Decreased Opioid Consumption in Bone Marrow Harvest Patients Using Quadratus Lumborum Blocks in a Standardized Protocol.

Purpose: Bone marrow harvesting is associated with significant postoperative pain that may have potential negative consequences for the patient and health care system. In the current absence of uniform guidelines, there exists considerable variability amongst providers with respect to perioperative analgesia, especially opioid administration. In this initiative, we explored the potential for preoperative bilateral quadratus lumborum blocks in combination with a standardized perioperative analgesic protocol to manage pain with the goal of reducing perioperative narcotic usage and thereby improving opioid stewardship. Methods: Adults who underwent bone marrow donation from 2018 to 2020 were included in this analysis (n = 32). The pre-implementation group (n = 19) was reviewed retrospectively while the implementation group (n = 13) was evaluated prospectively. Patient demographics, pain scores, and opioid consumption were evaluated. Results: Patient characteristics were equivalent except for anesthesia type with an increased number of patients in the implementation group undergoing spinal anesthesia. The implementation group showed significantly reduced median intraoperative (20.0 mg vs. 0.0 mg; p < 0.001) and total opioid consumption (20.5 mg vs. 0.0 mg; p < 0.001). The number of patients who received any opioids decreased from 84.2% (16/19) before implementation to 23.1% (3/13) after implementation. Conclusion: This change in practice suggests that implementation of a standardized perioperative protocol, including bilateral quadratus lumborum blocks, for bone marrow harvest patients leads to reduced perioperative opioid administration without compromising immediate perioperative pain control.

Longitudinal MRI Evaluation of Ischemic Stroke in the Basal Ganglia of a Rhesus Macaque (Macaca mulatta) with Seizures.

An adult rhesus macaque developed seizures after the induction of ischemic stroke. Initially, on the day of surgery, a focal ischemic lesion was present exclusively in the right caudate nucleus. By 48 h after stroke induction, the lesion had extended into the putamen, when a seizure was observed. Our report highlights the temporal changes in infarction of unilateral basal ganglia after acute stroke and the accompanying clinical symptoms. This unusual case may provide additional information regarding the involvement of the basal ganglia in seizures, given that prior case reports and studies usually have not described the temporal and spatial evolution of the lesion before clinical symptoms emerge.

Examination of intra-operative core temperature in joint arthroplasty: a single-institution prospective observational study.

PURPOSE: Peri-operative hypothermia is associated with increased blood loss, delayed wound healing, and surgical site infections. However, it is not known when or how rapidly hypothermia develops during arthroplasty. This study observed patients undergoing lower extremity arthroplasty to identify the times of greatest heat loss or gain. METHODS: This single-institution prospective observational study enrolled 120 patients undergoing elective knee or hip arthroplasty for peri-operative temporal temperature measurements at ten prespecified intervals. Incidence of hypothermia was the primary outcome. A secondary aim was to identify patient and operative factors associated with hypothermia. Descriptive statistics were calculated for fixed time variables. Associations for the occurrence of hypothermia over time were conducted using generalized linear mixed models with a logit link and a random subject effect to account for repeated measures on the same individual over time. RESULTS: Most patients, 72.6%, experienced hypothermia with 20.6% hypothermic for over one hour and 47.1% hypothermic after surgery. In the multivariable model, increased odds of hypothermia were associated with female gender (P = 0.017), knee arthroplasty (P < 0.001), neuraxial anaesthesia (P < 0.001), lower patient pre-operative temperature (P < 0.001), and lower operating room temperature (P = 0.042). A 0.5 °C decrease in patient pre-operative temperature or operating room temperature was associated with a 97 and 11% increase in the odds of hypothermia, respectively, controlling for other factors. CONCLUSION: In our series, peri-operative hypothermia remains common for patients undergoing arthroplasty. Female gender, low pre-operative temperature, knee arthroplasty, and neuraxial anesthesia were associated with hypothermia. Further preventative strategies and studies on interventions to reduce hypothermia are needed.

