[The use of head CT scan in adult trauma victims: an algorithm]. / Le scanner cérébral chez les adultes victimes de traumatismes crâniens mineurs: un arbre décisionnel.

INTRODUCTION: The purpose of this study was to identify, through recursive partitioning, clinically relevant criteria which predict the need for acute neurosurgical intervention in a group of patients with mild head injury. MATERIALS AND METHODS: A retrospective cohort of all adult patients, from April 2000 to March 2001, who sustained a blunt trauma and underwent head CT scan, was reviewed. The following inclusion criteria for mild head injury were used: initial Glasgow Coma Scale (GCS) ranging from 13 to 15; no loss of consciousness lasting more than one hour; no obvious skull fracture; a cranial CT scan performed. We collected demographic and trauma related data, interventions and outcome. Univariate and multivariate analyses were undertaken. In parallel, recursive partitioning was carried out using all variables to elaborate a decision algorithm. RESULTS: There were 405 patients in the sample. CT identified lesions in 12% of patients. Twelve patients (3%) required acute neurosurgical intervention. The recursive partitioning analysis identified three significant sequential nodes: deterioration of the GCS; an initial GCS of 13 vs 14 or 15; and the presence of associated injuries or comorbid conditions. CONCLUSIONS: A simple three step rule predicts the need for acute neurosurgical intervention based on clinical findings: a deteriorating GCS; an initial GCS of 13; and the presence of associated injuries or comorbid conditions.

The effects of iodixanol and iopamidol on hemodynamic and cardiac electrophysiologic parameters in vitro and in vivo.

Iodixanol is a new, nonionic, dimeric contrast medium which, in concentrations appropriate for radiographic use, is hypotonic with respect to plasma. The purpose of these in vivo and in vitro studies was to compare the effects of iopamidol, iodixanol formulated to isotonicity with sodium salts (sodium formulation), and iodixanol formulated to isotonicity with sodium, calcium, and magnesium salts (cationic formulation) on hemodynamic and electrophysiologic parameters. In vitro, the spontaneous rate of contraction by guinea pig right atrial and force development by right ventricular papillary muscles were evaluated in the presence of 1% to 100% (v/v) of the three contrast media. Iopamidol significantly (P less than .05) decreased the rate of atrial contraction to a greater extent than either formulation of iodixanol. Iopamidol decreased papillary muscle force development more than the sodium formulation of iodixanol (P less than .05). The cationic formulation of iodixanol had little effect (less than 30% change) on papillary muscle force development at concentrations up to 100%. The contrast media were also injected into the left coronary arteries of open-chest, anesthetized dogs at 0.8 mL/second for 5 to 30 seconds. All contrast media increased (P less than .05) systolic blood pressure (SBP), mean arterial pressure (MAP), and peak left ventricular pressure (LVP). Iopamidol increased LVP and LV end diastolic pressure to a greater extent (P less than .05) than the cationic formulation of iodixanol. We conclude that iopamidol affected cardiovascular parameters more than iodixanol.

Trophic stimulation of the ductal/islet cell axis: a new approach to the treatment of diabetes.

The purpose of this study was to demonstrate that the pancreas of the hamster contains a growth factor(s) that can induce cells associated with the ductular epithelium to differentiate along an endocrine pathway and thereby provide a means of regenerating a functioning islet cell mass. We have shown previously that partial obstruction of the pancreatic duct leads to the induction of nesidioblastosis. A cytosol extract prepared from the partially obstructed hamster pancreas was injected at a dose of 4000 microliters intraperitoneally twice a day for 2 days and produced significant increases in pancreatic weight, protein, and deoxyribonucleic acid of 18%, 18% and 42% respectively, over saline-treated control animals. To assess the effects of this extract on morphology, 150 microliters intraperitoneally twice a day was administered for 21 days. Tissue was processed for histologic, morphometric, and autoradiographic analysis. Budding of endocrine cells from cells of the terminal ductules was observed in cytosol-injected animals and the number of islets per square millimeter was determined to be increased by 100% compared with saline-treated controls (p less than 0.01). Tritiated thymidine uptake by ductal and islet cells was increased tenfold and sixfold, respectively, over that of control animals (p less than 0.01). Cytosol extract was also administered to hamsters rendered diabetic by streptozocin. Survival in these animals was 100% compared with only 60% for saline-treated control animals (p less than 0.05). Furthermore, the blood levels of glucose in cytosol-treated animals was significantly less than the levels in saline-treated controls (p less than 0.05). We conclude that the pancreas does indeed contain a growth factor(s) responsible for the induction of nesidioblastosis and the new islet tissue is functionally capable of stabilizing a diabetic state.

