Alternative fecal indicators and their empirical relationships with enteric viruses, Salmonella enterica, and Pseudomonas aeruginosa in surface waters of a tropical urban catchment.

The suitability of traditional microbial indicators (i.e., Escherichia coli and enterococci) has been challenged due to the lack of correlation with pathogens and evidence of possible regrowth in the natural environment. In this study, the relationships between alternative microbial indicators of potential human fecal contamination (Bacteroides thetaiotaomicron, Methanobrevibacter smithii, human polyomaviruses [HPyVs], and F+ and somatic coliphages) and pathogens (Salmonella spp., Pseudomonas aeruginosa, rotavirus, astrovirus, norovirus GI, norovirus GII, and adenovirus) were compared with those of traditional microbial indicators, as well as environmental parameters (temperature, conductivity, salinity, pH, dissolved oxygen, total organic carbon, total suspended solids, turbidity, total nitrogen, and total phosphorus). Water samples were collected from surface waters of urban catchments in Singapore. Salmonella and P. aeruginosa had significant positive correlations with most of the microbial indicators, especially E. coli and enterococci. Norovirus GII showed moderately strong positive correlations with most of the microbial indicators, except for HPyVs and coliphages. In general, high geometric means and significant correlations between human-specific markers and pathogens suggest the possibility of sewage contamination in some areas. The simultaneous detection of human-specific markers (i.e., B. thetaiotaomicron, M. smithii, and HPyVs) with E. coli and enterococcus supports the likelihood of recent fecal contamination, since the human-specific markers are unable to regrow in natural surface waters. Multiple-linear-regression results further confirm that the inclusion of M. smithii and HPyVs, together with traditional indicators, would better predict the occurrence of pathogens. Further study is needed to determine the applicability of such models to different geographical locations and environmental conditions.

Endovascular treatment of ruptured thoracic aortic aneurysm in patients older than 75 years.

OBJECTIVES: To investigate the outcomes of thoracic endovascular aortic repair (TEVAR) for ruptured descending thoracic aortic aneurysm (rDTAA) in patients older than 75 years. METHODS: We retrospectively identified all patients treated with TEVAR for rDTAA at seven referral centres between 2002 and 2009. The cohort was stratified according to age ≤75 and >75 years, and the outcomes after TEVAR were compared between both groups. RESULTS: Ninety-two patients were identified of which 73% (n = 67) were ≤75 years, and 27% (n = 25) were older than 75 years. The 30-day mortality was 32.0% in patients older than 75 years, and 13.4% in the remaining patients (p = 0.041). Patients older than 75 years suffered more frequently from postoperative stroke (24.0% vs. 1.5%, p = 0.001) and pulmonary complications (40.0% vs. 9.0%, p = 0.001). The aneurysm-related survival after 2 years was 52.1% for patients >75 years, and 83.9% for patients ≤75 years (p = 0.006). CONCLUSIONS: Endovascular treatment of rDTAA in patients older than 75 years is associated with an inferior outcome compared with patients younger than 75 years. However, the mortality and morbidity rates in patients above 75 years are still acceptable. These results may indicate that endovascular treatment for patients older than 75 years with rDTAA is worthwhile.

Effects of predictive mechanisms on head stability during forward trunk perturbation.

While much is known about reflex and mechanical contributions to the control of head stability, little is known about predictive control. The goal of this experiment was to determine the contribution of predictive mechanisms to head stability in space, in the pitch plane, during forward trunk perturbations. Eleven standing healthy subjects had their trunk pulled forward by a load-pulley apparatus. The perturbation was either self-triggered or imposed (triggered by the experimenter). Subjects were exposed to two loads: 2% and 4% of their body weight. The contributions of torques acting on the head-neck system were inferred from head and trunk kinematics, neck muscle EMG, and the torques acting on the head, which were computed using inverse dynamics. The results showed that both the head and trunk moved less during the self-triggered than imposed condition during both loads for most of the participants. There was no evidence of predictive neck countertorque or increased neck muscle co-contraction during the self-triggered condition. These findings suggest that most of the subjects improved head stability in the self-triggered condition by reducing trunk motion and the associated interactive torque that perturbed the head.

Impact of endovascular repair on open aortic aneurysm surgical training.