Accuracy of Human and Veterinary Point-of-Care Glucometers for Use in Rhesus Macaques (Macaca mulatta), Sooty Mangabeys (Cercocebus atys), and Chimpanzees (Pan troglodytes).

Handheld, point-of-care glucometers are commonly used in NHP for clinical and research purposes, but whether these devices are appropriate for use in NHP is unknown. Other animal studies indicate that glucometers should be species-specific, given differences in glucose distribution between RBC and plasma; in addition, Hct and sampling site (venous compared with capillary) influence glucometer readings. Therefore, we compared the accuracy of 2 human and 2 veterinary glucometers at various Hct ranges in rhesus macaques (Macaca mulatta), sooty mangabeys (Cercocebus atys), and chimpanzees (Pan troglodytes) with that of standard laboratory glucose analysis. Subsequent analyses assessed the effect of hypoglycemia, hyperglycemia, and sampling site on glucometer accuracy. The veterinary glucometers overestimated blood glucose (BG) values in all species by 26 to 75 mg/dL. The mean difference between the human glucometers and the laboratory analyzer was 7 mg/dL or less in all species. The human glucometers overestimated BG in hypoglycemic mangabeys by 4 mg/dL and underestimated BG in hyperglycemic mangabeys by 11 mg/dL; similar patterns occurred in rhesus macaques. Hct did not affect glucometer accuracy, but all samples were within the range at which glucometers generally are accurate in humans. BG values were significantly lower in venous than capillary samples. The current findings show that veterinary glucometers intended for companion-animal species are inappropriate for use in the studied NHP species, whereas the human glucometers showed clinically acceptable accuracy in all 3 species. Finally, potential differences between venous and capillary BG values should be considered when comparing and evaluating results.

Regional anesthesia in patients with pre-existing neurologic disease.

PURPOSE OF REVIEW: Regional anesthesia is controversial in patients with pre-existing neurologic disease. This study reviews the published evidence regarding the utilization and outcomes of regional anesthetics in this population. RECENT FINDINGS: Although publications are sparse, neuraxial and peripheral regional techniques have been successfully described in patients with spinal cord injury, multiple sclerosis, Guillain-Barre disease, neurofibromatosis, diseases of the neuromuscular junction, and Charcot-Marie Tooth disease without neurologic complications. Ultrasound guidance may aid in reduction in local anesthetic dose, anatomical evaluation and avoidance of needle trauma. SUMMARY: Regional anesthesia can be safely utilized in patients with pre-existing neurological disease and may have benefits over general anesthesia; however, a conservative approach is warranted. In addition, further publications regarding regional techniques in this population are needed.

Transgene-mediated suppression of the RNA interference pathway in Aedes aegypti interferes with gene silencing and enhances Sindbis virus and dengue virus type 2 replication.

RNA interference (RNAi) is the major innate antiviral pathway in Aedes aegypti that responds to replicating arboviruses such as dengue virus (DENV) and Sindbis virus (SINV). On the one hand, the mosquito's RNAi machinery is capable of completely eliminating DENV2 from Ae. aegypti. On the other, transient silencing of key genes of the RNAi pathway increases replication of SINV and DENV2, allowing the viruses to temporally overcome dose-dependent midgut infection and midgut escape barriers (MEB) more efficiently. Here we expressed Flock house virus B2 (FHV-B2) from the poly-ubiquitin (PUb) promoter in Ae. aegypti using the ΦC31 site-directed recombination system to investigate the impact of transgene-mediated RNAi pathway suppression on infections with SINV-TR339eGFP and DENV2-QR94, the latter of which has been shown to be confronted with a strong MEB in Ae. aegypti. FHV-B2 was constitutively expressed in midguts of sugar- and blood-fed mosquitoes of transgenic line PUbB2 P61. B2 over-expression suppressed RNA silencing of carboxypeptidase A-1 (AeCPA-1) in midgut tissue of PUbB2 P61 mosquitoes. Following oral challenge with SINV-TR339eGFP or DENV2-QR94, mean titres in midguts of PUbB2 P61 females were significantly higher at 7 days post-bloodmeal (pbm) than in those of nontransgenic control mosquitoes. At 14 days pbm, infection rates of carcasses were significantly increased in PubB2 P61 mosquitoes infected with SINV-TR339eGFP. Following infection with DENV2-QR94, midgut infection rates were significantly increased in the B2-expressing mosquitoes at 14 days pbm. However, B2 expression in PUbB2 P61 did not increase the DENV2-QR94 dissemination rate, indicating that the infection phenotype was not primarily controlled by RNAi.