Induction of islet cell differentiation and new islet formation in the hamster--further support for a ductular origin.

Partial obstruction of the adult hamster pancreas leads to islet cell differentiation and new islet formation. From morphologic and morphometric observations, we have tentatively identified the source of the new islet tissue to be from cells in the ducts. In this study, in vivo labeling with a single pulse of tritiated thymidine after partial duct obstruction was used to ascertain whether newly formed islet cells were in fact derived from cells in the ductal epithelium. Supportive evidence for this formulation was also sought using immunocytochemistry for islet hormones and in situ hybridization for glucagon and insulin mRNA to probe areas of proliferating duct cells. Endocrine cell differentiation was observed as a migration of cells out from small ducts beginning at about 10 days after obstruction. Duct and islet cell labeling indices (LI;%) in control animals remained at a low level (0.25 +/- 0.01 and 0.26 +/- 0.03, respectively) throughout the experiment. In contrast, at 2 weeks after partial obstruction, the duct and islet cell LI were 4.2 +/- 0.7 and 0.80 +/- 0.1 (p < 0.05 vs. control). After 2 weeks, there was a rapid and significant 86% decline in the duct cell LI to a low of 0.6 +/- 0.2 at 8 weeks, which was accompanied by a comparable, but reciprocal, 113% increase in the islet cell LI to a high of 1.7 +/- 0.8 (p < 0.05). In situ hybridization demonstrated glucagon and insulin mRNA-positive cells within intralobular ducts as early as 6 and 8 days, respectively, after obstruction. Glucagon and insulin peptides appeared in these cells at approximately 8 and 10 days, respectively, as cells migrated out from the duct wall. This study provides additional evidence that further supports our concept that pancreatic endocrine cell differentiation in this model reiterates the normal ontogeny of beta cell differentiation from cells in the ductular epithelium.

Zaprinast increases cyclic GMP levels in plasma and in aortic tissue of rats.

The purpose of this study was to determine if significant relationships exist between plasma and aortic cyclic GMP (cGMP) levels and pharmacodynamic effect after the i.v. administration of the cGMP-selective phosphodiesterase inhibitor zaprinast to conscious, spontaneously hypertensive rats. Zaprinast dose-dependently increased plasma and aortic cGMP levels at 10, 18 and 30 mg/kg and decreased mean arterial blood pressure (MAP) at 18 and 30 mg/kg. The concentrations of cGMP in the plasma and in the aorta were significantly correlated (r = 0.765, P < 0.0001). The changes in MAP were significantly correlated to aortic (r = -0.750, P < 0.0001) and plasma (r = -0.762, P < 0.0001) cGMP levels. We conclude that plasma cGMP may be an index of cGMP-selective phosphodiesterase inhibition in vivo.

