Exposure to increased pressure or hyperbaric oxygen suppresses interferon-gamma secretion in whole blood cultures of healthy humans.

This study examines the effects of hyperoxia, increased atmospheric pressure, and hyperbaric oxygen on cytokine synthesis. Five healthy volunteers were exposed to 90 min of room air, 100% oxygen, 10.5% oxygen at 2 atm abs, or 100% oxygen at 2 atm abs (HBO2). All subjects were blinded and randomly exposed to each of the 4 conditions. Immediately before entering the chamber, immediately after exposure, and 3 and 24 h later, blood was drawn and stimulated ex vivo with phorbol myristate acetate (PMA) and phytohemagglutinin A (PHA). Since lymphocytes are the primary source of PMA/PHA-induced interferon-gamma (IFN-gamma), these results were expressed as IFN-gamma production per 10(6) lymphocytes. Following the HBO2 exposure, PMA/PHA-stimulated lymphocytes released 51% less IFN-gamma than cells obtained before the exposure. This suppression persisted for 24 h following HBO2 (P < 0.05). Surprisingly, increased atmospheric pressure alone also inhibited IFN-gamma secretion (P < 0.05). Room air and hyperoxia alone had no significant effect upon IFN-gamma release. HBO2's anti-inflammatory effect may, in part, be due to inhibition of IFN-gamma release.

Ionic implantation of silicone chronic venous access devices does not alter thrombotic complications: a double-blinded, randomized clinical trial.

BACKGROUND: Ion implantation of silicone vascular catheters has been shown in preclinical and pilot studies to alter the thrombogenicity of silicone surfaces through the reduced adherence of thrombin. This prospective, randomized double-blinded study was designed to detect differences in function related to thrombotic events between ion-implanted and standard silicone chronic venous access devices (CVAD) placed in patients with cancer who are receiving chemotherapy. METHODS: Patients with nonleukemic malignancies who required venous access for chemotherapy and who were not receiving anticoagulants were randomized to receive standard or ion-implanted CVAD. Postoperative functional assessments of the ease of infusion or aspiration were performed by oncology nurses caring for the patients. RESULTS: Follow-up, available for 100 of 106 randomized patients, showed more episodes of occlusion to aspiration in the ion implantation group (47%) than in the control group (39%) but this difference was not significant. There were no significant differences between the 2 groups in the number of occasions when anticoagulation or local thrombolytic therapy was required nor were there differences in the numbers of infection or deep venous thromboses. CONCLUSIONS: Ion implantation of silicone catheter material does not alter the incidence of local thrombotic complications of CVAD. Although there were no serious complications resulting from this treatment, the use of ion-implanted catheters cannot be recommended on the basis of this trial.

Tyrosine kinase activation in breast carcinoma with correlation to HER-2/neu gene amplification and receptor overexpression.

The HER-2/neu oncogene encodes a transmembrane receptor with intrinsic tyrosine kinase activity. A pilot study was performed to investigate downstream effects of HER-2/neu (or related growth factor receptor) activation by identifying phosphorylated tyrosine. Fifty-four breast carcinomas were evaluated for HER-2/neu overexpression by the HercepTest (Dako, Carpinteria, CA) and the monoclonal CB11 antibody (Ventana, Tucson, AZ). Phosphotyrosine (an indication of tyrosine kinase activity) was detected by an antiphosphotyrosine mouse monoclonal antibody (Upstate Biotechnology, Lake Placid, NY). The gene amplification status was evaluated in 50 of the 54 cases by fluorescence in situ hybridization (FISH) using the Ventana gene probe. The HER-2/neu oncogene amplification was detected in 28% (14 of 50) of cases. Of the 14 cases showing oncogene amplification, tyrosine kinase activity was detected in 9 (64.2%) cases. There was moderate agreement between HER-2/neu gene amplification and tyrosine kinase activity (kappa = 0.43). Immunohistochemical staining of 3+ (with both HercepTest and CB11) showed better agreement with HER-2/neu oncogene amplification and increased tyrosine kinase activity than 2+ immunohistochemical staining. Overall, oncogene amplification and overexpression correlated with increased tyrosine kinase activity, supporting the mechanism of tyrosine kinase activation by HER-2/neu amplification and overexpression. However, 7 cases showing increased tyrosine kinase activity did not show gene amplification or 3+ receptor expression (by either HercepTest or CB11), raising the possibility of other growth factor receptors operating via the tyrosine kinase pathway. There was no apparent correlation between tyrosine kinase activity and hormone receptor status (estrogen or progesterone). Increased tyrosine kinase activity is more commonly associated with higher-grade tumors and thus may correlate with aggressive biologic behavior in breast carcinoma. The results of this pilot study suggest that a larger-scale investigation into downstream activation of tyrosine kinase and correlation to clinical outcome or response to Herceptin therapy may identify subsets of patients whose clinical response or outcome may be predicted by tyrosine kinase activation.

