Reconstruction after excision of soft tissue sarcomas of the limbs and trunk

From a retrospective analysis of 180 surgical interventions for soft tissue sarcoma of the limbs and trunk, it was concluded that complete excision of the tumour can usually be achieved without sacrifice of major artery, vein, nerve or bone. In this series five major arteries were resected but only one required reconstruction. None of six resected major veins or seven resected nerves were reconstructed. Bone resection in the limb required plating in only two of eleven patients who had limb-sparing resection (there were nine amputations). Both in the limbs and the thorax, resection of bone often involved such a wide excision of the superficial soft tissues as to require a flap repair: four were used in the limbs and three in five chest wall resections. In the majority of operations (140/180) primary wound closure was possible. After 15 procedures for tumour predominantly involving the superficial tissues, split skin grafts were used. These were generally successful (13/15), even occasionally when high-dose radiotherapy had been given. In 16 cases earlier radiotherapy influenced the decision to use a flap repair. A total of 18 flap repairs were performed. In various situations Mersiline mesh (Ethicon, Ltd., UK), Silastic implants and omental swings were used. Wound breakdown in heavily irradiated tissues presented a major challenge for reconstruction. Although major reconstruction was required in only 27 operations (15 per cent), a thorough knowledge of the available methods of reconstruction and repair is essential to allow uninhibited resection with an optimal aesthetic and functional result.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Surgical considerations in bypassing coronary arteries with 100% proximal occlusion.

Objective data on the ability of cineangiography to predict the size of reconstituted totally occluded coronary arteries, as well as the clinical outcome of such revascularization, are sparse. Accordingly, we reviewed 200 consecutive cases of coronary revascularization to determine the answers to these questions. Group I patients (n = 57, with 86 totally occluded coronary arteries) had at least one coronary artery with a 100% proximal occlusion that reconstituted distally. Group II patients (n = 143, with 205 subtotally occluded coronary arteries) had 50% to 99% proximal stenosis of at least one coronary artery. Cineangiograms were blindly reviewed to measure the size of the coronary arteries, which were compared with the actual vessel size at operation. In group I, the totally occluded coronary arteries had a cineangiographic size of 1.9 +/- 0.7 mm and an actual size of 1.6 +/- 0.4 mm (p = 0.00004). In group II, the subtotally occluded coronary arteries had a cineangiographic size of 1.8 +/- 0.4 mm compared with an actual size of 1.8 +/- 0.3 mm (p = not significant). The site of bypass grafting was significantly smaller in group I (1.6 +/- 0.4 mm versus 1.8 +/- 0.3 mm; p = 0.00008). The two groups were similar with respect to preoperative and intraoperative parameters. Operative mortalities were similar (group I, 1.8%; group II, 3.5%; p = 0.68). Creatine kinase isoenzyme profiles and electrocardiographic changes were similar, except for a significant late rise of creatine kinase-MB in group I (56.1 +/- 14.7 versus 30.7 +/- 33.7 MIU/mL; p < 0.001). In conclusion, cineangiography significantly overestimates the size of totally occluded coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of Amonafide in dogs

Summary Amonafide, one of a series of imide derivatives of 1,8-naphthalic acid synthesized by Brana et al. [2] has shown significant antitumor activity against a variety of experimental tumors, including L1210 leukemia and P388 leukemia. Along with the clinical trial at our institute, we have studied the disposition of Amonafide in dogs by HPLC and fluorometry. Six dogs received Amonafide i.v. at 5 mg/kg (100 mg/m²) over 15 min; three were sacrificed at 6 h, and three at 24 h. The initial plasma t_1/2, of Amonofide was 2.4±0.4 min, the intermediate t_1/2, 26.8±3.7 min, and the terminal t_1/2, 21.7±4.0 h. the peak plasma concentration achieved was 6.3±1.7 g/ml. The average apparent volume of distribution was 12.84±0.541/kg, and the total clearance was 0.56±0.161/kg/h. In 24 h, 9.5%±0.2% of the administered dose was excreted in the urine as the parent drug, and 7.4%±1.4% in the bile in 6 h. Amonafide penetrated the CSF readily and achieved the highest concentration 20–25 min after administration, which was 30% of the concurrent plasma level. Amonafide underwent extensive metabolism to at least three major metabolites and two or more minor metabolites. The and plasma t_1/2 of the major metabolite, an N-oxide derivative, were 24.8 min and 28.6 h, respectively. The 24-h cumulative urinary excretion was 1.4% of the injected dose, and the cumulative biliary excretion was 16.7% in 6 h. At autopsy 6 h after dosing, the liver contained the highest percentage (0.23% of administered dose) of unchanged Amonafide, followed by the stomach (0.11%), lung (0.04%), kidney (0.04%), and pancreas (0.03%). The rest of the major organs retained less than 0.02% of the Amonafide dose. One day after dosing, no detectable amount of Amonafide was found in any of these tissues, indicating that Amonafide appears to be extensively metabolized and not significantly retained in the dog.     