Factors determining conversion to laparotomy in patients undergoing laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) has been performed increasingly in an outpatient setting. Conversion from LC to open cholecystectomy (OC) is sometimes required. To predict conversion to OC, a single institutional study of 1,676 consecutive patients in whom LC was attempted was performed. Factors evaluated were age, sex, history of acute cholecystitis, pancreatitis, or jaundice, previous abdominal surgery, abnormalities of liver function tests, thickened gallbladder wall identified by preoperative ultrasound, obesity or morbid obesity, and cumulative institutional experience in LC. Conversion to OC was required in 90 of 1,676 (5.4%) patients. Significant preoperative predictors of conversion were acute cholecystitis, increasing age, male sex, obesity, and thickened gallbladder wall found by ultrasound. Nonobese women younger than age 65 years with symptoms of biliary colic and normal gallbladder wall thickness found by preoperative ultrasound required conversion only 1.9% of the time. These predictors may be useful in planning a program of ambulatory or short stay surgical units for patients undergoing LC and for comparing data between series.

Minimally invasive surgery in the elderly patient.

Minimal access surgery has been rapidly growing. It is essential that it be carefully evaluated and that quality assurance programs be developed. Indications for surgery should not be changed just because less invasive surgical techniques are available. Conversion to an open procedure may be required in any patient, and the risk in gallstone patients is higher in the elderly. The benefits of laparoscopic methods applied to the management of symptomatic gallstone disease in the older patient population appear clear. Similar evaluation is appropriate for each new procedure performed using new techniques.

Antagonism of the cardiodepressant effects of adenosine during acute hypoxia.

OBJECTIVE: To determine whether pharmacologic antagonism of adenosine A1-receptor-mediated cardiovascular changes can improve cardiac function and prolong survival during systemic hypoxia. METHODS: Rats were anesthetized with ketamine, instrumented [including left ventricular (LV) pressure transducing catheters], paralyzed with vecuronium, then ventilated to pCO2 = 35-40 torr. After 10 minutes of equilibration (baseline), treatment commenced with saline (n = 7), NPC-205, an adenosine A1 receptor selective antagonist, at doses of 1 mg/kg (n = 10) or 10 mg/kg (n = 10), or drug vehicle (n = 9). Ten minutes later, inspired oxygen was reduced to 5%. RESULTS: Survival duration (min) post-hypoxia increased in a dose-dependent fashion from 10.4 +/- 1.4 (mean +/- SEM) with vehicle control to 23.0 +/- 4.7 and 41.1 +/- 5.7 with 1 and 10 mg/kg NPC-205, respectively (p < 0.000). Five minutes post-hypoxia, dose-dependent increases were also seen in the percentage of pre-hypoxic values of LV contractility [25.9 +/- 8.1 (vehicle), 39.5 +/- 9.6 (1 mg/kg NPC-205), and 56.5 +/- 8.7 (10 mg/kg NPC-205), p = 0.01], heart rate [60.6 +/- 8.3 (vehicle), 74.7 +/- 8.2 (1 mg/kg NPC-205), and 90.4 +/- 24.1 (10 mg/kg NPC-205), p = 0.02], and blood pressure [16.1 +/- 4.8 (vehicle), 28.8 +/- 8.6 (1 mg/kg NPC-205), and 51.7 +/- 8.2 (10 mg/kg NPC-205), p = 0.004]. CONCLUSIONS: The adenosine A1 selective antagonist prolonged survival in this model. This prolongation was attributed to inhibition of adenosine A1 receptor-mediated decline in cardiac inotropy and chronotropy. Adenosine A1 receptor-selective antagonists show promise as adjunctive therapy for hypoxia-induced cardiac insufficiency by prolonging the treatment window until more definitive resuscitation measures are taken.

Hypertonic saline treatment of severe hyperkalemia in nonnephrectomized dogs.

