Compressive Mechanical Properties of Porcine Brain: Experimentation and Modeling of the Tissue Hydration Effects.

Designing protective systems for the human head-and, hence, the brain-requires understanding the brain's microstructural response to mechanical insults. We present the behavior of wet and dry porcine brain undergoing quasi-static and high strain rate mechanical deformations to unravel the effect of hydration on the brain's biomechanics. Here, native 'wet' brain samples contained ~80% (mass/mass) water content and 'dry' brain samples contained ~0% (mass/mass) water content. First, the wet brain incurred a large initial peak stress that was not exhibited by the dry brain. Second, stress levels for the dry brain were greater than the wet brain. Third, the dry brain stress-strain behavior was characteristic of ductile materials with a yield point and work hardening; however, the wet brain showed a typical concave inflection that is often manifested by polymers. Finally, finite element analysis (FEA) of the brain's high strain rate response for samples with various proportions of water and dry brain showed that water played a major role in the initial hardening trend. Therefore, hydration level plays a key role in brain tissue micromechanics, and the incorporation of this hydration effect on the brain's mechanical response in simulated injury scenarios or virtual human-centric protective headgear design is essential.

A Coupled Experiment-finite Element Modeling Methodology for Assessing High Strain Rate Mechanical Response of Soft Biomaterials.

This study offers a combined experimental and finite element (FE) simulation approach for examining the mechanical behavior of soft biomaterials (e.g. brain, liver, tendon, fat, etc.) when exposed to high strain rates. This study utilized a Split-Hopkinson Pressure Bar (SHPB) to generate strain rates of 100-1,500 sec(-1). The SHPB employed a striker bar consisting of a viscoelastic material (polycarbonate). A sample of the biomaterial was obtained shortly postmortem and prepared for SHPB testing. The specimen was interposed between the incident and transmitted bars, and the pneumatic components of the SHPB were activated to drive the striker bar toward the incident bar. The resulting impact generated a compressive stress wave (i.e. incident wave) that traveled through the incident bar. When the compressive stress wave reached the end of the incident bar, a portion continued forward through the sample and transmitted bar (i.e. transmitted wave) while another portion reversed through the incident bar as a tensile wave (i.e. reflected wave). These waves were measured using strain gages mounted on the incident and transmitted bars. The true stress-strain behavior of the sample was determined from equations based on wave propagation and dynamic force equilibrium. The experimental stress-strain response was three dimensional in nature because the specimen bulged. As such, the hydrostatic stress (first invariant) was used to generate the stress-strain response. In order to extract the uniaxial (one-dimensional) mechanical response of the tissue, an iterative coupled optimization was performed using experimental results and Finite Element Analysis (FEA), which contained an Internal State Variable (ISV) material model used for the tissue. The ISV material model used in the FE simulations of the experimental setup was iteratively calibrated (i.e. optimized) to the experimental data such that the experiment and FEA strain gage values and first invariant of stresses were in good agreement.

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

Decreased use of post-renal transplant imaging.

OBJECTIVES: The current need to evaluate necessity and cost of diagnostic and therapeutic procedures extends to transplant services. We reviewed our experience over the past 3 years as we have moved away from routine post-transplant nuclear medicine scans, ultrasounds, and cystograms. METHODS: From January 1, 1992 to December 31, 1994, 252 kidney transplants were performed at Virginia Mason Medical Center. There were 74 live donor and 178 cadaver donor kidneys transplanted. The records of these patients were reviewed for the type and number of post-transplant imaging done during their initial hospitalization. RESULTS: During the study period, the number of post-transplant imaging studies per patient decreased from 2.7 to 1.4 (P = 0.000), the percentage of patients discharged without any studies rose from 2.8% to 24.4% (P = 0.001), and the trend in 1-year actual graft survival increased from 84.7% to 93.0% (P = 0.187). CONCLUSIONS: Post-transplant imaging studies can be safely reduced. Many patients with good initial graft function can avoid having any studies.

Mild hypertension. Should all patients be treated?

The benefits of drug therapy for mild hypertension have been difficult to demonstrate. Evidence supports treatment of persons with diastolic blood pressures greater than 100 mm Hg and persons with preexisting cardiovascular abnormalities. However, drug therapy for others with mild hypertension should be individualized, and physicians should be aware of the expected benefits and limitations.

Small center kidney transplantation.

We herein present the results of our first 100 kidney transplants. The 1-year patient and graft survivals were 94 and 74 per cent, respectively, for living related grafts, and 85 and 57 per cent, respectively, for cadaver grafts. These results compare favorably to the recent standards set by the American Society of Transplant Surgeons Standards Committee (95.1, 78.6, 88.6 and 55 per cent). Initial hospitalization averaged 21 plus or minus 7 days, while hospitalization during the first year after transplantation averaged 35 plus or minus 21 days. Average expenses (Medicare reimbursed) during the first 12 months after kidney placement were $29,572 plus or minus $6,468 for 15 successive patients. A total of 22 complications occurred within 1 year of transplantation and 11 required surgical management. Of 24 patients who survived 1 year with loss of graft function 15 (62 per cent) required transplant nephrectomy. Causes of death and types of complications are presented. Our results suggest that high quality kidney transplantation may be available to patients in small transplant centers.

Double-blind comparison of minoxidil and hydrallazine in severe hypertension.

1. Thirty moderately severely hypertensive patients were studied in a double-blind comparison of minoxidil and hydrallazine in combination with frusemide and propranolol. 2. Blood pressure control in both groups of patients was satisfactory but long-term control appeared to be better in the minoxidil group. 3. Renal function was well preserved in both groups. Evidence of cardiac hypertrophy was slow to resolve despite good control of blood pressure. Side effects were negligible, and patient acceptance and rehabilitation was excellent.

The renal sympathetic system and juxtaglomerular cells in experimental renovascular hypertension.

Marked reduction of the monoaminergic nerve fluorescence and catecholamine tissue content were demonstrated in the ischemic kidney of rats made hypertensive by unilateral renal artery stenosis (two-kidney Goldblatt hypertension). The nonischemic kidney showed a normal degree of fluorescence and catecholamine content. The electron microscope failed to demonstrate recognizable nerves around most of the glomerular arterioles of the ischemic kidney, whereas a normal rich innervation was observed in the nonischemic side. The juxtaglomerular index and renal renin content were elevated in the ischemic kidney and markedly reduced in the nonischemic kidney. Juxtaglomerular cells were present in the glomerular mesangium and ultrastructurally showed changes consistent with increased renin synthesis. The extent of disruption of the sympathetic system in renal hypertension might play a role in the degree of hypersecretory response of the juxtaglomerular cells to renal artery constriction.

Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide.

Thirteen patients with severe hypertension were treated with combined minoxidil, propranolol, and furosemide (mean daily doses 33 mg, 475 mg, and 578 mg, respectively) for nine to twenty-five months (mean 13.8). Average mean blood pressure while on aggressive therapy with conventional medication was 144 +/- 14 mm Hg; on minoxidil and propranolol it was 108 "/- 10 mm Hg (P less thator to optimum blood pressure control and required large doses of furosemide to control. Propranolol blunted the reflex tachycardia associated with arteriolar dilator therapy but all patients continued with a clinically hyperdynamic circulation. Seven of seven had elevated ejection fractions on echocardiogram, and two of three had elevated cardiac indices. Three of three who had heart catheterization had pulmonary hypertension which was aggravated by exercise. An additional three patients on hydralazine, propranolol, and furosemide also had pulmonary hypertension suggesting this is not unique to minoxidil. Two of thirteen developed pericardial effusions. Renal function improved in three and worsened in three.