Generation of a zinc and rhodium containing metallomacrocycle by rearrangement of a six-coordinate precursor complex.

Two pentadentate N3,P2 ligands coordinate zinc(ii) by their N3 pocket. Four free phosphine donors allow the coordination of four AuCl moieties leading to a pentanuclear ZnAu4 complex. In contrast, the attempt to use the phosphines for chelating coordination of two Rh(CO)Cl units results in a well-organized rearrangement that ends up with the formation of a metallomacrocycle in high yields.

Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model. MATERIALS AND METHODS: Nine adult sheep were included. Temperature probes were introduced into the frontal and temporal brain cortices bilaterally. The cooling catheter system was introduced into a common carotid artery. Selective blood cooling was applied for 180 minutes. Systemic and local brain temperatures were measured during cooling and rewarming. Common carotid artery diameters and flow were measured angiographically and by Doppler sonography. RESULTS: The common carotid artery diameter was between 6.7 and 7.3 mm. Common carotid artery blood flow velocities increased moderately during cooling and after catheter removal. Maximum cerebral cooling in the ipsilateral temporal cortex was -4.7°C (95% CI, -5.1 to -4.0°C). Ipsilateral brain temperatures dropped significantly faster and became lower compared with the contralateral cortex with maximum temperature difference of -1.3°C (95% CI, -1.5 to -1.0°C; P < .0001) and compared with systemic temperature (-1.4°C; 95% CI, -1.7 to -1.0°C; P < .0001). CONCLUSIONS: Sheep proved a feasible animal model for the intracarotid cooling catheter. Fast induction of selective mild hypothermia was achieved within the cooled cerebral hemisphere, with stable temperature gradients in the contralateral brain and systemic blood. Further studies are required to demonstrate any therapeutic benefit of selective cerebral cooling in a stroke model.

Combined Selective Cerebral Hypothermia and Mechanical Artery Recanalization in Acute Ischemic Stroke: In Vitro Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment for patients with ischemic stroke. Selective, intracarotid blood cooling may initiate rapid and early brain hypothermia, reduce systemic effects, and allow combined endovascular mechanical thrombectomy. For this approach, a balloon cooling catheter system was designed and studied in vitro to optimize its cooling performance. MATERIALS AND METHODS: Computational fluid dynamics of blood cooling was performed within the common carotid artery lumen by using 3 different catheter designs (1-, 2-, and 4-balloon array). On the basis of these results, a first catheter prototype was manufactured, and its heat-exchange performance was tested in an artificial in vitro circulation simulating the common carotid artery lumen at different flow rates (inflow temperature of 37°C). RESULTS: In the computational fluid dynamics model, the catheter with the 4-balloon array achieved the highest cooling rate of -1.6°C, which may be attributed to disruption of the thermal boundary layers. In the in vitro study, cooling of the blood substitute at flow rates of 400 mL/min (normal common carotid artery flow) and 250 mL/min (reduced common carotid artery flow due to distal MCA occlusion) achieved a temperature drop inside the blood substitute along the cooling balloons of -1.6°C and -2.2°C, respectively. CONCLUSIONS: The feasibility of intracarotid blood cooling using a new catheter system was demonstrated in vitro. A serial 4-balloon array led to an optimized cooling capacity approaching optimum target temperatures of mild therapeutic hypothermia. To determine the therapeutic efficacy of combined selective therapeutic hypothermia and mechanical thrombectomy, further in vivo studies by using a model of temporary ischemia with large-vessel occlusion and recanalization are required.

Minimally invasive surgical treatment of coronary artery multivessel disease.

BACKGROUND: If coronary artery multivessel disease is the target of a minimally invasive procedure, either median sternotomy or cardiopulmonary bypass can be avoided. METHODS: We used an alternate technique instead of minithoracotomy and cardiopulmonary bypass to treat 102 patients (82 men, 20 women; age range, 39 to 82 years; median, 61.0 +/- 8.9 years) for coronary artery single-vessel, double-vessel, or multivessel disease between November 1996 and January 1998. Twenty-nine patients (22 men, 7 women; age range, 46 to 78 years; median, 69.0 +/- 8.4 years), who were in a high-risk group for the development of perioperative complications because of the use of cardiopulmonary bypass, received median sternotomy and a beating heart procedure using the Octopus stabilizing technique. The left anterior descending coronary artery was the target vessel in all patients except for 1, in whom the left internal mammary artery was used. RESULTS: There was no intraoperative death in either series. In the beating heart group (Octopus) 2 patients died on postoperative day 31 and 35, respectively, of postoperative pneumonia. CONCLUSIONS: Both techniques present safe alternative procedures to conventional coronary artery bypass grafting in patients with coronary artery multivessel disease.