PURPOSE: The purpose of this study was to determine the impact of an endovascular stent-graft program on vascular training in open aortic aneurysm surgery. METHODS: The institutional and vascular surgery fellow experience in aortic aneurysm repair during a 6-year period was reviewed. The 3-year period before introduction of endovascular repair was compared with the 3-year period after introduction of endovascular repair. All patients undergoing abdominal aortic aneurysm (AAA) or thoracoabdominal aortic aneurysm repairs were entered prospectively into a vascular registry and retrospectively analyzed to evaluate the changing patterns in aortic aneurysm treatment and surgical training. RESULTS: Between July 1994 and June 2000, a total of 588 patients with AAA or thoracoabdominal aneurysms were treated at Stanford University Medical Center. There were 296 (50%) open infrarenal AAA repairs, 87 (15%) suprarenal AAA repairs, 47 (8%) thoracoabdominal aneurysm repairs, and 153 (26%) endovascular stent-grafts. The total number of aneurysms repaired per year by vascular fellows before the endovascular program was 71.3 +/- 4.9 (range, 68-77) and increased to 124.7 +/- 35.6 (range, 91-162) after introduction of endovascular repair (P <.05). This increase was primarily caused by the addition of endovascular stent-graft repairs by vascular fellows (51.0 +/- 29.0/year [range, 23-81]). There was no change in the number of open infrarenal aortic aneurysm repairs per year, 53.0 +/- 6.6 (range, 48-56) before endovascular repair versus 47.0 +/- 1.7 (range, 46-49) after (P = not significant). There was a significant increase in the number of suprarenal AAA repairs per year by vascular fellows, 10.0 +/- 1.0 (range, 9-11) before endovascular repair compared with 19.0 +/- 6.5 (range, 13-26) after (P <.05). There was no change in the number of thoracoabdominal aneurysm repairs per year between the two groups, 8.0 +/- 3.0 (range, 4-11) before endovascular repair compared with 7.6 +/- 2.3 (range, 5-9) after. CONCLUSIONS: Introduction of an endovascular aneurysm stent-graft program significantly increased the total number of aneurysms treated. Although the number of open aneurysm repairs has remained the same, the complexity of the open aneurysm experience has increased significantly for vascular fellows in training.

Impact of aortoiliac tortuosity on endovascular repair of abdominal aortic aneurysms: evaluation of 3D computer-based assessment.

OBJECTIVE: The purpose of this study was to examine the effect of aortoiliac tortuosity, as assessed by observers and 3-dimensional (3D) computer-based methods, on the conduct and outcome of endovascular repair of abdominal aortic aneurysms. METHODS: Infrarenal aortoiliac tortuosity was measured in 75 patients (mean follow-up, 14.8 +/- 10.4 months) who underwent endovascular repair of abdominal aortic aneurysms by using the following four methods: (1) grading by 2 experienced observers; (2) tortuosity index measured as the inverse radius of curvature (cm(-1)) at 1-mm intervals along the median luminal centerline (MLC) on 3D reconstructions of computed tomography (CT) angiograms and was calculated as the sum of values greater than 0.3 cm(-1); (3) MLC-straight line length ratio from renal to hypogastric arteries; (4) manual measurement of angles at points of angulation on anteroposterior and lateral projections of 3D CT reconstructions. In evaluating association between these measures, correlation between human observers was accepted as the gold standard. RESULTS: For rating of overall aortoiliac tortuosity, interobserver correlation (r = 0.67) was comparable with correlation of observers with tortuosity index (r = 0.67 and 0.56), whereas correlations of each observer with MLC-straight line ratio (r = 0.50 and 0.56) and cumulative angulation (r = 0.44 and 0.44) were significant but weaker. For determining the relative tortuosity of right and left aortoiliac access, agreement between observers and tortuosity index (54% and 58%; P < .05; kappa, 0.33 and 0.38) was not as good as between observers (68%; P < .001; kappa, 0.53). This difference was primarily related to evaluation of the aorta, where interobserver correlation (r = 0.71) was better than that between each observer and tortuosity index (r = 0.47 and 0.55), whereas correlations in the iliac arteries were comparable (r = 0.64 and 0.67) (all coefficients P < .01). Increased tortuosity was associated with a more complex endovascular repair, as reflected by longer fluoroscopy time (P = .05), use of more contrast material (P = .03), use of extender modules (P = .04), and more frequent use of arterial reconstruction (P = .01), but was not associated with a higher overall complication rate. Increased tortuosity, when it occurred in the aortic neck, was associated with predischarge endoleak (P = .03) but not with late endoleak, intervention, or aneurysm-related adverse events. CONCLUSION: Aortoiliac tortuosity is associated with increased complexity of endovascular aneurysm repair and with predischarge endoleak but does not appear to affect intermediate-term results. Computer-based 3D measurement of aortoiliac tortuosity is feasible and clinically meaningful. Its ultimate role in relation to human assessment must be further defined in future studies.

Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood.

PMPA, an acyclic nucleoside phosphonate analog, is a potent inhibitor of HIV. In the cells, PMPA is efficiently phosphorylated by intracellular kinases to produce PMPApp, the pharmacologically active metabolite. Despite its demonstrated antiviral potency, PMPA has limited cell permeability presumably resulting from the presence of two negative charges on the phosphonyl group. To enhance intracellular concentrations of PMPA, we developed a prodrug, selectively metabolized inside cells. GS-7340 (9-[(R)-2-[[[[(S)-1-(isopropoxycarbonyl)ethyl] amino] phenoxy-phosphinyl]-methoxy] propyl] adenine) is a prodrug which is orally bioavailable in dogs as the intact prodrug and has demonstrated anti-HIV activity in cell culture of over 1000-fold greater than that of PMPA. The metabolism of PMPA in peripheral blood mononuclear cells (PBMC), red blood cells (RBC) and plasma was examined following exposure of whole blood to PMPA or GS-7340 at concentrations similar to ones observed systemically following oral administration in dogs. Following 1 hour incubation with whole blood, GS-7340 was stable in plasma, produced high levels of PMPA and its phosphorylated metabolites in PBMC but not in RBC. No intact prodrug was present in PBMC. The only other species present in PBMC was monoalaninyl PMPA. The levels of PMPA and the phosphorylated metabolites were over 20 times greater than those after incubation with PMPA. The dog and human blood data were similar. The intracellular levels of PMPA and PMPApp were roughly proportional to GS-7340 over a 10-fold concentration range indicating a lack of saturability of uptake and phosphorylation. Since PMPApp is the species responsible for antiviral activity of PMPA, the high intracellular levels of PMPApp should be an important indicator of greater clinical efficacy of GS-7340.

Pharmacokinetics of salicylate ester prodrugs of cyclic HPMPC in dogs.

A series of aryl ester prodrugs of cyclic HPMPC have been synthesized and their physicochemical properties, pharmacokinetics and metabolism have been evaluated. Chemical stability was dependent on the orientation of the exo-cyclic ligand; the equatorial isomers were 5.4 to 9.4 fold more reactive than the axial isomers. The oral bioavailability of cyclic HPMPC from the aryl ester prodrugs ranged from 11.2% for o-pentylphenyl cyclic HPMPC to 46.3% for butylsalicylyl cyclic HPMPC. Cyclic HPMPC was the major metabolite observed for all the salicylyl ester prodrugs. Cidofovir accounted for 2 to 12% of the total plasma AUC for butyl-, cyclohexyl- and phenethyl-salicylyl esters of cyclic HPMPC. Intact prodrug or the corresponding monosalicylyl esters of cidofovir each accounted for less than 10% of the total AUC for salicylyl ester prodrugs.

Spontaneous late carotid-cutaneous fistula following radical neck dissection: a case report.

The authors present an unusual case of a spontaneous carotid-cutaneous fistula occurring as a late complication 4 years after radical neck dissection and postoperative radiation therapy for tonsillar squamous cell carcinoma in a 50-year-old patient. The etiologic factors predisposing patients to carotid artery rupture following radical neck dissection and a surgical option for carotid artery reconstruction instead of ligation are discussed.

Glass vials for small volume parenterals: influence of drug and manufacturing processes on glass delamination.

