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Biomedical subjects

E Lin

Publications and source records attributed to E Lin.

18 recordsLinked to original sources

Panic disorder: relationship to high medical utilization.

The purpose of this review is to describe the relationship between panic disorder, somatization, functional disability, and high medical utilization. Data from community, primary-care, and specialty studies were reviewed to determine the prevalence of anxiety and panic disorder in these populations. Data from the Epidemiologic Catchment Area Study were reviewed to emphasize the effect of panic disorder on health-care utilization and health perception in a community population. Data on the prevalence of panic disorder in primary care and mode of presentation of primary-care patients with panic disorder were also reviewed. Finally, the epidemiologic psychiatric findings from our recent study of distressed high utilizers of primary care were presented. Panic disorder was found to occur in 1-3% of people in the study community and 1.4-8% of primary-care patients. Of people with or without psychiatric disorder, people with panic disorder in the community had the highest risk of having multiple medically unexplained symptoms and of being high utilizers of medical ambulatory services. People with panic disorder in the community compared to both community psychiatric and nonpsychiatric controls tend to perceive themselves as having poor physical health and to be high users of emergency and hospital inpatient services, as well as ambulatory services. Most patients with panic disorder present to their primary-care physician with somatic complaints, especially cardiac (tachycardia, chest pain), gastrointestinal (epigastric pain or irritable bowel syndrome), or neurologic complaints (headaches, dizziness, or presyncope). Patients who were distressed high utilizers of primary care had an extremely high prevalence of current panic disorder (12%) and lifetime panic disorder (30%), which supported the association between panic disorder and high medical utilization found in the Epidemiologic Catchment Area (ECA) Study.

Ambulatory Care

A randomized trial of psychiatric consultation with distressed high utilizers.

This study reports the results of a randomized trial of a psychiatric consultation intervention with distressed, high utilizing patients of 18 physicians in two primary care clinics. Psychiatric consultation was associated with a significant increase in the use of antidepressants in intervention patients compared with controls in the first 6 months after intervention. Intervention patients were also significantly more likely to continue antidepressant treatment than control patients. The primary care physicians receiving psychiatric consultations increased the rate of prescribing antidepressant medications in their practice from 32 prescriptions filled per 1,000 visits before their participation in four consultations to 44 new prescriptions per 1,000 visits in the 12-month period after. There were no significant differences between intervention patients and controls at 6 and 12 months after randomization in psychiatric distress, functional disability, or utilization of health care (ambulatory visits, radiographic and laboratory testing services, admissions to inpatient medical care).

Ambulatory Care

Spectroscopic imaging display and analysis.

A system for display of magnetic resonance (MR) spectroscopic imaging (SI) data is described which provides for efficient review and analysis of the multidimensional spectroscopic and spatial data format of this technique. Features include the rapid display of spectra from selected image voxels, formation of spectroscopic images, spectral and image data processing operations, methods for correlating spectroscopic image data with high resolution 1H MR images, and hardcopy facilities. Examples are shown for 31P and 1H spectroscopic imaging studies obtained in human and rat brain.

Humans

Adequacy and duration of antidepressant treatment in primary care.

Among a sample of 119 distressed high-utilizers of primary care, 45% of patients evaluated by a psychiatrist as needing antidepressant treatment had been treated in the year before the examination. However, only 11% of the patients needing antidepressants had received adequate dosage and duration of pharmacotherapy. In the year following the intervention, study patients whose physicians were advised regarding treatment during a psychiatric consultation were more likely to receive antidepressant medications (52.7%) relative to a randomized control group (36.1%). However, the intervention did not significantly increase the provision of adequate antidepressant therapy (37.1% vs 27.9%). Among study patients using antidepressants, patient characteristics did not differentiate patients who received adequate dosage and duration of antidepressant medications from those who did not. Analysis of data on the duration of antidepressant therapy for all health maintenance organization enrollees initiating use of antidepressants showed that only 20% of patients who had been given prescriptions for first-generation antidepressants (amitriptyline, imipramine, or doxepin) filled four or more prescriptions in the following six months, compared to 34% of patients who had prescriptions for newer antidepressants (nortriptyline, desipramine, trazodone and fluoxetine). Experimental research evaluating whether these newer medications (with more favorable side effect profiles) improve adherence, and thereby patient outcome, is needed.

Adult

A single transcription factor binds to two divergent sequence elements with a common function in cardiac myosin light chain-2 promoter.

