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.

Histologic and biochemical correlates of left ventricular chamber dynamics in man.

To investigate the relation between left ventricular chamber dynamics in humans and the quantitative analysis of the histologic and biochemical characteristics of left ventricular endomyocardial biopsy material, 15 patients with a wide range of ventricular function were studied. The pressure-volume relation was determined using simultaneous gated radionuclide angiography, echocardiography and micromanometer pressure. The derived chamber dynamics were then compared with quantitative histologic data (percent fibrosis and cell diameter) and adenosine triphosphate content measurements obtained from the left ventricular biopsy specimen obtained at the time of the pressure-volume studies. The measures of systolic function correlated linearly with high energy phosphate content. The adenosine triphosphate/protein ratio (nanomoles) was shown to parallel ejection fraction (r = 0.81), peak ejection rate (r = -0.73) and peak positive maximal rate of rise in left ventricular pressure (dP/dt) (r = 0.79). No correlation was observed between these variables and the percent fibrosis or cell diameter. Variable results were found in comparing the diastolic properties of the left ventricle with the biopsy data. In general, the high energy phosphate content correlated with measures of active relaxation, but not with the passive filling characteristics of the left ventricle. The adenosine triphosphate/protein ratio was linearly related to peak negative dP/dt (r = -0.74) and the peak filling rate (r = 0.76) but correlated less well with other measures of active and passive diastolic filling. No correlation was found between any diastolic variable and the percent fibrosis or cell diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of antigenemia in patients with invasive aspergillosis by solid phase (protein A-rich Staphylococcus aureus) radioimmunoassay.

A solid phase radioimmunoassay (RIA) was used to detect Aspergillus antigenemia in three patients, two with autopsy proved disseminated aspergillosis and one with a suspected infection. These RIA studies suggest that screening for antigenemia may be a specific and sensitive diagnostic test for disseminated aspergillosis.

Specificity in enzyme inhibition. 3. Synthesis of 5-substituted 2,2-dimethyl-4-imidazolidinones as inhibitors of tyrosine decarboxylase and histidine decarboxylase.

2,2-Dimethyl-4-imidazolidinone derivatives of the alpha-amino acids DL-phenylglycine (1), DL-phenylalanine (2), L-tyrosine (3), L-histidine (4), and L-tryptophan (5) were prepared in order to assess their specificity in inhibiting amino acid decarboxylases. Treatment of th alpha-aminonitriles with acetone in the presence of base and heat or treatment of the alpha-amino amides with acetone gave the title compounds in 48-85% yield. The compounds afforded moderate ability to inhibit the decarboxylation of L-phenylalanine, L-tyrosine, or L-histidine in vitro, using crude enzymes. 3 was a better inhibitor of tyrosine decarboxylase (S. faecalis) than 2. 4 and 5 were comparable to 3 in inhibiting tyrosine decarboxylase. 4 was more selective in inhibiting purified histidine decarboxylase (Cl. welchii) than 5, which was inactive. 4 was inactive against fetal rat histidine decarboxylase in vitro.

Synthetic inhibitors of Escherichia coli, calf thymus, and Ehrlich ascites tumor thymidylate synthetase.

In a study of active site binding the inhibition of thymidylate synthetase derived from Escherichia coli, calf thymus, and Ehrlich ascites tumor was examined using eight inhibitors. 5-Substituted 2'-deoxyuridine 5'-phosphate analogues used in this study are the hydroxymethyl, methoxymethyl, benzyloxymethyl, formyl, acetyl, allyl, and two potential active site alkylating substituents: 2,3-oxypropyl and the azidomethyl analogues. All compounds were competitive with the substrate, 2'-deoxyuridine 5'-phosphate; the most potent inhibitor was 5-formyl-dUMP (Ki = 0.1, 0.09, and 0.08 muM for the respective enzyme). The 5-hydroxymethyl, 5-benzyloxymethyl, and 5-azidomethyl derivatives of dUMP showed some differential inhibition; these compounds were two to three times more active against the ascites tumor enzyme than against the thymus enzyme.

Relation between premature ventricular contraction site of origin (defined by radionuclide phase analysis) and subsequent left ventricular function.

It has been suggested that the effect of a premature ventricular contraction (PVC) on left ventricular (LV) function depends on the site of origin of the PVC, and that the subsequent impairment of LV performance during a PVC may be more pronounced if baseline LV dysfunction is present. To evaluate these concepts, radionuclide angiographic phase image analysis of spontaneous PVCs was performed after acquisition of images from PVCs alone by a new gating procedure. The sites of the PVCs were localized to 1 of 3 right ventricular (RV) or 5 left ventricular (LV) regions by this method. LV function during PVCs was assessed and compared with baseline by noting the LV ejection fraction (EF) during PVCs, the difference between sinus LVEF and PVC EF, and the normalized PVC EF (PVC EF/sinus EF). Twenty-four patients had LV PVC sites and 19 had RV sites. LV function during a PVC appeared to be independent of either the ventricle of origin of the PVC or a specific site of origin within the ventricles. The resultant PVC ventricular function also appeared independent of sinus LVEF and sinus wall motion abnormalities. In addition, no correlation between coupling interval and any of the variables measured was demonstrated (although extremely short coupling intervals were not evaluated). These data suggest that the effects of PVCs on ventricular performance seen during ventricular ectopy are independent of the site of origin of the PVC, baseline wall motion abnormalities or PVC coupling interval in the population studied.

