Synchronous pancreatic and scrotal tuberculosis: Double jeopardy.

We describe a patient who presented with scrotal swelling followed by non-healing and discharging scrotal sinuses, following local trauma and was initially suspected to have an infected scrotal hematoma. An evaluation revealed it to be scrotal tuberculosis. He also complained of upper abdominal pain and on transabdominal ultrasonography was detected to have a mass in the head of the pancreas. Evaluation of the pancreatic mass revealed it to be pancreatic tuberculosis. Both lesions responded well to anti-tubercular therapy. This is an unusual case of two rare sites of extrapulmonary tuberculosis presenting simultaneously in the same individual. Care needs to be exercised while evaluating any non-healing ulcers or sinuses and mass lesions in countries endemic for tuberculosis as this disease can be a great masquerader.

Graft-versus-host disease and phimosis.

Graft-versus-host disease rarely causes genitourinary problems. We report a case of pathological phimosis in a child secondary to chronic graft-versus-host disease.

The cost-effectiveness of repairing ruptured abdominal aortic aneurysms.

BACKGROUND: Although advances in technology have reduced the operative risk of elective abdominal aortic aneurysm (AAA) repair, the surgical repair of ruptured AAAs is associated with a much poorer prognosis and a higher cost. Accordingly, it has been suggested that patients with predictably high rates of morbidity and mortality from ruptured AAA may not benefit from surgical intervention. METHODS AND RESULTS: A cost-effectiveness analysis was performed with the use of a Markov decision-analytic model to compute long-term survival in quality-adjusted life years and lifetime costs for a hypothetical cohort of patients with ruptured AAAs managed with either a strategy of open surgical repair or no intervention. Probability estimates for the various outcomes were based on a review of the literature. Average costs of (1) the immediate hospitalization ($28,356) and (2) complications resulting from the procedure were based on the average use of resources as reported in the literature and from a hospital's cost accounting system. Our measure of outcome was the incremental cost-effectiveness ratio. For our base-case analysis, the repair of ruptured AAAs was cost-effective with an incremental cost-effectiveness ratio of $10,754. (Society is usually willing to pay for interventions with cost-effectiveness ratios of less than $60,000; for example, the costeffectiveness ratios for coronary artery bypass grafting and dialysis are $9500 and $54,400, respectively.) In sensitivity analyses, the cost-effectiveness of repairing ruptured AAAs was influenced only by alterations in the operative mortality. If the operative mortality exceeded 88%, repair of ruptured AAAs was no longer cost-effective. As an independent variable, increasing age had no substantial impact on the cost-effectiveness, although it is reported to be associated with increased operative mortality. It was necessary that the patient's cost of the initial hospitalization for ruptured AAA exceed $195,000 before repairing ruptured AAAs was no longer cost-effective. CONCLUSIONS: Our analysis suggests that despite the high cost and poor outcomes, the surgical repair of ruptured AAAs is still cost-effective when compared with no intervention. The cost of repairing ruptured AAAs falls within society's acceptable limits and therefore should not be a consideration in the management of patients with AAAs.

Hypertensive encephalopathy: complication in children treated for myeloproliferative disorders--report of three cases.

We routinely perform echo-planar diffusion-weighted sequences in all brain magnetic resonance (MR) imaging studies. When three children undergoing chemotherapy for acute leukemia presented with seizures, conventional MR images demonstrated what appeared to be acute, posterior, parasagittal infarcts. However, diffusion-weighted images were normal. These MR imaging findings were consistent with those of hypertensive encephalopathy. Early recognition and treatment of minimal hypertension in these patients allows reversal of encephalopathy.

Is carotid endarterectomy cost-effective in symptomatic patients with moderate (50% to 69%) stenosis?