Detection of haematoporphyrin derivative and haematoporphyrin excited states in cell environments

The photosensitiser currently used in the photodynamic therapy of cancer is haematoporphyrin derivative. Pulsed laser studies of this material and also of the "parent" molecule haematoporphyrin in polyoma-transformed fibroblast cells have now been studied. We report, for the first time, the observation of the triplet absorption of these sensitisers in cells. The corresponding triplet-triplet spectra are red shifted compared to aqueous buffer, lambda(max) 420 nm shifts to 460 nm. We also report our failure to observe singlet oxygen from the cells even though the triplet state can be seen to interact with the oxygen and even though singlet oxygen can be readily detected with the same sensitisers bound to serum albumin.     

Effect of two different types of malnutrition on the rate of elimination of ethanol in rats

Rats were fed "3% casein" or a "calorie deficient" diet, in the form of commercial pellet diet (SDS) at 50% of the amount consumed by the control group, which was fed SDS pellets ad libitum. Both of the deficient groups showed failure of weight gain in comparison with the control group. Blood levels of ethanol were measured for 3 hr after intraperitoneal injection of 1 or 1.5 g/kg at 15, 29 and 36 days after commencement of the diet. In addition the calorie deficient group was studied immediately after feeding as well as in the fasting state. Blood levels of ethanol were measured and the apparent volume of distribution and rate of removal of ethanol from the blood were calculated. A rate of ethanol metabolism/g of liver was derived. The rate of removal of ethanol was markedly decreased in the 3% casein group to less than half of control values. Three hours after injection of ethanol circulating levels were less than 50 mg/100 ml in the control and calorie deficient groups but over 200 mg/100 ml in the group fed protein deficient diets. There were no major changes in volume of distribution and the only explanation for the finding is that there is a failure of ethanol metabolism in the rats fed the low protein diet. The implication is that protein deficient human populations who often consume considerable quantities of ethanol may have a high level of tissue exposure to ethanol though the rate of metabolite formation may be low.     

Respiratory distress syndrome in second-born versus first-born twins. A matched case-control analysis

The well-known increased risk of the respiratory distress syndrome in a twin born second as compared with the twin born first is usually attributed to the second twin's predisposition to depression at birth ("asphyxia"). We analyzed the etiologic roles of birth order, presentation, and depression at birth in the development of the respiratory distress syndrome in matched case-control populations drawn from 221 preterm twin pairs. Among the 39 twin pairs discordant for respiratory distress syndrome, the second twin was the affected member in 31 pairs. Second birth order was the only independent risk factor, but only in vaginal deliveries (matched odds ratio, 14.2; 95 percent confidence interval, 2.5 to 81.1). Second twins delivered abdominally did not have an increased risk relative to first twins (odds ratio, 0.9; confidence interval, 0 to 17.8). When depression at birth was evaluated as an outcome variable, malpresentation, rather than birth order, was the major risk factor (independent matched odds ratios of 2.7 [confidence interval, 1.0 to 7.5] and 1.3 [0.7 to 2.5], respectively). Thus, second twins' increased risk of respiratory distress syndrome cannot be explained by a predisposition to depression at birth; a more important factor may be that second twins do not benefit from the salutary effects of labor to the same extent as first twins.     

Advantages of branched peptides in serodiagnosis. Detection of HIV-specific antibodies and the use of glycine spacers to increase sensitivity.

The reactivities of antibodies with branched and monomeric peptides were compared in ELISA assays. We found that lower amounts of antibodies could be detected with branched peptides than with monomeric peptides. This was observed with a monoclonal antibody and with antibodies in the sera of various HIV-positive individuals. To investigate the physical aspects of branched peptides important for the observed increase in sensitivity, glycine spacers of different lengths were introduced between the branched lysine core and the epitope reacting with the monoclonal antibody. The effect of the number of glycine residues, both on the sensitivity of antibody detection and on the amount of branched peptide needed to produce a given signal, was studied and the optimum was found at 4-5 residues. We discuss the basis for these findings and conclude that the routine use of branched peptides for serodiagnosis will give both greater sensitivity and appreciable cost savings.