A Rare Case of Monomicrobial Necrotizing Fasciitis Associated With an Initial Acute Compartment Syndrome.

In this article we report a rare case of necrotizing fasciitis presenting with the possible initial symptom of compartment syndrome. After treatment with broad spectrum and targeted antibiotics in addition to multiple fasciotomies, surgical debridement, and grafts the patient went on to uneventful healing within 6 months. This case report highlights the possibility of a compartment syndrome as the only initial symptom of a monomicrobial necrotizing soft tissue infection. While multiple case reports have documented group A streptococcal cellulitis as initiating a later acute compartment syndrome, this is to our knowledge the first case in the foot and ankle of compartment syndrome as a possible early symptom of a group A streptococcal (monomicrobial) necrotizing fasciitis.

The 25-year health care costs of women who remain overweight after 40 years of age.

BACKGROUND AND PURPOSE: Previously published reports strongly suggest that being overweight is a risk factor for coronary heart disease, hypertension, diabetes, gallstones, and osteoarthritis in women. Substantial health care and medication costs are associated with these chronic health conditions. We used an incidence-based analysis to estimate the excess costs associated with women maintaining an overweight status during the 25-year period from age 40 to 65 years. METHODS: The health care costs of three hypothetical cohorts of 10,000 40-year-old women were extrapolated to age 65. The non-overweight cohort maintained a body mass index (BMI; weight [kg]/height [m2]) of 21 to 24.9; the moderately overweight cohort maintained a BMI of 25 to 28.9; the severely overweight cohort maintained a BMI of > or = 29. The number of fatal and nonfatal health outcomes in each cohort for heart disease, hypertension, diabetes mellitus, gallstones, and osteoarthritis was calculated with their associated costs. RESULTS: We estimated that when compared with the non-overweight cohort of 10,000 women, the cohort of 10,000 women who had a BMI of > or = 29 incurred excess costs of $53 million over a 25 year period (discounted at 3% per year) and 497 excess deaths. The cohort of 10,000 women who had a BMI of 25-28.9 incurred excess costs of $22 million (discounted at 3% per year) and 212 excess deaths, compared with the non-overweight cohort. CONCLUSIONS: The results of this study indicate that an estimated $16 billion will be spent during the next 25 years treating health outcomes associated with overweight in middle-aged women in the United States. Thus, a substantial health burden is associated with the increasing prevalence of overweight women in the United States. Preventing excess coronary heart disease, gall-stones, osteoarthritis, hypertension, and diabetes through prevention of weight gain, particularly among reproductive-aged women, may be a cost-effective strategy.

Episodic versus prophylactic infusions for hemophilia A: a cost-effectiveness analysis.

OBJECTIVE: To assess the incremental cost-effectiveness of prophylactic compared with episodic care in boys with severe hemophilia A. SETTING: Eleven U.S. hemophilia treatment centers. METHODS: Charge data from a randomly selected cohort of 70 boys receiving episodic infusions for bleeding events and from all 27 boys receiving infusions prophylactically were collected from documents obtained from the hemophilia treatment centers during a period of approximately 2 years. Published and public sources were used for conversion to cost, lifetime earnings, and earnings losses from disability. A model was constructed for a hypothetical patient from ages 3 to 50 years by means of three infusion scenarios. RESULTS: The cohort receiving prophylactic treatment had fewer bleeding events each year (median, 3 vs 31) but used more concentrate (3323 vs 1015 units/kg per year). Factor VIII concentrate accounted for more than 93% of the cost of both episodic and prophylactic care. Compared with episodic infusion, prophylaxis from ages 3 to 20 years costs $1100 per bleeding event prevented, in comparison with $1380 for prophylaxis from ages 3 to 50 years. The total cost of prophylactic care from ages 3 to 50 years would equal the current total cost of episodic care if the price of the concentrate were decreased by 50%. CONCLUSION: Prophylactic care markedly reduces the number of bleeding events and should prevent joint function impairment, but at substantial cost.

A cost-effectiveness evaluation of newborn hemoglobinopathy screening from the perspective of state health care systems.