PURPOSE: Studies were initiated to examine the effect of formulation and process variables on the delamination process and also the influence of the glass manufacturing process, supplier, and glass surface treatment. METHODS: Stress testing was performed by exposing filled vials to multiple sterilization cycles followed by accelerated stability testing. Delamination incidence was determined by visual examination, light obscuration (HIAC), and microscopical methods. The inner surface of vials from each supplier and lot were also examined by scanning electron microscopy. RESULTS: Vials sourced from Supplier A had smooth surfaces as demonstrated by SEM examination, whereas vials sourced from Suppliers B and C displayed extensive surface imperfections such as pitting and/or deposits. These imperfections were localized to the vial wall, adjacent to the vial bottom, and increased with sulfate treatment. Delamination incidence increased in those vial lots with increased surface imperfections. Thus, vials sourced from Supplier A had the lowest frequency of delamination. Sulfate treatment and high pH increased delamination incidence to as high as 100%. CONCLUSION: These results demonstrate the importance of the surface morphology created during the vial forming process. Given the diferences observed, final vial selection should include extensive microscopical and product stress testing studies on multiple vial lots.

Outcome after unilateral hypogastric artery occlusion during endovascular aneurysm repair.

PURPOSE: The purpose of this study was to determine the long-term functional outcome after unilateral hypogastric artery occlusion during endovascular stent graft repair of aortoiliac aneurysms. METHODS: During a 41-month period, 157 consecutive patients underwent elective endovascular stent graft repair of aortoiliac aneurysms with the Medtronic AneuRx device. Postoperative computed tomography scans were compared with preoperative scans to identify new hypogastric artery occlusions. Twenty-three (15%) patients had unilateral hypogastric occlusion, and there were no cases of bilateral occlusions. Telephone interviews about past and current levels of activity and symptoms were conducted, and pertinent medical records were reviewed. All 23 (100%) patients were available for the telephone interview. A disability score (DS) was quantitatively graded on a discrete scale ranging from 0 to 10 corresponding to "virtually bed-bound" to "greater-than-a-mile" exercise tolerance. Worsening or improvement of symptoms was expressed as a difference in DS between two time points (-, worsening/+, improving). RESULTS: Among the 23 patients, two groups were identified: 10 patients (43%) had planned and 13 patients (57%) had unplanned or inadvertent occlusions. The patients in the two groups did not differ significantly in the mean age (73.4 vs 73.7 years), sex (male:female, 9:1 vs 10:3), and duration of follow-up (15.6 vs 14.4 months). Nine (39%) of the 23 patients, five patients in the planned and four patients in the unplanned group, reported significant symptoms of hip and buttock claudication ipsilateral to their occluded hypogastric arteries. The mean decrement from baseline of these nine patients in their DS postoperatively was -3.3. The symptoms were universally noted on postoperative day 1. Although most patients improved (89%), one (11%) never got better. Among those whose symptoms improved, the mean time to improvement was 15 weeks, but with a plateau thereafter resulting in a net decrement of DS of -2.3 from baseline. Finally, when questioned whether they would undergo the procedure again, all 23 patients unanimously answered, "Yes." CONCLUSIONS: A significant number (39%) of patients who sustain hypogastric artery occlusion after endovascular aneurysm repair have symptoms. Although most patients with symptoms have some improvement, none return to their baseline level of activity. Despite this, all patients in retrospect would again choose endovascular repair over conventional open repair.

Eccentric stent graft compression: an indicator of insecure proximal fixation of aortic stent graft.

PURPOSE: The purpose of this study was to determine whether radiographically demonstrated proximal stent graft contour can be used as a marker for security of proximal neck fixation after endovascular aneurysm repair. METHODS: Stent graft structure was examined in 100 consecutive patients with abdominal aortic aneurysms who were treated with the stent graft. Stent graft integrity, stent contour, angulation, compression, and position were assessed by use of plain abdominal radiography, and the results were correlated with contrast computed tomography (CT) scanning, clinical findings, and outcomes. Repeated imaging was carried out during follow-up of 3 to 38 (mean, 12) months. RESULTS: Stent graft repair was successful in all 100 patients. No stent fractures were identified. Concentric compression of the proximal portion of the stent graft was visible in 69% of patients and reflected deliberate oversizing of the stent graft at the time of implantation. In 5% of patients, a short eccentric compression deformity of the proximal stent was observed. This finding was associated with an increased risk of stent graft migration (P <.01) and with an increased risk for development of a late proximal (type I) endoleak (P <.01). Compared with CT scanning, abdominal radiography was less useful for assessment of short distances of migration (sensitivity 67%; specificity 79%). However, they provided better definition of the stent graft in relation to bony landmarks and better visualization of aortic calcification than CT with three-dimensional reconstruction. CONCLUSION: Plain abdominal radiographs are important in the postoperative evaluation of patients with aortic stent grafts. They allow for more precise evaluation of the structural elements of the stent graft than CT scanning and may disclose inadequate proximal fixation by demonstration of an eccentric compression deformity. They are less useful for assessment of migration.

