Clinical and experimental studies of intraoperative autotransfusion using a new filtration device

The Haemocell S-350 device has recently been introduced for intraoperative autotransfusion. The system uses a novel membrane filter to process shed blood. In the first part of this study a 0.2-micron pore size filter was used in a randomized trial comparing the use of autotransfusion (n = 8) with bank blood controls (n = 9) during aortic reconstruction. This part of the trial was abandoned because of unexpected non-surgical bleeding. Bank blood requirements fell from a median of 3.0 (range 0.0-9.0) units to 1.5 (range 0.0-7.0) units when autotransfusion was used, but these patients had a greater perioperative blood loss (1791 (range 932-3104) versus 1140 (range 440-3840) ml). There was evidence of postoperative heparin excess with an activated partial thromboplastin time ratio of 1.3 (range 0.9-3.0) versus 1.0 (range 1.0-1.2) in controls and an activated clotting time of 206 (range 143-280) versus 137 (range 107-142) s. This was confirmed by raised plasma heparin levels and a prolonged thrombin time normalized by protamine. To improve performance a 0.6-micron pore size filter was studied in ten patients. Filtration efficiency doubled from 19 to 38 per cent. Electron micrographs demonstrated better filter clearance, but 44 per cent of the original concentration of heparin remained in the reinfusate. The S-350 device may be an attractive alternative to centrifugation for intraoperative autotransfusion but, until efficiency is improved, it should only be used for cardiovascular surgery when excess heparin can be reversed with protamine.     

One hundred years of orthopedics in the Netherlands. I. Introduction

One hundred years ago, on 1 May 1898, the Netherlands Orthopaedic Association was founded. This was prompted by the view that general surgeons paid insufficient attention to the treatment of the locomotor system; they were permitted to join the new association, however, at any rate until 1947. It was especially in the last 30 years that orthopaedic surgery underwent major changes. The most striking novelty was arthroplastic surgery. There have also been developments in the treatment of spinal abnormalities, rheumatological surgery, sports medicine, oncology and traumatology.     

Treatment of perianal fistulas with ND:YAG laser--results in twenty cases

Excision of perianal fistulas using a 1.064 micron wavelength neodymium:yttrium aluminum garnet (ND:YAG) contact tipped laser with primary wound closure was used to treat 20 dogs with perianal fistulas. Overall, 19 of 20 (95%) dogs had resolution of fistulas after one or more ND:YAG treatments. The period of resolution ranged from 10 to 42 months with a mean of 22.9 months. Sixteen of 20 (80%) dogs had resolved fistulas after one laser excision. Three of the four recurrences underwent additional laser treatments with successful results. The total number of laser procedures ranged from one to three with a mean of 1.2 procedures. Postoperatively, anal tone as judged by digital rectal examination was reduced in about 60% of the cases, but clinical evidence of fecal incontinence only occurred in four of 20 cases. This was managed effectively with diet modification. The tendency toward loss of anal tone or fecal incontinence depended on the severity of preexisting anal stenosis. On a client survey, 19 of 20 owners believed that their animals experienced less pain during defecation after surgery and rated the results as excellent or good. The overall success rate using ND:YAG laser excision compared very favorably with previously reported studies of other methods of treatment for perianal fistulas in dogs.     

Effect of nabumetone on hemostasis during arthroscopic knee surgery

The known effects of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) on hemostatic parameters have led to concern over their use in the perioperative period. Nabumetone, unlike other NSAIDs, has little effect on collagen-induced platelet aggregation. To evaluate the effect of nabumetone 2000 mg daily on other hemostatic parameters (e.g., bleeding time, prothrombin time, and partial thromboplastin time) in the clinical setting, this double-masked study was conducted in patients with osteoarthritis undergoing arthroscopic knee surgery. After a 1-week placebo washout period, 58 patients were randomized to receive nabumetone and 53 were randomized to receive placebo. They were assessed before surgery (after 1 to 2 weeks of treatment) and again after surgery (after an additional 3 weeks of treatment). The study was designed to have 90% power to show equivalence in bleeding time to within 1.5 minutes, a difference assumed to be of no clinical importance. No meaningful differences were observed between the groups in any of the measured hemostatic parameters. Before surgery, the bleeding time increased by only 0.3 minutes with nabumetone and decreased by 0.2 minutes with placebo. The mean (+/- SD) difference between the groups in change from baseline was 0.5 +/- 0.3 minutes. After surgery, the changes were 0.1 minutes and 0.0 minutes, respectively, and the difference between groups was 0.2 +/- 0.3 minutes. These differences were neither statistically nor clinically significant, and maximum individual increases were similar in each group. Furthermore, there were no reports of abnormal bleeding in the operative knees. The results of this study show that nabumetone had little or no effect on hemostasis and suggest that this drug can be used safely in the perioperative period.     