Effects of extended-release injectable naltrexone on self-injurious behavior in rhesus macaques (Macaca mulatta).

Self-injurious behavior (SIB) is a spontaneous behavior that threatens the health and wellbeing of multiple species. In humans, the opioid antagonist naltrexone hydrochloride has been used successfully to modulate the endogenous opioid system and reduce the occurrence of SIB. This study is the first to assess the efficacy of extended-release naltrexone in the pharmacologic treatment of SIB in rhesus macaques (Macaca mulatta). In an acute pharmacokinetic study of 4 macaques, we determined the mean naltrexone plasma concentration was maintained above the therapeutic level (2 ng/mL) after administration of a single dose (20 mg/kg) of 28-d extended-release naltrexone throughout the release period. For a subsequent treatment study, we selected 8 singly housed macaques known to engage in SIB. The study comprised a 4-wk baseline phase; an 8-wk treatment phase, during which each macaque received 2 doses of extended-release naltrexone 28 d apart; and a 4-wk posttreatment phase. Plasma samples were collected and analyzed weekly for naltrexone concentrations throughout the treatment and posttreatment phases. In addition, total of 6 h of video was analyzed per animal per phase of the study. Compared with baseline phases, both the frequency and the percentage of time spent displaying SIB decreased during the treatment phase, and the percentage of time remained decreased during the posttreatment phase. In contrast, extended-release naltrexone did not alter the expression of other abnormal, anxiety-related, or agonistic behaviors nor were levels of inactivity affected. The present study supports the use of naltrexone in the treatment of SIB in rhesus macaques.

Double-outlet right ventricle and double septal defects in a Rhesus macaque (Macaca mulatta).

A 6-year-old male India-origin Rhesus macaque (Macaca mulatta) presented with thin body condition and muscular atrophy. Thoracic auscultation revealed a grade VI/VI pansystolic murmur bilaterally. Radiographs showed cardiomegaly with significant left atrial and biventricular enlargement, a dilated pulmonary artery, and hepatomegaly. Electrocardiogram revealed a normal sinus rhythm interspersed with ventricular bigeminy. Hematology showed mild polycythemia and prerenal azotemia. Necropsy demonstrated double-outlet right ventricle with a large subaortic ventricular septal defect, subpulmonary stenosis, small atrial septal defect, and right ventricular hypertrophy. The major histological finding was severe chronic passive hepatic congestion. Double-outlet right ventricle is a rare congenital heart disease, both in human beings and animals.

Discovery of the short gamma-ray burst GRB 050709.

Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, the energy scale and the progenitors of the short bursts have remained a mystery. Here we report the discovery of a short-hard burst whose accurate localization has led to follow-up observations that have identified the X-ray afterglow and (for the first time) the optical afterglow of a short-hard burst; this in turn led to the identification of the host galaxy of the burst as a late-type galaxy at z = 0.16 (ref. 10). These results show that at least some short-hard bursts occur at cosmological distances in the outskirts of galaxies, and are likely to be caused by the merging of compact binaries.

Stroke after cardiac surgery: short- and long-term outcomes.

