Application research of master-slave cranio-maxillofacial surgical robot based on force feedback.

BACKGROUND: The complex anatomical structure, limited field of vision, and easily damaged nerves, blood vessels, and other anatomical structures are the main challenges of a cranio-maxillofacial (CMF) plastic surgical robot. Bearing these characteristics and challenges in mind, this paper presents the design of a master-slave surgical robot system with a force feedback function to improve the accuracy and safety of CMF surgery. METHODS: A master-slave CMF surgical robot system based on force feedback is built with the master tactile robot and compact slave robot developed in the laboratory. Model-based master robot gravity compensation and force feedback mechanism is used for the surgical robot. Control strategies based on position increment control and ratio control are adopted. Aiming at the typical mandibular osteotomy in CMF surgery, a scheme suitable for robot-assisted mandibular osteotomy is proposed. The accuracy and force feedback function of the robot system under direct control and master-slave motion modes are verified by experiments. RESULTS: The drilling experiment of the mandible model in direct control mode shows that the average entrance point error is 1.37 ± 0.30 mm, the average exit point error is 1.30 ± 0.25 mm, and the average posture error is 2.27° ± 0.69°. The trajectory tracking and in vitro experiment in the master-slave motion mode show that the average position following error is 0.68 mm, and the maximum force following error is 0.586 N, achieving a good tracking and force feedback function. CONCLUSION: The experimental results show that the designed master-slave CMF robot can assist the surgeon in completing accurate mandibular osteotomy surgery. Through force feedback mechanism, it can improve the interaction between the surgeon and the robot, and complete tactile trajectory movements.

Risk of cancer among workers exposed to trichloroethylene: analysis of three Nordic cohort studies.

BACKGROUND: Trichloroethylene (TCE) is a widely used chlorinated solvent with demonstrated carcinogenicity in animal assays. Some epidemiologic studies have reported increased risk of cancer of the kidney, cervix, liver and biliary passages, non-Hodgkin lymphoma, and esophageal adenocarcinoma. METHODS: We established a pooled cohort, including 5553 workers with individual documented exposure to TCE in Finland, Sweden, and Denmark. Study participants were monitored for the urinary TCE metabolite trichloroacetic acid from 1947 to 1989 and followed for cancer. Standardized incidence ratios (SIRs) were calculated based on cancer incidence rates in the three national populations. Cox proportionate hazard analyses were used for internal comparisons. Tests of statistical significance are two-sided. RESULTS: Overall, 997 cases of cancer (n = 683 in men; n = 314 in women) were identified during 154 778 person-years of follow-up. We observed statistically significant elevated standardized incidence ratios for primary liver cancer (1.93; 95% confidence interval [CI] = 1.19 to 2.95) and cervical cancer (2.31; 95% CI = 1.32 to 3.75). The standardized incidence ratio for kidney cancer was 1.01 (95% CI = 0.70 to 1.42) based on 32 cases; we did not observe a statistically significant increased risk of non-Hodgkin's lymphoma (SIR = 1.26; 95% CI = 0.89 to 1.73) or esophageal adenocarcinoma (SIR = 1.84; 95% CI = 0.65 to 4.65). Tobacco- and alcohol-associated cancers were not statistically significantly increased. CONCLUSIONS: Our results suggest TCE exposure is possibly associated with an increased risk for liver cancer. The relationship between TCE exposure and risks of cancers of low incidence and those with confounding by lifestyle and other factors not known in our cohort require further study.

Early stellate cell activation and veno-occlusive-disease (VOD)-like hepatotoxicity in dogs treated with AR-H047108, an imidazopyridine proton pump inhibitor.

Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two weeks. A detailed histopathological and immunohistochemical characterization of the liver lesions was conducted, including markers for fibrosis, Kupffer cell activation, apoptosis, and endothelial injury. In addition, hepatic retinoid and procollagen 1alpha2 mRNA levels in livers of dogs treated with AR-H047108 were analyzed. The results showed an early inflammatory process in central veins and centrilobular areas, present after one week of treatment. This inflammatory reaction was paralleled by activation of stellate/Ito cells to myofibroblasts and was associated with sinusoidal and centrivenular fibrosis. The early activation of stellate cells coincided with a significant decrease in retinyl ester levels, and a significant increase in procollagen 1alpha2 mRNA levels, in the liver. At later time points (three and six months), there was marked sinusoidal fibrosis in centrilobular areas, as well as occlusion of central veins resulting from a combination of fibrosis and increased thickness of smooth muscle bundles in the vessel wall. The pattern of lesions suggests a veno-occlusive-disease (VOD)-like scenario, possibly linked to the imidazopyridine chemical structure of the compound facilitated by specific morphological features of the dog liver.

Long-term effect of vaccination against gonadotropin-releasing hormone, using Improvac, on hormonal profile and behaviour of male pigs.

