Smart Kd-values, their uncertainties and sensitivities - Applying a new approach for realistic distribution coefficients in geochemical modeling of complex systems.

One natural retardation process to be considered in risk assessment for contaminants in the environment is sorption on mineral surfaces. A realistic geochemical modeling is of high relevance in many application areas such as groundwater protection, environmental remediation, or disposal of hazardous waste. Most often concepts with constant distribution coefficients (Kd-values) are applied in geochemical modeling with the advantage to be simple and computationally fast, but not reflecting changes in geochemical conditions. In this paper, we describe an innovative and efficient method, where the smart Kd-concept, a mechanistic approach mainly based on surface complexation modeling, is used (and modified for complex geochemical models) to calculate and apply realistic distribution coefficients. Using the geochemical speciation code PHREEQC, multidimensional smart Kd-matrices are computed as a function of varying (or uncertain) environmental conditions. On the one hand, sensitivity and uncertainty statements for the distribution coefficients can be derived. On the other hand, smart Kd-matrices can be used in reactive transport (or migration) codes (not shown here). This strategy has various benefits: (1) rapid computation of Kd-values for large numbers of environmental parameter combinations; (2) variable geochemistry is taken into account more realistically; (3) efficiency in computing time is ensured, and (4) uncertainty and sensitivity analysis are accessible. Results are presented exemplarily for the sorption of uranium(VI) onto a natural sandy aquifer material and are compared to results based on the conventional Kd-concept. In general, the sorption behavior of U(VI) in dependence of changing geochemical conditions is described quite well.

Stilbazulenyl nitrone decreases oxidative stress and reduces lung injury after hemorrhagic shock/resuscitation and LPS.

Multiorgan failure is a major cause of late morbidity and mortality after trauma. Reactive oxygen species generated during shock/resuscitation contribute to tissue injury by priming the immune system for an exaggerated response to subsequent inflammatory stimuli such as LPS. Stilbazulenyl nitrone (STAZN) is a novel second-generation azulenyl nitrone that has been shown to have potent antioxidant properties in a rat model of brain ischemia. We hypothesized that STAZN may confer protection against lung injury after shock/resuscitation and LPS by reducing oxidative stress and lowering the production of NF-kappaB-dependent pro-inflammatory cytokines. Sprague-Dawley rats were submitted to a two-hit model of lung injury involving hemorrhagic shock/resuscitation and subsequent intratracheal LPS injection, with and without intraperitoneal injections of STAZN. STAZN reduced overall lung injury in response to LPS alone and also after shock/resuscitation plus LPS. STAZN also reduced plasma levels of 8-isoprostane, a proxy measure of oxidative stress, indicating its antioxidant activity in vivo. The effect of STAZN was, at least in part, related to its effect on nuclear translocation of NF-kappaB and generation of the pro-inflammatory cytokine TNF-alpha. Azulenyl nitrones such as STAZN represent a promising novel class of antioxidants for treating organ injury.

New graphical method to measure silent periods evoked by transcranial magnetic stimulation.

OBJECTIVES: Manual methods of measuring duration of cortical silent periods (CSP) evoked by transcranial magnetic stimulation (TMS) depend upon subjective visual estimation of onset and offset. Because of this, the measurements are susceptible to poor rater reliability. We describe a graphical method to measure silent periods with greater precision. The statistical process underlying this new method is simple and particularly suited to signal detection in serially dependent data. METHODS: TMS-evoked silent periods were recorded in 13 healthy subjects. Two investigators subjectively measured silent period duration on each subject to estimate rater reliability. Using the graphical method, the mean and 99.76% variation limits of pre-stimulus electromyogram (EMG) activity were computed. Each averaged trial was displayed and CSP onset and offset detected when post-stimulus EMG activity moved outside the 99.76% limits. RESULTS: Maximum variation in silent period duration was 21.8 ms between the two investigators' subjective measurements. Silent period duration measured with the graphical method closely approximated measurements obtained using the manual method. It was possible to automate the procedure. CONCLUSIONS: This graphical method allowed precise measurement of CSP duration, independent of subjective estimations of onset or offset points. Further studies are necessary to determine if this method can provide a framework for other physiologic measures.

