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Biomedical subjects

Robert L Grubb

Publications and source records attributed to Robert L Grubb.

30 records · Page 2Linked to original sources

The Carotid Occlusion Surgery Study.

The St. Louis Carotid Occlusion Study demonstrated that ipsilateral increased O2 extraction fraction (OEF) (Stage II hemodynamic failure) measured by positron emission tomography (PET) is a powerful independent risk factor for subsequent stroke in patients with symptomatic complete carotid artery (CA) occlusion. The ipsilateral ischemic stroke rate at 2 years has been shown to be 5.3% in 42 patients with normal OEF and 26.5% in 39 patients with increased OEF (p = 0.004). In patients in whom hemispheric symptoms developed within 120 days, the 2-year ipsilateral stroke rates were 12% in 27 patients with normal OEF and 50% in 18 patients with increased OEF. Previous PET studies have demonstrated that anastomosis of the superficial temporal artery (STA) to a middle cerebral artery (MCA) cortical branch can restore OEF to normal. The authors discuss the undertaking of a study that will test the hypothesis that STA-MCA anastomosis, when combined with the best medical therapy, can reduce ipsilateral ischemic stroke by 40% at 2 years in patients with symptomatic internal CA occlusion and Stage II hemodynamic failure occurring within 120 days after surgery. Only patients with increased OEF distal to a symptomatic occluded CA will be randomized to surgery or medical treatment. The primary endpoint will be all strokes and death occurring between randomization and the 30-day postoperative cut off (with an equivalent period in the nonsurgical group), as well as subsequent ipsilateral ischemic stroke developing within 2 years. It is estimated that 186 patients will be required in each group. Assuming that 40% of PET scans will demonstrate increased OEF, this will require enrolling 930 clinically eligible individuals.

Anticoagulants↗

Signal pathway profiling of prostate cancer using reverse phase protein arrays.

Reverse phase protein arrays represent a new proteomics microarray technology with which to study the fluctuating state of the proteome in minute quantities of cells. The activation status of cell signaling pathways controls cellular fate and deregulation of these pathways underpins carcinogenesis. Changes in pathway activation that occur between early stage prostatic epithelial lesions, prostatic stroma and the extracellular matrix can be analyzed by obtaining pure populations of cell types by laser capture microdissection (LCM) and analyzing the relative states of several key phosphorylation points within the cellular circuitry. We have applied reverse phase protein array technology to analyze the status of key points in cell signaling involved in pro-survival, mitogenic, apoptotic and growth regulation pathways in the progression from normal prostate epithelium to invasive prostate cancer. Using multiplexed reverse phase protein arrays coupled with LCM, the states of signaling changes during disease progression from prostate cancer study sets were analyzed. Focused analysis of phospho-specific endpoints revealed changes in cellular signaling events through disease progression and between patients. We have used a new protein array technology to study specific molecular pathways believed to be important in cell survival and progression from normal epithelium to invasive carcinoma directly from human tissue specimens. With the advent of molecular targeted therapeutics, the identification, characterization and monitoring of the signaling events within actual human biopsies will be critical for patient-tailored therapy.

Antigens, Neoplasm↗

Laparoscopic pyeloplasty for secondary ureteropelvic junction obstruction.

PURPOSE: Laparoscopic pyeloplasty has become a viable option for the treatment of select patients with primary ureteropelvic junction obstruction with success rates similar to those of open surgery. However, little has been written on the application of this technique for secondary ureteropelvic junction obstruction. We report the largest series of secondary ureteropelvic junction obstruction managed by laparoscopic pyeloplasty. MATERIALS AND METHODS: Between March 1994 and March 2001, 36 patients underwent laparoscopic transperitoneal pyeloplasty for secondary ureteropelvic junction obstruction. The patients had undergone an average of 1.3 ureteropelvic junction procedures (range 1 to 4) prior to presentation, including cutting balloon retrograde endopyelotomy in 28, antegrade endoscopic endopyelotomy in 7, retrograde endoscopic endopyelotomy in 4, retrograde balloon dilation in 4 and open pyeloplasty in 3. A preoperative diagnosis of recurrent obstruction was confirmed by renal scan in 31 cases, retrograde pyelography in 2 and computerized tomography in 3. Of the 31 patients who underwent spiral computerized tomography angiogram 87% had crossing vessels. Laparoscopic repair comprised dismembered pyeloplasty in 31 cases, Fengerplasty in 3 and flap repair in 2. Postoperative renal scan or excretory urography objective followup was available for all patients at a mean of 10 months (range 3 to 40). Postoperative subjective patient well-being was assessed using an analog pain scale at a mean followup of 21.8 months (range 3 to 85). RESULTS: Average operative time was 6.2 hours (range 2.7 to 10). Average hospital stay was 2.9 days (range 1 to 7). One intraoperative complication occurred, that is bleeding necessitating conversion to an open procedure. Postoperative complications occurred in 8 cases, including anastomotic leakage in 4, and urinary tract infection, pneumonia, atelectasis, fever, bilateral upper extremity weakness and stone formation 2 months postoperatively in 1 each. On excretory urography, furosemide renal scan or the Whitaker test 32 of 36 patients (89%) had a widely patent ureteropelvic junction. Two patients (5.5%) had equivocal radiographic studies but were asymptomatic. In 2 patients the ureteropelvic junction was obstructed by renal scan. One patient had an indwelling stent for renal function deterioration and 1 was asymptomatic. Hence, 34 of the 36 patients (94%) had a reasonable objective response. Overall a 50% or greater decrease in pain was seen in 32 of 36 patients (89%). In the 4 patients with a less than 50% decrease in pain objective renal scans showed an open ureteropelvic junction. As such, the overall success rate of a greater than 50% decrease in pain, a patent ureteropelvic junction and stable or improved function of the affected renal unit was 83% (30 of 36 patients). CONCLUSIONS: For secondary ureteropelvic junction obstruction, laparoscopic pyeloplasty can be performed safely with a success rate comparable to that of standard open pyeloplasty. The patient benefits of laparoscopic ureteropelvic junction repair of secondary ureteropelvic junction obstruction are similar to the benefits of laparoscopic repair of primary ureteropelvic junction obstruction.