OBJECTIVE: To determine the most cost-effective strategy for newborn hemoglobinopathy screening from the perspective of state health care systems. STUDY DESIGN: Using Alaska as an example, we used decision analysis to compare a policy of no screening to universal or targeted screening with selective follow-up only of infants who are homozygous or compound heterozygous for an abnormal hemoglobin variant and to universal or targeted screening with complete follow-up, including follow-up of infants with clinically insignificant traits. Probabilities and costs were varied over values that might be expected for other states. RESULTS: Among the selective follow-up options, targeted screening would be the most cost-effective strategy for Alaska at a cost of $206,192 per death averted; by contrast, universal screening would prevent 50% more deaths at an incremental cost of $2,040,000 per death averted. Universal would be more cost-effective than targeted screening for several scenarios expected to occur in other states, including a high sickle cell disease prevalence, a low screening test cost, and a high cost per screen associated with racial targeting. Among the complete follow-up options, both targeted and universal screening would cost at least $200,000 per death averted over the range of all variables tested during sensitivity analysis; the incremental cost of universal versus targeted screening would be at least $600,000 per death averted. CONCLUSIONS: Our data suggest each state should determine the most cost-effective option based on state-specific values for sickle cell disease prevalence, test costs and racial targeting costs.

C-terminal truncation of the transcriptional activator encoded by areA in Aspergillus nidulans results in both loss-of-function and gain-of-function phenotypes.

Mutations truncating as many as 143 C-terminal residues from the transcriptional activator encoded by the areA gene, mediating nitrogen metabolite repression in Aspergillus nidulans, do not significantly reduce the ability of the areA product to activate expression of most genes under areA control. Such mutations can even have a gain-of-function, derepressed phenotype, consistent with a critical role for this region in modulating the activity of the areA protein. However, expression of a few genes under areA control is substantially impaired by such C-terminal truncations, indicating that regions of an activator protein can play differing roles in the control of different structural genes. This underlines the advantages of being able to monitor effects of areA mutations on expression of large numbers of structural genes. Additionally, it is shown that truncation of as many as 153 C-terminal residues, virtually all amino acids C-terminal to the DNA-binding region, is compatible with retention of some areA function.

Magnetic resonance imaging detection of early experimental periostitis. Comparison of magnetic resonance imaging, computed tomography, and plain radiography with histopathologic correlation.

This study characterizes the appearance of periosteal reaction by magnetic resonance imaging (MRI), and evaluates the efficacy of MRI versus computed tomography (CT), and plain film radiography (PF) in detecting early, experimentally induced periostitis. Acute Staphylococcus aureus osteomyelitis was induced in 30 legs of 20 New Zealand white rabbits. The rabbits were then imaged with MR, contrast-unenhanced CT, and PF 4 days after infection. Histologically, periosteal elevation was present in 27 cases. Periosteal ossification was seen in 23 cases, and cellular reaction without ossification in 4 cases. Periosteal reaction was demonstrated by PF in 21 (78%) and by CT in 20 (74%) cases. Evidence of periostitis was seen by MR in all 27% (100%) cases. MR resulted in two false-positive diagnoses. Multiple concentric, alternating high and low signal arcs demonstrated by MR in 19 (70%) cases represented periosteal ossification surrounded by fibrous or granulation tissue. These findings demonstrate the ability of MR to detect periostitis despite the absence of periosteal ossification. MR was more sensitive than CT (P less than .05) or PF (P less than .05) in the detection of experimentally induced periostitis.

Core decompression for avascular necrosis of the femoral head: correlation between long-term results and preoperative MR staging.

A long-term radiographic follow-up study was conducted on 24 patients (34 hips) who underwent core decompression of the femoral head for avascular necrosis (AVN). The purpose of the study was to assess the potential correlation between the extent of AVN, as determined with preoperative magnetic resonance (MR) imaging, and development of collapse. The preoperative MR results were classified into four categories: group A, no AVN; group B, less than 25% involvement of the weight-bearing portion of the femoral head; group C, 25%-50% involvement; and group D, more than 50% involvement. Histologic evidence of AVN was found in all 34 hips. Collapse occurred in none of the hips in groups A and B (n = 12), in three of seven hips (43%) in group C, and in 13 of 15 hips (87%) in group D. It is concluded that MR estimation of the extent of femoral head involvement with AVN may help in predicting which femoral heads will collapse shortly after core decompression, so that this invasive procedure can be avoided in patients at risk.

Acute experimental osteomyelitis and abscesses: detection with MR imaging versus CT.