The objective of this study was to evaluate the long-term effect of a gonadotropin-releasing hormone (GnRH) vaccine, Improvac (Pfizer Ltd.), on the levels of GnRH antibodies, testosterone, estrone sulphate (E1S) and androstenone, as well as skatole and indole in male pigs. Additionally, the long-term effect of immunocastration on social and sexual behaviour was studied. Male pigs were assigned to two treatment groups: a treatment group given two doses of Improvac (n=12) and a control group of entire male pigs (n=12). The pigs were kept either 16 or 22 weeks after vaccination. Blood samples were collected five or six times; prior to both first and second vaccination, then three or four times during the 16 or 22 week period after second vaccination. Immunocastration significantly reduced levels of testosterone and E1S in plasma, and levels of androstenone in fat (P<0.001 for all). Skatole and indole levels in plasma and fat were also lower in immunocastrated pigs than in entire male pigs. These effects lasted up to 22 weeks after the second vaccination. Testis weight and bulbourethral gland length were lower in immunocastrated pigs at slaughter and these pigs showed less social, manipulating and aggressive behaviour than entire male pigs. The immunocastrated pigs remained sexually inactive throughout the study. Our study represents a further step in the evaluation of the effectiveness of Improvac as an alternative to surgical castration of entire male pigs. It shows that Improvac may have an extended effect compared with that currently implied by the directions for use.

Development of a harmonised method for the profiling of amphetamines: III. Development of the gas chromatographic method.

This study focused on gas chromatographic analysis of target compounds found in illicit amphetamine synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The analytical method was investigated and optimised with respect to introduction of amphetamine samples into the gas chromatograph and separation and detection of the target substances. Sample introduction using split and splitless injection was tested at different injector temperatures, and their ability to transfer the target compounds to the GC column was evaluated using cold on column injection as a reference. Taking the results from both techniques into consideration a temperature of 250 degrees C was considered to be the best compromise. The most efficient separation was achieved with a DB-35MS capillary column (35% diphenyl 65% dimethyl silicone; 30 m x 0.25 mm, d(f) 0.25 microm) and an oven temperature program that started at 90 degrees C (1 min) and was increased by 8 degrees C/min to 300 degrees C (10 min). Reproducibility, repeatability, linearity, and limits of determination for the flame ionisation detector (FID), nitrogen phosphorous detector (NPD), and mass spectrometry (MS) in scan mode and selected ion monitoring (SIM) mode were evaluated. In addition, selectivity was studied applying FID and MS in both scan and SIM mode. It was found that reproducibility, repeatability, and limits of determination were similar for FID, NPD, and MS in scan mode. Moreover, the linearity was better when applying FID or NPD whereas the selectivity was better when utilising the MS. Finally, the introduction of target compounds to the GC column when applying injection volumes of 0.2 microl, 1 microl, 2 microl, and 4 microl with splitless injection respectively 1 microl with split injection (split ratio, 1:40) were compared. It was demonstrated that splitless injections of 1 microl, 2 microl, and 4 microl could be employed in the developed method, while split injection and splitless injections of 0.2 microl should be avoided.

Mechanism of action of AZD0865, a K+-competitive inhibitor of gastric H+,K+-ATPase.

AZD0865 is a member of a drug class that inhibits gastric H(+),K(+)-ATPase by K(+)-competitive binding. The objective of these experiments was to characterize the mechanism of action, selectivity and inhibitory potency of AZD0865 in vitro. In porcine ion-leaky vesicles at pH 7.4, AZD0865 concentration-dependently inhibited K(+)-stimulated H(+),K(+)-ATPase activity (IC(50) 1.0+/-0.2 microM) but was more potent at pH 6.4 (IC(50) 0.13+/-0.01 microM). The IC(50) values for a permanent cation analogue, AR-H070091, were 11+/-1.2 microM at pH 7.4 and 16+/-1.8 microM at pH 6.4. These results suggest that the protonated form of AZD0865 inhibits H(+),K(+)-ATPase. In ion-tight vesicles, AZD0865 inhibited H(+),K(+)-ATPase more potently (IC(50) 6.9+/-0.4 nM) than in ion-leaky vesicles, suggesting a luminal site of action. AZD0865 inhibited acid formation in histamine- or dibutyryl-cAMP-stimulated rabbit gastric glands (IC(50) 0.28+/-0.01 and 0.26+/-0.003 microM, respectively). In ion-leaky vesicles at pH 7.4, AZD0865 (3 microM) immediately inhibited H(+),K(+)-ATPase activity by 88+/-1%. Immediately after a 10-fold dilution H(+),K(+)-ATPase inhibition was 41%, indicating reversible binding of AZD0865 to gastric H(+),K(+)-ATPase. In contrast to omeprazole, AZD0865 inhibited H(+),K(+)-ATPase activity in a K(+)-competitive manner (K(i) 46+/-3 nM). AZD0865 inhibited the process of cation occlusion concentration-dependently (IC(50) 1.7+/-0.06 microM). At 100 microM, AZD0865 reduced porcine renal Na(+),K(+)-ATPase activity by 9+/-2%, demonstrating a high selectivity for H(+),K(+)-ATPase. Thus, AZD0865 potently, K(+)-competitively, and selectively inhibits gastric H(+),K(+)-ATPase activity and acid formation in vitro, with a fast onset of effect.