OBJECTIVE: Recently published data from the North American Carotid Endarterectomy Trial revealed a benefit for carotid endarterectomy (CEA) in symptomatic patients with moderate (50% to 69%) carotid stenosis. This benefit was significant but small (absolute stroke risk reduction at 5 years, 6.5%; 22.2% vs 15.7%), and thus, the authors of this study were tentative in the recommendation of operation for these patients. To better elucidate whether CEA in symptomatic patients with moderate carotid stenosis is a proper allocation of societal resources, we examined the cost-effectiveness of this intervention. METHODS: A decision-analytic Markov process model was constructed to determine the cost-effectiveness of CEA versus medical treatment for a hypothetical cohort of 66-year-old patients with moderate carotid stenosis. This model allowed the comparison of not only the immediate hospitalization but also the lifetime costs and benefits of these two strategies. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year saved. We assumed an operative stroke and death rate of 6.6% and a declining risk of ipsilateral stroke after the ischemic event with medical treatment (first year, 9.3%; second year, 4%; subsequent years, 3%). The hospitalization cost of CEA ($6,420) and the annual costs of major stroke ($26,880), minor stroke ($798), and aspirin therapy ($63) were estimated from a hospital cost accounting system and the literature. RESULTS: CEA for moderate carotid stenosis increased the survival rate by 0.13 quality-adjusted life years as compared with medical treatment at an additional lifetime cost of $580. Thus, CEA was cost-effective with a CER of $4,462. Society is usually willing to pay for interventions with CERs of less than $60,000 (eg, CERs for coronary artery bypass grafting at $9,100 and for dialysis at $53,000). CEA was not cost-effective if the perioperative risk was greater than 11.3%, if the ipsilateral stroke rate associated with medical treatment at 1 year was reduced to 4.3%, if the age of the patient exceeded 83 years, or if the cost of CEA exceeded $13,200. CONCLUSION: CEA in patients with symptomatic moderate carotid stenosis of 50% to 69% is cost-effective. Perioperative risk of stroke or death, medical and surgical stroke risk, cost of CEA, and age are important determinants of the cost-effectiveness of this intervention.

The cost-effectiveness of endovascular repair versus open surgical repair of abdominal aortic aneurysms: A decision analysis model.

PURPOSE: Endovascular repair (EVR) is a less-invasive method for the treatment of abdominal aortic aneurysms (AAAs) as compared with open surgical repair (OSR). The potential benefits of EVR include increased patient acceptance, less resource utilization, and cost savings. This study was designed to determine whether the EVR of AAAs is a cost-effective alternative to OSR. METHODS: A cost-effectiveness analysis was performed using a Markov decision analysis model to compute long-term survival rates in quality-adjusted life years and lifetime costs for a hypothetical cohort of patients who underwent either OSR or EVR. Probability estimates of the different outcomes of the two alternative strategies were made on the basis of a review of the literature. The average costs of (1) the immediate hospitalization ($16,016 for OSR, $20,083 for EVR), (2) the complications that resulted from each procedure, (3) the subsequent interventions, and (4) the surveillance protocol were determined on the basis of average resource utilization as reported in the literature and from our hospital's cost accounting system. Our measure of outcome was the cost-effectiveness ratio. RESULTS: For our base-case analysis (70-year-old men with 5-cm AAAs), EVR was cost-effective with a cost-effectiveness ratio of $22,826-society usually is willing to pay for interventions with cost-effectiveness ratios of less than $60,000 (eg, cost-effectiveness ratios for coronary artery bypass grafting and dialysis are $9500 and $54,400, respectively). This conclusion did not vary significantly with increases in procedural costs for EVR (ie, if the cost of the endograft increased from $8000 to $12,000, EVR remained cost-effective with a cost-effectiveness ratio of $32,881). The cost-effectiveness of EVR was critically dependent on EVR producing a large reduction in the combined mortality and long-term morbidity rate (stroke, dialysis-dependent renal failure, major amputation, myocardial infarction) as compared with OSR (ie, a reduction in the combined mortality and long-term morbidity rate of OSR from 9.1% to 4.7% made EVR no longer cost-effective). CONCLUSION: Despite the high cost of new technology and the need for close postoperative surveillance, EVR is a cost-effective alternative for the repair of AAAs. However, the cost-effectiveness of this new technology is critically dependent on its potential to reduce morbidity and mortality rates as compared with OSR. EVR may not be cost-effective in medical centers where OSR can be performed with low risk.

