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Biomedical subjects

M Kutner

Publications and source records attributed to M Kutner.

At least 19 recordsLinked to original sources

In-hospital cost of percutaneous coronary revascularization. Critical determinants and implications.

BACKGROUND: Hospital charges associated with percutaneous transluminal coronary revascularization (PTCR) in the United States exceeded $6 billion in 1994 and are likely to be constrained in some manner in the near future. Despite this high cost to the public, little is known about the major determinants and sources of variability of PTCR. METHODS AND RESULTS: From a consecutive series of 1258 procedures with attempted PTCR at a single tertiary referral center, we analyzed 65 clinical, angiographic, physician, and outcome variables as potential correlates of total (hospital and physician) cost. Direct and indirect costs, both hospital and physician, were determined on the basis of resource utilization using "top-down" methodology and were available for 1237 procedures (1086 patients) (98.3%). Mean (+/- SD) patient age was 62 +/- 11 years, 76% were male, 3% had acute myocardial infarction, 71% had unstable angina, 58% had multivessel disease, left ventricular ejection fraction was 54 +/- 12%, 26% had use of at least one nonballoon revascularization device, and median length of stay was 4.4 days. Procedural success was obtained in 89%, and major complications (death, bypass surgery, or Q-wave myocardial infarction) occurred in 3.8%. The median cost was $9176, but it was asymmetrically distributed, and the interquartile and total ranges were wide ($7333 to $13,845 and $3422 to $193,474, respectively). Analyses of independent correlates of cost and loge(cost) were performed using multivariate linear regression in training and test populations. Modeling found 15 independent preprocedural correlates of loge(cost) (R2 = .37) and 23 overall correlates (R2 = .65), excluding length of stay per se. Additional of length of stay to the model increased the explanatory power of the model to R2 = .82. Preprocedural variables most predictive of loge(cost) included presentation with acute myocardial infarction, decision delay (> 48 hours between admission and diagnostic angiography and/or > 24 hours between angiography and intervention), weekend delay, use of intra-aortic balloon counterpulsation, intention to stent, creatinine > or = 2.0 mg%, and lesion complexity (modified American College of Cardiology/American Heart Association score) (all P < .001). In the model that included postprocedural variables as well, length of stay, noncardiac death, urgent bypass surgery, use of the Rotablator, Q-wave myocardial infarction, rise in creatinine > or = 1.0%, and blood product transfusion were all strong independent correlates of loge(cost) (P < .001). CONCLUSIONS: The range of total hospital costs associated with percutaneous intervention is extraordinarily wide. Baseline patient characteristics account for nearly half of the explained variance, but procedural complications and system delays account for much of the remainder. Quantification of the determinants of cost may promote more economically efficient care in the future.

Aged

Elevated concentrations of dopamine sulfate in plasma of cocaine abusers.

This study investigated the effect of cocaine abuse on peripheral catecholamines. Specifically, we measured the concentration of free dopamine, dopamine sulfate, free norepinephrine, norepinephrine sulfate, free epinephrine and epinephrine sulfate in plasma samples obtained from the blood of a group of patients with cocaine addiction (N = 15). The concentrations of free and sulfoconjugated catecholamines in plasma were measured by a radioenzymatic technique. The results of this study revealed significant (P < 0.0001) elevation in plasma dopamine sulfate (8926 +/- 1204 pg/mL) of cocaine addicts upon admission to an in-patient treatment facility when compared with the level of this dopamine metabolite in plasma of control subjects (2356 +/- 121 pg/mL). Furthermore, there was a significant (P < 0.0001) relationship between elevation in plasma dopamine sulfate levels and severity of cocaine use among these patients, and in the majority of cases the plasma levels of dopamine sulfate declined appreciably in time with abstinence from cocaine. In contrast, no appreciable difference was observed in the concentrations of either free or sulfate-conjugated norepinephrine and epinephrine in plasma of cocaine addicts as compared with controls. Differences in plasma dopamine sulfate among these patients versus controls may be interpreted as a reflection of activation of extracellular dopamine metabolism associated with chronic cocaine exposure in humans.

Adult

Treatment of human immunodeficiency virus-associated Hodgkin disease. Is there a clue regarding the cause of Hodgkin disease?