BACKGROUND: Stroke remains a devastating complication of cardiac surgery, but stroke prevention remains elusive. Evaluation of early and long-term clinical outcomes and brain-imaging findings may provide insight into stroke prognosis, etiology, and prevention. METHODS: Five thousand nine hundred seventy-one cardiac surgery patients were prospectively studied for clinical evidence of stroke. Stroke and nonstroke patients were compared by early outcomes. Data collected for stroke patients included brain imaging results, long-term functional status, and survival. Outcome predictors were then determined. RESULTS: Stroke was diagnosed in 214 (3.6%) patients. Brain imaging demonstrated acute infarction in 72%; embolic in 83%, and watershed in 24%. Survival for stroke patients was 67% at 1 year and 47% at 5 years. Independent predictors of survival were cerebral infarct type, creatinine elevation, cardiopulmonary bypass time, preoperative intensive care days, postoperative awakening time, and postoperative intensive care days. Long-term disability was moderate to severe in 69%. CONCLUSIONS: Stroke after cardiac surgery has profound repercussions that are independently related to infarct type and clinical factors. These data are essential for clinical decision making and prognosis determination.

High failure rate after laparoscopic adjustable silicone gastric banding for treatment of morbid obesity.

OBJECTIVE: To report the results from one of the eight original U.S. centers performing laparoscopic adjustable silicone gastric banding (LASGB), a new minimally invasive surgical technique for treatment of morbid obesity. SUMMARY BACKGROUND DATA: Laparoscopic adjustable silicone gastric banding is under evaluation by the Food & Drug Administration in the United States in an initial cohort of 300 patients. METHODS: Of 37 patients undergoing laparoscopic placement of the LASGB device, successful placement occurred in 36 from March 1996 to May 1998. Patients have been followed up for up to 4 years. RESULTS: Five patients (14%) have been lost to follow-up for more than 2 years but at last available follow-up (3-18 months after surgery) had achieved only 18% (range 5-38%) excess weight loss. African American patients had poor weight loss after LASGB compared with whites. The LASGB devices were removed in 15 (41%) patients 10 days to 42 months after surgery. Four patients underwent simple removal; 11 were converted to gastric bypass. The most common reason for removal was inadequate weight loss in the presence of a functioning band. The primary reasons for removal in others were infection, leakage from the inflatable silicone ring causing inadequate weight loss, or band slippage. The patients with band slippage had concomitant poor weight loss. Bands were removed in two others as a result of symptoms related to esophageal dilatation. In 18 of 25 patients (71%) who underwent preoperative and long-term postoperative contrast evaluation, a significantly increased esophageal diameter developed; of these, 13 (72%) had prominent dysphagia, vomiting, or reflux symptoms. Of the remaining 21 patients with bands, 8 currently desire removal and conversion to gastric bypass for inadequate weight loss. Six of the remaining patients have persistent morbid obesity at least 2 years after surgery but refuse to undergo further surgery or claim to be satisfied with the results. Overall, only four patients achieved a body-mass index of less than 35 and/or at least a 50% reduction in excess weight. Thus, the overall need for band removal and conversion to GBP in this series will ultimately exceed 50%. CONCLUSIONS: The authors did not find LASGB to be an effective procedure for the surgical treatment of morbid obesity. Complications after LASGB include esophageal dilatation, band leakage, infection, erosion, and slippage. Inadequate weight loss is common, particularly in African American patients. More study is required to determine the long-term efficacy of the LASGB

Continuous negative abdominal pressure device to treat pseudotumor cerebri.

