Technology assessment of anaesthesia monitors: problems and future directions

Specific factors have limited the interpretation of studies regarding the efficacy, effectiveness and efficiency of technology in anaesthesia. Some of these problems are reviewed, including the lack of specific outcomes necessitating the use of intermediate measures (e.g., hypoxaemia, myocardial ischaemia), which are not necessarily related to ultimate patient outcomes. This emphasizes the need for anaesthesia investigators to define fundamental issues specifically and design studies accordingly. With respect to anaesthesia monitors, the “lead time” or early warning provided by a monitor relative to that required to alter therapy effectively needs to be defined better and compared with the “lead time” without the monitor. After defining the benefit of a monitor, investigators should analyze the cost relative to alternatives (cost-benefit and cost-effectiveness). A hierarchical model to guide technology assessment is presented that addresses in order, the scientific basis of the technology, and the influence on the patient followed by societal issues. Anaesthetists have relied on traditional methods of technology assessment adopted from other disciplines. These methodologies do not address specific issues related to anaesthesia practice (such as “lead time”). In defining problems specific to the specialty of anaesthesia, new outcome measures that focus on the human factors related to decision-making in the operating room need to be developed. Future evaluations of anaesthesia technology require innovative approaches that address specific anaesthesia-related problems. One such approach is the use of simulation-based studies of response patterns to critical incidents.     

Effects of different types of diet and sodium saccharin on proliferation at the limiting ridge of the rat forestomach

Sodium saccharin, at high doses in the diet, has been reported to cause hyperplasia of the forestomach (squamous portion of stomach), at the limiting ridge in F344 rats, in addition to its potential to induce proliferative effects on the urinary bladder epithelium. We have characterized this hyperplasia of the squamous epithelium of the forestomach at the limiting ridge in F344 and Sprague-Dawley rats given various doses of sodium saccharin for 4 to 95 wk. With increasing doses of sodium saccharin, the limiting ridge of the forestomach showed dose-related morphological changes: basal-cell hyperplasia, early papillary hyperplasia with basal-cell hyperplasia and papillary hyperplasia. Calcium saccharin in Prolab diet caused hyperplasia of the forestomach at the limiting ridge, similar to that caused by sodium saccharin. The severity of hyperplasia was influenced by the type of diet and by the strain of rats. AIN-76A diet without added sodium saccharin caused basal-cell hyperplasia in F344 rats, whereas Prolab, Purina and NIH-07 diets without added sodium saccharin had little or no effect on the forestomach. The effect of AIN-76A diet alone persisted through 95 wk of feeding without any evidence of tumour formation. In Sprague-Dawley rats, which appeared more sensitive to effects on the forestomach than F344 rats, Prolab 3200 and Purina diets without sodium saccharin caused basal-cell hyperplasia in more than half of the treated rats. The forestomach hyperplasia associated with AIN-76A or saccharin administration appears to be mild, limited in extent to the limiting ridge, and not associated with carcinogenesis.     

Canine, but not rat bladder contracts to serotonin via activation of 5HT2 receptors

Serotonin is a biogenic amine that can exert multiple effects on smooth muscle, including smooth muscle of the genitourinary tract; effects that may be species dependent. The present study using isolated tissues documents potent contractile responses to serotonin in canine bladder smooth muscle. Contractile responses to serotonin in canine bladder could be mimicked by alpha-methyl serotonin, a selective 5HT2 receptor agonist. In fact, although alpha-methyl serotonin was slightly less potent as a contractile agonist relative to serotonin, the contractile response to alpha-methyl serotonin was more persistent as evidenced by a greater recovery time to resting force following washout. In contrast, the 5HT1A receptor agonist, 8-OH-DPAT and the 5HT3 selective agonist, 2-methyl serotonin, did not markedly contract canine bladder. These data establish that contractile responses to serotonin in the canine bladder are mediated by activation of 5HT2 receptors. We further demonstrated that the 5HT2 receptor antagonist, LY53857, potently inhibited the contractile response to both serotonin and alpha-methyl serotonin in the canine bladder consistent with agonist activation of 5HT2 receptors. In contrast to the potent response to serotonin observed in the canine bladder, rat bladder preparations did not markedly contract in response to serotonin, alpha-methyl serotonin, 8-OH-DPAT, or 2-methyl serotonin. Thus, these studies reinforce the marked species variability in responsiveness to serotonin and indicate that contraction to serotonin in the canine bladder is mediated by activation of the 5HT2 receptor.     