BACKGROUND: The occurrence of human immunodeficiency virus (HIV)-associated Hodgkin disease (HD) offers a unique opportunity to study the cause of HD and compare HIV-HD with the well-characterized HIV-non-Hodgkin lymphoma (NHL). METHODS: Eight patients with HIV-HD and 17 with HIV-NHL were treated. RESULTS: The complete remission (CR) rate in HIV-HD was 100% with mechlorethamine, vincristine, procarbazine, and prednisone or doxorubicin, bleomycin, vinblastine, and dacarbazine (median survival, > 38.0 months). HIV-NHL patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CR, 80%; median survival, 13.0 +/- 1.3 months). Durable CR was achieved with one to six cycles of chemotherapy (median, 4). There were no late relapses. The difference between the survival rate associated with chemotherapy-treated HIV-HD and chemotherapy-treated HIV-NHL approached statistical significance (P = 0.06). Analysis indicated that all patients with HIV-HD (n = 8) may have acquired HIV through intravenous drug abuse (IVDA) compared with 1 of 17 patients with HIV-NHL (P = 0.0001). A combined analysis (metaanalysis) of 157 patients with chemotherapy-treated HIV-NHL and 51 with chemotherapy-treated HIV-HD confirmed the significantly better survival of those with HIV-HD (P < 0.0001). CONCLUSIONS: Standard combination chemotherapy, truncated as necessary, offers survival outcomes that are at least equivalent and, perhaps, superior to previously published experimental approaches for HIV-NHL and HIV-HD. HIV-HD has a significantly better prognosis than HIV-NHL and is associated with IVDA. These data suggest that the etiologic agents of HIV-HD and HIV-NHL may be transmissible, identifiable, and unique.

Adult

Interrelationship between activation of dopaminergic pathways and cerebrospinal fluid concentration of dopamine tetrahydroisoquinoline metabolite salsolinol in humans: preliminary findings.

The main objective of this study was to determine whether the activation of dopaminergic pathways, through adrenal-caudate transplantation, stimulated the production of dopamine and salsolinol in cerebrospinal fluid (CSF) of patients with Parkinson's disease. Dopamine sulfate and salsolinol sulfate in CSF specimens were measured by radioenzymatic technique. The results of this study demonstrated that the replacement of degenerative nigrostriatal neurons with new dopamine-producing cells by adrenal brain transplants in patients with Parkinson's disease resulted in significant increase (p less than 0.05) in CSF levels of free dopamine, dopamine sulfate, free salsolinol, and salsolinol sulfate as compared with preoperative levels. Moreover, the oral administration of L-dopa to these transplanted patients caused substantial (p less than 0.001) elevation in CSF levels of free dopamine (before L-dopa, 146 +/- 57 pg/ml; after L-dopa, 575 +/- 207 pg/ml), dopamine sulfate (before L-dopa, 1966 +/- 945 pg/ml; after L-dopa, 41679 +/- 29326 pg/ml), free salsolinol (before L-dopa, 43 +/- 29 pg/ml; after L-dopa, 186 +/- 90 pg/ml), and salsolinol sulfate (before L-dopa, 405 +/- 477 pg/ml; after L-dopa, 2908 +/- 2572 pg/ml), respectively.

Adrenal Medulla

Physicians' attitudes toward oral anticoagulants and antiplatelet agents for stroke prevention in elderly patients with atrial fibrillation.

The use of oral anticoagulants and antiplatelet agents for the prevention of strokes in elderly patients with atrial fibrillation is controversial. Recent studies suggest that warfarin and aspirin can be safe and effective in selected patients. To determine attitudes toward this subject, we sent a questionnaire to 480 attending physicians at two major university-affiliated medical centers. Among the 251 responses (52.3%), 46 respondents (18.3%) used warfarin in atrial fibrillation of any cause, 175 (69.7%) used it in atrial fibrillation with transient ischemic attacks, 161 (64.1%) used it in patients with cerebrovascular accidents, and 196 (78.0%) used it in patients with mitral valve disease. One hundred twenty-nine (51.4%) believed that the risk of hemorrhage associated with warfarin outweighs the benefit, 61 (24.3%) were not convinced that warfarin prevents strokes in atrial fibrillation, and 42 (16.7%) believed it was difficult to monitor prothrombin time in the elderly because of poor compliance. Aspirin was used by 91 physicians (36.2%) in atrial fibrillation of any cause, 161 (64.1%) in patients with transient ischemic attacks, 140 (55.7%) in patients with cerebrovascular accidents, and 48 (19.1%) when patients were in sinus rhythm. We concluded that physicians are still hesitant to use oral anticoagulants and antiplatelet agents for the prevention of strokes in their elderly patients with atrial fibrillation. These agents are used most frequently after an ischemic episode (transient ischemic attack or cerebrovascular accident) has occurred or in patients with mitral valve disease.

