The post-operative changes in the level of inflammatory markers after posterior lumbar interbody fusion.

Inflammatory markers such as the C-reactive protein (CRP), white blood cell count and body temperature are easy to measure and are used as indicators of infection. The way in which they change in the early post-operative period after instrumented spinal surgery has not been reported in any depth. We measured these markers pre-operatively and at one, four, seven and 14 days postoperatively in 143 patients who had undergone an instrumented posterior lumbar interbody fusion. The CRP proved to be the only sensitive marker and had returned to its normal level in 48% of patients after 14 days. The CRP on day 7 was never higher than that on day 4. Age, gender, body temperature, operating time and blood loss were not related to the CRP level. A high CRP does not in itself suggest infection, but any increase after four days may presage infection.

Gene transfection activities of amphiphilic steroid-polyamine conjugates.

The design and evaluation of a novel potent class of DNA delivery agents based on steroid-polyamine conjugates bearing a flexible linker are reported. The hydrophobic regions are based on steroids, i.e. chlolestane and lithocholic acid motifs. The linker, which couples a hydrophobic steroid and a hydrophilic polyamine, in this study can be regarded as a two-atom extension of the conventional carbamate linker. We found that the gene transfection activity of the steroid-polyamine conjugates is influenced by the polyamine chain length and steroid structure. Molecular modeling of the relevant amphiphilic molecules revealed low-energy structures in which the polyamine chains are folded rather than stretched. This work suggests a significant effect of space-filling, i.e. the shape and orientation of the hydrophilic and hydrophobic regions, upon the efficiency of gene transfection.

Granulocyte-macrophage colony-stimulating factor prevents the progression of atherosclerosis via changes in the cellular and extracellular composition of atherosclerotic lesions in watanabe heritable hyperlipidemic rabbits.

BACKGROUND: A cytokine network is involved in atherogenesis. This study was conducted to investigate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the development and composition of atherosclerotic lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. METHODS AND RESULTS: GM-CSF (10 microg. kg-1. d-1) was administered to 4-month-old WHHL rabbits (n=9) 5 days a week for 7.5 months, whereas an equal dose of human serum albumin was administered to controls (n=9). The cholesterol levels were not changed significantly by the treatment. Age-matched 4-month-old rabbits (n=7) had atheromatous plaques over 30.7+/-5.7% of the inner surface area of the aortic arch. After treatment, the percentages of surface atheromatous plaques to total aortic arch area were 45.0+/-12.6% in the GM-CSF group and 74.3+/-11.0% in controls (P<0.0001). Histological examination demonstrated that GM-CSF reduced the ratio of intima to media (P<0.01) and cross-sectional areas of atherosclerotic lesions (P<0.0001). Quantitative analysis indicated a marked decrease in the areas of smooth muscle cells (P=0.0001), collagen (P=0.0001), and extracellular lipid deposits (P<0.05) of atheromatous plaques in GM-CSF-treated rabbits compared with controls. The terminal deoxynucleotidyltransferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method and immunohistochemistry were performed to examine the relationship between decreased atherosclerotic lesions and apoptosis. The percentage of TUNEL-positive cells increased in the GM-CSF group (GM-CSF, 24.1+/-4.4% versus control, 11.6+/-3.2%; P<0.0001). GM-CSF enhanced the apoptosis of smooth muscle cells in the shoulder region and the fibrous cap (P<0.0001), suggesting one of the mechanisms for the antiatherogenic effect. CONCLUSIONS: GM-CSF altered the composition of atherosclerotic lesions and reduced the atherosclerosis in WHHL rabbits.

Morphological and functional changes in coronary vessel evoked by repeated endothelial injury in pigs.