Peripheral retinal neovascularization and rubeosis iridis after a bilateral circular buckling operation

This report describes a young high-myopic patient who developed rubeosis iridis with peripheral retinal neovascularization one year after a circular buckling operation. Subsequently, vitreous bleeding and exudation led to traction retinal detachment which was treated successfully by anterior vitrectomy and cryopexy. It is suggested that this case represents a mild form of anterior-segment ischemia, combined with peripheral retinal ischemia.     

Detection of Bacteroides fragilis Enterotoxin Gene by PCR

Bacteroides fragilis constitutes about 1% of the bacterial flora in intestines of normal humans. Enterotoxigenic strains of B. fragilis have been associated with diarrheal diseases in humans and animals. The enterotoxin produced by these isolates induces fluid changes in ligated intestinal loops and an in vitro cytotoxic response in HT-29 cells. We developed a nested PCR to detect the enterotoxin gene of B. fragilis in stool specimens. After DNA extraction, a 367-bp fragment was amplified with two outer primers. The amplicon from this reaction was subjected to a second round of amplification with a set of internal primers. With these inner primers, a 290-bp DNA fragment was obtained which was confirmed as part of the B. fragilis enterotoxin gene by Southern blotting with a nonradioactive internal probe and a chemiluminescence system. By this approach, B. fragilis enterotoxin gene sequences were detected in eight known enterotoxigenic human isolates and nine enterotoxigenic horse isolates. No amplification products were obtained from DNA extracted from 28 nonenterotoxigenic B. fragilis isolates or B. distasonis, B. thetaiotaomicron, B. uniformis, B. ovatus, Escherichia coli, or Clostridium difficile. The sensitivity of this assay allowed us to detect as little as 1 pg of enterotoxin DNA sequences or 100 to 1,000 cells of enterotoxigenic B. fragilis/g of stool. Enterotoxin production of all isolates was confirmed in vitro in HT-29 cells. A 100% correlation was obtained between enterotoxin detection by cytotoxin assay and the nested PCR assay. This rapid and sensitive assay can be used to identify enterotoxigenic B. fragilis and may be used clinically to determine the role of B. fragilis in diarrheal diseases.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer''s disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups has smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey

 The behavioral effects of GBR 12909, a selective dopamine uptake inhibitor, were determined in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of stimulus termination and a second-order schedule of IV drug self-administration. Intermediate doses of GBR 12909 increased FI response rate markedly, and the highest dose decreased response rate below control values. The 5HT uptake inhibitors, alaproclate and fluoxetine, and the 5HT agonist, quipazine, attenuated the behavioral-stimulant effects of GBR 12909, whereas the 5HT_2A/2C antagonist, ritanserin, enhanced the behavioral-stimulant effects of the lowest dose. GBR 12909 reliably maintained self-administration, and ritanserin increased response rate maintained by the highest dose. The dopamine agonist, quinpirole, increased FI response rate in only one of three subjects, and ritanserin enhanced the behavioral-stimulant effects of quinpirole in that subject. The dopamine agonist, apomorphine, only decreased FI response rate, and ritanserin did not alter its behavioral effects. The pharmacological profile of GBR 12909 administered alone and in combination with selective 5HT drugs in the present study was similar to that obtained previously with cocaine, further demonstrating that 5HT can reliably modulate the behavioral effects of psychomotor stimulants with prominent dopaminergic actions. Received: 9 July 1996 / Final version: 22 November 1996