Administration, Oral

Elevation of plasma salsolinol sulfate in chronic alcoholics as compared to nonalcoholics.

This report describes a radioenzymatic assay for the measurement of salsolinol and dopamine sulfate levels in plasma. It is based on a sulfatase-catalyzed hydrolysis of the sulfoconjugates followed by catechol-O-methyltransferase and [methyl-3H]-S-adenosylmethionine-catalyzed O-methylation of the resulting free salsolinol and dopamine. Rapid thin-layer chromatographic separation of the formed labeled metabolites attributed to the specificity of the differential enzymatic assay of salsolinol and dopamine. This assay was used to study plasma salsolinol and dopamine levels in a group of adult males (n = 36) serving as controls and a group of hospitalized chronic alcoholics (n = 18). The results (mean and range) of this preliminary study show that alcoholics had significantly (p less than 0.0001) elevated plasma concentration of salsolinol sulfate (497; 50-1331 pg/ml) as compared to controls (93; 0-232 pg/ml). This was accompanied by significant (p less than 0.0003) elevation in plasma levels of dopamine sulfate. Elevation of plasma salsolinol sulfate reported here may be interpreted as a reflection of abnormalities in oxidative metabolism of dopamine, metabolically derived acetaldehyde, and/or biological carbonyls in chronic alcoholics.

Adult

Resting energy expenditure in lung and colon cancer.

Elevated resting energy expenditure (REE) is a possible mechanism of cancer cachexia. We measured REE by whole-body direct calorimetry in patients with colon and non-small cell lung cancer and compared the results with REE in groups of healthy subjects and in patients with anorexia nervosa, with nonmalignant gastrointestinal (GI) disease, with miscellaneous reasons for weight loss, and with chronic lung disease. The mean REE of the cancer patients was not different from healthy subjects, those with GI disease, miscellaneous causes of cachexia, and chronic lung disease, and there was no significant difference in REE between those cancer patients with weight loss and controls with weight loss, except for the anorexia nervosa patients. The REE of the anorexia nervosa patients (female) was significantly lower than the REE of females with lung cancer. Weight loss correlated with REE in female lung cancer patients. Serial comparison of REE of ten cancer patients who lost 5% to 18% of their body weight during study showed no consistent change in REE. We conclude that patients with colon and non-small cell lung cancer, including those with weight loss, have REE similar to normal controls. Relative hypermetabolism may contribute to cancer cachexia, as may absolute hypermetabolism in some subsets of cancer patients.

Anorexia Nervosa

Pyridoxal 5'-phosphate levels in children with sickle cell disease.

Pyridoxal 5'-phosphate (PLP), the major coenzyme form of vitamin B6, is known to have antisickling properties in vitro. Recently, low plasma PLP levels were reported in a group of adults with sickle cell anemia. We measured the plasma PLP levels in a group of 55 asymptomatic nontransfused children with sickle cell diseases (SCD) to determine the prevalence of low plasma PLP levels in this population. Comparative studies were made with the measurement of PLP in three other groups serving as controls: Group A (black children, n = 36); Group B (white children, n = 37); and Group C (black adults, n = 13). PLP was measured directly in plasma by a radioenzymatic technique. The results of these comparisons showed that there was no statistically significant difference in plasma PLP of black children with SCD (10.7 +/- 10.0 ng/ml) as compared with black control children (group A, 9.0 +/- 12.3 ng/ml). The low plasma levels PLP in these two groups were significantly lower than that of the plasma PLP of white control children (group B, 15.85 +/- 15.92 ng/ml). This data suggest that a high prevalence of low PLP levels exists in black children seen at Grady Memorial Hospital, both with and without SCD.

Adolescent

Plasma concentrations of immunoreactive atrial natriuretic peptide in hospitalized cirrhotic and noncirrhotic patients: evidence for a role of deficient atrial natriuretic peptide in pathogenesis of cirrhotic ascites.