Subjective reactions of children to single-pulse transcranial magnetic stimulation.

Single-pulse transcranial magnetic stimulation is a useful tool to investigate cortical function in childhood neuropsychiatric disorders. Magnetic stimulation is associated with a shock-like sensation that is considered painless in adults. Little is known about how children perceive the procedure. We used a self-report questionnaire to assess children's subjective experience with transcranial magnetic stimulation. Normal children and children with attention-deficit hyperactivity disorder (ADHD) underwent transcranial magnetic stimulation in a study of cortical function in ADHD. Subjects were asked to rate transcranial magnetic stimulation on a 1 to 10 scale (most disagreeable = 1, most enjoyable = 10) and to rank it among common childhood events. Thirty-eight subjects completed transcranial magnetic stimulation; 34 said that they would repeat it. The overall rating for transcranial magnetic stimulation was 6.13, and transcranial magnetic stimulation was ranked fourth highest among the common childhood events. These results suggest that although a few children find transcranial magnetic stimulation uncomfortable, most consider transcranial magnetic stimulation painless. Further studies are necessary to confirm these findings.

Infection after total knee arthroplasty. A retrospective study of the treatment of eighty-one infections.

BACKGROUND: The clinical presentation of an infection at the site of a total knee arthroplasty can be used as a guide to treatment, including the decision as to whether the prosthesis should be retained or removed. We reviewed the results of treatment of infection after total knee arthroplasty to evaluate the effectiveness of four treatment protocols based on the clinical setting of the infection. METHODS: We retrospectively evaluated the results of treatment of eighty-one infections in seventy-six consecutive patients who either had an infection after a total knee arthroplasty or had multiple positive intraoperative cultures of specimens of periprosthetic tissue obtained during a revision total knee arthroplasty performed because of presumed aseptic loosening. The patients were managed according to one of four protocols. Five infections in five patients who had positive intraoperative cultures were treated with antibiotic therapy alone. Twenty-three early postoperative infections in twenty-one patients were treated with débridement, antibiotic therapy, and retention of the prosthesis. Twenty-nine late chronic infections in twenty-eight patients were treated with a delayed-exchange arthroplasty after a course of antibiotics. Seven acute hematogenous infections in six patients were treated with débridement, antibiotic therapy, and retention of the prosthesis. Seventeen infections in seventeen patients were not treated according to one of the four protocols. Sixteen late chronic infections were treated either with an arthrodesis (five infections) or with débridement, antibiotic therapy, and retention of the prosthesis (eleven infections). One acute hematogenous infection was treated with resection arthroplasty because of life-threatening sepsis. RESULTS: The mean duration of follow-up was 4.0 years (range, 0.3 to 14.0 years). Eleven patients who had an arthrodesis, a resection arthroplasty, or an above-the-knee amputation after less than two years of follow-up were included in the study as individuals who had a failure of treatment. In the group of patients who were managed according to protocol, the initial course of treatment was successful for all five infections that were diagnosed on the basis of positive intraoperative cultures, five of the ten deep early infections, all thirteen superficial early infections, twenty-four of the twenty-nine late chronic infections, and five of the seven acute hematogenous infections. Only one of eleven prostheses in patients who had a late chronic infection that was not treated according to protocol was successfully retained after débridement. CONCLUSIONS: Our treatment protocols, which were based on the clinical setting of the infection, were successful for most patients. A major factor associated with treatment failure was a compromised immune status. Bone loss and necrosis of the soft tissues around the joint also complicated the treatment of these infections.

Treatment of congenital dislocated hip by arthroplasty with femoral shortening.