Increased flexibility of AneuRx stent-graft reduces need for secondary intervention following endovascular aneurysm repair.

PURPOSE: To evaluate the impact of a change in the manufacturing of the AneuRx stent-graft on the long-term results of endovascular abdominal aortic aneurysm (AAA) repair. METHODS: The first 70 AAA patients treated with the AneuRx stent-graft between October 1996 and December 1998 were reviewed. The early stiff bifurcated design (STIFF) was used in 23 patients (mean age 71.7 +/- 9.3 years, range 45-87) and the current flexible bifurcated design (FLEX) in 47 mean age 75.0 +/- 7.3 years, range 61-96). Data on patient demographics, aneurysm morphology, technical success, complications, secondary procedures, and outcomes were compared using Kaplan-Meier estimates to evaluate patient survival and freedom from surgical conversion, rupture, and secondary interventions at 6, 12, and 24 months. RESULTS: The 2 groups were equally matched with regard to age, preoperative comorbidities, proximal neck dimensions, and aneurysm diameter. Mean follow-up times were 22.42 +/- 11.72 months (range 1-46) for the STIFF cohort and 18.08 +/- 6.14 months (range 1-30) for the FLEX (p = 0.057). Eleven (48%) of 23 STIFF patients required secondary interventions versus 6 (13%) of 47 FLEX patients (p < 0.05). There were no ruptures. At the 24-month interval, survival estimates were 86% for STIFF and 76% for FLEX (p = NS); freedom from surgical conversion was 100% for STIFF and 97% for FLEX (p = NS) and freedom from secondary interventions was 18% for STIFF and 90% for FLEX (p < 0.05) at 24 months. CONCLUSIONS: The AneuRx stent-graft was effective in achieving the primary objective of preventing aneurysm rupture in all patients. However, increasing the flexibility of the bifurcated module significantly improved the primary success rate by reducing the need for subsequent secondary interventions.

Distal emboli as an unusual late complication of a thrombosed arteriovenous hemodialysis graft.

The creation of an arteriovenous fistula for long-term hemodialysis access is one of the most commonly performed procedures in vascular and transplantation surgery. Prosthetic conduits are frequently prone to failure within their first year of construction, and after one or two revisions, they are left in their thrombosed state as permanent subcutaneous foreign bodies in the extremities. Conventional teaching has regarded these chronically thrombosed grafts to have a benign natural history, and their removal has been considered unnecessary. We describe an unusual late complication of distal thromboemboli from a chronically occluded arteriovenous graft that was implanted 10 years before and appeared as acute hand ischemia.

Relative stability improves with experience in a dynamic standing task.

This study tested the hypothesis that subjects improve their relative stability as they learn a dynamic pulling task. Healthy adult subjects practiced making brief horizontal pulls (<300 ms) on a handle to a range of target forces ranging from 20 to 80% of their estimated maximum for 5 days. They were instructed to always keep their feet flat and begin and end their motion in an upright posture. In order to do this, subjects had to develop the appropriate body momentum prior to the pull and then recover their balance following the pull. We analyzed relative stability during balance recovery, using two measures: spatial safety margin (minimum distance of the center of pressure, COP, to the edges of the feet) and temporal safety margin (minimum extrapolated time for the COP to reach the edges of the feet). We hypothesized that: (1) spatial and temporal safety margins would be uncorrelated; (2) safety-margin means would increase with practice; and (3) safety-margin standard deviations would decrease with practice. Two experiments were conducted: one where subjects practiced three force targets and positioned their initial COP in a small window, and one where subjects practiced two force targets with no initial COP constraint. Results showed that spatial and temporal safety margins were correlated but shared less than 6% variance, indicating that they reflected different aspects of control. Safety-margin averages increased with practice and standard deviations decreased with practice, indicating that the stability of balance control in the execution of this task became more robust. We suggest that the nervous system could use safety margins in both feedback and feedforward control of balance.