OBJECTIVE: To study the effects of an externally applied negative abdominal pressure device designed to lower the effects of intra-abdominal pressure (IAP) on headaches and pulsatile tinnitus in severely obese women with pseudotumor cerebri (PTC). DESIGN: Short-term clinical intervention trial in the Clinical Research Center. Days 1 and 3 were 'control' days; on days 2 and 4-6 patients were in the device from 8:00 am to noon and from 1:00 to 5:00 pm, and on nights 7-11 they were in the device from 10:00 pm to 8:00 am. The last four patients were treated in a device with a counter-traction mechanism. SUBJECTS: Seven centrally obese women with PTC. MEASUREMENTS: Headache and pulsatile tinnitus severity were graded by the patient using visual analog scale (1-10) and averaged for the time that the device was in use or not in use. IAP was estimated from urinary bladder pressure (UBP) before and during device use. The internal jugular vein (IJV) elliptical cross-sectional area was measured with B-mode ultrasonography; the timed average velocity was measured by Doppler. RESULTS: There was a decrease in both headache (6.8+/-0.8 to 4.2+/-0.8, P<0.05) and pulsatile tinnitus (4.2+/-0.5 to 1.8+/-0.5, P<0.02) within 5 min, and in headache (to 2.2+/-0.8, P<0.01) and tinnitus (to 1.7+/-0.5, P<0.01) within 1 h of device activation. UBP decreased (P<0.001) from 19.1+/-3 to 12.5+/-2.8 cmH2O. Headache remained improved throughout time that the device was used. During the second week, five of seven patients slept in the device without difficulty and four awoke without headache. There was a progressive decrease (P<0.01) in headache during the day after sleeping in the device at night as compared with days 1 and 3 when it was not used (6.5+/-0.5, day 1; 4.1+/-0.7, day 3; 3.1+/-0.8, day 8; 2.3+/-0.8, day 10). Headaches returned late in the afternoon in two patients; the device was reactivated and headache again improved. Five patients underwent IJV sonography; the IJV area decreased (129+/-53 to 100+/-44 mm2, P=0.06) without a change in IJV flow (1004+/-802 to 1000+/-589 ml/min) with the device. When activated, the device was pulled into the patient, creating discomfort that was alleviated with the counter-traction mechanism in the last four patients. One patient developed a 5 cm area of blisters that resolved when the device was worn over a hospital gown. CONCLUSIONS: Decreasing IAP relieved headaches and pulsatile tinnitus in PTC. When patients slept in the device, they awoke without headache or tinnitus, which remained markedly improved throughout most of the following day. This study supports the hypothesis that PTC in obese women is secondary to an increased IAP.

Cardiac valve replacement with mitral homograft.

The purpose of this study was to review the results of mitral and tricuspid valve replacement with mitral valve homograft. Twenty-two mitral homografts were used to replace cardiac valves in 20 patients. The mitral valve was replaced in 18 patients, applying the method described by Acar. The tricuspid valve was replaced in 2 patients, attaching one papillary muscle of the graft to the anterior papillary muscle and bringing the other papillary muscle of the graft through a tunnel in the anterior wall of the right ventricle. A concomitant Maze III procedure was performed in 3 patients. Accuracy of the repair was confirmed by intraoperative echocardiography. All patients survived operation and are currently alive. One patient was lost to follow-up. Patients have been followed for up to 3.25 years. All patients have good exercise ability (NYHA class I). Five homografts (25%) have been explanted from the mitral position and one from the tricuspid position. All events occurred during the first year after reoperation. Cardiac valve replacement with mitral valve homograft may be accomplished safely. A technically good operation does not guarantee that the valve will remain competent and an unacceptably high early explant rate may be expected. Use of mitral valve homograft for cardiac valve replacement should be restricted to young patients in whom anticoagulant medication is not indicated or undesirable and for those with resistant infection.

Effects of increased renal parenchymal pressure on renal function.