This was a retrospective study of 15 hips in 11 patients with complete congenital dislocation of the hip treated by total hip arthroplasty and femoral shortening with a subtrochanteric double chevron derotation osteotomy. The mean age at the time of surgery was 51 years (range, 21-74 years), and the mean followup was 5.5 years (range, 2-8.5 years). Functional evaluation using the modified Harris hip rating system showed an excellent result in five hips and a good result in seven hips (80% success rate). The location of the hip center was lowered by a mean of 8.3 cm (range, 5.7-10.4 cm). Leg length discrepancy in seven patients with unilateral involvement was reduced from a mean of 3.9 cm (range, 1.7-8.2 cm) before surgery to a mean of 1.4 cm at the latest followup (range, 0-4 cm). The Trendelenburg sign was assessed in 10 of 15 hips and was corrected from a positive preoperative status to a negative postoperative status in eight of these 10 hips. There were no cases of nonunion, dislocation, nerve palsy, or radiographic loosening. The only complications were a supracondylar fracture below the femoral component in a patient with severe osteoporosis 6 months after surgery and loosening of the cemented titanium metal backed acetabular component in the same patient 1.5 years after surgery. The current series showed that total hip arthroplasty in combination with a subtrochanteric double chevron derotation osteotomy has promising short to midterm results in the treatment of complete congenital dislocation of the hip in adults.

Diagnostic and therapeutic applications of azulenyl nitrone spin traps.

Azulenyl nitrones have been recently demonstrated to constitute a new class of nitrone-based spin traps with the unprecedented capacity to tag free radicals by yielding characteristically colored and highly visible diamagnetic (and paramagnetic) spin adducts. In addition, a comparison of the oxidation potentials of azulenyl nitrones such as 1 and congeners to those of conventional nitrone spin traps previously investigated as potential antioxidant therapeutics such as N-tert-butyl-alpha-phenylnitrone and its related ortho-sodium sulfonate reveals that the azulene-derived spin traps are far more readily oxidized. These special features render azulenyl nitrones of interest with regard to both their distinct ability to engender the convenient use of colorimetric detection to monitor free radical-mediated oxidative stress in biological systems, and to their potentially enhanced efficacy as neuroprotective antioxidants vs. those conventional nitrone spin traps earlier examined as such. Herein is reported an overview of recent developments pertaining to the use of azulenyl nitrones in the detection of oxidative stress in animal models of amyotrophic lateral sclerosis and stroke, and to their neuroprotective activity in animal models of Parkinson's disease, stroke and neurodegeneration within the retina.

Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis.

Mutations of the SOD1 gene encoding copper/zinc superoxide dismutase (CuZnSOD) cause an inherited form of amyotrophic lateral sclerosis. When expressed in transgenic mice, the same SOD1 mutations cause progressive loss of spinal motor neurons with consequent paralysis and death. In vitro biochemical studies indicate that SOD1 mutations enhance free radical generation by the mutant enzyme. We investigated those findings in vivo by using a novel, brain-permeable spin trap, azulenyl nitrone. Reaction of azulenyl nitrone with a free radical forms a nitroxide adduct that then fragments to yield the corresponding azulenyl aldehyde. Transgenic mice expressing mutant SOD1-G93A show enhanced free radical content in spinal cord but not brain. This correlates with tissue-specific differences in the level of transgene expression. In spinal cord, the increase in free radical content is in direct proportion to the age-dependent increase in mutant human CuZnSOD expression. This increase precedes motor neuron degeneration. The higher level of human CuZnSOD expression seen in spinal cord compared with brain, and consequent difference in free radical generation, provides a basis for understanding the selective vulnerability of the spinal cord in this disease model.

Mutant CuZn superoxide dismutase in motor neuron disease.

CuZn superoxide dismutase (CuZn SOD) is one of several antioxidant enzymes that defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding CuZn SOD are found in patients with familial amyotrophic lateral sclerosis (FALS), a progressive and fatal paralytic disease that is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease can be reproduced in transgenic mice by expression of mutant human CuZn SOD. Recent studies both in vitro and in vivo suggest that the effect of mutation is to enhance the generation of oxygen radicals by the mutant enzyme. Thus, mutation converts a protective, antioxidant enzyme into a destructive, prooxidant form that catalyses free radical damage to which motor neurons are selectively vulnerable. Recent studies of neuroprotective agents in the FALS model show that inhibition of oxidative mechanisms (copper chelation therapy, dietary antioxidants, and coexpression of bcl-2) delays disease onset but does not extend disease duration. In contrast, inhibition of glutamatergic or apoptotic mechanisms (riluzole, gabapentin, and coexpression of glutamatergic or apoptotic mechanisms (riluzole, gabapentin, and coexpression of an inhibitor of caspase-1) has no effect on disease onset but extends survival by increasing the duration of symptomatic disease. Thus, neuroprotective agents differentially target the processes underlying disease initiation and propagation.