Practice-related changes in lumbar loading during rapid voluntary pulls made while standing.

OBJECTIVE: To determine if five days of practice on a novel dynamic, multi-joint pulling task resulted in lower magnitudes of lumbar loading or a more consistent relationship between pulling force and lumbar loading. DESIGN: A repeated measures design compared how practice influenced the magnitude of lumbar torque and the correlations between lumbar torque and pulling force. BACKGROUND: Previous studies suggest that practice can decrease the magnitude of lumbar loading on simple manual material handling tasks, but it is unknown whether practice reduces lumbar loading for more complex tasks. Neither is it known whether the consistency of lumbar loading increases with practice. METHODS: Ten healthy adults practiced impulse-like horizontal pulls to targets equaling 20%, 40% and 80% of their estimated maximal dynamic pulling force over 5 days. Movements were unrestrained, other than keeping the feet flat on the ground. We used a four-segment, sagittal plane inverse dynamics model to compute lumbar, hip, knee, and ankle torques on days 1 and 5 from ground reaction forces and moments, pulling forces, and kinematics. RESULTS: An analysis of variance showed significant practice-related changes in lumbar torque at the time of peak pulling force (lumbar torque(peakPF)). The lumbar torque(peakPF) decreased for the 20% pulls, did not change for the 40% pulls, and increased for the 80% pulls. Two subjects showed a significant decrease in lumbar torque(peakPF) for all three force levels. Coefficients of determination between pulling force and lumbar torque (r(2)(PF,LT): a measure of the consistency of the relationship between these two variables) were significantly higher on day 5 than day 1. CONCLUSIONS: Practice on a novel pulling task changed the magnitude of lumbar torques and increased their correlation with pulling force, suggesting that subjects learned strategies that improve motor control of lumbar torques. Relevance The study showed that the magnitude and consistency of lumbar loading changed spontaneously as subjects practiced a novel multijoint pulling task. Such changes may decrease the risk of low-back injury.

Will endovascular repair replace open surgery for abdominal aortic aneurysm repair?

OBJECTIVE: To evaluate of the impact of endovascular aneurysm repair on the rate of open surgical repair and on the overall treatment of abdominal aortic aneurysms (AAAs). METHODS: All patients with AAA who were treated during two consecutive 40-month periods were reviewed. During the first period, only open surgical repair was performed; during the subsequent 40 months, endovascular repair and open surgical repair were treatment options. RESULTS: A total of 727 patients with AAA were treated during the entire period. During the initial 40 months, 268 patients were treated with open surgical repair, including 216 infrarenal (81%), 43 complex (16%), and 9 ruptured (3%) aortic aneurysms. During the subsequent 40 months, 459 patients with AAA were treated (71% increase). There was no significant change in the number of patients undergoing open surgical repair and no significant difference in the rate of infrarenal (238 [77%]) and complex (51 [16%]) repairs. A total of 353 patients were referred for endovascular repair. Of these, 190 (54%) were considered candidates for endovascular repair based on computed tomography or arteriographic morphologic criteria. Analyzing a subgroup of 123 patients, the most common primary reasons for ineligibility for endovascular repair were related to morphology of the neck in 80 patients (65%) and of the iliac arteries in 35 patients (28%). A total of 149 patients underwent endovascular repair. Of these, the procedure was successful in 147 (99%), and 2 (1%) patients underwent surgical conversion. The hospital death rate was 0%, and the 30-day death rate was 1%. During a follow-up period of 1 to 39 months (mean 12 +/- 9), 21 secondary procedures to treat endoleak (20) or to maintain graft limb patency (1) were performed in 17 patients (11%). There were no aneurysm ruptures or aneurysm-related deaths. CONCLUSIONS: Endovascular repair appears to have augmented treatment options rather than replaced open surgical repair for patients with AAA. Patients who previously were not candidates for repair because of medical comorbidity may now be safely treated with endovascular repair.