OBJECTIVE: Acute renal failure is seen with the acute abdominal compartment syndrome (AACS). The cause of acute renal failure in AACS is thought to be multifactorial, including increased renal venous pressure, renal parenchymal pressure (RPP), and decreased cardiac output. Previous studies have established the role of renal venous pressure as an important mediator of this renal derangement. In this study, we evaluate the role of renal parenchymal compression on renal function. METHODS: Two groups of swine (20-26 kg) were studied after left nephrectomy and placement of a renal artery flow probe and ureteral cannula. Two hours were allowed for equilibration, and an inulin infusion was begun to calculate inulin clearance as a measurement of glomerular filtration. In group 1 animals (n = 6), RPP was elevated by 30 mm Hg for 2 hours with renal parenchymal compression. RPP then returned to baseline for 1 hour. In group 2 (n = 6), the RPP was not elevated. The cardiac index, preload, and mean arterial pressure remained stable. Blood samples for plasma renin activity and plasma aldosterone were taken at baseline and at hourly intervals. RESULTS: Elevation of RPP in the experimental group showed no significant decrease in renal blood flow index or glomerular filtration when compared with control animals. There were no significant elevations of plasma aldosterone or plasma renin activity in the experimental animals when compared with control. CONCLUSION: Elevated renal compression alone did not create the pathophysiologic derangements seen in AACS. However, prior data from this laboratory found that renal vein compression alone caused a decreased renal blood flow and glomerular filtration and an increased plasma renin activity, plasma aldosterone, and urinary protein leak. These changes are partially or completely reversed by decreasing renal venous pressure as occurs with abdominal decompression for AACS. These data strengthen the proposal that renal vein compression, and not renal parenchymal compression, is the primary mediator of the renal derangements seen in AACS.

Cardiac valve operations using a partial sternotomy (lower half) technique.

BACKGROUND AND AIM: Operations on cardiac valves are being performed more frequently through smaller incisions than traditional midline sternotomy. A variety of alternate incisions have been used, but most of the interest appears to focus on partial sternotomy. The purpose of the study was to review results using a partial lower sternotomy for cardiac valve operations. METHODS: A standard partial lower one-half or two-thirds sternotomy was used for cardiac valve operations in 112 patients. The sternum was divided transversely in the third or second intercostal space and vertically from that point through the xyphoid process. Standard instruments and retraction devices were used. This incision provided adequate exposure for even complex operations to be performed. Small cannulae were placed into the aorta and heart through the primary incision for cardiopulmonary bypass. Vacuum-assisted venous drainage was used. RESULTS: Seventy-four single valve operations were performed. There were 35 double valve and 5 triple valve operations (35.4%) performed. Operative mortality (5.3%) and major complication rates were comparable to full the sternotomy approach. CONCLUSIONS: Partial sternotomy (lower half) provides a smaller incision through which virtually all cardiac valve operations may be performed. Results achieved with this approach are similar to those associated with full sternotomy. The smaller incision is appreciated by patients.

Effect of increased renal venous pressure on renal function.

OBJECTIVE: Acute renal failure is seen with the acute abdominal compartment syndrome (AACS). Although the cause of acute renal failure in AACS may be multifactorial, renal vein compression alone has not been investigated. This study evaluated the effects of elevated renal vein pressure (RVP) on renal function. METHODS: Two groups of swine (18-22 kg) were studied after left nephrectomy and placement of a renal artery flow probe to measure renal artery blood flow, renal vein catheter, and ureteral cannula. Two hours were allowed for equilibration and an inulin infusion was begun to calculate inulin clearance for measurement of glomerular filtration rate. Group 1 animals (n = 4) had RVP elevated by 30 mm Hg for 2 hours with renal vein constriction. RVP was then returned to baseline for 1 hour. In group 2 (n = 4), the RVP was not elevated. The cardiac index (2.9 +/- 0.5 L/min/m2) and mean arterial pressure (101 +/- 9 mm Hg) remained stable. Plasma renin activity and serum aldosterone were measured every 60 minutes. RESULTS: Elevation of RVP (0-30 mm Hg above baseline) in the experimental group showed a significant decrease in renal artery blood flow index (2.7 to 1.5 mL/min per g) and glomerular filtration rate (26 to 8 mL/min) compared with control. In addition, there was significant elevation of plasma serum aldosterone (14 to 25 microng/dL) and plasma renin activity (2.6 to 9.5 microng/mL per h) as well as urinary protein leak in the experimental animals compared with control. These changes were partially or completely reversible as RVP returned toward baseline. CONCLUSION: Elevated RVP alone leads to decreased renal artery blood flow and glomerular filtration rate and increased plasma renin activity, serum aldosterone, and urinary protein leak. These changes are consistent with the renal pathophysiology seen in AACS, morbid obesity, and preeclampsia. The changes are partially or completely reversed by decreasing renal venous pressure as occurs with abdominal decompression for AACS.