OBJECTIVE: We examined the morphological changes induced by repeated endothelial denudation in coronary artery (CA), as well as functional changes in the endothelium-dependent and smooth muscle responses to various vasoactive agents during the process of intimal thickening. METHODS: We observed vascular responses in denuded and non-denuded portions of pig CA while being fed a normal diet (n = 11, N group) or 2% cholesterol diet (n = 25, C group) to intracoronary acetylcholine (ACh), 5-hydroxytryptamine (5-HT), substance P (SP), and isosorbide dinitrate (ISDN) with and without the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v.) over a period of 8 weeks. Balloon endothelial denudation of the left anterior descending CA was carried out every 2 weeks. RESULTS: In N group, maximum vasoconstriction was obtained with ACh 2 weeks after the first denudation [26 +/- 5% vs. 1 +/- 1% pre-denudation, p < 0.05]. L-NAME did not affect ACh-induced CA diameter changes. Thereafter, the response to ACh was attenuated by repeated denudation in N groups. However, the degree of 5-HT-induced CA narrowing at the denuded portion increased from 7 +/- 4% (0 week) to 88 +/- 8% (8 weeks) (p < 0.05). The changes resulted in severe myocardial ischaemia, and suggested that endothelium-dependent vasodilation was progressively attenuated while hyperreactivity of vascular smooth muscle simultaneously increased. Vasodilation induced by SP was attenuated somewhat, but ISDN-induced vasodilation was preserved. Although mild hypercholesterolaemia was induced in C group, the vascular responses to these vasoactive agents did not differ from those of N group. CONCLUSIONS: Repeated CA endothelial injury and regeneration induce the change of morphology and vascular reactivity in the denuded portion regardless of atherogenic diet. This study strongly suggests that intimal thickening caused by repeated endothelial injury and regeneration induces specific vascular responses to vasoactive agents. Moreover, it is also suggested that during the progression of intimal thickening, increased vascular smooth muscle contraction and decreased endothelium-dependent dilation appear in a stimulus-dependent manner, often leading to severe coronary vasoconstriction accompanied with definitive ECG ST change.

Isolation and some properties of a 34-kDa-membrane protein that may be responsible for ribosome binding in rat liver rough microsomes.

We have isolated, by hydroxyapatite chromatography with a non ionic detergent and a high salt concentration, a non-glycosylated, membrane protein with a relative molecular weight of 34 kDa that had previously been found to be a major constituent of the membrane protein fraction showing ribosome-binding activity derived from rat liver rough microsomes (RM). The isolated 34 kDa protein (p34), when incorporated into a liposome model membrane, exhibited significant binding activity toward ribosomes, its binding properties being similar to those observed with intact RM. Immunochemical analyses using antibodies directed against p34 suggested that it is a membrane-embedded RM surface protein, which is specifically localized in ribosome-attached organelles and widely distributed among mammalian tissues. These results would constitute evidence that p34 is a likely candidate for an RM ribosome-binding protein.

Release site of TNF alpha after intravenous and intraperitoneal injection of LPS from Escherichia coli in rats.

Lipopolysaccharide (LPS) concentrations in the portal vein after intraperitoneal (i.p.) injection were slightly higher than those in the arteries. The tumor necrosis factor (TNF alpha) levels in arterial serum were higher after i.p. injection than after i.v. injection and rose to a peak at 90 min after some delay. Infusion of LPS into the portal vein increased the TNF alpha levels in the arterial serum. Pretreatment with indomethacin further increased the arterial levels of TNF alpha after portal infusion, but did not after them after i.p. injection, because of the reduction by indomethacin of LPS absorption after i.p. Injection of LPS. TNF alpha was also generated in the peritoneal cavity after i.p. injection of LPS. The TNF alpha concentrations in the arterial serum and in the peritoneal cavity were accelerated by mast cell degradation. In conclusion, TNF alpha was generated mainly in the liver, but also in the peritoneal cavity, after i.p. injection of LPS, and was negatively regulated by prostaglandins.

Evaluation of potential fat emboli during placement of intramedullary nails after orthopedic fractures.

STUDY OBJECTIVE: To evaluate material with high echogenicity demonstrated by transesophageal echocardiography (TEE) during the reamed intramedullary nailing procedure in long-bone fracture patients, and to analyze BAL fluid (BALF) in these patients as well as in those with the fat embolism syndrome (FES). DESIGN: Prospective cohort study. SETTING: Emergency and critical care center of a university hospital. PATIENTS: Fifteen patients with long-bone fractures in whom reamed intramedullary nailing was performed, and five patients diagnosed with FES. MEASUREMENTS: During reamed nailing procedures, TEE was performed. We measured the differential cell counts, percentage of lipid-laden cells, and albumin concentration in BALF after the operation. We compared TEE findings and BALF analysis in the surgical patients. In addition, we compared BALF findings in the surgical patients and in the FES patients. RESULTS: We divided 15 patients who underwent TEE into three subtypes based on the appearance of embolic material within the chambers of the right heart. The lipid-laden cells in BALF increased significantly in those patients with highly echogenic material by TEE (p < 0.05). The percentage of the lipid-laden cells in BALF was not significantly different between the TEE patients and those with FES. On the other hand, FES patients showed a statistically significant increase in leukocyte counts and albumin concentration (p < 0.05). CONCLUSIONS: The highly echogenic material seen in TEE during reamed intramedullary nailing could be fat globules on the basis of BALF analysis. However, all patients with large emboli by TEE do not develop FES. A factor other than mechanical obstruction by fat globules may be necessary for the development of FES.

