Relationship of seizure duration to antidepressant efficacy in electroconvulsive therapy

BACKGROUND: Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin, $1,080 vs. epsilon-aminocaproic acid, $11) has generated significant controversy regarding their relative efficacies and costs. METHODS: In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high-dose regimen of aprotinin (total dose, 6 x 10(6) kallikrein inactivator units) or epsilon-aminocaproic acid (total dose, 270 mg/kg). RESULTS: Two hundred four patients were studied. Overall (data are median [25th-75th percentiles]), aprotinin-treated patients had less postoperative thoracic drainage (511 ml [383-805 ml] vs. 655 ml [464-1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0-1] vs. 1 [range, 0-2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction. CONCLUSIONS: Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022).     

Myoblast-mediated gene transfer to the joint

Several genetic and acquired pathologic conditions of the musculoskeletal system, such as arthritis and damage to ligament, cartilage, and meniscus, may be amenable to gene therapy. Even though ex vivo gene transfer with synovial cells has been shown to deliver genes encoding for anti-arthritic proteins into the rabbit knee joint, its success has been limited by a transient transgene expression. In this study, data were investigated regarding the use of muscle cells as an alternative gene-delivery vehicle to the joint in newborn rabbit and adult severe combined immunodeficiency mice. We demonstrated that myoblasts were transduced more efficiently than synovial cells with use of the same adenoviral preparation in vitro. After intra-articular injection, the engineered muscle cells adhered to several structures in the joint, including the ligament, capsule, and synovium. In addition, myoblasts fused to form many post-mitotic myotubes and myofibers at different locations of the joint of the newborn rabbit 5 days after the injection. In the knee of the adult mouse, myoblasts fused and expressed the reporter gene for at least 35 days after the injection. The presence of post-mitotic myofibers in the knee joint raises the possibility of long-term expression of the secreted protein. Currently, numerous tissues in the joint (ligament, meniscus, and cartilage) have poor intrinsic healing capacity and frequently need surgical corrections. A stable gene-delivery vehicle to the joint producing proteins that ameliorate these different musculoskeletal conditions may change the clinical implications of these pathologies.     

Association between cigarette smoking and lipid peroxidation in a controlled feeding study

BACKGROUND: Cigarette smoke may promote atherogenesis by producing oxygen-derived free radicals that damage lipids. However, evidence in support of this hypothesis is inconsistent because most studies did not control for aspects of diet (antioxidants and lipid substrate) that may confound the association between smoking and measures of lipid peroxidation. METHODS AND RESULTS: The relationships between cigarette smoking and two measures of lipid peroxidation, breath ethane (an in vivo assay) and thiobarbituric acid-reactive substances (TBARS, an in vitro assay), were examined in 123 adults (11% of whom were smokers) participating in a controlled feeding study. After 3 weeks of controlled feeding on a common diet (36% total fat, 14% saturated fats, 6% polyunsaturated fats, and 12% monounsaturated fats), breath and fasting serum samples were collected for measurement of ethane and TBARS, respectively. Baseline characteristics of smokers and nonsmokers were similar, including several indices related to diet and nutritional status (albumin, cholesterol, body mass index, and oxygen radical-absorbing capacity). Cigarette smokers had significantly higher breath ethane (8.88 versus 1.71 pmol/L; P<.0001) and TBARS (24.0 versus 20.7 micromol/mL; P=.008) than nonsmokers. The interval between breath collection and the time the last cigarette was smoked was significantly and inversely correlated with breath ethane. Neither measure of lipid peroxidation was associated with measures of serum cholesterol or albumin, body mass index, or serum oxygen radical-absorbing capacity. CONCLUSIONS: Cigarette smokers have higher rates of in vivo and in vitro lipid peroxidation. These results support the hypothesis that the atherogenic effects of smoking are mediated in part by free radical damage to lipids.     

