Biomedical subjects
A Livingstone
Publications and source records attributed to A Livingstone.
The radiosensitivity of human neuroblastoma cells estimated from regrowth curves of multicellular tumour spheroids.
Multicellular tumour spheroids may provide a suitable in-vitro model for micrometastases in vivo. In this paper, the results are reported of experimental studies on the radiation response of two lines of spheroids derived from human neuroblastoma. Spheroids of approximately 200-250 microM mean diameter were exposed to graded doses of X rays (50-350 cGy) and, following a static or regression phase, regrew at rates which approximated those of unirradiated spheroids. Clonogenic surviving fraction was estimated, at each dose level, by extrapolation of the regrowth curve to zero dose. It is proposed that this procedure is more suitable for regrowth curves of spheroids than in-vivo tumours, because of the absence in vitro of complicating factors which occur only in vivo. By this means, survival curves were deduced and were found (for both cell lines) to be almost exponential in form, with little indication of capacity for accumulation of sublethal damage (multitarget parameters: DQ values: 17 and 25 cGy; Do values: 104 and 81 cGy respectively). These results contribute to the evidence for high radiosensitivity of neuroblastoma cells in vitro and provide a rationale for the use of hyperfractionation in the clinical treatment of neuroblastoma by radiotherapy.
Decreased biliary excretion of cefamandole after percutaneous biliary decompression in patients with total common bile duct obstruction.
The biliary penetration of cefamandole was studied in six patients with total biliary obstruction before and after placement of a transhepatic bile drainage catheter. Biliary levels of cefamandole remained depressed even when the drug was administered as late as 7 days after decompression of the biliary tract.
Ampicillin versus cefamandole in biliary tract surgery. A prospective, randomized clinical and bacteriological study.
A prospective, randomized study was conducted on 219 surgical patients with biliary tract disease. There were 100 patients undergoing elective biliary surgery, and 119 others with suspected biliary sepsis who were assigned to Prophylactic or Therapeutic clinical categories, then randomized into ampicillin or cefamandole treatment groups. Organisms resistant to the antibiotics given were found less often among patients in the cefamandole groups than among those in the ampicillin groups. No postoperative wound or intra-abdominal sepsis (IAS) occurred in the Prophylactic category. In the Therapeutic category there were two cases (3.2%) of wound and IAS in the ampicillin group and one case (1.8%) of wound infection in the cefamandole group. Overall, cefamandole showed superior coverage in vitro against the biliary flora, but both drugs were equally effective in maintaining a low incidence of postoperative sepsis as well as a minimal number of febrile or total hospital days. The authors suggest that the choice of antimicrobials may not be as critical as effective surgical management in the prevention of septic complications following biliary tract surgery.
Plea for clear labelling: amoxycillin prescribing information.
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A possible hepatic factor in the control of plasma free fatty acid levels.
Insulin acts as a regulator of lipid metabolism by inhibiting the rate of lipolysis. Hyperinsulinemia, produced by the peripheral infusion of glucose, therefore, causes a lowering of plasma free fatty acids (FFA) by decreasing the mobilization of fats from peripheral deposits. Based on previous studies, it was postulated that a lowering of plasma FFA could be produced, in the absence of hyperinsulinemia, by the infusion of glucose directly into the liver. This study was undertaken to investigate the existence of endogenous factors other than insulin, which inhibit lipolysis. It was determined that glucose at a dosage of 0.125 gm/kg/hr could be infused into the portal vein of dogs without increasing plasma insulin levels. This dosage significantly lowered plasma FFA levels when injected into the portal vein but had no effect on plasma FFA when infused peripherally. There were significant decreases in FFA turnover following portal glucose administration, with no changes in fractional turnover. This indicated that the lowered plasma FFA concentrations found following portal infusions of glucose, were due to reduced lipid mobilization from adipose tissue, rather than increased tissue uptake of FFA. These results suggested the existence of an hepatic factor, stimulated by portal glucose infusion, which lowered FFA mobilization from adipose tissue.
Early hepatic failure or upper gastrointestinal bleeding following a distal splenorenal shunt.
Hepatic failure and upper gastrointestinal bleeding following a distal splenorenal shunt is distinctly unusual. Should either or both of these complications develop in the immediate or early postoperative period, adequate angiographic studies should be done without delay so as to identify accurately the status of the portal and splenic venous systems. If an unligated coronary vein is apparent, transhepatic clotting should be accomplished. The presence of other major collateral vessels between the portal and splenic circulations may require surgical ligation. The presence of thrombosis of the portal vein represents a more serious problem, with thrombectomy and arterialization of the portal vein offering the best chance for survival in a patient with a deteriorating condition.
Therapeutic percutaneous aspiration of pancreatic pseudocysts.
The therapeutic efficacy and safety of percutaneous aspiration of chronic pancreatic pseudocysts was evaluated. Eight patients underwent aspiration a total of ten times. Permanent resolution was obtained in two patients and a third nonsurgical candidate was offered an alternative therapeutic modality. This procedure is simple, rapid, and safe and could become the initial approach to selected patients with a chronic pancreatic pseudocyst.
Biliary excretion of moxalactam.
