A single-channel implantable microstimulator for functional neuromuscular stimulation

This paper describes a single-channel implantable microstimulator for functional neuromuscular stimulation. This device measures 2 x 2 x 10 mm3 and can be inserted into paralyzed muscle groups by expulsion from a hypodermic needle. Power and data to the device are supplied from outside by RF telemetry using an amplitude-modulated 2-MHz RF carrier generated using a high-efficiency class-E transmitter. The transmitted signal carries a 5-b address which selects one of the 32 possible microstimulators. The selected device then delivers up to 2 microC of charge store in a tantalum chip capacitor for up to 200 microseconds (10 mA) into loads of < 800 omega through a high-current thin-film iridium-oxide (IrOx) electrode (approximately 0.3 mm2 in area). A bi-CMOS receiver circuitry is used to: generate two regulated voltage supplies (4.5 and 9 V), recover a 2-MHz clock from the carrier, demodulate the address code, and activate the output current delivery circuitry upon the reception of an external command. The overall power dissipation of the receiver circuitry is 45-55 mW. The implant is hermetically packaged using a custom-made glass capsule.     

Variations in the postoperative length of stay according to patient characteristics in a general surgery service

With the purpose of identifying factors that explain variations in length of postoperative stay in a general surgery unit, information from 666 clinical records of discharged alive patients was collected. Factors related to the surgical procedure, the severity of the disease and the medical team together with sociodemographic characteristics of the patients were analyzed. Statistical analysis was based on analysis of variance and multiple linear regression. Variables with statistically significant regression coefficients (p < 0.001) were in this order: severity of complications, type of intervention, need for reintervention and severity of diagnosis. Sixty-seven percent of length of stay variation was explained by the included variables. Results allow to suggest an evaluation procedure which takes into account patient and operation characteristics.     

ANALYSIS OF FREE-EDGE STRESS AND DISPLACEMENT FIELDS IN SCARF JOINTS SUBJECTED TO A UNIFORM CHANGE IN TEMPERATURE

The role of free-edge stresses in controlling the initiation of failure from the interface corner of a scarf joint subjected to a uniform change in temperature is examined. In general, the stress field can be expressed by σ _ij = Hr ^{λ −1} + σ _{ij 0} , where r is the radial distance from the interface corner, λ − 1 is the order of the stress singularity, H is the intensity of the singularity, and σ _{ij 0} is a non-singular constant stress. A combination of the finite element method and a path-independent integral is used to evaluate the magnitude of H for two joint configurations: (i) a scarf joint between two long bi-material strips; and (ii) a scarf joint consisting of a thin elastic layer sandwiched between two substrates. The magnitude of H is linearly dependent on a non-dimensional constant function a; the magnitude of a decreases with increasing level of mismatch in the elastic properties of the bonded materials. A comparison between the values of H evaluated by the path-independent integral method and the commonly used extrapolation method indicate that the extrapolation method could be in error by as much as 25%.     

Eudistomin V, a new beta-carboline from the Australian ascidian Pseudodistoma aureum

Chemical investigation of the Australian ascidian Pseudodistoma aureum has resulted in the isolation of a new beta-carboline, eudistomin V (1). The known compounds eudistomin H (2) and I (3) were also isolated, and all compounds had their structures determined by spectroscopic means.     

IKP104-induced decay of tubulin: role of the A-ring binding site of colchicine

Tubulin, the major subunit protein of microtubules, has a tendency to lose its ability to assemble or to interact with ligands in a time-dependent process known as decay. Decay involves the increase in exposure of sulfhydryl groups and hydrophobic areas. The antimitotic drug IKP104 [2-(4-fluorophenyl)-1-(2-chloro-3, 5-dimethoxyphenyl)-3-methyl-6-phenyl-4(1H)-pyridinone] accelerates the decay of tubulin [Ludue?a et al. (1995) Biochemistry 34, 15751-15759]. In the presence of colchicine, however, IKP104 stabilizes tubulin against decay. We have shown that the stability and the acceleration of the decay of tubulin are mediated respectively by the high- and low-affinity binding site(s) of IKP104 [Chaudhuri et al. (1998) J. Protein Chem. 17, 303-309]. To better understand the mechanism by which colchicine protects tubulin from IKP104-induced decay, we examined the effect of colchicine and its analogues on this process. We found that IKP104 unfolds tubulin in a process involving a specific domain where colchicine interacts, although the binding sites of these two drugs are distinctly different. 2-Methoxy-5-(2',3',4'-trimethoxyphenyl) tropolone (MTPT), the bicyclic analogue of colchicine that lacks the B-ring, can also protect tubulin from IKP104-induced decay. An A-ring analogue of colchicine, 3,4,5-trimethoxybenzaldehyde (TMB), can also stop IKP104-induced unfolding of tubulin significantly. Interestingly, the C-ring analogue of colchicine, tropolone methyl ether (TME), does not prevent this process. Our results thus suggest that neither the B-ring nor the C-ring binding regions of colchicine are involved in the IKP104-induced decay and that the A-ring binding site of colchicine on tubulin plays a crucial role in IKP104-induced decay.     