Localization of the site of ventricular premature complexes by radionuclide angiographic phase imaging.

To investigate whether gated radionuclide angiographic phase imaging is useful for visually displaying the origin of ventricular premature complexes (VPCs), 82 patients were studied by gating only VPCs. The VPC "origin" by the scintigraphic method was defined as the area of earliest phase and was compared with that predicted by 12-lead electrocardiographic criteria in all patients and to invasive electrophysiologic mapping in 10. Separating the right ventricle into 3 and the left ventricle into 4 segments, the phase imaging method and the electrocardiographic criteria agreed as to ventricle of VPC origin in 69 patients (84%) and segment of origin within each ventricle in 46 (56%). When baseline ventricular wall motion was analyzed, the 2 methods agreed to the ventricle of VPC origin in 31 of 33 patients (94%) with normal wall motion, 20 of 23 (87%) with segmental wall motion abnormalities and 19 of 26 (73%) with diffuse wall motion abnormalities. Agreement between the 2 methods as to specific segmental localization of the arrhythmia focus was noted in 21 of 33 patients (64%) with normal wall motion, 11 of 23 (48%) with segmental wall motion abnormalities and 12 of 26 (46%) with diffuse hypocontractility. In the 10 patients with endocardial mapping studies, the phase imaging technique confirmed the segment of VPC origin in all 10; the electrocardiographic method was accurate in 8. Thus, gated radionuclide angiographic phase imaging methods may be of value in noninvasively defining the origin of spontaneous VPCs. The visual format allows ready interpretation of the arrhythmia origin, and there may be an advantage to this approach over electrocardiographic morphometric criteria.

Hemodynamic correlates for timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve.

This study was designed to more clearly define the relation between various invasive hemodynamic measurements and left ventricular (LV) timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve. Twenty-eight patients were studied with simultaneous intracardiac micromanometer pressure and dP/dt recordings, gated radionuclide angiography and M-mode echocardiography. These techniques permitted multiple variables of systolic and diastolic function to be measured at a constant atrial paced rate of 100 beats/min. There was a strong correlation between peak ejection rate and ejection fraction (r = -0.97) and between peak ejection rate and maximum positive dP/dt (r = -0.85). There also was a strong correlation between peak filling rate and maximum negative dP/dt (r = -0.85). A weaker correlation existed between the time constant of LV relaxation and the peak filling rate (r = -0.49) and between the LV end-diastolic pressure and the peak filling rate (r = -0.62). There was no correlation between the modulus of chamber stiffness and filling rates, and no association was observed between the time to peak filling rate and the hemodynamic variables. Thus, under the conditions studied, the measured peak ejection and filling rate, determined from the radionuclide angiographic volume curve, correlated well with accepted invasive hemodynamic measurements.

Nondominant right coronary artery disease. A source for right ventricular infarction, anginal pain, and a positive exercise electrocardiogram.

A patient is described who presented with isolated episodes of typical angina pectoris. Subsequent exercise electrocardiogram was positive, and cardiac catheterization revealed a 90 percent lesion of a nondominant right coronary artery supplying only the right ventricular (RV) myocardium. The left coronary artery was normal. Stress gated equilibrium radionuclide angiograms (RNA) revealed a normal left ventricular exercise response and a markedly abnormal RV response (RV ejection fraction decreased from 31 percent at rest to 27 percent at peak stress). Nondominant right coronary artery lesions can be a source of angina pectoris, RV infarction, and a positive ECG response to exercise. Stress RNA can be useful in evaluating the functional significance of these lesions.

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.

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.

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.

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.

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)

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.

Right ventricular aneurysm due to ischemic disease. Diagnosis by radionuclide angiography with localization of the site of PVC origin by phase analysis.

A case of right ventricular aneurysm due to coronary artery disease in a 69-year-old male with no prior history of surgery or chest trauma is reported. The presence of the aneurysm was diagnosed by gated radionuclide angiography and confirmed by contrast angiography. This is the first description of an isolated right ventricular aneurysm on the basis of ischemic disease. In addition, the patient had recurrent ventricular tachycardia and frequent premature ventricular contractions (PVC's). Using radionuclide angiographic phase analysis of the PVC's, their apparent origin was localized to the margin of the right ventricular aneurysm.