Adolescent↗

Use of titanium staples during upper tract laparoscopic reconstructive surgery: initial experience.

PURPOSE: Using nonabsorbable titanium staples in the lower urinary tract during laparoscopic nephroureterectomy has been shown to be safe. Laboratory studies of titanium staples in the upper urinary tract have likewise been favorable. Therefore, we used titanium Endo-GIA tissue staples (United States Surgical, Norwalk, Connecticut) to facilitate laparoscopic reduction pelvioplasty during laparoscopic pyeloplasty. MATERIALS AND METHODS: Of the 17 cases of reduction pelvioplasty closure was done in 12 using absorbable sutures, while in 5 reduction was done with an Endo-GIA stapler. Followup consisted of office visits and telephone interviews plus radionuclide renal scans. RESULTS: Average operative time was 5.5 hours in the Endo-GIA group compared with 6.8 hours in the sutured group. In the latter group extravasation in 2 patients postoperatively was managed conservatively. There was no extravasation in the stapled group. At a median subjective followup of 27 months none of the 5 patients who underwent reduction with titanium staples had symptomatic nephrolithiasis, although new onset urolithiasis developed in 1 in the sutured group. All patients had a greater than 50% decrease in pain. Renal scans at a median of 9 months showed that all ureteropelvic junction repairs were unobstructed. Additional radiographic studies in 2 patients in the stapled group showed a patent ureteropelvic junction and no stones. CONCLUSIONS: Titanium staples provide rapid, secure closure of the renal pelvis during laparoscopic pyeloplasty. While the risk of stone formation is an ongoing concern, it has yet to materialize.

Adult↗

Use of gelatin matrix to rapidly repair diaphragmatic injury during laparoscopy.

Iatrogenic diaphragmatic injury during laparoscopy has necessitated intracorporeal suturing and occasionally thoracostomy tube placement. We describe a technique to repair the diaphragm quickly using a novel gelatin thrombin matrix. The matrix can be administered through a trocar or hand-assist device and can rapidly seal small injuries, obviating the need for formal suture repair. The presented case and technique should be considered in selected small diaphragmatic injuries.

Carcinoma, Renal Cell↗

Variability of cerebral blood volume and oxygen extraction: stages of cerebral haemodynamic impairment revisited.