A longitudinal study of hospitalization rates for patients with chronic disease: results from the Medical Outcomes Study

OBJECTIVE: To prospectively compare inpatient and outpatient utilization rates between prepaid (PPD) and fee-for-service (FFS) insurance coverage for patients with chronic disease. DATA SOURCE/STUDY SETTING: Data from the Medical Outcomes Study, a longitudinal observational study of chronic disease patients conducted in Boston, Chicago, and Los Angeles. STUDY DESIGN: A four-year prospective study of resource utilization among 1,681 patients under treatment for hypertension, diabetes, myocardial infarction, or congestive heart failure in the practices of 367 clinicians. DATA COLLECTION/EXTRACTION METHODS: Insurance payment system (PPD or FFS), hospitalizations, and office visits were obtained from patient reports. Disease and severity indicators, sociodemographics, and self-reported functional status were used to adjust for patient mix and to compute expected utilization rates. PRINCIPAL FINDINGS: Compared to FFS, PPD patients had 31 percent fewer observed hospitalizations before adjustment for patient differences (p = .005) and 15 percent fewer hospitalizations than expected after adjustment (p = .078). The observed rate of FFS hospitalizations exceeded the expected rate by 9 percent. These results are not explained by system differences in patient mix or trends in hospital use over four years. Half of the PPD/FFS difference in hospitalization rate is due to intrinsic characteristics of the payment system itself. CONCLUSIONS: PPD patients with chronic medical conditions followed prospectively over four years, after extensive patient-mix adjustment, had 15 percent fewer hospitalizations than their FFS counterparts owing to differences intrinsic to the insurance reimbursement system.     

Molecular dynamics simulation of the stability of a 22-residue alpha-helix in water and 30% trifluoroethanol

A molecular dynamics (MD) simulation was performed on the alpha-helix H8-HC5, the C-terminal part of myoglobin (residue 132-153), under periodic boundary conditions in two different solutions, water and water with 30% (v/v) 2,2,2-trifluoroethanol (TFE), at 300 K to investigate the stability of the helix. In both simulations, the initial configuration was a canonical right-handed alpha-helix. In the course of the MD trajectory in water (200 ps), the helix clearly destabilized and began to unfold after 100 ps. In the TFE solution, two stable parts of helical regions were observed after 70 ps of a 200-ps MD simulation, supporting the notion that TFE acts as a structure-forming solvent.     

Metabolic response to standardised exercise test in standardbred trotters with red cell hypervolaemia

Plasma concentrations of lactate, amino acids, ammonia and products of purine catabolism were studied before, during and after a standardised incremental exercise test in 29 Standardbred trotters admitted to the clinic for exercise tolerance testing. According to their red cell volume the horses were divided into red cell normovolaemic and red cell hypervolaemic (polycythaemic) groups. The exercise-response curve for taurine differed significantly in the two groups, whereas all the other amino acids behaved similarly. The [branched-chain amino acid]/[alanine] ratio, a proposed indicator for the use of amino acids in gluconeogenesis, was at rest significantly higher in the polycythaemic horses. Post-exercise concentrations of ammonia and allantoin, both end products of ATP breakdown, were lower in the polycythaemic horses. No differences were observed in the VLA4 and V200 markers for lactate and heart rate responses to incremental exercise, the oxidative capacity of the gluteus medius muscle, the enzyme activities or the post-exercise concentration of lactate, uric acid and hypoxanthine. It is concluded that horses with red cell hypervolaemia behave in a submaximal standardised exercise test on a treadmill in the same way as do red cell normovolaemic horses. The results suggest that the rate of amino acid utilisation in gluconeogenesis and the ability of amino acids to produce energy aerobically may be elevated in polycythaemic horses.     

Up-regulation of neutral endopeptidase (CALLA) in human neutrophils by granulocyte-macrophage colony-stimulating factor

Neutral endopeptidase 24.11 (NEP/CALLA/CD10), an enzyme expressed on early lymphoid progenitors, neutrophils, and various other cell types, inactivates many biologically active peptides, including the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Inhibition of CD10/NEP on the surface of human neutrophils (PMNs) in vitro inhibits migration toward this chemotaxin, suggesting that enzymatic inactivation by NEP regulates the neutrophil response to fMLP. Because PMNs in inflammatory sites are exposed to various cytokines, we evaluated the effects of selected cytokines on CD10/NEP activity in vitro. Of five cytokines tested--interleukin-1 (IL-1), IL-6, and IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor (GM-CSF)--GM-CSF provided the most consistent increase in surface NEP activity. Low concentrations (10(-9)-10(-7) M) of GM-CSF increased NEP activity in a time- and concentration-dependent manner to more than 225% that of control (phosphate-buffered saline-treated) cells. Cytofluorometry of cells stained with a fluorescent antibody to CD10 indicated that GM-CSF increased expression of surface CD10/NEP antigen in a similar manner. The effect of GM-CSF on NEP activity was enhanced still further by simultaneous exposure to IL-1, suggesting that combinations of cytokines may direct and regulate the neutrophil response within an inflammatory site. Rapid upregulation of CD10/NEP underscores the importance of this enzyme for control of peptide mediators of inflammation.