Atrial natriuretic peptide(s) (ANP), are thought to be released from the cardiac atria in response to distension. If decreased effective circulating blood volume is important in pathogenesis of ascites, plasma ANP levels would be expected to be decreased in ascitic subjects because of decreased atrial distension. To test this hypothesis, we measured plasma ANP by competitive radioimmunoassay in three groups of fasted, supine hospitalized subjects: nine noncirrhotic control subjects, 12 cirrhotics without ascites, and 17 cirrhotics with moderate to marked ascites. Immunoreactive plasma ANP concentrations were 195 +/- 41, 171 +/- 31, and 137 +/- 34 pg/ml (m +/- SD), respectively, in the three groups. The mean concentration in the group with cirrhosis and ascites was significantly (p less than or equal to 0.01) les than those of the other two groups, which did not differ from one another. These results support the concept that decreased effective circulating volume plays a role in pathogenesis of cirrhotic ascites, and that a relative deficiency of ANP plays a role in the sodium retention of decompensated cirrhosis.

Adult

Prevalence of low monoamine oxidase function in alcoholism.

Several studies have found a trend for low platelet monoamine oxidase activity (MAO) in alcoholism but with a great deal of overlap in MAO activity of alcoholics versus controls. The main objective of this study was to carry out a detailed assessment of MAO function that included the measurement of key kinetic parameters (i.e., Km, Vmax) in three groups of male subjects: (a) 51 hospitalized chronic alcoholics, (b) 16 recovering alcoholics with 2-10 years of abstinence, and (c) 21 controls. MAO activity was assayed radiochemically with [14C]tyramine as substrate (43-729 microM). The present study demonstrated that alcoholics had low platelet MAO activity (p less than 0.05). Kinetic analysis revealed a substantial reduction (p less than 0.01) in enzyme Vmax values of chronic and recovering alcoholics. Greater than 95% of the alcoholics had Vmax values lower than the smallest value of control subjects. Moreover, 100% of the alcoholics in both groups exhibited exceedingly low Vmax values that were below the 25th percentile of controls. In summary, results of MAO Vmax determinations provided us with a better separation of the alcoholics from controls. Measurements of platelet MAO function that include enzyme Vmax may provide us a reliable biochemical marker for alcoholism.

Adult

High-carbohydrate diet: antinatriuretic and blood pressure response in normal men.

The hypothesis that high-carbohydrate feeding leads to increased insulin secretion, sodium retention, and elevation in blood pressure was examined in seven healthy men. A baseline 7-day balance study on low (13%) or high (52%) carbohydrate was followed by a 2-wk balance on the alternate diet and a 1-wk balance on the baseline diet. Results indicated that changing carbohydrate intake caused a rapid (2-3 day) inverse change in urinary sodium excretion and balance. By the second week, however, urinary-sodium level returned to baseline accompanied by an inverse change in plasma aldosterone. No significant rise in blood pressure was detected throughout the study. High-carbohydrate feeding promotes sodium retention in normal subjects, but the effect is counterregulated by a reduction in plasma aldosterone. A high-carbohydrate diet in healthy subjects does not cause a significant short-term increase in blood pressure.

Aldosterone

Restriction mapping and close relationship of the DNA of Streptomyces erythraeus phages 121 and SE-5.

The biological properties and genome structure of two actinophages, 121 and SE-5, infecting Streptomyces erythraeus were characterized. They had the same host range (limited to S. erythraeus) and similar DNA G + C contents (around 60 mol %). Restriction maps of their genomes also showed many similarities. The close relationship between the two phages was confirmed by DNA hybridization experiments: large parts of their genomes were homologous, except for a segment in the middle of the map, where no hybridization was detected.

Bacteriophages

Technetium 99m pertechnetate measurement of renal blood flow distribution.

The accuracy of measuring anatomical blood flow using the rising slopes of first-pass time-activity curves were studied in six isolated dog kidneys. In each case, the canine kidney was placed on an open-circuit in vitro perfusion apparatus, which included an in-line flow meter and an in-line variable resistance for adjusting the flow rate. Time-activity curves from images acquired at 2-second intervals were generated for each kidney following injection of 4 mCi of 99mTc pertechnetate into the perfusate solution for each flow rate condition studied. The flow rate was calculated from the average slope of the ascending segment, initial rise to peak, of the time-activity curves. Excellent agreement was found between the radioactive tracer and established flow meter measurements (r = 0.995). With the availability of mobile gamma camera/computer systems, this technique could easily be utilized in evaluating perfusion function of transplant kidneys prior to surgery. Also, this technique can be useful in monitoring the renal anatomical distribution of blood flow in postsurgical patients.

Animals

Low levels of pyridoxal 5'-phosphate in patients with cystic fibrosis.