OBJECTIVES: To determine whether a hypertonic saline bolus improves cardiac conduction or plasma potassium levels more than normal saline infusion within 15 minutes of treatment for severe hyperkalemia. Previously with this model, 8.4% sodium chloride (NaCl) and 8.4% sodium bicarbonate (NaHCO(3)) lowered plasma potassium equally effectively. METHODS: This was a crossover study using ten conditioned dogs (14-20 kg) that received, in random order, each of three intravenous (IV) treatments in separate experiments at least one week apart: 1) 2 mmol/kg of 8.4% NaCl over 5 minutes (bolus); 2) 2 mmol/kg of 0.9% NaCl over one hour (infusion); or 3) no treatment (control). Using isoflurane anesthesia and ventilation (pCO(2) = 35-40 torr), 2 mmol/kg/hr of IV potassium chloride (KCl) was infused until conduction delays (both absent p-waves and >/=20% decrease in ventricular rate in

Comparisons of the depressor, inotropic and renal effects of milrinone and CI-930 to different pure vasodilators and diuretics in conscious instrumented dogs.

The cardiovascular and renal effects of graded i.v. dosages of two low Km cAMP cGMP-inhibitable (cGi) phosphodiesterase (PDE) inhibitors: CI-930 and milrinone (both 10-300 micrograms/kg), and three pure vasodilators: fenoldopam (0.1-3 micrograms/kg), Na nitroprusside (3-100 micrograms/kg) and hydralazine (0.1-3 mg/kg), were compared in conscious dogs. Mean arterial pressure was decreased by CI-930 at 0.3 mg/kg, milrinone at doses greater than or equal to 0.1 mg/kg (both by approximately -17 mmHg [max. change]), nitroprusside at doses greater than or equal to 0.01 mg/kg (-60 +/- 5 mmHg, [mean +/- SEM, max. change]), fenoldopam at doses greater than or equal to 0.001 mg/kg, and hydralazine at all doses (both by approximately -26 mmHg). Heart rate was increased by milrinone and CI-930 at dosages greater than or equal to 0.03 mg/kg (both by approximately 57 beats/min), nitroprusside and hydralazine at all dosages (54 +/- 18 and 91 +/- 18 beats/min, respectively) and fenoldopam at 3 micrograms/kg (21 +/- 2 beats/min). The cGi PDE inhibitors at 0.01-0.3 mg/kg and the pure vasodilators (except fenoldopam) at all dosages increased dP/dt (approximately 1500 and 900 mmHg/s, respectively). Milrinone (greater than or equal to 0.1 mg/kg), CI-930 (greater than or equal to 0.03 mg/kg), nitroprusside (greater than or equal to 0.01 mg/kg) and hydralazine (0.3-1 mg/kg) decreased left ventricular end diastolic pressure (all by approximately -4 mmHg). None of the agents adversely affected urinary volume, Na+ and K+ excretion rates. In conclusion, all agents (except fenoldopam) induced positive inotropic and chronotropic effects, and preload and afterload reduction. The cardiac effects of the pure vasodilators may be reflexly induced, whereas those of the cGi PDE inhibitors may be primarily due to inhibition of cardiac cGi PDE.

Comparison of a conscious versus anesthetized canine model in response to milrinone, hydralazine and nitroprusside.

The purpose of this study was to demonstrate, based on previous and new data, that the differences between a conscious and anesthetized canine model in the cardiovascular responses to cardiovasoactive agents were beyond their difference in the sensitivity of the compensatory mechanisms. In both conscious and anesthetized canine models, mean arterial pressure (MAP) was decreased by hydralazine (at 1-3 mg/kg and 0.3-3 mg/kg; by -26.5 +/- 4.5 and -18.8 +/- 11.7% [max. changes expressed as mean +/- SEM], respectively). MAP was also decreased by nitroprusside (both at 0.01-0.1 mg/kg, by 54.6 +/- 2.8 and -60.5 +/- 3.0%, respectively) in the conscious and anesthetized models. However, the differential MAP responses to hydralazine and nitroprusside between the two models are inconsistent with a difference in the sensitivity of the two models. Hydralazine at 1 mg/kg decreased MAP greater in the conscious than anesthetized model, whereas nitroprusside decreased MAP similarly in the two models. In conclusion, not all differential responses to hydralazine and nitroprusside between conscious and anesthetized canine models can be explained by a difference in the sensitivity of their compensatory mechanisms.

