Continuous-infusion cisplatin, 5-fluorouracil, and bolus methotrexate in the treatment of advanced non-small cell lung cancer.

BACKGROUND. Cisplatin and 5-fluorouracil have noted synergy in preclinical systems. The authors combined methotrexate with infusional cisplatin and 5-fluorouracil in an attempt to produce a regimen with improved activity in advanced NSCLC. METHODS. Twenty-six ambulatory patients with previously untreated non-small cell lung cancer were treated with continuous-infusion cisplatin (25 mg/m2/day for 5 days), 5-fluorouracil (800 mg/m2/day for 5 days), and intermediate-dose methotrexate (200 mg/m2 on days 15, 22), followed by leucovorin rescue (PFM regimen). RESULTS. Patients received a median of four cycles of therapy. Two patients had a complete response, and 10 had a partial response (overall response rate, 46.2% or 12 of 26). The median time to treatment failure was 22.5 weeks; the median survival was 55 weeks from the start of chemotherapy. There were no toxic deaths attributed to chemotherapy. Thrombocytopenia was the only Grade 4 toxicity (27%). Grade 1/4 and 2/4 peripheral neuropathy occurred in 17 of 26 patients (66%) and was associated with a cumulative cisplatin dose of more than 300 mg/m2. CONCLUSIONS. PFM (using continuous-infusion cisplatin) produced a high response rate but resulted in an high incidence of low-grade peripheral neuropathy.     

Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia.

BACKGROUND AND PURPOSE: Neutrophils are critically involved with ischemia and reperfusion injury in many tissues but have not been studied under conditions of reperfusion after focal cerebral ischemia. The present studies were conducted to confirm our previous observations quantifying neutrophils in rat permanent focal stroke using a myeloperoxidase activity assay and to extend them to transient ischemia with reperfusion. In addition, leukotriene B4 receptor binding in ischemic tissue was evaluated as a potential marker for inflammatory cell infiltration. METHODS: Histological, enzymatic, and receptor binding techniques were used to evaluate neutrophil infiltration and receptor binding in infarcted cortical tissue 24 hours after permanent middle cerebral artery occlusion (n = 25) or temporary occlusion for 80 (n = 12) or 160 (n = 22) minutes followed by reperfusion for 24 hours in spontaneously hypertensive rats. RESULTS: Sham surgery (n = 26) produced no changes in any parameter measured. After permanent middle cerebral artery occlusion, neutrophil accumulation was observed histologically, but the infiltration was moderate and typically within and adjacent to blood vessels bordering the infarcted cortex. After temporary middle cerebral artery occlusion with reperfusion, marked neutrophil infiltration was observed throughout the infarcted cortex. Myeloperoxidase activity was increased (p less than 0.05) after permanent occlusion and to a greater extent after temporary occlusion with reperfusion. Myeloperoxidase activity (units per gram wet weight) in ischemic cortex was increased over that in nonischemic (control) cortex 32.2-fold, 54.6-fold, and 92.1-fold for permanent occlusion and 80 and 160 minutes of temporary occlusion with reperfusion, respectively (p less than 0.05). Sham surgery produced no changes in myeloperoxidase activity. Leukotriene B4 receptor binding also was increased (p less than 0.05) after focal ischemia and paralleled the increases in myeloperoxidase activity. Ischemic cortex-specific receptor binding (femtomoles per milligram protein) was 3.87 +/- 0.63 in sham-operated rats and 4.57 +/- 0.98, 8.98 +/- 1.11, and 11.12 +/- 1.63 for rats subjected to permanent occlusion and 80 and 160 minutes of temporary occlusion with reperfusion, respectively (all p less than 0.05 different from sham-operated). Cortical myeloperoxidase activity was significantly correlated with the degree of cortical leukotriene B4 receptor binding (r = 0.66 and r = 0.79 in two different studies, p less than 0.01). CONCLUSION: These data indicate that neutrophils are involved in focal ischemia and that there is a dramatic accumulation of neutrophils in infarcted tissue during reperfusion that can be quantified using the myeloperoxidase activity assay. Leukotriene B4 receptor binding increases in infarcted tissue in a parallel manner, which suggests that the increased leukotriene B4 binding is to receptors located on the accumulating neutrophils.     

Unplanned admissions after outpatient cardiac catheterization

Increasing numbers of patients are undergoing diagnostic catheterization as outpatients; however, a small proportion of patients requires hospital admission following the procedure. Unplanned admissions after consecutive outpatient cardiac catheterizations performed during 1 year were prospectively reviewed to determine the incidence of and reasons for admission. Among 847 patients undergoing outpatient cardiac catheterization, 130 patients (15%) required hospital admission after the procedure. Admitted patients were divided into four groups: patients undergoing immediate percutaneous transluminal coronary angioplasty (PTCA) (Group 1; 33%), patients with severe cardiac disease requiring urgent intervention (Group 2; 48%), patients suffering complications or hemodynamic instability (Group 3; 15%), and patients whose procedures were completed too late to allow same-day discharge (Group 4; 4%). Patients over 65 were more likely to require admission and women were more likely to be admitted with complications or hemodynamic instability. Findings are compared with results of other outpatient series, and implications regarding appropriate setting for outpatient catheterization are discussed.     