Multicenter review of protease inhibitors in 89 pregnancies.

CONTEXT: Despite the success of highly active antiretroviral therapy, the optimal approach for preventing perinatal HIV-1 transmission is not known. OBJECTIVE: A retrospective survey was conducted at six centers in the United States and Puerto Rico from January 1997 to October 1998 to evaluate the effects of protease inhibitor use during pregnancy on maternal and infant safety, prematurity rate, and frequency of perinatal HIV-1 transmission. RESULTS: In the study, 91 live infants, including 3 sets of twins, and 1 neonate who died shortly after birth were born to 89 women. HIV perinatal transmission rate in this series was 0 (95% confidence interval [CI], 0%-3%). Prematurity rate was 19.1%, comparable to rates in earlier reports of HIV-1-infected women. In multiple regression analysis, only cocaine use and premature rupture of membranes were associated with prematurity (p =.03 and.008, respectively). The gestational week during which the protease inhibitors were initiated was not found to be significantly associated with prematurity. Adverse maternal, obstetric, and infant events possibly related to protease inhibitors were uncommon. CONCLUSIONS: Protease inhibitors appeared generally safe in mothers and infants in this series. No perinatal HIV-1 transmission occurred. Further prospective, controlled studies are needed to define the optimal management of HIV-1 in pregnancy.

Angiogenic therapy for the chronically ischemic lower limb in a rabbit model.

The purpose of this study was to evaluate the long-term effectiveness of basic fibroblast growth factor (bFGF) in achieving neovascularization following ischemia from arterial ligation and to determine an optimal dosage level. We used an Ameroid constrictor to produce progressive occlusion of the left femoral artery of rabbits. At 2 weeks, the rabbits were randomized to receive intravenous injection of vehicle (group A, n = 15); 3 microg/kg/day bFGF (group B, n = 12); 10 microg/kg/day bFGF (group C, n = 12); or 16 microg/kg/day bFGF (group D, n = 15) for 3 days. At 1 to 37 days after surgery, we assessed limb neovascularization by transcutaneous oximetry (TCPO(2)), angiography, heart rate, arterial pressure, peripheral vascular resistance (PRU), and muscle blood flow (MBF) during steady-state intra-arterial infusion of saline (basal), acetylcholine, papaverine, or serotonin under anesthesia and capillary density (cap/mm(2)) and capillary per muscle fiber ratio (cap/F). Groups B and C showed significantly greater change in TCPO(2) over time than groups A and D (P < 0.0001). Group D showed the lowest TCPO(2) values from days 14 to 37 and group C the highest. Groups B and C showed a higher number of vessels filled with contrast agent than groups A and D (P < 0.0001). Calf cap/mm(2) and cap/F were significantly higher in groups B and C than groups A and D (P < 0.0001). Calf basal MBF values were higher in groups B and C than in groups A and D, but were not statistically significant. Group D showed the highest level in basal PRU. There were no significant differences in heart rate or blood pressure among the groups. These results show (1) treatment with bFGF has no adverse hemodynamic effects, (2) bFGF enhances angiogenesis and circulation at moderate doses, and these effects persist at least several weeks, and (3) high doses of bFGF may inhibit angiogenesis and collateral circulation.

Routine chest roentgenography is unnecessary in the work-up of stage I and II breast cancer.