Inhibition of epidermal growth factor receptor-associated tyrosine phosphorylation in human carcinomas with CP-358,774: dynamics of receptor inhibition in situ and antitumor effects in athymic mice.

Phosphorylation of tyrosine residues on the epidermal growth factor (EGF) receptor (EGFr) is an important early event in signal transduction, leading to cell replication for major human carcinomas. CP-358,774 is a potent and selective inhibitor of the EGFr tyrosine kinase and produces selective inhibition of EGF-mediated tumor cell mitogenesis. To assess the pharmacodynamic aspects of EGFr inhibition, we devised an ex vivo enzyme-linked immunosorbent assay for quantification of EGFr-specific tyrosine phosphorylation in human tumor tissue specimens obtained from xenografts growing s.c. in athymic mice. When coupled with pharmacokinetic analyses, this measurement can be used to describe the extent and duration of kinase inhibition in vivo. CP-358,774 is an effective, orally active inhibitor of EGFr-specific tyrosine phosphorylation (ED(50) = 10 mg/kg, single dose). It has a significant duration of action, producing, on average, a 70% reduction in EGFr-associated phosphotyrosine over a 24-h period after a single 100 mg/kg dose. Inhibition of EGFr phosphotyrosine in an ex vivo assay format effectively estimates the potency and degree of inhibition of EGFr-dependent human LICR-LON-HN5 head and neck carcinoma tumor growth. Substantial growth inhibition of human tumor xenografts was achieved with p.o. doses of the compound (ED(50) = 10 mg/kg q.d. for 20 days). Combination chemotherapy with cisplatin produced a significant response above that of cisplatin alone with no detectable effects on body weight or lethal toxicity. Taken together, these observations suggest that CP-358,774 may be useful for the treatment of EGFr-driven human carcinomas.

Initial experience with MIDCAB grafting using the gastroepiploic artery.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting with the gastroepiploic artery can be used in primary operations and reoperations to revascularize the inferior or anterior surface of the heart. METHODS: Patients who had symptomatic coronary artery disease limited to a single coronary distribution were selected. Coronary targets were grafted with the pedicled gastroepiploic artery through a small midline epigastric incision. Patients were followed with scheduled outpatient clinic visits, Doppler examination, and selective recatheterization. RESULTS: Between May 1995 and November 1997, 74 patients underwent gastroepiploic artery minimally invasive direct coronary artery bypass grafting; 33 (45%) had a primary operation and 41 (55%), a reoperation. Grafting was performed to the distal right coronary artery (n = 38), the posterior descending artery (n = 28), or the distal left anterior descending coronary artery (n = 8). There were six deaths (8%) within 30 days after operation. Twenty patients (28%) underwent recatheterization; there were two graft occlusions, two graft stenoses, and five anastomotic stenoses. Of 60 patients seen 2 or more weeks after operation, 53 (88%) had resolution of anginal symptoms at a mean follow-up of 10.9 months (range, 0 to 30 months). CONCLUSIONS: Inferior minimally invasive direct coronary artery bypass grafting with the gastroepiploic artery avoids the risks of repeat sternotomy, aortic manipulation, and cardiopulmonary bypass. Patency rates, however, were lower than expected, and there is significant morbidity and mortality associated with high-risk patients undergoing the procedure. Continued follow-up is essential to evaluate long-term graft patency and patient survival.

Assessing the impact of cerebral injury after cardiac surgery: will determining the mechanism reduce this injury?