The presence or degree of haemodynamic impairment due to occlusive cerebrovascular disease is often inferred from measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), oxygen extraction fraction (OEF) and the cerebral rate for oxygen metabolism (CMRO2). However, the relationship of these variables, in particular CBV, to regional cerebral haemodynamics is not clearly established in humans with subacute or chronic disease. In the present study, we investigated the relationship of CBV to OEF, CBF and CMRO2, and to subsequent stroke risk in patients with unilateral carotid artery occlusion, in order to define better the associated haemodynamic and metabolic changes. We reviewed data from 81 patients with symptomatic carotid occlusion enrolled in a prospective study of haemodynamic factors and stroke risk. Measurements of CBV, CBF, OEF and CMRO2 were made on entry using PET. Patients were divided into groups by hemispheric ratios and absolute ipsilateral values of OEF and CBV, based on comparison with normal controls. Haemodynamic and metabolic values, risk factors and stroke risk were compared between groups. Based on hemispheric ratios, 45 patients had increased ipsilateral OEF; CBV was increased in 19 of these 45 patients. No differences in CBF, CMRO2 or clinical risk factors were found between these 19 patients and the remaining 26 patients with increased OEF and normal or reduced CBV. Thirteen ipsilateral strokes occurred during follow-up, and 10 of the 13 occurred in the 19 patients with increased OEF and CBV (log rank P < 0.0001). Thirty-two of the 68 patients with complete quantitative PET data had increased OEF by absolute ipsilateral values. CBV was increased in 20 of the 32 patients. No differences in CBF, CMRO2 or clinical risk factors were found between these 20 patients and the remaining 12 patients with increased OEF and normal CBV. Seven of the nine ipsilateral strokes that occurred in the 68 patients occurred in those 20 patients with increased OEF and increased CBV (log rank P = 0.003). The higher risk of ischaemic stroke in patients with increased OEF and CBV suggests that their degree of haemodynamic compromise is more severe than those with increased OEF and normal CBV. In patients with chronic carotid occlusion and increased OEF, increased CBV may indicate pronounced vasodilation due to exhausted autoregulatory vasodilation. The physiological explanation for the measurement of normal CBV in patients with increased OEF is less certain and may reflect preserved autoregulatory capacity.

Adult↗

Frameless stereotaxy without rigid pin fixation during awake craniotomies.

OBJECTIVE: The accuracy and precision of resection with awake brain mapping is augmented when combined with frameless stereotaxy. Frameless stereotactic assisted surgery, however, typically involves immobilization in Mayfield pins. Rigid fixation, however, may be problematic for individuals undergoing awake craniotomy. We describe an alternate method of frameless stereotaxy without the use of pin fixation. METHODS: The MRI fiducials are placed in proximity to the proposed incision and prepared and draped in the operative field. After craniotomy, the epidural skull clamp (standardly used to support the electrode holder during corticography) is attached. Using the Stealth Navigational System, a spinal reference arc is then clamped onto the skull clamp base. After the fiducials and arc are registered, the probe is used for frameless guidance. RESULTS: In 14 of 15 cases (93%), this technique was successful. One case failed because of close proximity of the fiducials to the incision. The accuracy of the 14 successful cases was less than 4 mm. The error within the lesion itself was always less than 2 mm. Overall, these results are comparable to those achieved using a Mayfield head holder. In all tumor cases, postoperative imaging concurred with intraoperative assessment of a total versus subtotal resection. CONCLUSIONS: By affixing the spinal arc to the skull, the complications and discomfort associated with pin fixation are avoided completely. The patient is free to move without affecting the accuracy. The spine arc, in combination with the skull clamp, provides an efficient, well-tolerated, and accurate method of frameless navigation for the awake patient undergoing craniotomy.

Awareness↗

Long-term outcome after angioplasty for symptomatic extracranial carotid stenosis in poor surgical candidates.

BACKGROUND AND PURPOSE: The optimal treatment of patients with symptomatic carotid stenosis who are poor surgical candidates is uncertain. The purposes of this study were to report the long-term outcome after angioplasty in a series of these patients and to compare these data with historical control data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS: We identified 42 consecutive patients with >70% carotid stenosis and ipsilateral ischemic symptoms within 120 days of treatment with angioplasty. All were considered poor surgical candidates by experienced surgeons. Baseline epidemiological stroke risk factors were obtained from review of medical records. Follow-up was from clinic records and by telephone. RESULTS: Baseline epidemiological stroke risk factors were similar to those of medically treated NASCET patients. Angioplasty patients tended to have higher degrees of stenosis (45% with >90% stenosis versus 24% in NASCET) and more frequent contralateral stenosis or occlusion (30% versus 9%) than NASCET patients. Three patients suffered procedural strokes; 2 of the 3 made nearly complete recoveries. One additional patient suffered a central retinal occlusion 48 hours after angioplasty. No ipsilateral strokes occurred during the mean follow-up period of 1.7 years. Three patients were lost to follow-up. The cumulative risk of stroke was 9.5% (4 of 42) compared with 26% at 2 years for medically treated patients in NASCET. CONCLUSIONS: These pilot data suggest a beneficial effect of angioplasty for patients with high-grade symptomatic carotid stenosis who are not good surgical candidates.

Adult↗

Regional cerebrovascular and metabolic effects of hyperventilation after severe traumatic brain injury.