PURPOSE: Clinical practice guidelines of many professional societies call for routine staging chest x-rays (SCXR) for all patients with invasive cancer. Given the estimated 157,000 patients annually for whom this recommendation pertains, this screening examination represents a considerable health care expenditure. If it were shown that SCXR rarely changed the management of low-risk subsets of this population, it might be possible to selectively omit this practice from the care of these patients with substantial resultant cost savings. PATIENTS AND METHODS: All patients with clinical stage I and II breast cancer presenting to the Baystate Medical Center from 1989 through 1997 were identified through the Tumor Registry. Their hospital records were reviewed for clinical presentation and documentation of SCXR. RESULTS: One thousand four hundred ninety-four patients were identified with clinical stage I and II disease. SCXR were available for review on 1,003 patients. Only one asymptomatic patient was upstaged to stage IV based on a SCXR. Two patients with primary lung tumors were also identified. These data demonstrate an asymptomatic pulmonary metastasis detection rate of 0. 099% (95% confidence interval, 0.0% to 0.6%). The total charges of SCXR for this group approached $180,000. CONCLUSION: These data demonstrate the low diagnostic yield and high cost of routine SCXR in the management of asymptomatic patients with clinical stage I and stage II breast cancer. Because other studies have shown that SCXR changes neither quality of life nor overall survival, SCXR should be limited to symptomatic patients in whom metastatic disease is suspected.

Risk of dysphagia after transesophageal echocardiography during cardiac operations.

BACKGROUND: Dysphagia can be a significant complication following cardiac operations. This study evaluates its incidence and relationship to intraoperative transesophageal echocardiography (TEE) for specific indications versus known factors such as stroke or prolonged intubation. METHODS: Records of 838 consecutive cardiac surgical patients were reviewed, and categorized into those who received TEE for specific indications versus those who did not (nonTEE). Dysphagia was recorded when symptoms were confirmed by barium cineradiography. Multiple logistic regression identified significant factors causing dysphagia. RESULTS: TEE was significantly related to the development of postoperative dysphagia by multiple logistic regression (p < 0.001). After controlling for other significant factors (stroke, left ventricular ejection fraction, intubation time, duration of operation), the odds of dysphagia for TEE patients was 7.8 times greater than for nonTEE patients. CONCLUSIONS: TEE may be an independent risk factor for dysphagia following cardiac operations.

The unsatisfactory margin in breast cancer surgery.

BACKGROUND: Surgical margin involvement with breast cancer usually results in obligatory reexcision or mastectomy. While unalterable occult host and pathologic factors may interfere with margin clearance during the initial excision, it is possible that alterations in surgical technique might increase the likelihood of obtaining satisfactory margins. METHODS: Two hundred and thirty-five patients who were candidates for breast conservation therapy were identified for 1991 and 1996 using the Tumor Registry. Margins were defined as "unsatisfactory" if there was microscopic involvement with tumor or the margin was close at initial excisional biopsy and the surgeon opted for reexcision. Multiple logistic regression analyses of factors associated with margin status were performed. RESULTS: One hundred thirty-two (56%) patients had positive or close (unsatisfactory) margins; this rate increased from 51% in 1991 to 59% in 1996. Patients with unsatisfactory margins underwent more procedures (mean 2.0 versus 1.2; P <0.0001) than patients whose margins were satisfactory. The breast conservation rate for patients with unsatisfactory margins was 64% compared with 99% for patients with satisfactory margins. A multiple logistic regression demonstrated that patients with unsatisfactory margins were 67 times more likely to have a mastectomy than patients whose margins were satisfactory after adjusting for other significant factors (P <0.0001). The practice of fine needle aspiration biopsy, orientation of specimen margins by the surgeon, and reexcision of tumor at the first operation were statistically significant technical factors in obtaining satisfactory margins. Significant pathology factors were extensive intraductal component (EIC), lobular or ductal extension, and tumor size. CONCLUSION: These data show that technical factors in the surgical management of breast cancer, as well as biological factors such as EIC, can influence the success of breast conservation.

Endoscopic biopsy pathology of Helicobacter pylori gastritis. Comparison of bacterial detection by immunohistochemistry and Genta stain.