Evolution in the management of the complex liver injury at a Level I trauma center.

BACKGROUND: Management of the severe liver injury evolved from mandatory surgical repair to a more selective approach. This paper reviews the changes in management of the severe liver injury at a Level I trauma center. METHODS: We reviewed the records of patients with severe liver injury admitted to a Level I trauma center between January 1984 and December 1995. The patients were divided into two groups, G1 and G2, based on their date of admission before or after January 1991. The two groups were compared for blood products use, management of the liver injury, and outcome. RESULTS: One hundred six patients were compared for age, sex, Acute Physiology and Chronic Health Evaluation II score, Injury Severity Score, abdominal Abbreviated Injury Scale score, and the presence of concomitant injuries. There was no difference in management or outcome of the victims of penetrating injury between G1 and G2 (n = 48). The blunt injury patients in G1 (n = 22) had more liver surgery (p = 0.006), blood transfusion (p = 0.040), intra-abdominal sepsis (6 vs. 0), and higher mortality (p = 0.041) than those in G2 (n = 36). CONCLUSION: Isolated severe blunt liver injury may be managed nonoperatively with better survival and less blood products use.

Nifedipine inhibits cholecystokinin-induced gallbladder contraction.

Nifedipine is a calcium channel blocker which results in relaxation of smooth muscle. Although it has been utilized clinically to treat cardiovascular disease, and more recently spastic disorders of the esophagus and colon, its effects on gallbladder contractility have not been clearly defined. We tested the effects of nifedipine on gallbladder contraction stimulated by cholecystokinin (CCK) in a conscious guinea pig model and in healthy human volunteers. Gallbladder contraction was measured in response to repeated injections of CCK before and after intravenous nifedipine given to groups of five guinea pigs in a dose of 100, 200, or 300 micrograms. Nifedipine virtually abolished spontaneous interdigestive gallbladder contractile activity and decreased resting gallbladder tone. The mean amplitude of gallbladder contraction in response to CCK was decreased by 45, 73, and 67% (P less than 0.01), in response to the nifedipine doses of 100, 200, and 300 micrograms, respectively. The integrated gallbladder contractile response and the rate of rise of gallbladder pressure in response to CCK were also significantly decreased by nifedipine. In nine healthy human volunteers, gallbladder emptying was measured by radionuclide cholescintigraphy in response to CCK infusion; on another day the study was repeated after oral administration of 10 mg nifedipine. Ejection fraction was significantly decreased by nifedipine from 72 +/- 5 to 51 +/- 5% (P less than 0.001). These data demonstrate that nifedipine is a potent inhibitor of gallbladder contractility in guinea pigs and man. This may provide the basis for the use of nifedipine clinically in the treatment of biliary colic and also raises questions about the potential effect of long-term nifedipine use on gallstone formation and cholecystitis.

Adverse effects of cyclosporine on islet growth and differentiation.

In light of recent evidence that cyclosporine (CsA) inhibits growth of the exocrine pancreas, we decided to examine the effects of cyclosporine in a hamster model of islet cell proliferation and differentiation induced by partial pancreatic duct obstruction (PPDO), in which the growth of pancreatic endocrine tissue is mediated by production of an islet cell growth factor (ICGF) contained in a cytosolic extract of pancreas. In Part I of this study, extract was prepared from PPDO pancreas, from PPDO pancreas in animals treated with CsA (20 mg/kg ip daily for 10 days), and from pancreas in control animals. Data obtained from an in vivo bioassay confirmed that administration of the extract derived from PPDO and PPDO + CsA animals increased pancreatic organ weight significantly by 10 and 17%, respectively, compared to control. Similarly, total pancreatic DNA content was increased significantly by 25 and 41%, respectively. In Part II of the study, the direct effect of CsA on islet cell proliferation and differentiation induced by PPDO was examined. The number of islets per square millimeter and the uptake of tritiated thymidine by islet cells (%) were increased significantly in PPDO animals (2.4 +/- 0.1 and 0.56 +/- 0.06) compared to those in PPDO + CsA animals (1.2 +/- 0.1 and 0.24 +/- 0.01) and to those in controls (1.1 +/- 0.0 and 0.22 +/- 0.07). It is concluded from the data in Part I that CsA does not inhibit ICGF production, but the results of Part II suggest that CsA acts to block ICGF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential hemodynamic responses to selective inhibitors of cyclic nucleotide phosphodiesterases in conscious rats.

