Proteomics in pharmaceutical research and development.
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Biomedical subjects
Publications and source records attributed to W Man.
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A systematic review of the 2.1 mu holmium-YAG laser for gall stone lithotripsy was undertaken. This infrared laser, which can be used endoscopically and percutaneously, has safety advantages over other lasers and has potential as a general purpose vascular and surgical tool. Twenty nine gall stones (mean mass 1.3 g) were fragmented in vitro using pulse energies of 114 to 159 mJ/pulse at 5 Hz with a 0.6 mm fibre, while being held in an endoscopy basket. All stones were successfully fragmented, requiring an average of 566 pulses with a 5 Hz pulse repetition frequency. The number of pulses required increased with gall stone size and mass (p < 0.01), and decreased with both pulse energy (p < 0.01) and operator experience (p < 0.05). The biochemical content of the stone did not significantly affect the number of pulses needed. The potential hazard of the laser to the biliary endothelium was investigated. At the pulse energies used, five pulses at close contact penetrated into the serosa of fresh gall bladder wall. No damage was seen when two pulses were fired. This laser shows considerable promise in gall stone lithotripsy. Until further safety data are available, however, its use with endoscopic vision is advised.
Cefozopran (CZOP, SCE-2787), a new parenteral cephem, was evaluated for its antibacterial activity and clinical efficacy. CZOP, 24.0-78.0 mg/kg/day, was given to 11 pediatric patients in 3 dose a day via 30-minute drip infusion. Clinically evaluated were nine patients including 4 with acute pneumonia, 2 with urinary tract infections, 2 with lymphadenitis and 1 with sepsis. Two patients were excluded because of possible non-bacterial infections. Clinical efficacies were excellent in 5, good in 3 and fair in 1. Bacteriological responses were confirmed for 5 strains in 5 patients. Four strains were eradicated, but one strain was not. MICs of CZOP were equal to those of ceftazidime. Side effects or abnormal laboratory test results were observed in 3 patients; diarrhea in 1, elevated GPT in 1 and thrombocytosis in 1, but none of them was significant.
We have previously reported our findings of very high plasma histamine levels in the extracorporeal blood primes of infants undergoing cardiopulmonary bypass (CPB) for correction of congenital cardiac defects and have now extended this enquiry to examine the whole peri-operative period. In this preliminary study, samples of blood for plasma histamine were drawn from a mixed group of congenital cardiac patients featuring varying degrees of cyanosis, differing hypothermic operative conditions and utilising two oxygenator systems. Despite the diversity of this group a common pattern of histamine release emerged with a clear origin at the commencement of bypass, and continuing during the operative period. Our results suggest that priming procedures using stored donor blood provide a major contributing source of histamine release with inevitable deleterious consequences to the post-operative outcome.
Recently there has been a renewed interest in the neurosurgical treatment of large cerebral aneurysms and AV malformations utilising cardiopulmonary bypass (CPB) and total circulatory arrest (TCA). However, the differing tolerance limits of coagulation and bleeding, pH control and fluid constraint are difficult to reconcile. Although clinical assessment, electro encephalogram (EEG) and intracranial pressure-monitoring assist in identification of cerebral damage, CPB and TCA inflict their own penalties with resultant uncertainty in post-operative neurological evaluation, and producing difficulties in interpretation and management. Additionally, an unanswered question is, to what extent the known cardiac and cerebral effects of circulating histamine might influence the post-circulatory arrest recovery in these patients, and whether this would further compromise the neurological result. We report our experience of 9 such cases who underwent this procedure, and were able to achieve a satisfactory neurological result in 7 patients with differing lesions. During the operation both CSF (from the open cranium) and blood (from the right internal jugular vein) were sampled at intervals for subsequent plasma histamine estimation. Despite markedly elevated histamine levels during CPB and TCA, this was not associated with an unfavourable neurological outcome. These early findings have given us encouragement to the useful role of CPB and TCA in these complex neurosurgical presentations, and raise interesting questions about the clinical importance of histamine-evoked cerebral ischaemia that has been demonstrated in experimental models.
Recent studies have reported pathologically elevated plasma histamine levels in adult patients during and after open heart surgery. In paediatric practice, the increased use of donor-blood primes might be expected to produce even greater rises in the histamine levels, by creating histamine release in the prime before initial perfusion commences. The present study covered 40 arbitrarily chosen paediatric cases. Pathologically elevated plasma histamine levels (greater than 1 ng/ml) were found in the prime of 26 out of 37 cases (73%). Histamine levels were substantially higher than levels encountered in previously reported studies, and massively elevated prime histamine levels (greater than 80 ng/ml) were encountered in 9 out of the 40 cases (22%). These results suggest that in conventional paediatric cardiac surgical practice, the prime content of histamine is markedly elevated in the majority of patients. The inevitable delivery of this prime histamine load at the onset of perfusion might be expected to produce systemic pathological effects.
A model for the production of gastric mucosal haemorrhages and ulcers, similar in morphology and distribution to those seen in stress states in man, has been produced by the intraperitoneal injection of adrenaline in single, double or treble doses of 0.6 mg/kg. Lesions were produced in 2 or 3 h, without ligation of the pylorus. Severe mucosal changes were associated with a fall in gastric mucosal histamine concentration. Mucosal serotonin did not change. Rises in mucosal adrenaline were accompanied by a fall noradrenaline, total catecholamine levels being unchanged.
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