Differential binding of P. aeruginosa and S. aureus to corneal epithelium in culture

Adherence of bacteria to corneal epithelium is a prerequisite for corneal infection. We used two methods to study the binding of Pseudomonas aeruginosa and Staphylococcus aureus to rabbit corneal epithelial cells in culture. In the first method, rabbit corneal epithelial cells grown on glass slides were incubated with P. aeruginosa or S. aureus (10(7) CFU/ml) at room temperature for 90 min, and the bacterial binding to the epithelial cells was examined by light microscopy. Both P. aeruginosa and S. aureus bound to epithelial cells. P. aeruginosa was bound to the cell periphery whereas S. aureus was bound randomly to the cell surface. In the second method, suspension cultures of corneal epithelial cells were used. In contrast to the findings in cultures on slides, binding pattern with cells in suspension was similar for both species and resembled that for S. aureus in cultures on slides. A much greater number of P. aeruginosa (186 +/- 11 bacteria/epithelial cell) than S. aureus (30 +/- 1.5 bacteria/epithelial cell) bound to epithelial cells grown on glass slides. In contrast, a similar number of P. aeruginosa (25 +/- 5.1) and S. aureus (20 +/- 4.7) bound to epithelial cells grown in suspension cultures. Using either method, Escherichia coli and Streptococcus pyogenes did not bind significantly (less than 5/cell) to corneal epithelial cells. The above methods should prove useful for characterization of bacterial binding to corneal epithelial cells in culture.     

Videothoracoscopy in the treatment of early empyema: an initial experience.

Seventeen consecutive patients were referred for management of empyema between April 1991 and March 1992. Fourteen patients defined as having an 'early' empyema were initially treated by videothoracoscopy. The other three patients, defined as having a 'late' empyema proceeded directly to thoracotomy. Videothoracoscopy was successful in 10 out of the 14 patients. The mean postoperative stay was 7.8 days. At a mean follow-up at 16.7 months, these patients were rendered apyrexial with full lung expansion and no residual pleural collection. The postoperative results were at least equivalent to other conventional forms of treatment without an undue level of complications. In this series, thoracoscopy was found to be successful when symptoms had been present up to 31 days before presentation at the first hospital, and the mean length of treatment before referral to Harefield was 47 days. It is now our policy to videothoracoscope all patients with empyema thoracis, regardless of the length of referral. It may circumvent the need for a thoracotomy, it does not add any increased risk of complications, and does not appreciably increase the length of hospital stay should thoracotomy ultimately be required.     

P07Reduction of Allogeneic Red Cell Transfusion using Autologous Blood Cell Salvage in Knee Arthroplasty

Recent Hospital Transfusion Committee (HTC) audit at the Royal Bournemouth Hospital (RBH) confirmed an allogeneic red cell transfusion rate of 20% for primary Total Knee Replacement (TKR). Current policy at RBH states that when blood stocks reach 67% of normal (amber alert) then surgery with a >20% likelihood of blood transfusion will be cancelled. At current transfusion rates this would include primary TKR. Recent studies have shown a reduction in allogeneic transfusion rates when autologous transfusion drains are utilized. The purpose of this study was to see whether the current rate of allogeneic transfusion could be reduced with the introduction of the CellTransTM Autologous Knee Drainage Blood Transfusion System (ABT) in TKR at RBH. Over a 3 month period all patients undergoing primary, bilateral or revision knee arthroplasty received an ABT. Demographic data was collected from the orthopaedic pre‐assessment clinic. Following surgery further data was collected relating to volume of blood loss into the drain, volume of autologous blood re‐transfused, units of allogeneic blood required and the transfusion trigger, postoperative haemoglobin levels, infection rates and length of stay in hospital. We then compared this data set with retrospective data. Of 170 patients undergoing knee arthroplasty 141 received the ABT. The data collected was compared retrospectively with 169 patients from the previous 3 month period. We demonstrated a reduction in transfusion rates of 13% for primary TKR, 42% for bilateral TKR and 57% for revision TKR with the use of the ABT. In addition we demonstrated a reduction in total allogeneic blood use (99 units to 26 units) and a reduction in mean length of stay in hospital (8.6 days to 7.5 days) with the ABT. Further analysis of the data collected showed a 46% reduction in the allogeneic transfusion rate and a reduction in total allogeneic blood usage (99 units to 9 units) of anaemic patients presenting for surgery. This study has demonstrated a dramatic reduction in allogeneic blood transfusion rates with the use of the CellTransTM Autologous Blood Transfusion System. We have also shown a reduction in length of stay in hospital. Prior to the study primary total knee replacement would have been cancelled during times of limited blood availability (amber alert). The use of the ABT is good for the patient in reducing the need for allogeneic blood, and in addition has demonstrated a significant cost saving due to the reduced blood usage and potential prevention of cancelled operation lists.