Selective inhibition of either the low Km cyclic AMP (cAMP) or low Km cyclic GMP (cGMP) phosphodiesterase (PDE) promotes vasorelaxation and, consequently, produces depressor effects. To evaluate the systemic and regional hemodynamic effects of selective inhibitors of these PDE isozymes, CI-930 (0.1-10 mg/kg), an inhibitor of low Km cAMP PDE, or zaprinast (3-30 mg/kg), an inhibitor of low Km cGMP PDE, was given i.v. to conscious, normotensive rats. The rats were chronically instrumented with vascular catheters and either an ultrasonic transit-time flow probe around the ascending aorta or miniaturized pulsed Doppler flow probes around the superior mesenteric and left renal arteries and the abdominal aorta. CI-930 and zaprinast, at cumulative doses of 3 and 30 mg/kg, respectively, produced comparable reductions in mean arterial pressure (-22 +/- 3 and -19 +/- 4 mm Hg, respectively) and total peripheral resistance (-0.41 +/- 0.07 and -0.42 +/- 0.06 mm Hg/ml/min, respectively) but affected other hemodynamic variables differently. CI-930 at 3 mg/kg increased the heart rate (HR), maximal aortic flow acceleration (dF/dt), and peak aortic flow and decreased the stroke volume (SV). Cardiac output (CO) was not affected by CI-930. Zaprinast at 30 mg/kg increased the CO, dF/dt, and peak aortic blood flow. The HR and SV were unaffected by zaprinast. Although both CI-930 and zaprinast increased the dF/dt and peak aortic flow, these parameters were affected more by CI-930 than by zaprinast. CI-930 decreased hindquarter, mesenteric, and renal vascular resistances in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and renal effects of the protein kinase inhibitor staurosporine in conscious rats.

To evaluate the pattern of hemodynamic responses produced by an inhibitor of protein kinase C (PKC), staurosporine 0.03-0.55 mg/kg was administered intravenously (i.v.) to conscious, normotensive rats chronically instrumented with vascular catheters for direct measurement of blood pressure (BP) and i.v. administration of drugs and either an aortic flow probe for measurement of cardiac output (CO) or miniaturized pulsed Doppler flow probes for measurement of hindquarter, renal, and mesenteric vascular resistances. Staurosporine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR) and increased heart rate (HR) in a dose-dependent manner. Because staurosporine decreased resistance in all three vascular beds monitored (hindquarter, renal, and mesenteric), staurosporine is probably a nonselective vasodilator that decreases MAP by decreasing resistance in a number of peripheral vascular beds. Staurosporine produced biphasic effects on CO, dF/dtmax and peak aortic blood flow; these parameters were significantly increased at doses less than 0.3 mg/kg and decreased to levels equal to or significantly less than control values at doses greater than 0.3 mg/kg. In comparison, the calcium channel blocker nitrendipine decreased MAP and TPR and increased HR, CO, dF/dtmax, and peak aortic flow in a dose-dependent manner over the entire dose range (0.01-1 mg/kg i.v.). Staurosporine (0.3 mg/kg) and nitrendipine (1 mg/kg) produced similar changes in MAP (-44 +/- 3 and -33 +/- 2 mm Hg, respectively), yet staurosporine affected dF/dtmax to a lesser extent than nitrendipine (-5 +/- 36 and 390 +/- 46 ml/s/s, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)