To determine the effect of cystic fibrosis on the regulation of plasma pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6, we measured this compound in plasma from 56 patients with cystic fibrosis. The concentration of PLP in plasma was assayed by a radioenzymatic technique. The results of this study showed that PLP concentration was decreased significantly (6.44 +/- 5.20 ng/mL, mean +/- SD; median 4.45 ng/mL) in patients with cystic fibrosis as compared with a group of hospitalized children with neither cystic fibrosis nor hepatic disease serving as a control group (13.2 +/- 5.04 ng/mL, mean +/- SD; median 12.5 ng/mL). Additionally, 25% of the population with cystic fibrosis exhibited exceedingly low plasma PLP level (less than 2.75 ng/mL). In patients with cystic fibrosis, significant inverse linear associations were found between plasma PLP and serum levels of SGOT and SGPT (PLP v SGOT: r = -.60, P less than .03; PLP v SGPT: r = -.50, P less than .03). This study demonstrated that a deficiency of plasma PLP is a common abnormality in cystic fibrosis and that the low PLP level may be a reflection of impaired vitamin B6 metabolism associated with this disorder.

Adolescent

Plasma L-dopa in the diagnosis of malignant melanoma.

We determined the concentration of L-dopa in the plasma of 98 patients with biopsy-proven melanoma, a dermatological neoplasm that is characterized biochemically by abnormal tyrosine metabolism. For 21 patients previously diagnosed as having melanoma but who were clinically free of disease (stage I), the mean concentration of L-dopa in plasma, 1.01 (SD 0.12) micrograms/L, was not significantly different from that of 32 normal controls, 1.23 (SD 0.16) micrograms/L. However, L-dopa was increased significantly (p less than 0.001) in the plasma of all of 65 patients with active disease (stage II), 2.08 (SD 0.46) micrograms/L, and was highest in 12 patients with stage III malignant melanoma, 8.40 (SD 3.50) micrograms/L. The development of metastases in four patients with stage II melanoma was accompanied by an increase in the concentration of plasma L-dopa. These studies suggest that measurement of plasma L-dopa may be useful in the diagnosis of melanoma.

Adult

Platelet-monoamine oxidase activity in Reye's syndrome.

Platelet and liver monoamine oxidase (MAO) activity (mean +/- SD) was evaluated in patients with liver-biopsy-proven Reye's syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 +/- 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] was observed in platelets on admission in all patients (n = 13) with Reye's syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 +/- 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1] and with liver disease (n = 10) [9.1 +/- 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 X h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reye's syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reye's syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reye's syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Adolescent

Development of a sensitive radioassay of histamine for in vitro allergy testing.

A radioenzymatic assay for the measurement of histamine is described, based on the incubation of histamine in the presence of histamine-N-methyl-transferase from rat kidney and [3H-methyl]-S-adenosyl-L-methionine (sp act 15 Ci/mmol) in phosphate buffer, 0.05 mole/l, pH 7.9, at 37 degrees C for 60 min. The N-[3H]-methyl]histamine generated was selectively extracted into toluene/isoamyl alcohol (3:2) and the quantity of the tritium in the sample was determined by liquid- scintillation counting. As little as 1 nmol/l of histamine can be detected. The assay is specific, with no cross-reactivity noted for several compounds closely related to histamine. The assay was used to measure the released histamine of a group of allergic subjects following the incubation of their blood with various allergens. A good correlation was found between histamine release from whole blood and the response of skin mast cells to intradermal antigen administration.

Allergens

Hypercatecholaminemia in Reye's syndrome.

To evaluate the role of catecholamines in Reye's syndrome, a specific and sensitive radioenzymatic assay was used to study plasma and CSF concentration of dopamine, norepinephrine, and epinephrine in 14 patients with liver-biopsy-proven Reye's syndrome. The results (median and range) revealed significant (P less than .04, P less than .0024, and P less than .030, respectively) elevation in plasma dopamine (131, 0 to 1,193 pg/mL), norepinephrine (1,455, 20 to 5,271 pg/mL), and epinephrine (345, 7.6 to 2,504 pg/mL) at the onset of the disease when compared with the level of these neurotransmitters in a group of hospitalized patients without hepatic disorders. There was a positive correlation between plasma catecholamines and stage of coma on admission (r = .54 to .86; P less than .001 to .024). Furthermore, the concentration of dopamine, norepinephrine, and epinephrine in the CSF increased significantly during the development of cerebral edema in all patients with Reye's syndrome as compared with concentrations in a control population. Hypercatecholaminemia may contribute to the encephalopathy of Reye's syndrome.

Adolescent