Azulenyl nitrone spin traps protect against MPTP neurotoxicity.

Azulenyl nitrones are a unique class of free radical spin-trapping compounds. We administered both a water-soluble and a lipid-soluble azulenyl nitrone to mice prior to administration of MPTP. Both compounds produced significant neuroprotection against depletions of dopamine and its metabolites measured 1 week after MPTP administration. There were no effects on MPP+ levels. These findings provide further evidence that free radical scavengers can produce significant neuroprotection against MPTP neurotoxicity.

Azulenyl nitrones: colorimetric detection of oxyradical end products and neuroprotection in the gerbil transient forebrain ischemia/reperfusion model.

We present analytical and neuroprotective data on a unique spin trapping agent derived from a novel chemical class known as an azulenyl nitrone (AZN). Based on Colorimetric properties, AZN was used to assess the formation of free radicals in a bilateral carotid occlusion (BCO) model in gerbils by monitoring the conversion of the nitrone to the aldehyde in affected tissue. In addition, AZN was tested as a neuroprotectant in this model regarding the preservation of CA1 pyramidal cells of the hippocampus following transient ischemia/reperfusion. AZN was electrochemically oxidized to give the aldehyde using an HPLC system with on line electrochemical oxidation. The oxidation potential associated with a 50% loss of AZN occurred at about 600 mV (half-wave potential versus palladium electrode). The major product detected as AZN oxidation occurred in an aqueous methanolic medium was the corresponding azulenyl aldehyde. Oxidation of AZN was inversely related to the formation of the aldehyde. Based on this test, we considered the in vivo conversion of AZN to aldehyde to be a measurement of oxidative stress in tissue. Results show that 0.3% of hippocampal AZN was converted to aldehyde in animals treated as shams. However, in gerbils subjected to a 7-min ischemic insult plus 7-min reperfusion, the conversion rate was about 3 times higher at 1.0%. In this model, surviving CA1 hippocampal neurons were counted from gerbils that were subjected to 7 mins of BCO followed by 5 days of reperfusion. In sham animals, about 89 cells were counted in a selected field of CA1 neurons. With injury, only 27 cells on average survived (70% loss) and were counted from this selected field. Under similar conditions and AZN treatment, 57 cells survived (36% loss). We conclude, therefore, that the demonstrated neuroprotection occurs because AZN neutralizes radicals which contribute to neuronal damage following ischemia/reperfusion.

Mutant Cu,Zn superoxide dismutase in motor neuron disease.

Cu,Zn superoxide dismutase (Cu,Zn SOD) is one of several anti-oxidant enzymes which defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding Cu,Zn SOD are found familial amyotrophic lateral sclerosis, a progressive and fatal paralytic disease which is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease can be reproduced in transgenic mice by expression of mutant human Cu,Zn SOD. Recent studies both in vitro and in vivo suggest that the effect of mutation is to enhance the generation of oxygen radicals by the mutant enzyme. Thus, mutation converts a protective, antioxidant enzyme into a destructive pro-oxidant form which catalyzes free radical damage to which motor neurons are uniquely vulnerable.

Comparison of the costs associated with medical and surgical treatment of obesity.

BACKGROUND: We compared the long-term costs and outcomes of gastric bypass versus medical therapy (very low-calorie diet plus weekly behavioral modification) for obese patients. METHODS: A successful outcome was defined as the loss of at least one third of excess weight that was maintained for the duration of the study. A minimal cost was assigned: $3000 for medical and $24,000 for surgical treatment. A cost per pound of weight lost for all patients successfully monitored was calculated. The Federal Trade Commission recently asked all weight loss programs to report this cost for patients at least 2 years after therapy. RESULTS: A total of 201 patients entered surgical and 161 entered medical therapy. The surgical group was initially heavier (mean body mass index [kg/m2] +/- SE = 49.3 +/- 0.6 versus 41.2 +/- 0.7, p < 0.01), but each group's lowest mean body mass index was similar (31.8 versus 32.1, respectively). A significantly higher percentage of patients in the surgical versus the medical group were still successful at year 5: 89% versus 21%. The cost per pound lost for medical therapy exceeded the cost of surgical therapy in the sixth posttreatment year (both more than $250/pound). CONCLUSIONS: Surgical treatment appears to be more cost-effective at producing and maintaining weight loss. It is imperative that long-term follow-up studies be funded to definitely establish this finding.