Acute experimental osteomyelitis and abscesses were induced in the proximal tibia and surrounding soft tissues, respectively, in 67 New Zealand white rabbits. Fifty-three rabbits were injected with a Staphylococcus aureus solution and 26, with sterile saline in tibial medullae and/or surrounding soft tissues. Contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging were performed 7 days after inoculation. Immediately after imaging, the animals were killed and necropsy was performed. MR imaging was more sensitive than CT in the detection of osteomyelitis (94% vs 66%, P less than .025) and abscesses (97% vs 52%, P less than .001). MR imaging was equally specific as CT in the exclusion of osteomyelitis (93% vs 97%, chi 2 = 0) but less specific than CT in the exclusion of abscesses (77% vs 100%, P less than .025). The overall accuracy of MR imaging was somewhat, although not significantly, greater than that of CT in the detection of both osteomyelitis (93% vs 80%) and abscesses (87% vs 75%).

Hepatic recovery after biliary decompression of experimental obstructive jaundice.

Obstructive jaundice was produced in 11 dogs by common bile duct ligation for 4 weeks, then biliary decompression was performed by bilioenteric anastomosis. Animals were regularly studied over the 2 months after decompression by the following methods: (1) serum biochemistry was monitored; (2) light microscopic changes in serial liver biopsies were graded; (3) the respiratory characteristics of isolated hepatic mitochondria, obtained by open liver biopsy, were studied using an oxygen micro-electrode system; (4) in vivo handling of an hepatobiliary imaging agent (diisopropyl iminodiacetic acid) was studied by dynamic liver scintiscanning. None of these liver assessments were normalized after 7 to 10 days of biliary decompression. Our study suggests that biliary decompression of patients with extrahepatic biliary obstruction requires long periods of time to enable major recovery of the abnormal liver function induced by biliary obstruction.

Augmentation of diastolic function with phosphodiesterase inhibition in congestive heart failure.

Phosphodiesterase inhibition promotes both cellular uptake and release of calcium, which should thus facilitate both myocardial relaxation and myocardial contraction. To test the hypothesis that phosphodiesterase inhibition augments both diastolic and systolic ventricular function, parameters of left ventricular ejection and filling were measured in patients with dilated cardiomyopathy before and after therapy with the phosphodiesterase inhibitor enoximone. Baseline radionuclide ventriculography was performed in all subjects with derivation of left ventricular ejection fraction and peak diastolic filling rate. These parameters were again assessed after 3 months of therapy with either placebo (six patients) or enoximone (seven patients). Ejection fraction increased significantly (p less than 0.05) in the enoximone group (change from baseline = 11 +/- 14 ejection fraction units) but did not change in the placebo group (0.2 +/- 5 ejection fraction units). Enoximone administration was associated with a significant (p less than 0.05) increase in peak filling rate, from 0.9 +/- 0.5 to 1.4 +/- 0.5 end-diastolic volumes per second, which was noted in the placebo group (1.2 +/- 0.6 to 1.4 +/- 0.9 end-diastolic volumes per second; p = not significant). Thus, in comparison with placebo, exoximone augmented both diastolic and systolic function in dilated cardiomyopathy. This identifies an additional influence of this class of inotropic agent on the function of the intact ventricle that is consistent with previously described cellular mechanisms and that may significantly contribute to a restoration of normal hemodynamic status in dilated cardiomyopathy.

DISIDA kinetics measure liver function in dogs.

We have investigated the ability of 99Tcm-disofenin (DISIDA) kinetics to measure liver function. Two approaches have been used: first, quantitative analysis of serial liver images, and second, clearance estimation from whole blood concentration-time data. Graded liver dysfunction was produced in 11 dogs over three months by common bile duct ligation and surgical relief of biliary obstruction one month later. The kinetic analysis of serial liver images showed clear abnormalities during biliary obstruction, with calculated rates of liver uptake falling in stages from 11.09 to 5.15 cts s-1 (p less than 0.001), and rates of elimination from the liver from 8.8 to 1.6 x 10(-4) cts s-1 (p less than 0.0001). These parameters paralleled the deterioration and recovery of liver function through the experimental period, and had not fully recovered 7 weeks after relief of biliary obstruction (10.5 and 6.2 x 10(-4) cts s-1 respectively). Serial blood sampling after injection of DISIDA permitted calculation of whole blood disposition rates (for hepatic clearance). Mean values fell from 256 to 67 ml min-1 with chronic biliary obstruction (p less than 0.001), and returned to almost normal (206 ml min-1) 10 days after surgical relief of biliary obstruction. It is clear that the gradual nature of recovering liver function was more sensitively identified by image analysis than serial blood data. Serial liver biopsies showed marked changes following biliary obstruction. These improved over a period of 7 weeks following its relief, when there was still considerable residual abnormality. This work supports the view that hepatic abnormalities caused by biliary obstruction do not recover quickly following its relief. DISIDA kinetics can quantitate both major and minor degrees of hepatic dysfunction, and may prove to be a valuable method to quantitative liver function.