The cardiac myosin light chain-2 (MLC-2) gene promoter contains several positive and negative cis-acting sequences that are involved in the regulation of its expression. We describe here the properties of two activator sequences, elements A and P, and their DNA-binding factors (ABFs). Element A (CCAAAAGTGG), located at -61, has homology with the evolutionarily conserved sequence CC(A/T)6GG, present in the genes of many contractile proteins. Element P (TAACCTTGAAAGC), located 114 bp upstream of element A, is conserved in both chicken and rat cardiac MLC-2 gene promoters. Deletion mutagenesis demonstrated that these two elements are involved in the positive regulation of MLC-2 gene transcription. At least two sequence-specific element A-binding proteins, ABF-1 and ABF-2, were identified by gel shift analysis of the fractionated cardiac nuclear proteins. ABF-1 binds to element A with strict dependence on the internal element A sequence AAAAGT. In contrast, ABF-2 exhibits a relaxed sequence requirement, as it recognizes the consensus CArG and CCAAT box sequences as well. ABF-2 also recognizes the distal element P despite the fact that the sequences of elements A and P are divergent. DNase I footprinting, methylation interference, and gel shift analyses demonstrated unequivocally that the element A-DNA affinity-purified protein ABF-2 binds to element P with sequence specificity. Since both elements A and P play a positive regulatory role in MLC-2 gene transcription and bind to a single protein (ABF-2), it would appear that ABF-2 is a key transcription factor with the ability to recognize divergent sequence elements involved in a common regulatory pathway during myogenesis.

Animals

Biochemical liver profile in hemochromatosis. A survey of 100 patients.

To determine the frequency of liver profile abnormalities in hereditary hemochromatosis, we under took a retrospective survey in 100 patients, all of whom had undergone liver biopsy. Liver histology was compared with the biochemical profile, which included aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin and albumin determinations. Mild abnormalities in the AST and ALT levels were seen in more than 65% of patients. Patients with cirrhosis had significantly greater elevations in AST, ALT, and alkaline phosphatase, and a significant decrease in albumin (p less than 0.05). Proband cases had more frequent abnormalities than discovered cases within families. Accordingly, we find that mild abnormalities in the biochemical liver profile are common in hemochromatosis and suggest that patients with an unexplained abnormality in the liver profile should be screened for hemochromatosis with a serum ferritin and transferrin saturation.

Adolescent

Respiratory failure as presentation of achalasia of the oesophagus.

A 68-year-old woman with a history of hiatus hernia developed aspiration pneumonia after operation for fractured neck of femur. After 8 days, acute respiratory failure was caused by massive retention of air and food in the oesophagus. This was relieved by aspiration, and treated by balloon dilation of the gastric cardia.

Aged

Somatization: a spectrum of severity.

OBJECTIVE: The DSM-III-R diagnosis of somatization disorder requires that a patient have a specific number of medically unexplained somatic symptoms. This number of symptoms was developed by committee consensus, and it is not clear whether patients with this specific number of symptoms can be differentiated from patients with lower but still substantial numbers of somatic symptoms. METHOD: Fifty-one percent of 767 high utilizers of two primary care clinics were identified as distressed by an elevated SCL anxiety, depression, or somatization scale score or by their primary care physician. The Diagnostic Interview Schedule (DIS) was completed on 119 distressed high utilizers who were randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The 119 distressed high utilizers were separated into four categories according to the number of unexplained somatic symptoms found on the DIS and were compared on demographic, psychiatric distress, disability, medical, and health utilization variables. RESULTS: The data suggest that many clinical and behavioral features of somatization are significantly more common in patients with four to 12 medically unexplained somatic symptoms rather than changing dramatically at the diagnostic threshold for somatization disorder. The data also showed that patients who meet the DSM-III-R criteria for somatization disorder are severely ill and have a high burden of psychiatric illness and disability. CONCLUSIONS: The results suggest that the DSM-IV somatoform disorders section should include somatization disorder, an abridged definition of somatization disorder often associated with anxiety and depression, as well as a type of somatization associated with an adjustment disorder.

Activities of Daily Living

Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption.

To determine the relative importance of patent ductus arteriosus, indomethacin, and intestinal distension as factors that promote terminal ileum ischemia, eight near-term fetal lambs were surgically prepared by in situ cannulation of the proximal and distal ends of a loop of terminal ileum, formalin infiltration of the ductus arteriosus, and placement of a snare around the ductus arteriosus to control its patency. The incisions were closed; the lambs were delivered and mechanically ventilated. Terminal ileum blood flow and oxygen consumption were measured after the loop of ileum had been distended with 0.9% NaCl to luminal pressures of 1-2, 7, and 18 mm Hg (0.13-0.26, 0.93, and 2.38 kPa) (pressures observed in the intestinal lumen after feeding and during pathologic conditions). The effect of these pressures on terminal ileum blood flow and oxygen consumption was examined: 1) with ductus closed, 2) with ductus open, and 3) 1 h after administration of indomethacin (0.3 mg/kg; 0.8 mumol/kg) with ductus closed. Both open ductus and indomethacin produced a significant decrease in intestinal blood flow. This occurred over the entire range of luminal pressures examined. In all three study conditions, terminal ileum blood flow fell commensurate with a fall in perfusion pressure. Despite this absence of pressure-flow autoregulation, oxygen consumption was maintained when the ductus was closed or open. In contrast, indomethacin inhibited the ability of the terminal ileum to autoregulate its oxygen consumption. These findings suggest that both open ductus and indomethacin present an increased risk of intestinal ischemia. We hypothesize that indomethacin's beneficial effect on ductus closure may be counterbalanced by its negative effect on intestinal perfusion and metabolism.

