Variable phenotypes are associated with PMP22 missense mutations

Charcot-Marie-Tooth disease (CMT) is the commonest hereditary neuropathy encompassing a large group of clinically and genetically heterogeneous disorders. The commonest form of CMT, CMT1A, is usually caused by a 1.4 megabase duplication of chromosome 17 containing the PMP22 gene. Mutations of PMP22 are a less common cause of CMT. We describe clinical, electrophysiological and molecular findings of 10 patients carrying PMP22 missense mutations. The phenotype varied from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe CMT1. We identified six different point mutations, including two novel mutations. Three families were also found to harbour a Thr118Met mutation. Although PMP22 point mutations are not common, our findings highlight the importance of sequencing the PMP22 gene in patients with variable CMT phenotypes and also confirm that the PMP22 Thr118Met mutation is associated with a neuropathy albeit with reduced penetrance.     

A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation.

To investigate therapeutic strategies for hepatoma, it is necessary to have a reproducible animal model with a tumor growth pattern allowing accurate assessment of results. Many techniques of intrahepatic tumor implantation (IHTI) have been devised for intrahepatic tumor models. Most of them, however, have the disadvantage of high rates of artificial tumor dissemination during tumor implantation, which interferes with the evaluation of therapy. To overcome this problem, we have developed a technique of IHTI in which a piece of Gelfoam is placed into a small incision in the liver for the purpose of both hemostasis and formation of a tension-free pocket to accept the tumor implant. In 583 ACI rats receiving IHTI with Morris hepatoma 3924A, the tumor take rate was 100%. Resembling the natural course of human hepatoma, the implanted tumor grows locally early in the course of disease and eventually invades the surrounding organs causing ascites and also metastasizes to the lung. Liver microangiography demonstrated that the tumor received blood supply mainly from the hepatic artery. This IHTI technique was also compared to two other methods of IHTI: insertion of fragments without using Gelfoam and implantation with a tumor cell suspension. A significantly lower rate of early lung metastases was achieved with our technique (0%) in comparison with other two techniques (41 and 80%). We conclude that this rat liver cancer model is reproducible and allows efficient evaluation of treatment modalities for liver cancer without interference from tumor at undesirable sites.     

Cost savings achieved through cephalosporin use review and restriction

Attempts to control costs associated with antimicrobial therapy and surgical prophylaxis with injectable cephalosporins in a 335-bed, acute-care, county teaching hospital are described. An ABC analysis of our pharmacy inventory revealed that 11.8% of the annual pharmaceutical budget was represented by cefamandole and that this agent was used primarily for surgical prophylaxis. Initial attempts to replace cefamandole with cefuroxime met with unexpected resistance from the department of surgery and were unsuccessful. A cost analysis revealed that annual savings in supply and personnel costs of $115,819 could be realized if cefazolin were substituted for cefamandole. Substitution of cefazolin resulted in an additional cost savings of $40,000 above our original proposal involving cefuroxime. Persistent efforts of the department of pharmacy aided the effective implementation of this alteration in cephalosporin prescribing practices.     

A combined chest drain and intrapleural catheter for post-thoracotomy pain relief

This study examined the effectiveness of a new type of chest drain, which incorporates an additional lumen within its wall to facilitate the administration of intrapleural bupivacaine. Nine patients who received a bolus dose of 1.5 mg.kg⁻¹ bupivacaine with 1:200 000 adrenaline through this chest drain used less morphine, and had lower visual analogue pain scores in the first 6 h after thoracotomy than patients in whom a standard chest drain had been used. Bupivacaine levels were found to be within safe limits in all patients.     

Attenuation of conditioned taste aversions by external stressors

Conditioned taste aversions (CTAs) were produced by low doses of toxins injected 30 or 60 min after rats finished drinking saccharin solution. Attempts were made to attenuate these CTAs by subjecting the rats to stress or to injections of glucocorticoids (primarily dexamethasone) during the interval between saccharin consumption and injection of the toxin. The stressors used were statistically indistinguishable in their effects: swimming, constant footshock (for 2 min), or intermittent footshock (for 10 min). The extent to which different agents attenuated CTAs depended on which toxin was used to produce the CTA as follows. The stressors produced marked CTA attenuation when lithium was the toxin, but none when cisplatin was the toxin. The glucocorticoids exhibited an opposite pattern of marginal CTA attenuation with lithium and marked CTA attenuation with cisplatin. CTAs produced by morphine were more like those produced by cisplatin than like those produced by lithium. Our belief that the CTA attenuation demonstrated here indicates alleviation of the distress produced by the toxin was supported by the results of the final two experiments as follows: 1) The stress does not raise saccharin preference independently of interference with the aversiveness of the toxin since, in similar experiments in which toxins were not administered, footshock administered in conjunction with exposure to saccharin solution reduced later saccharin preference. 2) Probably CTA attenuation does not occur because stress interferes with the taste-toxin association since footshock administered before the saccharin drinking session (instead of after it) also produced CTA attenuation.     

Strategies for improving fixation of femoral components in total hip arthroplasty

As strategies are considered for improving fixation of femoral components in total hip arthroplasty (THA), one is challenged to exceed the standard set by contemporary cement procedures. However, despite the improved ten- to 15-year clinical results anticipated with current cementing techniques, the limited fatigue strength of polymethylmethacrylate warrants continued investigation of alternative systems, particularly for younger patients and in revision arthroplasty. Design considerations for femoral stems for cementless THA include (1) initial mechanical stability afforded by the stem shape, (2) strength and stiffness of the stem, and (3) surface features relating to biocompatibility and attachment to bone. In one approach a fit-and-fill algorithm has been implemented to design stems that maximize contact between prosthesis and cortex in priority areas to achieve stability. Titanium is recommended for the fabrication of such stems because of its corrosion resistance, its biocompatibility, and its modulus, which is lower than that of cobalt-chromium alloy. Long-term fixation of these implants will be dependent upon the maintenance of normal strain patterns in the host bone. Achievement of this goal will require additional strategies that combine optimal fit and optimal material properties of the prosthesis.     

Doppler ultrasound, laser Doppler, and perfusion fluorometry in bowel ischemia

Improved accuracy and objectivity in the evaluation of intestinal viability has been reported by some investigators using Doppler ultrasound, and more recently laser Doppler velocimetry and perfusion fluorometry. To compare the sensitivity and clinical applicability of these techniques, intestinal viability was evaluated by each method in nine 15- to 50-cm loops of small bowel prepared by division of the mesenteric vasculature in five anesthetized dogs. The sensitivity of Doppler ultrasound was 86%, of laser Doppler flow velocity 85%, of laser Doppler index 94%, and of perfusion fluorometry 95%. Though the sensitivity of Doppler ultrasound is significantly less than that of laser Doppler and perfusion fluorometry, this is not unexpected since the latter two techniques are more quantitative than Doppler ultrasound. Clinically, Doppler ultrasound compares favorably with laser Doppler and perfusion fluorometry, and its low cost and simplicity suggest its adjunctive use in the operative setting.