Rapid fall in blood myoglobin in massive rhabdomyolysis and acute renal failure.

OBJECTIVE: Myoglobin kinetics of removal from the circulation were studied in patients following massive rhabdomyolysis, to see if myoglobin remains for long in the circulation in the anuric state and if myoglobin elimination was affected by therapeutic manipulation such as haemofiltration or haemodialysis. DESIGN: Randomised and controlled study. SETTING: Intensive care unit of a tertiary care teaching hospital. PATIENTS: 26 patients of rhabdomyolysis whose serum myoglobin exceeded more than 500 nmol/l. Thirteen patients developed acute renal failure and underwent treatment with blood purification (Group HD). The remaining 13 patients did not require treatment with blood purification (control subjects, Group non-HD). INTERVENTIONS: In patients of group HD, twelve were treated with haemofiltration and/or haemodialysis. One was treated with peritoneal dialysis. The patient of group non-HD were treated with fluid infusion alone. MEASUREMENTS AND RESULTS: The serum concentrations of myoglobin were serially determined. The highest levels of myoglobin was 1641 +/- 484 nmol/l (mean +/- SEM) in the group non-HD and were 8957 +/- 2300 in the group HD. In the group non-HD, the blood myoglobin fell exponentially once myoglobin release into the circulation ceased. This was also noted in the group HD. The exponential decrease was observed even on the days when the patient passed little urine or treatment with blood purification was not performed. CONCLUSION: In patients with massive myoglobinaemia, the blood myoglobin rapidly fell independent of renal function or any therapeutic manipulation. The results indicate that extrarenal factors played a major role in disposing circulating myoglobin in such patients.

Long-term follow-up of coronary artery dissection due to blunt chest trauma with spontaneous healing in a young woman.

We report a previously healthy 17-year-old woman who experienced coronary artery dissection with an acute transmural anterior myocardial infarction and myocardial contusion following blunt chest trauma in a motorcycle accident. A chest roentgenogram on admission was normal, and an electrocardiogram showed an acute transmural anterior myocardial infarction with complete right-bundle-branch block. A 2D echocardiogram revealed an akinesis of the anterior wall and a hypokinesis of the posterior wall in the left ventricle. Initial coronary angiography demonstrated severe stenosis with delayed antegrade filling in the proximal left anterior descending artery. Technetium-99m pyrophosphate myocardia scintigraphy demonstrated diffuse tracer uptake in the left ventricular wall. Follow-up coronary angiography performed 1 year after the accident showed a minor stenosis without any filling defects. We describe long-term follow-up of the coronary artery dissection following blunt chest trauma with spontaneous healing.

The effect of a hemofilter during extracorporeal circulation on hemodynamics in patients with SIRS.

OBJECTIVE: To evaluate the hypothesis that extracorporeal hemopurification with a hemofilter contributes to the stabilization of hemodynamics in patients with systemic inflammatory response syndrome (SIRS) due to a mechanism other than the removal of cytokines. DESIGN: Prospective study. SETTING: Intensive care unit (ICU) in a university hospital. PATIENTS: Seven critically ill patients who met criteria for SIRS with unstable hemodynamics requiring vasopressors after emergency surgery. INTERVENTIONS: Before initiation of continuous hemofiltration (CHF) extracorporeal circulation through the hemofilter (ECC) with a hollow-fiber polyacrylonitrile hemofilter was performed for 6 h. MEASUREMENTS AND RESULTS: Vital signs were monitored continuously and hemodynamics were evaluated intermittently. The blood level of endotoxin and the plasma levels of cytokines were measured at 0 and 6 h. Changes in plasma levels of cytokines passing through the hemofilter were evaluated at 3 h. A significant decrease of body temperature (P < 0.05 at 3 and 6 h vs 0 h), a significant elevation of mean arterial pressure (P < 0.05 at 0.5 h, P < 0.01 at 3 and 6 h vs 0 h), and a significant increase of urinary flow rate (P < 0.05 at 0 to 3 h vs -3 to 0 h) were observed with ECC. Neither the blood level of endotoxin nor the plasma levels of cytokines decreased. A significant increase of plasma IL-6 as it passed through the hemofilter was noted. CONCLUSIONS: The beneficial effects of hemopurification with a hemofilter on SIRS patients are possibly due to mechanisms other than the elimination of cytokines with ultrafiltration, diffusion, or adsorption.

Urinary excretions of albumin and type IV collagen in normotensive and hypertensive subjects.