Are cementless acetabular components the cause of excess wear and osteolysis in total hip arthroplasty?

The authors reviewed 175 primary cementless Biologic Ingrowth Anatomic System stem total hip arthroplasties with average followup of 7 years for wear and osteolysis. Group I (24 hips: fixed titanium heads, cemented polyethylene cups) had a wear rate of 0.10 mm per year, and lysis of 0%. Group II (62 hips: fixed titanium heads, cemented metal-backed cups) had a wear rate of 0.13 mm per year, and lysis of 31%. Group III (15 hips: fixed titanium heads, cementless cups) had a wear rate of 0.25 mm per year, and lysis of 87%. Group IV (74 hips: modular cobalt chromium heads, cementless cups) had a wear rate of 0.17 mm per year, and lysis of 24%. Wear rate was associated with younger age and male patients, but not polyethylene thickness. Age, gender, weight, and component stability had no effect on osteolysis rates. Group III had the statistically highest osteolysis rate. Group I had the statistically lowest osteolysis rate. Therefore, features of cementless acetabular cups, such as the screw holes, roughness of the metal shell, and locking mechanism, may cause increased wear and osteolysis.

Double-chevron subtrochanteric shortening derotational femoral osteotomy combined with total hip arthroplasty for the treatment of complete congenital dislocation of the hip in the adult. Preliminary report and description of a new surgical technique.

Total hip arthroplasty for the treatment of complete congenital dislocation of the hip in the adult has been associated with high rates of complications, including acetabular component loosening, femoral or sciatic nerve palsy, and prosthetic dislocation. Placement of the acetabular component in the true acetabulum has yielded the most durable results, but leads to significant limb lengthening, which is associated with sciatic and femoral nerve palsy. Femoral shortening with a transverse osteotomy tends to be torsionally unstable. Increased femoral anteversion complicates femoral component placement and, if not corrected, can lead to postoperative anterior instability and component dislocation. A new surgical technique that combines total hip arthroplasty with a femoral subtrochanteric shortening derotational double-chevron osteotomy in complete congenital hip dislocation using standard components is described. This procedure has been successfully performed in seven hips.

Can morbidly obese patients safely lose weight preoperatively?

BACKGROUND: Preoperative weight loss is often suggested as a means of reducing operative risk in obese patients requiring laparotomy but there are no large studies documenting that this is feasible or helpful. Although several commercial products are available that provide high levels of protein with low levels of carbohydrates in convenient liquid preparations, recommendations regarding the extent to which weight loss can be pursued preoperatively are not available. PURPOSE: To determine whether it is practical and safe to have obese patients lose weight preoperatively. PATIENTS AND METHODS: We asked 100 severely obese patients requesting gastric bypass surgery to diet before their operations. Seventy patients agreed to diet by consuming a 420 Kcal, 70 g protein liquid diet daily for at least 1 month. RESULTS: Forty-seven patients lost at least 7.5 kg (mean +/- SD 17.1 +/- 0.7). The patients who successfully lost weight preoperatively (dieters group) were significantly heavier than patients (nondieters group) who did not lose weight (251% +/- 45% of ideal body weight [IBW] versus 229% +/- 33% IBW, respectively; P < 0.01), had a significantly higher ratio of men to women, and had psychiatric evaluations and psychological test scores that suggested significantly more psychopathology. Other biosocial and medical characteristics were similar. Postoperatively, the dieters and nondieters had similar rates for morbidity. Dieters and nondieters had no differences in wound-healing complications, and subgroups who had collagen deposition measured experimentally had similar amounts of hydroxy-proline accumulation in their wounds. CONCLUSION: These results suggest that a preoperative diet program appeals more to certain subgroups of severely obese patients than to others. An aggressive preoperative weight loss program that encourages patients to lose an average of 17 kg is safe and can be accomplished practically using available commercial products.