Microsatellite instability and alteration of E2F-4 gene in adenosquamous and squamous cell carcinomas of the stomach.

Microsatellite instability (MSI) due to defective DNA mismatch repair (MMR) is a form of genomic instability underlying the tumorigenesis of various human neoplasms. To evaluate the roles of MSI in the pathogenesis of gastric carcinomas with squamous differentiation, 17 primary stomach cancer patients (15 adenosquamous and two squamous cell carcinomas) were examined for MSI frequency using five microsatellite markers and the criteria for MSI recommended by the National Cancer Institute Workshop. The molecular causes and consequences of MSI in these neoplasms were further researched through the immunohistochemistry of MMR proteins and the mutational analysis of cancer-associated genes targeted by MSI, respectively. Two of the 17 (12%) cases demonstrated MSI at the most examined loci and were classified as having high level MSI (MSI-H). These tumors also exhibited frame-shift mutations at mononucleotide repeats in the target genes, including TGFbetaRII, IGFIIR, BAX, and hMSH6. It is interesting to note that the mutations of the serine (AGC)13 repeats within the E2F-4 gene were found only in the squamous cell carcinoma portions of them, whereas such alterations were not detected in any of the adenocarcinomatous portions. This suggests that E2F-4 might be implicated in the transformation of adenocarcinoma into squamous cell carcinoma and further studies are needed to understand its role in squamous differentiation.

Surgical intervention is not required for all patients with subclavian vein thrombosis.

PURPOSE: The role of thoracic outlet decompression in the treatment of primary axillary-subclavian vein thrombosis remains controversial. The timing and indications for surgery are not well defined, and thoracic outlet procedures may be associated with infrequent, but significant, morbidity. We examined the outcomes of patients treated with or without surgery after the results of initial thrombolytic therapy and a short period of outpatient anticoagulation. METHODS: Patients suspected of having a primary deep venous thrombosis underwent an urgent color-flow venous duplex ultrasound scan, followed by a venogram and catheter-directed thrombolysis. They were then converted from heparin to outpatient warfarin. Patients who remained asymptomatic received anticoagulants for 3 months. Patients who, at 4 weeks, had persistent symptoms of venous hypertension and positional obstruction of the subclavian vein, venous collaterals, or both demonstrated by means of venogram underwent thoracic outlet decompression and postoperative anticoagulation for 1 month. RESULTS: Twenty-two patients were treated between June 1996 and June 1999. Of the 18 patients who received catheter-directed thrombolysis, complete patency was achieved in eight patients (44%), and partial patency was achieved in the remaining 10 patients (56%). Nine of 22 patients (41%) did not require surgery, and the remaining 13 patients underwent thoracic outlet decompression through a supraclavicular approach with scalenectomy, first-rib resection, and venolysis. Recurrent thrombosis developed in only one patient during the immediate period of anticoagulation. Eleven of 13 patients (85%) treated with surgery and eight of nine patients (89%) treated without surgery sustained durable relief of their symptoms and a return to their baseline level of physical activity. All patients who underwent surgery maintained their venous patency on follow-up duplex scanning imaging. CONCLUSION: Not all patients with primary axillary-subclavian vein thrombosis require surgical intervention. A period of observation while patients are receiving oral anticoagulation for at least 1 month allows the selection of patients who will do well with nonoperative therapy. Patients with persistent symptoms and venous obstruction should be offered thoracic outlet decompression. Chronic anticoagulation is not required in these patients.

Effects of vision on head stability and torques during voluntary pulls made by standing humans.

This study tested the hypothesis that vision would improve pitch-plane stabilization of the head by increasing how well neck muscle torque compensates for torques associated with body motion, in a task where standing human subjects made rapid voluntary pulls. Ten subjects performed abrupt horizontal pulls on a handle to two peak force targets, with the eyes open and closed. We evaluated head angular velocity with respect to space. Inverse dynamics were used to subdivide the torque acting on the head into gravito-interactive and muscle components. A torque compensation ratio was computed from those two components. Head angular velocity was lower and the compensation ratio was higher during pulls made with the eyes open, for both force targets. The data suggest that vision enhances head stability by increasing the effectiveness with which muscle torques oppose gravito-interactive torques during voluntary pulls made while standing.