Is thrombolysis of lower extremity acute arterial occlusion cost-effective?

BACKGROUND: The TOPAS (thrombolysis or peripheral artery surgery) trial randomized 544 patients with acute lower extremity ischemia to either surgery or thrombolysis. Although statistically equivalent 1-year morbidities and mortalities were demonstrated, the comparative cost-effectiveness of these two interventions has not been explored. MATERIALS AND METHODS: We constructed a Markov decision-analytic model to determine the cost-effectiveness of thrombolysis relative to surgery for a hypothetical cohort of patients with acute lower extremity arterial occlusion. Our measure of outcome was the cost-effectiveness ratio (CER), defined as the incremental lifetime cost per quality-adjusted life year gained. Estimates of 1-year outcomes were based on the TOPAS trial: mortality (lysis, 20%; surgery, 17%), amputation (lysis, 15%; surgery, 13%), the number of additional interventions required following the initial procedure (lysis, 544; surgery, 439). Procedural costs were estimated from the cost accounting system at the New York Presbyterian Hospital as well as from the literature. RESULTS: Operative intervention for acute lower extremity arterial occlusion extended life and was less costly compared to thrombolysis. The projected life expectancy for patients who underwent initial surgery was 5.04 years versus 4.75 years for initial thrombolysis. The lifetime costs were $57,429 for surgery versus $dollar;76,326 for thrombolysis. In performing sensitivity analyses, a threshold CER of $60,000 was considered what society would pay for accepted medical interventions. Thrombolysis became cost-effective if the 1-year mortality rate for lysis was lowered from 20 to 10.7%, if the amputation rate for lysis diminished from 15 to 3.9%, or if the 1-year cost of lysis could be reduced to a level below $13,000. CONCLUSIONS: Initial surgery provides the most efficient and economical utilization of resources for acute lower extremity arterial occlusion. The high cost of thrombolysis is related to the expense of the lytic agents, the need for subsequent interventions in patients treated with initial lysis, and the long-term costs of amputation in patients who fail lytic therapy.

Risk factors and their role in the diseases of the arterial wall.

The leading cause of death and disability in developed nations is atherosclerosis. Multiple risk factors, including hyperlipidemia, cigarette smoking, diabetes mellitus, and hypertension, predispose to the development of atherosclerosis. The mechanisms by which these risk factors exacerbate atherosclerosis involve the potentiation of endothelial and smooth muscle cell dysfunction as well as disturbances in coagulation. These mechanisms are discussed in detail in this chapter. Understanding the pathophysiology of how risk factors accelerate the progression of atherosclerosis will aid the clinician in attempts to treat the atherosclerotic patient.

Is routine duplex ultrasound surveillance after carotid endarterectomy cost-effective?

BACKGROUND: Although duplex ultrasound surveillance of patients after carotid endarterectomy (CEA) is routinely performed, the use of this policy has been questioned. We evaluated the cost-effectiveness of this strategy. METHODS: Using a decision-analytic Markov model that depicts the natural history of patients after CEA, we compared a strategy of duplex ultrasound surveillance to a strategy of no surveillance. Probability estimates were derived from the literature and costs were obtained from the hospital's cost accounting system. Sensitivity analyses were performed to test the robustness and stability of our base-case conclusion to variations in the underlying assumptions. RESULTS: Using baseline estimates we determined that duplex ultrasound surveillance after CEA reduced the incidence of stroke; however, this required significant additional expense, which resulted in an incremental cost-effectiveness ratio of $126,950. This ratio could decrease to a more acceptable level (less than $100,000) if a subset of patients could be identified whose rate of progression to greater than 80% stenosis exceeded 6% per year or whose stroke rate associated with uncorrected asymptomatic stenosis exceeded 2.6% per year. Also, the cost-effectiveness ratio was reduced to less than $100,000 if patients were younger than 55 years old at the time of initial CEA or if the cost of CEA could be reduced to less than $7,000. CONCLUSIONS: Duplex ultrasound surveillance after CEA is associated with an unfavorable cost-effectiveness ratio. However, this strategy may be cost-effective in younger patients or in those patients who have a more progressive form of disease.