BACKGROUND: Central nervous system dysfunction continues to produce significant morbidity and associated mortality in patients undergoing cardiac surgery. Using a closed-chest canine cardiopulmonary bypass model, dogs underwent 2 h of hypothermic circulatory arrest (HCA) at 18 degrees C, followed by resuscitation and recovery for 3 days. Animals were assessed functionally by a species-specific behavioral scale, histologically for patterns of selective neuronal necrosis, biochemically by analysis of microdialysis effluent, and by receptor autoradiography for N-methyl-D-aspartate (NMDA) glutamate receptor subtype expression. RESULTS: Using a selective NMDA (glutamate) receptor antagonist (MK801) and an AMPA antagonist (NBQX), glutamate excitotoxicity in the development of HCA-induced brain injury was documented and validated. A microdialysis technique was employed to evaluate the role of nitric oxide (NO) in neuronal cell death. Arginine plus oxygen is converted to NO plus citrulline (CIT) by the action of NO synthase (nNOS). CIT recovery in the cerebrospinal fluid and from canine cortical homogenates increased during HCA and reperfusion. These studies demonstrated that neurotoxicity after HCA involves a significant and early induction of nNOS expression, and neuronal processes leading to widespread augmentation of NO production in the brain. To further investigate the production of excitatory amino acids in the brain, we hypothesized the following scenario: HCA--> increased glutamate, increased aspartate, increased glycine--> increased intracellular Ca2+--> increased NO + CIT. Using the same animal preparation, we demonstrated that HCA caused increased intracerebral glutamate and aspartate that persists up to 20 h post-HCA. HCA also resulted in CIT (NO) production, causing a continued and delayed neurologic injury. Confirmatory evidence of the role of NO was demonstrated by a further experiment using a specific nNOS inhibitor, 7-nitroindazole. Animals underwent 2 h of HCA, and then were evaluated both physiologically and for NO production. 7-Nitroindazole reduced CIT (NO) production by 58.4 +/- 28.3%. In addition, dogs treated with this drug had superior neurologic function compared with untreated HCA controls. CONCLUSIONS: These experiments have documented the role of glutamate excitotoxicity in neurologic injury and have implicated NO as a significant neurotoxin causing necrosis and apoptosis. Continued research into the pathophysiologic mechanisms involved in cerebral injury will eventually yield a safe and reliable neuroprotectant strategy. Specific interventional agents will include glutamate receptor antagonists and specific neuronal NO synthase inhibitors.

Superior vena cava obstruction: bypass using spiral vein graft.

BACKGROUND: Previous midterm experience with the composite spiral saphenous vein graft to bypass the obstructed superior vena cava (SVC) has been favorable. This study looks at the long-term results in patients followed for up to 23 years. METHODS: Sixteen patients aged 17 to 68 years had operation for obstruction of the SVC with SVC syndrome caused by benign disease. Eleven patients had fibrosing mediastinitis with or without caseous necrosis, 4 had thrombosis caused by a catheter or a pacemaker electrode, and 1 had spontaneous thrombosis. All operations were performed using a composite spiral vein graft constructed from the patient's own saphenous vein. Graft diameter ranged from 9.5 to 15.0 mm. Ten grafts were from the left innominate vein, and six grafts were from the right or left internal jugular vein. The grafts were placed to the right atrial appendage in all patients except 1. Follow-up extends from 1 month to 23 years 8 months (mean follow-up, 10.9 years). RESULTS: Fourteen of 16 grafts remain patent for up to 23 years, and all patients but 1 are free from SVC syndrome. One patient required revision of the graft for thrombosis 4 days after operation. Two grafts closed during the first year after operation: one because of recurrence of spontaneous venous thrombosis and the other because of aggressive fibrosing mediastinitis requiring operation for graft revision three times over a 12-year period prior to death. CONCLUSIONS: These data demonstrate that a spiral vein bypass graft for treatment of the obstructed SVC relieves SVC syndrome and has excellent long-term patency.