The biliary excretion of moxalactam was studied in 11 postsurgery patients who had indwelling T-tubes inserted in their common bile ducts. Peak levels of moxalactam in the bile reached mean levels of 33.7 +/- 11.1 and 173.7 +/- 67.0 micrograms/ml 2 h after intravenous administration of a single 500- or 2,000-mg dose, respectively. In 5 of the 10 patients given the 2,000-mg dose, peak moxalactam concentrations in the bile were 2 to 12 times higher than simultaneous serum levels, but considerable variation in the biliary excretion of moxalactam was observed among the individual patients.
A longitudinal study of tryptophan involvement in hepatic coma.
Previous cross-sectional studies have demonstrated that hepatic coma is associated with abnormally high levels of plasma free tryptophan. Establishment of a more definitive relationship between this biochemical abnormality and hepatic coma requires an evaluation of biochemical changes in individual patients as they undergo alterations in the function of their central nervous systems. The present report is an evaluation of tryptophan and substances believed to influence its entry into the brain in six patients whose clinical status progressed from hepatic coma to complete recovery. Consistent significant decreases in plasma free tryptophan and free fatty acids were demonsrated to occur as the patients recovered. No consistent changes, however, were found in the plasma levels of the amino acids which have been reported to compete with tryptophan for transport across the blood-brain barrier, except for leucine which was significantly decreased in all six patients upon recovery from coma. Assay of lumbar cerebrospinal fluid for both tryptophan and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), showed no consistent changes as the patients recovered from hepatic coma.
Pancreatic duct ligation in the therapy of chronic pancreatitis.
Total ligation of the pancreatic ducts of a normal gland in dogs and man results in atrophy of the acinar cells with preservation of islet cell function. Theoretically, this might be applied in the therapy of chronic pancreatitis since, in effect, an exocrine pancreatectomy results. Sustained islet cell function, as evidenced by a normal glucose tolerance test, following pancreatic duct ligation, was demonstrated in dogs for periods of up to two years. Resection of the head of the pancreas and ligation of the distal gland in six patients with chronic pancreatitis and an abnormal glucose tolerance test resulted in the development of insulin-dependent diabetes in all instances. Insulin-dependent diabetes was also demonstrated in one patient with a normal preoperative glucose tolerance test. Recurrent pancreatitis developed in only one patient. The study suggests that pancreatic duct ligation is effective in treating chronic pancreatitis but casts considerable doubt on the effectiveness of this procedure in preventing the development of diabetes, if the glucose tolerance test is abnormal
Mutants of Acinetobacter calcoaceticus NCIB 8250 constitutive for the mandelate enzymes.
Methods for isolating mutants of Acinetobacter calcoaceticus NCIB 8250 constitutive for the mandelate enzymes were compared. Non-inducing substrates were not available. Continuous culture gave no stable constitutive mutants. Alternate culture in inducing (L-mandelate) and non-inducing (L-glutamate) media led to the isolation of mutants mesoconstitutive for L-mandelate dehydrogenase and phenylgloxylate carboxy-lyase, and hyperinducible for benzaldehyde dehydrogenase I. Screening of possible anti-inducers showed that 2-phenyl-propionate was very effective; it was a competitive inhibitor of gratuitous induction by thiophenoxyacetate, and was used for the isolation of constitutive mutants. Some of the mutants were magnoconstitutive for L-mandelate dehydrogenase, phenylglyoxylate carboxylyase and benzaldehyde dehydrogenase I and could not be further induced; others had lower specific activities which could be increased by induction with phenylglyoxylate or thiophenoxyacetate. Similar constitutive mutants were derived from a mutant which lacked L-mandelate dehydrogenase.
Tryptophan and hepatic coma.
To clarify the involvement of tryptophan in the pathogenesis of hepatic coma, plasma and cerebrospinal fluid (CSF) tryptophan was studied in three patient groups (hepatic coma, stable cirrhosis, and control). An assessment of free fatty acids, some of the amino acids reported to compete with tryptophan for brain uptake, and albumin was also made. The data demonstrated that, whereas the elevated CSF tryptophan levels in cirrhotic patients compared to controls may have been attributable to decreased plasma branched chain amino acids, the elevated CSF tryptophan levels in hepatic coma compared to stable cirrhotic patients were probably attributable to increased plasma free tryptophan concentrations. Associated with the elevated plasma free tryptophan in coma patients was an increase in plasma free fatty acids and a marked decrease in serum albumin levels. Of all the amino acids investigated in the CSF, only tryptophan was significantly increased in patients in hepatic coma compared to cirrhotic patients not in coma.
Evaluation of the effect of portal plasma on cerebral function - an animal model.
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An improved technique for total gastrectomy.
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Metabolism of monofluorobenzoates by Acinetobacter calcoaceticus N.C.I.B. 8250. Formation of monofluorocatechols.
None of the monofluorobenzoates serves as sole source of carbon and energy for growth of Acinetobacter calcoaceticus but all can contribute to growth on other substrates. The monofluorobenzoates are oxidised by bacteria pre-induced for benzoate oxidation and can themselves induce the appropriate enzymes. The initial products of oxidation have been separated and identified by gas-liquid chromatography. 2-Flurobenzoate is oxidised to catechol, fluoride and 3-fluorocatechol; 3-fluorobenzoate gives 3- and 4-fluorocatechol; 4-fluorobenzoate gives 4-fluorocatechol. The fluorocatechols appear to be partially oxidised beyond the stage of 3-oxoadipate by suitably pre-induced bacteria.
Immunologic diagnosis of human cancers.
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