Perception of cockpit environment among pilots on commercial aircraft.

UNLABELLED: Impaired cockpit environment may influence both well-being and performance of pilots. OBJECTIVE: To study the perception of cockpit environment among pilots, in relation to demographic factors, and type of aircraft (B767-300, B737-600, DC9/21-41, MD 81/90 series). METHODS: A standardized questionnaire was mailed to all pilots in one airline company; 81% participated (n = 622). All flights were non-smoking flights and the B767 was the only aircraft operated on intercontinental flights. The DC9 was the only aircraft without air recirculation. Multiple logistic regression analysis was applied, controlling for age, gender, smoking, perceived psychosocial work environment, and type of aircraft. RESULTS: Younger age and a history of atopy and stress due to excess work were the main predictors of symptom and environmental perceptions. The most common symptoms were fatigue (14%), facial dermal (10%), and nasal symptoms (9%). Common complaints on cockpit environment were dry air (53%), dust and dirt (48%), noise (46%), and inadequate illumination (34%). Using the DC9 as a reference category, Boeing 767 pilots had more fatigue (OR 19.5; p < 0.001), throat symptoms (OR = 4.40; p < 0.05), complaints on dry air (OR = 2.93; p < 0.01), stuffy air (OR = 4.60; p < 0.01), static electricity (OR = 6.39; < 0.05), and dust (OR = 2.01; p < 0.05). Boeing 737 pilots had more complaints on noise (OR = 4.01; p < 0.001) and dust (OR = 1.81; p < 0.05). MD 81/90 pilots had more complaints on dry air (OR = 1.76; p < 0.05), dust (OR = 1.92; p < 0.05), and inadequate illumination (OR = 2.08; p < 0.05). CONCLUSION: Complaints on the cockpit environment were common and differed between different types of aircraft. This indicates a need to optimize the cockpit environment, e.g., increase the cleaning and relative air humidity.

Early post-natal exposure to low dose oral di(2ethylhexyl) phthalate affects the peripheral LH-concentration in plasma, but does not affect mating behavior in the post-pubertal boar.

In a split-litter design experiment, boars were exposed orally three times weekly to 300 mg/kg of di(2-ethylhexyl) phthalate (DEHP) between 3 and 7 weeks of age. Post-puberty, i.e. at 6 months of age the effects on endocrinology and mating behavior were examined. The response to stimulation with a synthetic GnRH-analogue at 9 months of age resulted initially in lower concentration of LH in the exposed animals, compared to the control animals. We did not find any effects of DEHP on the mating behavior. Also, the effects of DEHP during the treatment period on the plasma concentrations of testosterone, oestradiol and LH were examined. During the exposure period there was a transient decrease in plasma concentrations of LH in the control group, which did not occur in the boars exposed to DEHP. The data suggest that DEHP in low repeated oral doses causes lasting effects on the hypothalamus-pituitary-gonadal axis.

Pharmacological treatment of osteopenia induced by gastrectomy or ovariectomy in young female rats.

BACKGROUND: Both gastrectomy (GX) and ovariectomy (OVX) induce osteopenia in man and experimental animals. The present study addresses the question--can alendronate, estrogen or parathyroid hormone (PTH) be used to treat established GX- or OVX -evoked osteopenia? METHODS: Rats were GX-, OVX- or SHAM-operated 8 weeks before starting the treatment with drugs. Each group was then treated for 8 weeks with 50 microg/kg/day alendronate, 10 microg/kg/day estrogen or 75 microg/kg/day PTH(1-84); n = 8 rats/group. Peripheral Quantitative Computed Tomography (pQCT) was used to measure trabecular bone mineral density (BMD) and various cortical bone parameters. RESULTS: At killing, 16 weeks after surgery, GX and OVX rats had a greatly reduced trabecular BMD in the metaphysis of the distal femur (GX -44% and OVX -55%). Alendronate increased the trabecular BMD by 44% in GX rats and by 64% in OVX rats, while PTH increased it by 51% and 115%, respectively. However, estrogen increased the trabecular BMD in GX rats (35%), but not in OVX rats (15%, not significant). Cortical bone parameters were adversely (but moderately) affected by GX, but not by OVX or by treatment with the three drugs. INTERPRETATION: Alendronate, estrogen and PTH restored the trabecular bone loss in rats with an established GX-evoked osteopenia. In contrast, alendronate and PTH, but not estrogen, restored the trabecular bone loss after OVX. Hence, the mechanism underlying GX-evoked bone loss differs from that underlying OVX-evoked bone loss. The ability of alendronate, estrogen and PTH to reverse the GX-evoked osteopenia in the rat may be of clinical interest when dealing with bone loss in humans after GX.