Fabellar impingement in total knee arthroplasty. A case report.

Fabellar impingement can cause postoperative pain, swelling, and catching, and can significantly compromise the results of total knee arthroplasty. The appearance of a large fabella on preoperative radiographs should raise suspicion about possible impingement. Impingement against the femoral or tibial component of the prosthesis should be assessed by inspection and palpation during trial reduction. The fabella can be removed via the anterior approach prior to component fixation, although it tends to be firmly embedded in the lateral head of the gastrocnemius tendon and requires careful dissection. A separate posterolateral approach will most likely be needed to accomplish complete fabellar excision after the components are secured.

Fluoroscopically positioned radiographs of total shoulder arthroplasty.

Between January 1990 and January 1991, 87 patients (100 shoulder arthroplasties) were radiographically examined with both standard and fluoroscopically positioned views. The sets of radiographs were compared and assessed for acceptability (the ability to interpret the interfaces), presence or absence of radiolucent zones, and differences between size and location of radiolucent zones. Fifty-six of the standard radiographs were unacceptable because of obliquity of the x-ray beam protection; only three localized views were unacceptable (p < 0.0001). Nineteen of the unacceptable standard views had radiolucent zones detected on the comparable fluoroscopic views. Forty-four radiographic sets were acceptable for evaluation. Of these, 27 sets had no differences; standard views showed the interface changes better in one, and localized views were better in 76 (p < 0.001). Thus in 68 of 100 total shoulder arthroplasties evaluated, clinical information that was not seen on standard radiographs was identified on fluoroscopic views. We conclude that fluoroscopic positioning is superior to standard radiographs in detecting implant-bone interface changes.

Preoperative insurance status influences postoperative complication rates for gastric bypass.

One hundred morbidly obese patients who had gastric bypass surgery were studied to determine how various demographic and medical variables affected complication rates, weight loss, and reduction in comorbidities associated with obesity. During the follow-up period (range: 12 to 59 months), 42 patients developed at least 1 complication. Twenty-three patients developed postoperative medical complications, 9 developed psychiatric complications, and 24 developed complications related to food ingestion. No significant relationships were observed between outcome and age, sex, age of obesity onset, or associated medical disorders. Striking differences in outcome were noted, however, when patients were contrasted according to their preoperative insurance status. Patients dependent on medical assistance, social security disability, or workman's compensation (publicly funded group) (n = 40) developed significantly more medical and psychiatric complications than did those (n = 60) who had private medical insurance (p less than 0.02). Despite the higher complication rate, both groups had the same average weight loss (44.9 +/- 15.3 kg for the publicly funded group versus 43.1 +/- 12.9 kg for those with private insurance) and similar reductions in percent excess weight (66.0 +/- 18.4% versus 75.7 +/- 23.0%) during the first postoperative year. All patients also had similar reductions in medication requirements for hypertension, diabetes, and degenerative joint disease. Additionally, 45% of the publicly funded insurance group who either received public welfare (n = 26) or disability benefits (n = 14) preoperatively were able to attain either full-time or part-time employment postoperatively which allowed them to decrease their level of support (58% and 21%, respectively). Forty-six percent of women in the private insurance group who were not working outside the home also began part-time or full-time employment postoperatively. All patients who were working preoperatively continued to work. These data suggest that although the risks associated with gastric bypass surgery are greater in patients dependent on public funding, these patients benefit significantly from the surgery.

Homogeneity and evaluation of the new NIST leaf certified reference materials.

The NIST has produced and is in the process of certifying two new leaf CRMs, SRM1515 Apple Leaves and SRM 1547 Peach Leaves, as replacements for the no longer available NBS Orchard Leaves and the almost depleted Citrus Leaves. These two new materials have been processed and are being thoroughly evaluated and should provide the most advanced natural matrix botanical trace-element reference materials available. Caution should be used in determining a basis weight (drying) for these CRMs because of their very fine particle size. Homogeneity has been established by instrumental neutron activation analysis on both leaf materials for five elements, to date, to better than 1.5% (1 s) for 100-mg sample sizes.