An asparaginase of Aspergillus nidulans is subject to oxygen repression in addition to nitrogen metabolite repression.

Of five amidohydrolase activities subject to nitrogen metabolite repression in Aspergillus nidulans, L-asparaginase shows clearest evidence of also being subject to repression by atmospheric oxygen. Such oxygen repressibility is only evident under nitrogen metabolite derepressed conditions. Asparaginase levels are also considerably elevated by areA300, an altered function allele of the positive acting wide domain regulatory gene areA mediating nitrogen metabolite repression and are drastically reduced by loss of function mutations in areA. A. nidulans has two L-asparaginase enzymes and it has been shown by the use of appropriate mutants that these regulatory effects are exerted on the expression of that specified by the ahrA gene but probably not that specified by the apnA gene.

Experimental infections of the musculoskeletal system: evaluation with MR imaging and Tc-99m MDP and Ga-67 scintigraphy.

Acute osteomyelitis, soft-tissue infection, or both were experimentally produced in 38 New Zealand white rabbits, and three-phase technetium-99m methylene diphosphonate, gallium-67, and magnetic resonance (MR) images were obtained 7 or 14 days after infection. There was no significant difference between radionuclide studies and MR images in the detection of osteomyelitis, but MR imaging was significantly more sensitive (100% vs. 69%; P less than .01) in the detection of soft-tissue infection. In addition, cellulitis could not be distinguished from soft-tissue abscess on radionuclide studies, whereas MR imaging was 92% accurate in depicting soft-tissue abscesses. Further research is necessary to determine how to relate these findings to true human clinical situations.

Pharmacokinetic studies of DISIDA disposition. II. Clinical studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) has been studied in normal subjects and patients with documented liver disease. The apparent overall whole blood disposition rates of radioactivity were calculated from serial blood data, in order to evaluate liver clearance of DISIDA. The measurements obtained clearly discriminated 9 normal subjects from 7 patients with severe liver disease causing jaundice--1233 mls/min vs 384 mls/min (P less than 0.002). Nine subjects with liver disease of insufficient severity to cause jaundice also had clearly abnormal DISIDA disposition--642 ml/min (P less than 0.05 for difference to controls). The time activity curves from all subjects showed biexponential elimination of blood activity, with a rapid (T1/2 = 3.8 min) and a slow disposition phase (T1/2 = 75 min) in normals. These curves were fitted by computer to the timed rate of hepatic uptake, simultaneously obtained by gamma imaging over the liver. It was not possible to satisfactorily fit these using a model which assumed distribution of a single compound within two body compartments. However, another which assumed the administration of two radioactive agents satisfactorily fitted the two types of data. This conclusion is consistent with our animal experiments which indicate the existence of two compounds in injected DISIDA with contrasting high and low hepatic extraction efficiency (Fraser et al. 1988). A pharmacokinetic approach to DISIDA disposition can yield quantitative information which discriminates different degrees of liver dysfunction, but the mechanisms involved are more complicated than previously thought, so that further study should permit very precise quantification.

Pharmacokinetic studies of DISIDA disposition. I. Animal studies.

The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced by chronic bile duct ligation (256 vs 58 ml/min, P less than 0.001). Blood levels of radioactivity fell in a biexponential fashion characterized by rapid and slow disposition phases, whose half times were 2.4 and 58 min in normal animals. On 3 occasions, plasma was obtained from 1 animal by exsanguination 35 min after the administration of DISIDA and rapidly transfused into a 2nd animal. The whole blood pharmacokinetics of the second (recipient) animal showed a predominance of the slow disposition phase and a small rapid phase. The hepatic extraction ratio of blood radioactivity was measured in 3 dogs and was high (75%-90%) early after injection of DISIDA, but fell rapidly to remain around 10%. These experiments suggest the presence of two different species in the radiopharmaceutical studied, each being removed from the blood stream by the liver, but at different rates. The contribution of renal clearance to overall whole blood pharmacokinetics was negligible, since three nephrectomized dogs displayed similar pharmacokinetics to normals. Whole blood DISIDA pharmacokinetics are more complex than previously thought but appear to be capable of providing an accurate measure of liver function.