Threshold voltage-minimum gate length trade-off in buried channelPMOS devices for scaled supply voltage CMOS technologies

The trade-off between threshold voltage (V_th) and the minimum gate length (L_min) is discussed for optimizing the performance of buried channel PMOS transistors for low voltage/low power high-speed digital CMOS circuits. In a low supply voltage CMOS technology it is desirable to scale V_th and L_min for improved circuit performance. However, these two parameters cannot be scaled independently due to the channel punch-through effect. Statistical process/device modeling, split lot experiments, circuit simulations, and measurements are performed to optimize the PMOS transistor current drive and CMOS circuit speed. We show that trading PMOS transistor V_th for a smaller L_min results in faster circuits for low supply voltage (3.3 to 1.8 V) n⁺-polysilicon gate CMOS technology, Circuit simulation and measurements are performed in this study. Approximate empirical expressions are given for the optimum buried channel PMOS transistor V _th for minimizing CMOS circuit speed for cases involving: (1) constant capacitive load and (2) load capacitance proportional to MOS gate capacitance. The results of the numerical exercise are applied to the centering of device parameters of a 0.5 μm 3.3 V CMOS technology that (a) matches the speed of our 0.5 μm 5 V CMOS technology, and (b) achieves good performance down to 1.8 V power supply. For this process the optimum PMOS transistor V_th (absolute value) is approximately 0.85-0.90 V     

A patient's perspective on the management of peptic esophageal stricture: experience and results in 113 consecutive cases

A retrospective analysis of 113 consecutive cases of benign esophageal stricture, all secondary to gastroesophageal reflux, 100 treated conservatively, 13 treated surgically, has been carried out in conjunction with a postal questionnaire of patients. Patients were requested to grade both their swallowing ability and the acceptability of their treatment. Of those responding to questionnaire, 88% of patients treated conservatively found their treatment acceptable or better, and 72% were left with either no or minimal restriction of diet. There was no correlation between either the total number or frequency of dilatations and the result achieved. Similarly, patient satisfaction appears largely independent of these variables. Doctors should be wary of taking recurrence of a stricture after initial dilatation as indicating a poor eventual outcome or a dissatisfied patient. There was no difference in terms of either the result or patient satisfaction between conservatively treated and surgically treated patients.     

The genotype of the human cancer cell: implications for risk analysis

An extremely large database describes genotypes associated with the human cancer phenotype and genotypes of human populations with genetic predisposition to cancer. Aspects of this database are examined from the perspective of risk analysis, and the following conclusions and hypotheses are proposed: (1) The genotypes of human cancer cells are characterized by multiple mutated genes. Each type of cancer is characterized by a set of mutated genes, a subset from a total of more than 80 genes, that varies between tissue types and between different tumors from the same tissue. No single cancer-associated gene nor carcinogenic pathway appears suitable as an overall indicator whose induction serves as a quantitative marker for risk analysis. (2) Genetic defects that predispose human populations to cancer are numerous and diverse, and provide a model for associating cancer rates with induced genetic changes. As these syndromes contribute significantly to the overall cancer rate, risk analysis should include an estimation of the effect of putative carcinogens on individuals with genetic predisposition. (3) Gene activation and inactivation events are observed in the cancer genotype at different frequencies, and the potency of carcinogens to induce these events varies significantly. There is a paradox between the observed frequency for induction of single mutational events in test systems and the frequency of multiple events in a single cancer cell, suggesting events are not independent. Quantitative prediction of cancer risk will depend on identifying rate-limiting events in carcinogenesis. Hyperproliferation and hypermutation may be such events. (4) Four sets of data suggest that hypermutation may be an important carcinogenic process. Current mechanisms of risk analysis do not properly evaluate the potency of putative carcinogens to induce the hypermutable state or to increase mutation in hypermutable cells. (5) High-dose exposure to carcinogens in model systems changes patterns of gene expression and may induce protective effects through delay in cell progression and other processes that affect mutagenesis and toxicity. Paradigms in risk analysis that require extrapolation over wide ranges of exposure levels may be flawed mechanistically and may underestimate carcinogenic effects of test agents at environmental levels. Characteristics of the human cancer genotype suggest that approaches to risk analysis must be broadened to consider the multiplicity of carcinogenic pathways and the relative roles of hyperproliferation and hypermutation. Further, estimation of risk to general human populations must consider effects on hypersusceptible individuals. The extrapolation of effects over wide exposure levels is an imprecise process.     

Autoxidation of ubiquinol-6 is independent of superoxide dismutase

Ubiquinone (Q) is an essential, lipid soluble, redox component of the mitochondrial respiratory chain. Much evidence suggests that ubiquinol (QH2) functions as an effective antioxidant in a number of membrane and biological systems by preventing peroxidative damage to lipids. It has been proposed that superoxide dismutase (SOD) may protect QH2 form autoxidation by acting either directly as a superoxide-semiquinone oxidoreductase or indirectly by scavenging superoxide. In this study, such an interaction between QH2 and SOD was tested by monitoring the fluorescence of cis-parinaric acid (cPN) incorporated phosphatidylcholine (PC) liposomes. Q6H2 was found to prevent both fluorescence decay and generation of lipid peroxides (LOOH) when peroxidation was initiated by the lipid-soluble azo initiator DAMP, dimethyl 2,2'-azobis (2-methylpropionate), while Q6 or SOD alone had no inhibitory effect. Addition of either SOD or catalase to Q6H2-containing liposomes had little effect on the rate of peroxidation even when incubated in 100% O2. Hence, the autoxidation of QH2 is a competing reaction that reduces the effectiveness of QH2 as an antioxidant and was not slowed by either SOD or catalase. The in vivo interaction of SOD and QH2 was also tested by employing yeast mutant strains harboring deletions in either CuZnSOD and/or MnSOD. The sod mutant yeast strains contained the same percent Q6H2 per cell as wild-type cells. These results indicate that the autoxidation of QH2 is independent of SOD.