Plasma albumin leaks into urine as a result of glomerular hypertension and basement membrane injury, while urinary type IV collagen derives from mesangial matrix and glomerular basement membrane. The purpose of this study was to elucidate the pathophysiological significance of these urinary microproteins as an indicator of cardiovascular organ injuries in hypertension. In health-checkup participants without diabetes, proteinuria, or microhematuria, and who were not being treated for hypertension or any other disease at the time of enrollment, urinary albumin and type IV collagen were measured and their relations to organ injuries and cardiovascular risk factors were evaluated. Of 1,079 subjects (40- to 65-year-old; 256 men and 823 women) enrolled in the study, 120 (11.1%) had untreated hypertension exceeding 140/90 mmHg. Urinary albumin was positively correlated with both age (r=0.16, p<0.001) and systolic blood pressure (r=0.27, p<0.001). Urinary type IV collagen was not only positively correlated with age (r=0.12, p<0.001) and diastolic blood pressure (r=0.14, p<0.001) but also negatively correlated with blood hemoglobin (r=-0.12, p<0.001). Urinary albumin, but not type IV collagen, had a significant relation to electrocardiographic signs of left ventricular hypertrophy (p=0.012) and retinal arteriosclerosis on fundoscopy (p <0.001). Thus both albumin and type IV collagen would seem to have increased in association with age and hypertension in this cohort. It is suggested that urinary albumin is an indicator not only of renal injury, but also possibly of development of cardiac hypertrophy and arteriosclerotic changes. Urinary type IV collagen, on the other hand, may be associated with renal tissue injuries that affect erythrokinetics.

Mechanically assisted intraoperative peritoneal lavage for generalized peritonitis as a result of perforation of the upper part of the gastrointestinal tract.

BACKGROUND: The efficiency of intraoperative peritoneal lavage (IOPL) and peritoneal drainage in patients with generalized peritonitis remains controversial. The benefit of large volume IOPL, using a newly designed device, and of peritoneal drainage were evaluated in 101 patients with generalized peritonitis. STUDY DESIGN: Patients were divided into two groups, one treated by mechanically assisted IOPL (group 1), and the other treated by manual IOPL (group 2). They were further divided into two groups, one undergoing drainage (DR group) and the other undergoing no drainage (ND group). Based on data in the progress notes, patients in these groups were compared with each other with respect to disease process, volume of IOPL fluid, incidence of infectious complications, and other prognostic factors. RESULTS: In group 1, the incidence of infectious complications was significantly lower than in group 2 (10.8 versus 62.9 percent, p < 0.01). Patients who underwent operative treatment 12 hours or more after onset of peritonitis had a lower incidence of infection following high volume IOPL (greater than or equal to 30 L) compared with those patients who underwent low volume IOPL. The incidence of infectious complications was significantly higher in the DR group (32.8 versus 12.9 percent). CONCLUSIONS: A large volume of saline (greater than or equal to 30 L) was needed for IOPL. The new device for IOPL proved to be very successful and efficient. When IOPL was successful, it seemed that peritoneal drainage did not provide any additional benefits to the treatment of generalized peritonitis.

Pathophysiologic assessment of stagnating arteries after removal of arteriovenous malformations.

PURPOSE: To assess the hemodynamics and pathophysiology of stagnating arteries after removal of arteriovenous malformations (AVMs). SUBJECTS: 50 patients with supratentorial pial AVMs underwent pre- and postoperative angiographic studies. RESULTS: The following characteristics were found to correlate with stagnating arteries: 1) advanced patient age, 2) large AVM size, 3) markedly dilated feeders, 4) early postoperative angiograms, and 5) delayed restoration of feeding artery diameter. CONCLUSIONS: The rate of blood flow in the former feeding arteries, expressed as v x pi x r2 (v = mean velocity, r = vessel radius), suddenly decreases after removal of AVMs. When dilatation persists postoperatively in these arteries the flow velocity decreases and stagnation takes place. Delayed postoperative restoration of feeding artery diameter may be caused by a decrease of elasticity due to long-standing hemodynamic stresses, and by increased postoperative vascular resistance of these arteries.

Superselective embolization for severe traumatic epistaxis caused by fracture of the skull base.

Intractable epistaxis developed in a 13-year-old girl after she fell down a flight of stairs sustaining facial fractures and fracture of the skull base. Epistaxis was found to emanate from a right ascending pharyngeal artery, which the authors promptly and successfully embolized using polyvinyl alcohol particles and microfibrillar collagen.

An unruptured arteriovenous malformation with edema.