OBJECTIVES: To describe the endoscopic biopsy pathology of Helicobacter pylori gastritis, compare bacterial detection by immunohistochemistry using a specific antibody with the Genta stain, and to compare the relative costs of the 2 techniques. DESIGN: One hundred cases of gastritis identified as positive for H pylori by Genta stain and 100 cases considered negative by the same technique were stained using an anti-H pylori-specific polyclonal antibody. Laboratory reagent and labor costs for the 2 methods were compared. RESULTS: Chronic active gastritis with lymphoid follicles was significantly associated with H pylori infection (P <.0001). The immunohistochemical method had a sensitivity of 97% and a specificity of 98% compared with the Genta stain, with strong agreement for grading density of organisms (kappa = 0.85; P <.001). Reagent costs were similar for both methods, but immunohistochemistry using an autoimmunostainer required less dedicated technical time and hence was less expensive than the Genta stain. CONCLUSIONS: Immunohistochemistry using a specific antibody is an accurate and cost-effective method for H pylori detection in gastric biopsies.

The 'primeless pump': a novel technique for intraoperative blood conservation.

PURPOSE: Hemodilution during cardiopulmonary bypass may lead to anemia requiring intraoperative transfusions. Prime removal from the cardiopulmonary bypass circuit was used to limit dilution and intraoperative transfusions. METHODS: The technique of prime removal consists of arterial and then venous side evacuation of crystalloid prior to cardiopulmonary bypass. The effectiveness of this technique, to maintain a higher hematocrit and reduce intraoperative transfusions, was studied prospectively in two consecutive groups of patients undergoing coronary revascularization (controls versus primeless). RESULTS: Intraoperative hematocrits were significantly higher (P < 0.0001) and transfusions lower (4%) in the primeless versus the control group (19%) (P = 0.003). Prime removal is of particular benefit in anemic (hematocrit < or = 35%) and/or small patients (body surface area < or = 2 m2). CONCLUSION: The technique of prime removal is simple, safe and cost-effective, reducing intraoperative transfusions, especially in small and/or anemic patients. It could be part of blood conservation strategies in most adult cardiac operations.

Use of extrafascially harvested radial artery for coronary artery revascularization: technical considerations.

BACKGROUND: The use of the radial artery for coronary artery revascularization was abandoned due to its tendency for spasm; the revival was attributed to improved harvesting technique as well as the use of calcium channel blockers. METHODS: Between February 1996 and June 1997, the radial artery graft was used in 77 of 89 consecutive patients undergoing coronary artery bypass graft surgery. Only the patients with positive Allen's test or forearm deformity were denied the use of the radial artery. We used an extrafascial, no-touch technique using low-strength electrocautery for harvesting the radial artery. Calcium channel blockers were not used in any of these patients. RESULTS: There were no early deaths. No patient sustained perioperative myocardial infarction or required intra-aortic balloon pump. Only one patient required inotropic agents. Three noncardiac late deaths occurred during the follow-up of 6 to 24 months. No early or late ischemic or functional forearm disability was reported in any of the patients. CONCLUSIONS: The radial artery is easy to harvest and safe to use routinely. When harvested extrafascially, diltiazem infusion may not be necessary. Maximal arterial-global revascularization using the left internal thoracic artery-to-left anterior descending coronary artery and radial artery-to-circumflex artery system may improve the early and long-term results.

Reoperative median sternotomy using a cast spreader.

Repeat median sternotomy carries a high mortality rate secondary to a higher incidence of injury to the underlying vital structures. The reported incidence of reentry accidents may be as high as 6% to 10%. We describe a new technique of redo sternotomy using a nitrogen-powered oscillating saw and a cast spreader. The new technique was used for 89 consecutive cases without any incidence of injury to the underlying structures. The use of a case spreader during repeat median sternotomy may enhance the safety of reentry.

Basic fibroblast growth factor stimulates angiogenesis in the hindlimb of hyperglycemic rats.

Angiogenic growth factors including basic fibroblast growth factor (bFGF) have therapeutic value for chronic ischemia in nondiabetic animals. However, angiogenic therapy for chronic ischemia in a background of diabetes remains unexplored. In the present study, we evaluated the effects of exogenous bFGF on angiogenesis in streptozotocin-induced diabetic rats with ischemic and nonischemic limbs. We produced ischemia of the left lower limb by excising the superficial femoral artery. At 2 weeks, the rats received an intramuscular injection of vehicle (group A), 0.3 microg bFGF/day (group B), or 1 microg bFGF/day (group C), daily for 2 weeks. At 4 weeks, we assessed limb angiogenesis by skeletal muscle capillary density (cap/mm2) and capillary per muscle fiber ratio (cap/F) counts. Group C had significantly higher mean levels compared to group A for calf capillary density (P < 0.0024) and capillary per muscle fiber ratio in both thigh (P < 0.0015) and calf (P < 0.0001). There was a trend toward increased mean capillary per muscle fiber ratio with increasing dose. This trend was significant in the calf (P < 0.0015) and just missed statistical significance in the thigh. There was a similar trend in calf capillary density. We conclude that exogenous bFGF enhances angiogenesis and, possibly, collateral circulation in ischemic limbs of diabetic rats.

