Diaspirin crosslinked hemoglobin (DCLHb): characterization of the process and the product manufactured under GMP requirements for clinical studies.

Initiation of Clinical Trials in 1992 necessitated product manufacture under FDA Good Manufacturing Practice (GMP) requirements. To this end, all product components used were characterized to meet established requirements and processes and analytical methods were validated to confirm and document their utility and reproductibility. Manufacture of multiple 50+ liter lots of 10%g DCLHb under GMP requirements resulted in a pure and homogeneous product which reproducibly met a rigorous and complete set of product specifications. Final release testing of five consecutive GMP lots showed hemoglobin concentrations of 10.2 +/- 0.2g%, pH of 7.33 +/- 0.02 (37 degrees C), methemoglobin concentrations of 3.2 +/- 0.6%, degree of crosslinking of 99.8 +/- 0.1% and a P50 of 32.4 +/- 1.0 mmHg (37 degrees C). The mean overall yield for production of these five lots was 55 +/- 2%. Products were all endotoxin free as indicated by rabbit, cytokine and LAL testing (< 0.06 EU/mL); a critical characteristic for a molecule which may bind endotoxin. All lots were sterile as indicated by compendial testing.

Haematological effects of reinfused mediastinal blood after cardiac surgery.

OBJECTIVE: To explore the risk of inducing a coagulation defect in cardiac surgery patients by the reinfusion of mediastinal blood. DESIGN: Ten patients who underwent coronary artery surgery were prospectively studied for the haematological effects of reinfusion of blood drained from the chest drain tubes after the operation by a Sorenson autologous transfusion system. SETTING: Surgery was performed at a private hospital and patient selection was made at the time of reinfusion. PATIENTS: Nine patients had primary coronary artery surgery and one had a reoperation. MAIN OUTCOME MEASURES: Blood samples were taken from the patients before reinfusion, one hour after reinfusion, and 24 hours later as well as from the collected blood. Measurements were made of the haemoglobin content, white cell and platelet counts, fibrinogen and fibrinogen degradation products, D-dimer, antithrombin III and plasma haemoglobin content. Estimations were also made of the prothrombin time, the thrombin clotting time and the activated partial thromboplastin time. The hypothesis to be tested by this study was that the reinfusion of mediastinal blood after the operation did not cause any significant disturbance of the patient's blood clotting profile. RESULTS: An average of 535 mL (range, 400-950 mL) was reinfused after a period of three hours drainage (range, 45 minutes to 5 hours). While the initial patient samples contained a raised plasma haemoglobin level (0.19 g/L) significantly related to the cardiopulmonary bypass time (P less than 0.001), these were free of fibrinogen degradation products except for a sample from one patient who had a reoperation. The blood drained by the Sorenson system was lower in haemoglobin content (7.7 g/dL), and had a significant content of fibrinogen degradation products (147 mg/L) and D-dimer (6.4 mg/L) together with reduced clotting factors when compared with the patients' blood. After reinfusion, the patient sample showed evidence of altered coagulation with mildly increased clotting times (activated partial thromboplastin time 57 s, thrombin clotting time 123 s), the extent of which was related to the volume reinfused (P less than 0.001), but 24 hours later, these effects had all disappeared. All samples were sterile in aerobic and anaerobic culture media. CONCLUSION: We conclude that the Sorenson system of retrieval of mediastinal blood after cardiac surgery provides a safe and simple method of blood conservation provided that the volume of reinfusion is not excessive.

Pulmonary diffusing capacity as a predictor of performance in competitive swimming.

Pulmonary diffusing capacity has been noted by many investigators to be higher in championship swimmers than in average swimmers and in the non-swimming population. We measured pulmonary diffusing capacity (DLCO) and other parameters in 22 members of a collegiate swimming team and studied the relationship between pulmonary diffusing capacity and swimming performance. We also investigated change in lung function over a season of training and racing. Results suggested that while most good swimmers had above average diffusing capacities, there was no statistically significant difference in performance between those swimmers with high DLCO (greater than or equal to 110% predicted value) and those with a low DLCO (less than 100% predicted value). It was also determined that there was not a good correlation between performance (measured by either "best time" or "average time") and lung function (DLCO or VC).

Blood-conservation techniques for coronary-artery bypass surgery at a private hospital.