Medicare and Medicaid financing of pain management.

Many Americans who endure pain are beneficiaries of the Medicare and Medicaid programs; however, these programs have many gaps and deficiencies and fail to cover some vital pain management services. Moreover, Medicare and Medicaid provider certification requirements and payment provisions fail to attend to pain management issues, creating disincentives for the provision of adequate pain treatment. Finally, Medicare and Medicaid surveillance and enforcement programs might be deterring adequate provision of pain management. This article reviews these problem areas, and suggests reforms that would address them.

Comparative study of laser damage threshold energies in the artificial retina.

Laser damage threshold energies produced from ultrashort (i.e., ⩽1 ns) laser pulses are investigated as a function of both pulse width and spot size for an artificial retina. A piece of film acts as the absorbing layer and is positioned at the focus of a variant on the Cain artificial eye [C. Cain, G. D. Noojin, D. X. Hammer, R. J. Thomas, and B. A. Rockwell, "Artificial eye for in vitro experiments of laser light interaction with aqueous media," J. Biomed. Opt.2, 88-94 (1997)]. Experiments were performed at the focal point and at two and ten Rayleigh ranges (RR) in front of the focus with the damage end point being the presence of a bubble imaged at the film plane. Pulse energy thresholds were determined for wavelengths of 1064, 580, and 532 nm with pulse durations ranging from the nanosecond (ns) to the femtosecond (fs) regime. For the at-focus data in the visible regime, the threshold dropped from 0.25 µJ for a 532 nm, 5 ns pulse to 0.11 µJ for a 580 nm, 100 fs pulse. The near-infrared (NIR) threshold changed from 5.5 µJ for a 5 ns pulse to 0.9 µJ for a 130 fs pulse at a distance two RR in front of the focus. The experiment was repeated using the same pulse widths and wavelengths, except the water path was removed to determine the impact of nonlinear self-focusing in water. A vertical microscope imaging system was employed in order to observe the threshold event. The NIR fluence threshold of 0.5 J/cm2 remained constant within an experimental uncertainty for all pulse widths, which corresponds to values in the literature [C. P. Lin and M. W. Kelly, "Ultrafast time-resolved imaging of stress transient and cavitation from short pulsed laser irradiated melanin particles," SPIE Laser-Tissue Interactions VI, Proc. SPIE2391, 294-299 (1995)]. The visible data also demonstrated a nearly constant fluence of 0.07 J/cm2. The disparity in thresholds between the two techniques arises from nonlinear optical phenomena related to propagation differences in the ocular fluid. © 1999 Society of Photo-Optical Instrumentation Engineers.

Differential effects of adult and perinatal lead exposure on morphine-induced locomotor activity in rats.

The effects of adult and perinatal lead treatment on the development of locomotor sensitization produced with repeated morphine administration was investigated. In Experiment 1, adult male rats received a diet containing 250 ppm lead acetate or a control diet for 43 days. Animals then received 10 mg/kg morphine sulfate or water vehicle (ip) and locomotor activity was monitored for 14 consecutive days. While both control and lead-exposed animals demonstrated a locomotor sensitization to morphine, the magnitude of the increased locomotor response was reduced in lead-treated animals. Subsequent analysis of blood-lead in the adult lead-exposed animals indicated residue levels ranging between 20 and 30 microg/dl. In Experiment 2, adult female rats were treated daily with 0, 8, or 16 mg lead via gavage for 30 days before breeding with non-exposed males. Lead exposure in dams continued through gestation and until pups were weaned at postnatal day (PND) 21. At PND 60, male offspring received morphine or vehicle challenges identical to those described in Experiment 1. Animals perinatally exposed to dams receiving 16 mg lead daily demonstrated an enhanced behavioral response to morphine relative to control animals. Analysis of offspring blood indicated lead levels below detectable limits (<1 microg/dl) for all animals. The results suggest exposure to lead at environmentally relevant levels produces long-lasting changes in drug-induced behavior, and the developmental period in which lead exposure occurs is a significant contributor to the manifestation of these effects.

Influence of median sternotomy on the psychosomatic outcome in coronary artery single-vessel bypass grafting.