Long-term complications associated with prosthetic repair of incisional hernias.

OBJECTIVE: To determine whether the type of prosthetic material and technique of placement influenced long-term complications after repair of incisional hernias. DESIGN: Retrospective cohort analytic study. SETTING: University-affiliated hospital. PATIENTS: Two hundred patients undergoing open repair of abdominal incisional hernias with prosthetic material between 1985 and 1994. INTERVENTIONS: Four types of prosthetic material were used and placed either as an onlay, underlay, sandwich, or finger interdigitation technique. The materials were monofilamented polypropylene mesh (Marlex, Davol Inc, Cranston, RI), double-filamented mesh (Prolene, Ethicon Inc, Somerville, NJ), expanded polytetrafluroethylene patch (Gore-Tex, WL Gore & Associates, Phoenix, Ariz) or multifilamented polyester mesh (Mersilene, Ethicon Inc). MAIN OUTCOME MEASURES: The incidence of recurrence and complications such as enterocutaneous fistula, bowel obstruction, and infection with each type of material and technique of repair were compared with univariate and multivariate analysis. RESULTS: On univariate analysis, multifilamented polyester mesh had a significantly higher mean number of complications per patient (4.7 vs 1.4-2.3; P<.002), a higher incidence of fistula formation (16% vs 0%-2%; P<.001), a greater number of infections (16% vs 0%-6%; P<.05), and more recurrent hernias (34% vs 10%-14%; P<.05) than the other materials used. The additional mean length of stay to treat complications was also significantly longer (30 vs 3-7 days; P<.001) when polyester mesh was used. The deleterious effect of polyester mesh on long-term complications was confirmed on multiple logistic regression (P=.002). The technique of placement had no influence on outcome. CONCLUSION: Polyester mesh should no longer be used for incisional hernia repair.

Fluoroscopy-free placement of standard chest wall subcutaneous chronic venous access devices.

BACKGROUND: This study was undertaken to evaluate the potential benefits of using an electromagnetic detection system to guide the intraoperative placement of chronic venous access devices (CVADs). STUDY DESIGN: An electromagnetic detection system was used to guide catheter placement during 54 procedures. Surgery and radiation exposure times were recorded. An oncology nursing follow-up questionnaire assessed device function. A cost analysis was performed. Outcomes were compared to similar data from a fluoroscopic historical control group. RESULTS: Eight study patients required intraoperative fluoroscopy; in 46 procedures (85%) the electromagnetic detection system was the sole modality employed to guide CVAD placement. One line was subsequently found in the internal mammary vein (2% false negative rate). Mean surgery times for placement of CVADs were 79.5 and 84.5 minutes for the study and control groups (p = NS). Mean radiation exposure rates were 0.16 and 0.86 minutes per patient for the study and control groups (p < 0.01). There was no significant difference in device function between groups. Major complications in the study group were rare. Mean cost of CVAD placement was $1993 and $2517 for the study and control groups (p = 0.005), respectively. CONCLUSIONS: The use of the electromagnetic detection system resulted in accurate placement of chest wall CVADs in the majority of patients. This resulted in significant reductions in radiation exposure and cost of CVAD placement.

A prospective comparison of two expanded polytetrafluoroethylene grafts for linear forearm hemodialysis access: does the manufacturer matter?