Isolation and characterization of a monomethioninesulfoxide variant of interferon alpha-2b.

PURPOSE: To isolate and characterize a monomethioninesulfoxide variant of the commercially available therapeutic protein interferon alpha-2b. METHODS: The methionine (Met)-oxidized variant was isolated by reverse-phase high performance liquid chromatography and characterized by SDS-PAGE, peptide mapping and mass spectrometric analysis of the trypsin/V8-generated peptide fragments. The biological and immunological activities of the isolated variant were also evaluated. RESULTS: The rHuIFN alpha-2b variant was found to contain a Met sulfoxide residue at position 111 of the rHuIFN alpha-2b molecule. The far-UV CD spectra showed a slight loss of alpha-helical content and an increase in the beta-sheet contribution. The CD spectra indicate that both chromatographic conditions and Met oxidation contribute to the observed secondary structure changes. Both interferon alpha-2b main component and its methionine-oxidized variant showed different reactivity to monoclonal antibodies employed in immunoassays for the protein. CONCLUSIONS: A monomethioninesulfoxide rHuIFN alpha-2b variant was found to be present in the rHuIFN alpha-2b bulk drug substance in solution. The Met(111) residue was identified as Met sulfoxide by comparative tryptic/V8 mapping and mass spectrometric analysis. Nevertheless, the oxidation of the Met(111) residue did not seem to have a detectable effect on the biological activity of the molecule.

Selective precipitation of interleukin-4 using hydrophobic ion pairing: a method for improved analysis of proteins formulated with large excesses of human serum albumin.

In order to ensure the stability of protein pharmaceuticals, human serum albumin (HSA) is often added as an excipient, frequently in large excess. This makes chromatographic analysis of the stability of the active protein difficult. In the case of interleukin-4 (IL-4), separation from HSA can be achieved to some degree by size exclusion chromatography, but some HSA co-elutes with the IL-4. Hydrophobic ion pairing provides a method for selective precipitation of IL-4 from HSA. Hydrophobic ion pairing involves the electrostatic interaction of ionic detergents with oppositely charged polypeptides. Even when HSA is present in fifty-fold excess (w/w), the resulting precipitate contains greater than 70% of the IL-4. Selective precipitation with SDS produces enhancements in IL-4 over HSA of more than 2000-fold. This approach permits subsequent facile analysis of IL-4 by conventional reverse phase HPLC.

Pharmacologic effects of 4-chlorophenol in rats: comparison to clofibrate.

4-Chlorophenol (4-CP) is an identified trace contaminant in commercial clofibrate preparations and the pharmacologic effects of 4-CP have not yet been widely established. We have examined the dose-dependent effects of oral 4-CP and clofibrate administration on selected hepatic parameters and on serum glucose, cholesterol, and triglyceride concentrations in male rats. 4-CP treatment (0.00125-0.08 mmol/kg, twice a day) of rats for 2 weeks increased hepatic microsomal protein (20-30%) and cytochrome P-450 (20-190%) contents without changing liver/body weight ratios. Both 4-CP (0.0025 mmol/kg body wt, twice a day) and CPIB (0.4 mmol/kg body wt, twice a day) treatment to rats for 2 weeks caused significant elevations in microsomal cytochrome P-450 content and in the maximal activities of ethylmorphine, aminopyrine, and benzphetamine N-demethylase, but not in the activity of zoxazolamine 6-hydroxylase. With the same dose of 4-CP, time-dependent increases in hepatic microsomal protein, cytochrome P-450, and the activity of benzphetamine N-demethylase were observed for a 4-week period, and the induction of hepatic microsomal benzphetamine N-demethylase activity by 4-CP was associated with an increased enzyme synthesis. 4-CP treatment produced a marked morphologic change in liver cell ultrastructure, including a proliferation of mitochondria and endoplasmic reticulum at lower 4-CP doses. A clustering of intracellular organelles (mitochondria and endoplasmic reticulum) and a foamy cytoplasm were seen at doses greater than 0.01 mmol/kg, twice a day for 2 weeks, and at 0.0025 mmol/kg, twice a day for greater than 4 weeks. The effects of 4-CP and clofibrate on fasting blood glucose and fasting serum lipid levels were also monitored throughout an 8-week period. Both 4-CP (0.005 mmol/kg body wt, twice a day) and clofibrate (0.2 mmol/kg body wt, twice a day) produced significant elevations in fasting serum glucose levels, but this dosage of 4-CP did not alter serum lipid and lipoprotein parameters, whereas clofibrate significantly reduced serum total cholesterol and high density lipoprotein cholesterol levels. These results lead us to conclude that 4-CP does not contribute to the antilipidemic effects of clofibrate.