OBJECTIVES: New less invasive surgical techniques for the treatment of coronary artery single-vessel disease have been developed by either avoiding median sternotomy or cardiopulmonary bypass or both, however, until now no prospective randomized trial has been carried out to compare these techniques to the conventional approach with special respect to the psychosomatical effects. METHODS: In a prospective randomized trial four different surgical techniques were compared. Group 1: conventional technique (median sternotomy, cardiopulmonary bypass) in ten patients (eight male, two female, age 59.6 +/- 11.0 years); Group 2: off-pump coronary artery bypass with median sternotomy in nine patients (six male, three female, age 65.7 +/- 11.1 years); Group 3: lateral minithoracotomy and cardiopulmonary bypass in eight patients (five male, three female, age 62.3 +/- 9.9 years). Group 4: off-pump procedure and lateral minithoracotomy in nine patients (eight male, one female, age 63.8 +/- 11.3 years). All patients due to coronary artery single-vessel disease. The tests used for psychosomatic situation were post-traumatic stress disorders scale, pain behavior rating scale, pain visual analog scale, and 6' walking-distance. For detection of false results due to surgical technical failures 3-month follow-up was undertaken including echocardiography and coronary angiogram. RESULTS: There were no deaths or major complications. Operative time was longer in lateral minithoracotomy procedures, but intensive care unit stay and hospitalization were equal in all groups. Pain visual analog scale and pain behavior rating scale showed a peak on post-operative day 4 in median sternotomy procedures. Post-traumatic stress disorder scale revealed higher values on post-operative day 4 and equalizing with lateral minithoracotomy procedures 1 month post-operatively. Six-minutes walking distance on post-operative day 4 was longer in the group with lateral minithoracotomy. Three-month follow-up revealed patency of all grafts. CONCLUSIONS: Even if surgery is successful in all procedures, operative time is longer in lateral minithoracotomy procedures without compromising intensive care unit stay and hospital stay. More pain with multiple post-traumatic stress disorders is related to median sternotomy, and post-operative convalescence is superior for lateral minithoracotomy procedures.

Public financing of pain management: leaky umbrellas and ragged safety nets.

Although many people in pain depend on public health care programs for aid, these programs cover pain relief only fragmentarily. He examines the gaps and deficiencies in Medicare and Medicaid funding of pain relief, and explores the effects of Medicare and Medicaid fraud enforcement on pain management.

Selling cost containment.

Health care expenditures in the United States have continued to grow despite efforts to control them. This Article discusses the need for health care reform, outlines the model that reform should follow, and considers why the United States has not progressed toward a workable solution. It introduces a single-payer approach to cost containment and explains how such an approach could be "sold" in the United States. Finally, the Article examines various ways to mobilize support for such health care reform.

Continuous monitoring of Naproxen by a cytochrome P450-based electrochemical sensor.

This paper reports the characterization of an electrochemical biosensor for the continuous monitoring of Naproxen based on cytochrome P450. The electrochemical biosensor is based on the drop-casting of multi-walled carbon-nanotubes (MWCNTs) and microsomal cytochrome P4501A2 (msCYP1A2) on a graphite screen-printed electrode (SPE). The proposed biosensor was employed to monitor Naproxen (NAP), a well-known anti-inflammatory compound, through cyclic voltammetry. The dynamic linear range for the amperometric detection of NAP had an upper limit of 300 µM with a corresponding limit of detection (LOD) of 16 ± 1 µM (S/N=3), which is included in NAP physiological range (9-300 µM). The MWCNT/msCYP1A2-SPE sensor was also calibrated for NAP detection in mouse serum that was previously extracted from mice, showing a slightly higher LOD (33 ± 18 µM). The stability of the msCYP1A2-based biosensor was assessed by longtime continuous cyclic voltammetric measurements. The ability of the sensor to monitor drug delivery was investigated by using a commercial micro-osmotic pump. Results show that the MWCNT/msCYP1A2-SPE sensor is capable of precisely monitoring the real-time delivery of NAP for 16 h. This work proves that the proposed electrochemical sensor might represent an innovative point-of-care solution for the personalization of drug therapies, as well as for pharmacokinetic studies in both animals and humans.

German health care reform: the next steps.

From the U.S. perspective, the German health care system offers much to be desired: universal access, moderate costs, and freedom of choice. The Germans consider their health care system to be in crisis, however, because the mechanisms on which they currently rely for financing and paying for health care, as well as the structures through which medical care is delivered, seem increasingly less viable. Germany has recently adopted modest reforms to partially address these problems. For longer term solutions, however, some in Germany are looking to U.S. managed care models, for better or for worse.