BACKGROUND: The function and patency of standard 6-mm Goretex (W.L. Gore and Associates, Flagstaff, AZ) and Impra (Impra, Inc., Tempe, AZ) expanded polytetrafluoroethylene (e-PTFE) grafts for hemodialysis as radial-antecubital linear arteriovenous fistulae for dialysis are compared. STUDY DESIGN: A randomized clinical trial was conducted in two community dialysis centers and in one hospital-based center serviced by one vascular surgical practice, that performed the access surgery. Selection of linear forearm access, as opposed to other hemodialysis graft configurations, was at the discretion of the surgeon. Candidates for linear grafts had palpable radial pulses with a normal Allen test and normal digital Doppler flow in the hand. Linear grafts were placed using end-to-side anastomoses to the artery and vein, and the graft type was determined by randomization. Primary patency was determined by first episode of thrombosis, first revision, or angioplasty of the graft. Secondary patency after thrombectomy, revision, or angioplasty was determined when the graft was no longer clinically usable, and a new graft needed to be placed as a parallel conduit in the forearm or in another site. Statistical analysis was by actuarial life-table methods. RESULTS: There were 131 linear forearm grafts in 117 patients. The Impra and Goretex groups were equally matched for gender and major risk factors, except for smoking, which was more common in the Goretex group. Minimum followup was 24 months. Life table primary patencies at 1 year (Impra 43%, Goretex 47%) and at 2 years (Impra 30%, Goretex 26%) were not statistically different (p = 0.78); secondary patency was also equal at 1 year (Impra 49%, Goretex 69%) and at 2 years (Impra 33%, Goretex 41%) (p = 0.15). Discontinuance of use of a patent graft, complications, episodes of thrombosis, and the need to replace the original graft occurred in the two groups without a statistically significant difference. CONCLUSIONS: In the linear forearm position from the radial artery to an antecubital vein, there is no difference in the performance of 6-mm standard e-PTFE grafts on the basis of manufacturer, whether Goretex or Impra. On the basis of performance, linear forearm dialysis grafts are an acceptable method for hemodialysis access.

Long-term functional status and mortality of elderly patients with severe closed head injuries.

OBJECTIVE: To evaluate long-term clinical outcome of elderly patients with severe closed head injuries. DESIGN: Retrospective study. PATIENTS AND METHODS: All patients older than 65 years of age admitted to a regional trauma center with a diagnosis of closed head injury and an admission Glasgow Coma Scale (GCS) score of 8 or less. Using chi 2 analysis, Student's t test, and multiple logistic regression, we correlated age, sex, mechanism of injury, pupillary reactivity, alcohol and drug use, admission GCS score, Injury Severity Score, Revised Trauma Score, heart rate, and blood pressure to the main outcome measures, i.e. long-term functional outcome and mortality. RESULTS: Among 40 elderly patients who met the criteria, 27% were still alive at the end of 38 +/- 3 month follow-up. Eighty-five percent of patients who were discharged from the hospital were still alive long-term, but did not show significant neurologic improvement. In a univariate analysis, GCS and pupillary reactivity were predictive for long-term functional outcome and mortality. In a multivariate analysis, GCS and heart rate were predictive. All patients with an admission GCS score of 3 died in-hospital. All patients with an admission GCS score of 3 to 7 were either deceased or lived in persistent vegetative or dependent functional states. CONCLUSIONS: Elderly patients with severe closed head injuries have high in-hospital mortality. Those who survived the hospital stay had high long-term survival, but did not show significant functional improvement. Prediction of long-term functional status is vital to the trauma care of elderly patients with severe closed head injuries.

[10 year results of preoperative radiotherapy in treatment of rectal carcinoma]. / 10-Jahres-Ergebnisse der präoperativen Radiotherapie in der Behandlung des Rectumcarcinoms.

BACKGROUND: We have previously reported improvements in survival and disease-free survival at five years using preoperative radiation in the treatment of rectal cancer. The current update was undertaken to determine if these favorable results were durable with longer follow-up. METHODS: Patients found to have resectable rectal cancer between 1972 and 1979 were treated with 40-45 Gy of preoperative radiation (40 patients) or resection alone (109 patients). Follow-up information beyond five years was obtained from the Tumor Registry, physician contact and a survey of the National Death Index. Of the 149 patients followed for five years, 144 were evaluable at ten years. RESULTS: After a median follow-up of 125 months, survival of the irradiated patients was significantly better than that of controls (77 versus 57% at 5 years and 74 versus 41% at 10 years, p = 0.0044). Disease-free survival of those patients whose resection margins were free was also superior for the irradiated group (85 versus 59% at 5 years and 80 versus 45% at 10 years, p = 0.0045). CONCLUSIONS: The results show that the survival advantage for 40 to 45 Gy preoperative radiation in the treatment of rectal cancer persist at 10 years follow-up.