Serum lipoprotein and apoprotein concentrations in 4-(4-chlorophenyl)-2-hydroxytetronic acid and clofibrate-treated cholesterol and cholic acid-fed rats.

Influence of clofibrate and an aci-reductone, 4-(4-chlorophenyl)-2-hydroxytetronic acid (CHTA) on lipoproteins and apoproteins was studied in cholesterol- plus cholic acid-fed rats. CHTA (0.4 mmol/kg body wt, twice daily) significantly lowered serum total cholesterol and triglyceride concentrations at both 10 and 16 days, whereas clofibrate at the same dose did not alter serum cholesterol levels, but elevated serum triglyceride concentrations at 16 days. The abnormal cholesterol-rich very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL) produced by cholesterol plus cholic acid were significantly reduced in their cholesterol content by treatment with CHTA, a compound having an oxidation reduction potential. Conversely, clofibrate administration increased VLDL-cholesterol with concomitant decreases in IDL- and LDL-cholesterol concentrations. Administration of CHTA to cholesterol- plus cholic acid-fed rats significantly increased concentrations of VLDL and IDL, but had no effect on HDL protein. Both CHTA and clofibrate administration to cholesterol- plus cholic acid-fed rats significantly lowered IDL protein concentrations. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) studies of apoproteins revealed that clofibrate treatment significantly reduced apoC-III and C-II in VLDL, C-II in IDL, and apoA-IV and A-I in HDL. Rats treated with CHTA significantly raised apoC-II and C-III in HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential biochemical markers for infantile autism.

Biochemical markers are crucial to the development of early diagnosis of infantile autism. The blood concentrations of neuroanalytes epinephrine, norepinephrine, dopamine, and serotonin were elevated in autistic subjects (n = 13) as compared to normal controls (n = 10). Autistic subjects had peptide patterns (peaks I-V, Sephadex G-25) that were different from those of normal controls. Methionine-enkephalin has been tentatively identified from fraction I of autistic subjects by HPLC as one of a large number of peptides that appears to be elevated. The HPLC chromatographic patterns of fraction V from all autistic subjects show a peak with retention time of 7.6 min. The HPLC of control urine fraction V revealed no comparable peaks.

Assays of serum lipase: analytical and clinical considerations.

We evaluated three commercially available methods for determining lipase (EC 3.1.1.3) in serum--the Du Pont aca, Boehringer Mannheim Diagnostics (BMD), and Kodak Ektachem (EK) procedures--for their analytical properties and diagnostic efficiencies. Titrimetry was used as the comparative method. The BMD and EK methods showed better agreement with the titrimetric method, owing to the presence of the necessary cofactor, colipase, in their reagents. Colipase also increased the analytical sensitivity of the BMD and EK procedures as compared with the aca method. Determinations of serum lipase, by all methods, had a clinical sensitivity in excess of 80% for acute pancreatitis; the specificity of the lipase test was about 60%, or twice that of serum amylase. Serum lipase determinations with the current, simpler technology are superior to total amylase in the diagnosis of patients with acute pancreatitis. When a colipase-supplemented method is used, a serum lipase value greater than 10-fold the upper reference limit appears to be pathognomonic for acute pancreatitis or inflammation of organs close to the pancreas.