Hyperdynamic circulation of cirrhotic rats: role of substance P and its relationship to nitric oxide

BACKGROUND: It has been suggested that excessive formation of nitric oxide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by the liver and causes vasodilatation through the activation of the endothelial NO pathway. However, there are no previously published data concerning the plasma level of substance P in cirrhotic rats and its relationship to NO. METHODS: Plasma concentrations of substance P and nitrate/nitrite (an index of NO production) were determined in control rats and cirrhotic rats with or without ascites using an enzyme-linked immununosorbent assay and a colorimetric assay, respectively. In addition, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. RESULTS: Cirrhotic rats with and without ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3.9 +/- 0.4 mmHg ml(-1) x min x 100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rats (6.5 +/- 0.3 mmHg x ml(-1) x min x 100 g BW and 6.8 +/- 0.2 mmHg, respectively, P < 0.05), and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control rats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substance P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values between control rats and cirrhotic rats without ascites (P > 0.05). No correlation was found between plasma levels of substance P and nitrate/nitrite (r = 0.318, P > 0.05). CONCLUSIONS: Excessive formation of NO may be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.     

Effects of design parameters on geared two-link mechanisms

The design of a specialized agricultural harvesting machine required the use of a path generation mechanism that was compact, accurate, inexpensive to manufacture and difficult attempts involved the use of a cam and follower, but they were expensive to manufacture and difficult to operate. This paper discusses an alternative method of using a coupled, open loop, two-link mechanism to generate a polygon-like closed path (pseudo-polygon) with an integer number of curved sides and apexes. A complete development of the path and path curvaturei equations are presented. The influence of the design variables on the coupler shape (flatness of each side) is shown in equation and design chart form. An example of a successful application of this design method applied to a plant cutting mechanism is presented.     

On the variation with flux and frequency of the core loss coefficients in electrical machines

A model of core losses, in which the hysteresis coefficients are variable with the frequency and induction (flux density) and the eddy-current and excess loss coefficients are variable only with the induction, is proposed. A procedure for identifying the model coefficients from multifrequency Epstein tests is described, and examples are provided for three typical grades of non-grain-oriented laminated steel suitable for electric motor manufacturing. Over a wide range of frequencies between 20-400 Hz and inductions from 0.05 to 2 T, the new model yielded much lower errors for the specific core losses than conventional models. The applicability of the model for electric machine analysis is also discussed, and examples from an interior permanent-magnet and an induction motor are included.     

Correlated response of udder dimensions to selection for milk yield in Holsteins

Response to selection for milk yield in Holsteins was examined by a controlled selection experiment initiated in 1964. Foundation cows were paired by sire and divided randomly into two breeding groups, selection and control. Selection group was mated to four sires each year highest for Predicted Difference milk. Twenty bulls selected in 1964 as near breed average for milk sired all control cows. Milk yield was recorded for each lactation, and height of udder from ground, distances between teats, and perimeter and area bound by the four teats were measured at 30 to 75 days postpartum on 153 selection and 202 control cows over 14 yr. Most estimates of repeatability and heritability of udder dimensions before and after milking were .45 or larger. Correlations with milk yield were negative for udder height and positive for other udder measurements. Selection cows exceeded controls for lactational milk yield. Daughters of high milk bulls had greater distances between teats, greater perimeters, and larger areas of udder floor. Selection cows did not differ from controls in udder height for first parity but were below controls in udder height and had udders that collapsed more for all parities.     

Effects of selenium and vitamin E on incidence of retained placenta

In a series of experiments over 3 yr, relatively low doses of selenium and vitamin E were injected intramuscularly 3 wk prepartum to pregnant Israeli-Holstein dairy cows in a high-producing herd (9000 kg milk/yr) with a history of retained placenta in 17% of the primiparous and 28% of the multiparous animals, as recorded for the 12 mo preceding the study. Selenium ranged from .035 to .109 ppm in the prepartum diet and from .160 to .200 ppm in the postpartum diet. Doses of selenium ranging from 2.3 to 23.0 mg reduced the incidence of retained placenta in 186 primiparous and in 428 multiparous to 7 and 15%, which was half of that of controls. Low doses of selenium (2.3 to 4.6 mg) tended to be more effective than higher ones. Selenium alone was at least as effective as a combination of selenium and vitamin E. Dosage, timing, mechanism, and interactions of selenium with other factors in reducing the incidence of retained placenta need clarification.