event increases the concern that serious cardiac dysrhythmias may be a limiting factor during long-duration spaceflight.

Management of choledocholithiasis in the time of laparoscopic cholecystectomy.

BACKGROUND: The best way to detect and manage common duct stones in conjunction with laparoscopic cholecystectomy is not agreed upon at the present time. PATIENTS AND METHODS: Our experience with choledocholithiasis in a consecutive series of 1,123 cholecystectomies (94% by laparoscopy) has been reviewed. Suspected duct stones were investigated preoperatively or postoperatively by endoscopic retrograde cholangiography (ERC), and if necessary, duct clearance was attempted by endoscopic sphincterotomy (ES). No attempt was made to identify choledocholithiasis intraoperatively. RESULTS: Endoscopic retrograde cholangiography was performed in 11% of patients, and 32% of these required ES. The complication rate of ERC and ES was 8%, without mortality. Two patients required a second operation for missed choledocholithiasis, for a reoperation rate of 0.2%. CONCLUSION: We believe that primary or secondary open surgery is only occasionally necessary for the management of choledocholithiasis. Preoperative ERC and ES for suspected duct stones, with the same strategy employed as a salvage for stones presenting after cholecystectomy, was safe and efficient.

Differential performance of TRISS-like in early and late blunt trauma deaths.

OBJECTIVES: (1) To independently validate the Trauma and Injury Severity Score-Like (TRISS-Like) model derived by Offner et al. (Revision of TRISS for intubated patients. J Trauma. 1992;32:32-35) in a population of Canadian blunt trauma victims, and (2) to compare the ability of this model to predict mortality in early and late trauma deaths. STUDY POPULATION: Prospective cohort of blunt trauma cases with Injury Severity Score > 12 identified from the Ontario Trauma Registry over a 5-year period. STUDY DESIGN: The TRISS-Like model consisting of age, Injury Severity Score, systolic blood pressure, and best motor response of the Glasgow Coma Scale was evaluated as to its ability to predict mortality by determining the sensitivity, specificity, and the area under the receiver operating characteristic curve. The sample was then divided into early (< or = 7 days) and late mortality subgroups in which model performance was evaluated with respect to time of death. RESULTS: A total of 7,703 patients were included in this analysis. The overall mortality was 12.3%. The TRISS-Like model allowed for assessment of an additional 23% of patients than would standard TRISS and performed with a sensitivity of 97.1%, specificity of 39.8% and an area under the receiver operating characteristic curve of 0.873. Analysis of mortality with respect to time demonstrated that 75% of deaths occurred by day 7. The specificity and receiver operating characteristic area increased in the early (< or = 7 days) subgroup, 46.5% and 0.935, respectively, compared with 20.8% and 0.778 in the late mortality group. CONCLUSIONS: TRISS-Like demonstrated similar performance to that reported with the standard TRISS model but with the additional advantage that it is more generalizable because it can be applied to intubated patients. TRISS-Like demonstrated substantially superior performance in early trauma deaths compared with those that occurred late. This differential performance may be because the model does not include risk factors for late mortality.