Pulsus alternans induced by inferior vena caval occlusion in man.

To assess the effect of rapid preload reduction on left ventricular performance in nonischemic cardiomyopathy, 11 patients were studied during inferior vena caval (IVC) balloon occlusion. Five developed sustained pulsus alternans. During pulsus alternans, the strong beats demonstrated systolic performance characteristics similar to baseline values, despite a drop in both left ventricular (LV) end-diastolic diameter (66 +/- 13 to 61 +/- 13 mm; p less than 0.05) and LV end-diastolic pressure (21 +/- 8 to 9 +/- 6 mmHg; p less than 0.05). In contrast, the weak beats demonstrated a reduction in peak systolic pressure (130 +/- 36 to 109 +/- 33 mmHg; p less than 0.02), fractional shortening (20% +/- 4% to 17% +/- 9%; p less than 0.05) and peak positive dP/dt (1,006 +/- 224 to 921 +/- 287 mmHg; p less than 0.05). Measures of diastolic performance (peak negative dP/dt, the time constant of LV relaxation, the length of diastasis, and LV end-diastolic stress) were not different between baseline beats and the strong beats; and only LV end-diastolic stress differed when baseline beats were compared to the weak beats. When the strong beats were compared to the weak beats during induced pulsus alternans, significant differences were observed in peak systolic pressure, peak positive dP/dt, and fractional shortening, but no differences in any measured diastolic parameter was observed. A slight difference was noted in the left ventricular end-diastolic diameters, with the weak beat consistently beginning at a slightly smaller diameter (61 +/- 13; mm vs 59 +/- 13; p less than 0.05). In summary, these data are consistent with an augmentation and deletion of intrinsic contractile forces in association with an alternation in preload on a beat-to-beat basis as best describing left ventricular performance during pulsus alternans.

Failure of normalized ventricular filling rates to predict true filling rates.

Ventricular filling rates derived from radionuclide angiographic (RNA) time-activity curves are commonly expressed as normalized values. The assumption that normalized filling rates have a relationship to the actual filling rates was tested. RNA and contrast angiography were performed within 20 min of one another in 21 patients with widely disparate volumes. The RNA time-activity curve was converted from counts to milliliters by equating the contrast angiography derived end diastolic volume to the end diastolic count rate determined by RNA. Peak filling rates were normalized to end diastolic volume (EDV), stroke volume (SV, and peak ejection rate (ER). No significant correlation between the normalized filling rates and the true filling rate was found. Significant correlations were found between the EDV normalized filling rate and the EDV (r = -0.70) and the ejection fraction (r = 0.89). Normalized filling rates are dependent upon the normalizing variable and are not a pure measure of ventricular filling rates. As the technique of gated radionuclide angiography has matured, it has become apparent that there is more information in the time-activity curve than just the ejection fraction. The emptying rates, filling rates, time to peak emptying, and time to peak filling are parameters that are also available from the time-activity curve. Several authors have used this information to quantitate ventricular ejection and filling rates [1-6]. Since the contrast angiography literature would indicate that in some disease states ventricular filling is impaired [7,8], attempts have been made to identify impaired filling rates by radionuclide techniques. Using this method, decreased normalized filling rates have been found in groups of patients with coronary artery disease and it has been suggested that the observed decrease is due to impairment of active relaxation and/or to reduced compliance [2,3,5,6]. It has even been suggested that the decrease seen in the normalized filling rates may be a reflection of ischemia in the resting patient [6]. While these RNA derived parameters have been normalized to end diastolic volume by most authors, normalization to stroke volume and maximum ejection rate have also been suggested [9,10]. A possible rationale for normalization is that the activity measured over the ventricle is dependent upon many factors, including radionuclide dose, attenuation from the patient's chest wall, the specific type of collimator used, thickness of the crystal, and the window width.(ABSTRACT TRUNCATED AT 400 WORDS)