OBJECT: Recently, concern has been raised that hyperventilation following severe traumatic brain injury (TBI) could lead to cerebral ischemia. In acute ischemic stroke, in which the baseline metabolic rate is normal, reduction in cerebral blood flow (CBF) below a threshold of 18 to 20 ml/100 g/min is associated with energy failure. In severe TBI, however, the metabolic rate of cerebral oxygen (CMRO2) is low. The authors previously reported that moderate hyperventilation lowered global hemispheric CBF to 25 ml/100 g/min but did not alter CMRO2. In the present study they sought to determine if hyperventilation lowers CBF below the ischemic threshold of 18 to 20 ml/100 g/ min in any brain region and if those reductions cause energy failure (defined as a fall in CMRO2). METHODS: Two groups of patients were studied. The moderate hyperventilation group (nine patients) underwent hyperventilation to PaCO2 of 30 +/- 2 mm Hg early after TBI, regardless of intracranial pressure (ICP). The severe hyperventilation group (four patients) underwent hyperventilation to PaCO2 of 25 +/- 2 mm Hg 1 to 5 days postinjury while ICP was elevated (20-30 mm Hg). The ICP, mean arterial blood pressure, and jugular venous O2 content were monitored, and cerebral perfusion pressure was maintained at 70 mm Hg or higher by using vasopressors when needed. All data are given as the mean +/- standard deviation unless specified otherwise. The moderate hyperventilation group was studied 11.2 +/- 1.6 hours (range 8-14 hours) postinjury, the admission Glasgow Coma Scale (GCS) score was 5.6 +/- 1.8, the mean age was 27 +/- 9 years, and eight of the nine patients were men. In the severe hyperventilation group, the admission GCS score was 4.3 +/- 1.5, the mean age was 31 +/- 6 years, and all patients were men. Positron emission tomography measurements of regional CBF, cerebral blood volume, CMRO2, and oxygen extraction fraction (OEF) were obtained before and during hyperventilation. In all 13 patients an automated search routine was used to identify 2.1-cm spherical nonoverlapping regions with CBF values below thresholds of 20, 15, and 10 ml/ 100 g/min during hyperventilation, and the change in CMRO2 in those regions was determined. In the regions in which CBF was less than 20 ml/100 g/min during hyperventilation, it fell from 26 +/- 6.2 to 13.7 +/- 1 ml/ 100 g/min (p < 0.0001), OEF rose from 0.31 to 0.59 (p < 0.0001), and CMRO2 was unchanged (1.12 +/- 0.29 compared with 1.14 +/- 0.03 ml/100 g/min; p = 0.8). In the regions in which CBF was less than 15 ml/100 g/min during hyperventilation, it fell from 23.3 +/- 6.6 to 11.1 +/- 1.2 ml/100 g/min (p < 0.0001), OEF rose from 0.31 to 0.63 (p < 0.0001), and CMRO2 was unchanged (0.98 +/- 0.19 compared with 0.97 +/- 0.23 ml/100 g/min; p = 0.92). In the regions in which CBF was less than 10 ml/100 g/min during hyperventilation, it fell from 18.2 +/- 4.5 to 8.1 +/- 0 ml/100 g/min (p < 0.0001), OEF rose from 0.3 to 0.71 (p < 0.0001), and CMRO2 was unchanged (0.78 +/- 0.26 compared with 0.84 +/- 0.32 ml/100 g/min; p = 0.64). CONCLUSIONS: After severe TBI, brief hyperventilation produced large reductions in CBF but not energy failure, even in regions in which CBF fell below the threshold for energy failure defined in acute ischemia. Oxygen metabolism was preserved due to the low baseline metabolic rate and compensatory increases in OEF; thus, these reductions in CBF are unlikely to cause further brain injury.

Adolescent↗

Postprocedure ischemic events after treatment of intracranial aneurysms with Guglielmi detachable coils.

OBJECT: Ischemic stroke or transient ischemic attack (TIA) may occur after the treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The purpose of the present study is to investigate possible risk factors for thromboembolic events and to determine their frequency and time course. METHODS: The records of 178 consecutive patients with 193 treated intracranial saccular aneurysms were reviewed. A total of 159 GDC procedures were performed to treat 143 aneurysms in 133 of those patients who were in good neurological condition, allowing clinical detection of postprocedure ischemic events (TIA or stroke). The association of clinical, anatomical, and pharmacological factors with intraprocedure intraarterial thrombus and with postprocedure ischemic events was investigated by using uni- and multivariate analyses. Thrombus protruding into the parent artery was noted during six of 159 GDC procedures, resulting in a clinical deficit in one patient. No factor was associated with intraprocedure intraarterial thrombus. Ten postprocedure ischemic events occurred in nine patients. Seven events occurred within 24 hours, and three events occurred between 24 hours and 58 days. Aneurysm diameter and protruding coils were significant independent predictors of postprocedure ischemic events in multivariate analysis (both p = 0.02). The actuarial risk of stroke was 3.8%. CONCLUSIONS: Larger aneurysm diameter and protruding loops of coils are associated with postprocedure ischemic events after GDC placement. It is unlikely that GDC-treated aneurysms retain thromboembolic potential beyond 2 months.

Adult↗