The utilization of homologous blood and blood products was recorded in 100 consecutive patients who underwent primary coronary-artery bypass surgery. Nine patients underwent saphenous-vein grafts only, 55 patients underwent a single internal-mammary-artery graft that was supplemented by vein grafts and 36 patients underwent bilateral internal-mammary-artery grafts and vein grafts. All patients underwent normovolaemic haemodilution, and autologous blood was collected before bypass surgery. Residual blood was collected from the cardiopulmonary bypass machine and was washed and concentrated in a cell processor, and blood also was scavenged postoperatively from the mediastinal drainage tubes as methods to conserve blood. The mean (+/- SD) utilization of homologous blood was 1.3 +/- 1.5 units with 0.2 +/- 0.7 units of fresh-frozen plasma being used, and 0.8 +/- 2.1 units of platelets being used. The utilization of homologous blood was not different among the three different methods of coronary-artery bypass surgery, but patients who underwent bilateral internal-mammary-artery grafts suffered a greater postoperative loss of blood than did those patients who underwent saphenous-vein grafts or single internal-mammary-artery grafts. A comparison of patients who were taking aspirin or a non-steroidal anti-inflammatory drug preoperatively with those patients who were not showed no difference in the utilization of homologous blood but a statistically-significant difference was found in the loss of blood postoperatively.

Combined measurement and significance of lipid-bound sialic acid and carcinoembryonic antigen in detection of human cancer.

We evaluated the clinical usefulness of lipid-bound sialic acid (LSA) as a "tumor marker" and assessed individual and carcinoembryonic antigen (CEA) in cancer patients. Serum LSA and CEA concentrations were measured by the resorcinol method after total lipid extraction and isolation of the sialolipid fraction, and by Abbott enzyme immunoassay procedures, respectively. Results indicate that the frequency of elevation and mean LSA values were highest in patients with lung cancer (318 mg/liter), intermediate in miscellaneous (210 mg/liter) and colorectal cancers (200 mg/liter), and lowest in breast cancer (175 mg/liter); while mean CEA values were highest in colorectal cancer (162.5 micrograms/liter), followed by lung (33.8 micrograms/liter), miscellaneous (30.3 micrograms/liter), and breast cancers (11.6 micrograms/liter). Statistically, LSA and CEA values for cancer patients were significantly (P less than 0.001) higher than for normal subjects. The combined measurement of LSA and CEA in serum provides better detection potential for cancer patients than either of the two markers alone.

Vectorcardiographic detection of early hemodynamic abnormalities in chronic obstructive pulmonary disease.

The ability of the vectorcardiogram to detect mild circulatory abnormalities in patients with chronic obstructive pulmonary disease (COPD) is unclear. Therefore, vectorcardiographic changes were correlated with hemodynamic measurements made at rest and during supine exercise in 32 patients with COPD and no clinical or electrocardiographic evidence of right ventricular hypertrophy. Twelve patients had normal hemodynamic data (group 1), nine had abnormal hemodynamic data only during exercise (group 2), and 11 had abnormal hemodynamic data at rest and during exercise (group 3). The extent of rightward terminal QRS forces noted on the vectorcardiogram was significantly less in group 1 (5.5 +/- 8.7 percent) than in either group 2 (19.0 +/- 10.7 percent) or group 3 (17.8 +/- 14.8 percent). Sixty-five percent (13) of the 20 patients with hemodynamic abnormalities had rightward terminal QRS forces of 15 percent or more, whereas only 8 percent (one) of the 12 patients with normal hemodynamic data had such forces of 15 percent or more. The mean of the rightward terminal QRS forces in 27 age-matched normal subjects was 5.0 +/- 5.4 percent, and only one subject had forces of 15 percent or more. We conclude that hemodynamic abnormalities are frequent in patients with COPD and no clinical evidence of right ventricular hypertrophy and that the vectorcardiogram provides an indirect method of detecting these abnormalities.

The frequency of middle phalangeal hair in Saudi Arabia.

Middle phalangeal hair was found to be present in 71% if Saudi Arabian males. For those exhibiting this trait, the frequency of combinations of digits with hair was similar to the frequency in other populations.

Calcium content and exchange in frog skeletal muscle.

Calcium content and exchange in frog ELD IV muscle were examined employing the efflux technique. 2. Muscle calcium was found to exchange with four time constants, 21-5 sec 2-7, 32 and 1244 min. 3. All calcium was found to be exchangeable with more than half the total amount residing in an extracellular compartment. 4. Results obtained from ELD IV muscles and single fibres were identical. 5. Muscle calcium content was found to remain constant up to 20 hr in vitro. 6. Extra exchange of calcium occurs upon contraction. This extra exchange appears to occur in the most slowly exchanging component. 7. The data are discussed in relation to morphological and autoradiographic findings and a model of calcium exchange in skeletal muscle is presented.