Triglyceride-lowering effect of dietary vitamin E in streptozocin-induced diabetic rats. Increased lipoprotein lipase activity in livers of diabetic rats fed high dietary vitamin E.

High vitamin E supplementation in the diets of streptozocin-induced diabetic rats eliminates accumulation of lipid peroxides in the plasma and the liver, returns the plasma triglycerides toward normal levels, and increases the activity of lipoprotein lipase. Vitamin E has no effect on the levels of insulin or glucose. These findings suggest that vitamin E increases the total hepatic triglyceride lipase activity by increasing the lipoprotein lipase activity possibly by protecting the membrane-bound lipase against peroxidative damage.

Serum lipids and lipoprotein composition in spontaneously diabetic BB Wistar rats.

Serum lipid and lipoprotein composition in spontaneously diabetic BB Wistar rats, nondiabetic littermates, and control Wistar rats was studied to elucidate diabetes-related abnormalities of lipoprotein composition. Serum total triglycerides and pre-beta-lipoprotein concentrations of insulin-treated spontaneously diabetic BB and nondiabetic littermate rats were significantly higher than those of control Wistar rats. Serum cholesterol and HDL cholesterol concentrations of spontaneously diabetic BB and nondiabetic littermate rats did not differ from controls. Concentrations of very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) of spontaneously diabetic BB and nondiabetic littermate rats were higher than those of normal rats. With sodium dodecylsulfate-polyacrylamide gel electrophoresis it was observed that the spontaneously diabetic BB and nondiabetic littermate rat VLDL contained higher percentages of apoE relative to total apoC when compared with control Wistar rats. With isoelectric focusing, apoC-II relative percentages in VLDL and HDL of both spontaneously diabetic BB and nondiabetic littermate rats were higher than apoC-II proportions in VLDL and HDL of controls. Apolipoprotein A-I of the control rat HDL showed four isoforms that focused at pI 5.8 (17.3%), 5.75 (30.6%), 5.65 (31.8%), and 5.55 (20.5%); however, the spontaneously diabetic BB and nondiabetic littermate rat HDL apoA-I was mainly represented by two isoforms that focused at pI 5.8 and 5.75. VLDL of both diabetic and nondiabetic BB rats contained higher levels of acidic apoE isoforms compared to their counterparts in control Wistar rats. Although HDL cholesterol concentrations of spontaneously diabetic BB rats remained normal, protein concentrations were higher resulting in a low cholesterol/protein ratio in HDL suggesting that the cholesterol-carrying capacity of spontaneously diabetic BB rat HDL could be less than normal and may be due to an abnormal apoA-I composition. Quantitative alterations of lipid and lipoprotein composition appear in the BB Wistar rat when compared to the Wistar rat, but some of the changes are more pronounced in the spontaneously diabetic BB Wistar rat.

Inhibition of macrophage-mediated tumor cell destruction by oxidized lipoproteins.

Lipoproteins (LP), isolated from human sera by column chromatography and density ultracentrifugation, were tested for their ability to inhibit macrophage (M phi)-mediated tumor cell destruction. None of the LP subclasses isolated by ultracentrifugation inhibited M phi-mediated cytolysis. Chromatography on a Sephadex G-200 column, prior to or following ultracentrifugation, resulted in the isolation of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) that prevented tumor cell destruction by M phi. High-density lipoprotein did not acquire the ability to inhibit M phi-mediated tumor cell killing under any condition. The acquisition of inhibitory activity by VLDL and LDL subclasses could be prevented by incorporation of EDTA and the bubbling of nitrogen gas into the chromatography buffer. These conditions inhibited the formation of lipid peroxides and thus prevented the formation of LP that inhibit M phi-mediated cytotoxicity. The mechanism by which oxidized LP prevents M phi from destroying tumor targets is not known. However, the mechanism does not appear to be related to a decrease in M phi viability.