We report a case of unruptured arteriovenous malformation in which an extensive zone of increased signal intensity in the brain parenchyma adjacent to the nidus is demonstrated on T2-weighted MR. This area of perilesional hyperintense signal exerts a compressive effect, suggesting that it represents perilesional edema.

Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report.

A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM.

Cervical radiculomyelopathy caused by deposition of calcium pyrophosphate dihydrate crystals in the ligamenta flava. Case report.

A case of cervical radiculomyelopathy caused by multiple calcified nodules in the ligamenta flava is presented. Roentgenological examination of the cervical spine showed radiopaque nodular lesions, 7 x 7 x 5 mm in size, located in the paramedian portion of the posterior spinal canal. The nodules were removed surgically and they were confirmed to be calcifications of ligamenta flava. Microscopic examination of the nodules with the polarized light revealed extensive deposition of crystals. By x-ray diffraction study, the crystal was determined as calcium pyrophosphate dihydrate (CPPD: Ca2P2O7 . 2H2O). Although CPPD deposition in the cartilage has been known as pseudo-gout syndrome, deposition in the ligament has been reported only in a few cases. This is the first case with radiopaque calcified nodules in the ligamenta flava causing spinal cord compression, the composition of which proved to be CPPD.

Retrograde thrombosis of feeding arteries after removal of arteriovenous malformations.

Five cases of retrograde thrombosis of former feeding arteries after removal of an arteriovenous malformation (AVM) are reported. The clinical features of these patients were studied and compared to those of 71 patients without this complication. The following characteristics were found to correlate with retrograde thrombosis: 1) advancing age of the patient; 2) large AVM size; and 3) markedly dilated and elongated feeders. It is suggested that the slow flow in the former feeding arteries that was observed immediately after AVM removal and pathological changes in these vessels due to long-standing hemodynamic stresses contributed to the development of retrograde thrombosis. Neurological manifestations related to retrograde thrombosis were noted in three of the five cases. Although infrequent, this complication should be considered as a serious possibility following removal of an AVM.

Serial changes in acute extradural hematoma size and associated changes in level of consciousness and intracranial pressure.

The authors report the cases of 37 patients encountered during the past 4 years who exhibited acute extradural hematoma but were initially treated conservatively because no or only small hematomas were observed on admission. The frequency of hematoma enlargement, hematoma size, and changes in the level of consciousness and intracranial pressure (ICP) were examined in these patients. The hematomas enlarged in 24 (64.9%) of the 37 patients, and attained a maximum thickness of 25 mm or greater in 19 patients (51.3%). The level of consciousness could be closely observed during enlargement of the hematomas in 13 patients: the level remained unchanged in eight, deteriorated in two, and improved in three, indicating relative stability in the state of consciousness despite the marked changes in hematoma size. The patients whose hematoma enlarged after the initial examination included three who underwent initial CT examination 5 hours after the injury. In five patients enlargement of extradural hematomas was observed unexpectedly during conservative treatment under ICP monitoring. The ICP also remained stable in three patients until the follow-up examination, but showed a rapid increase in two after a period of stability. However, there was no difference in the final size of the hematomas between the patients showing an increase in ICP and those who did not. These findings suggest that extradural hematomas enlarge progressively at rates varying with the condition of the source of hemorrhage. Moreover, a period of stability in the level of consciousness, such as the lucid interval seen in patients with extradural hematoma, is considered to be a period during which compensatory mechanisms can maintain the stability of the intracranial condition during progressive enlargement of the hematoma.

An analysis of the venous drainage system as a factor in hemorrhage from arteriovenous malformations.

The authors studied the venous drainage system and its impairment in relation to risk of hemorrhage in 108 cases of supratentorial arteriovenous malformation (AVM). The proportion of AVM's undergoing hemorrhage (hemorrhagic rate) was calculated in relation to: 1) the number of draining veins (one, two, or three or more); 2) the presence or absence of impairment in venous drainage (severe stenosis or occlusion in draining veins); and 3) the location of draining veins (deep venous drainage alone, superficial venous drainage alone, or a combination of the two). Statistical analysis demonstrated that AVM's with the following characteristics had a high risk of hemorrhage: 1) one draining vein (hemorrhagic rate 89% in 54 patients); 2) severely impaired venous drainage (hemorrhagic rate 94% in 18 patients); and 3) deep venous drainage alone (hemorrhagic rate 94% in 32 patients). The present study suggests that the venous drainage system of AVM's is significantly associated with the risk of hemorrhage of these lesions. Therefore, careful preoperative angiographic evaluation of the venous drainage system is mandatory for decision making in the management of patients with AVM's.