Animals

The effect of human recombinant erythropoietin on iron absorption and hepatic iron in a rat model.

In order to ascertain whether recombinant human erythropoietin (EPO) therapy would result in further intestinal iron absorption in the setting of systemic iron loading, iron absorption was measured in iron-loaded rats receiving EPO therapy and a control group of iron-loaded rats. Parenteral iron dextran (100 mg) resulted in hepatic siderosis with predominantly a reticuloendothelial distribution. EPO was given by intraperitoneal injection (100 U/kg) for 10 days. Radioiron absorption was measured by total body counting. Iron absorption in EPO-treated rats was 4.8 +/- 2.0% (n = 12) and 4.5 +/- 2.2% (n = 10) in the control rats (p greater than 0.05). Mean hemoglobin in the EPO rats was 201 +/- 12.5 g/L and 140 +/- 18.2 g/L in the control rats (p less than 0.001). Mean hepatic iron concentration was 73 +/- 16 mumol/g in the control rats and 34 +/- 9.1 mumol/g in the EPO-treated rats (p less than 0.001). This study suggests that iron-loaded rats do not demonstrate an increase in intestinal iron absorption with EPO therapy despite a significant erythropoiesis. The reduction in hepatic iron concentration suggests that reticuloendothelial iron is accessible and mobilized to produce new red blood cells.

Animals

Enhanced biliary iron excretion with amphiphilic diethylenetriaminepentaacetic acid.

The elimination of toxic metal ions metabolically accumulated by patients remains a difficult clinical problem and a target of drug development. DTPA (diethylenetriaminepentaacetic acid) is a hydrophilic chelating agent with high affinity for divalent and trivalent metal ions including iron but with a limited ability to cross cell membranes for access to iron stores. In this study we have synthesized an amphiphilic form of this chelator-DTPA covalently linked to the phospholipid phosphatidylethanolamine (PE)--to produce a chelator that incorporates completely and stably into liposome membranes for efficient delivery to the liver and reticuloendothelial system. Biliary and urinary excretion of iron were studied in iron-loaded rats (n = 15) in association with a 2-hr intravenous infusion of sonicated liposomes of 1:1 amphiphilic phosphatidylethanolamine-DTPA/egg phosphatidylcholine (L-PE-DTPA) and compared with excretion obtained using equivalent amounts of water-soluble DTPA (alone or mixed with egg phosphatidylcholine liposomes [L-DTPA] as controls). For a 6-hr period, the administration of L-PE-DTPA resulted in approximately a 20-fold increase in biliary iron excretion (480 +/- 160 micrograms/6 hr, mean +/- S.D.) compared with that seen with DTPA (21.2 +/- 4.0 micrograms/6 hr) and L-DTPA (23.1 +/- 5.0 micrograms/6 hr) (p less than 0.05, analysis of variance). Urinary iron excretion was significantly decreased with L-PE-DTPA (41.5 +/- 38 micrograms/6 hr) compared with DTPA (154 +/- 110 micrograms/6 hr) and L-DTPA (86 +/- 17 micrograms/6 hr) (p less than 0.05). Combined biliary and urinary excretion of iron was three to four times greater with L-PE-DTPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Distressed high utilizers of medical care. DSM-III-R diagnoses and treatment needs.

Among a sample of 767 high utilizers of health care, 51% were identified as distressed by an elevated score on the SCL anxiety and depression scales, the SCL somatization scale, or by their primary-care physician. These distressed high utilizers were found to have a high prevalence of chronic medical problems and significant limitation of activities caused by illness. In the prior year, they made an average of 15 medical visits and 15 telephone calls to the clinic. The Diagnostic Interview Schedule was completed on 119 distressed high utilizers randomly assigned to an intervention group in a controlled trial of psychiatric consultation. The following DSM-III-R disorders were most common: major depression 23.5%, dysthymic disorder 16.8%, generalized anxiety disorder 21.8%, and somatization disorder 20.2%. Two thirds had a lifetime history of major depression. The examination resulted in an improved diagnostic assessment for 40% of intervention patients and a revised treatment plan for 67%.

Adolescent

Biodistribution, tissue reaction, and lung retention of pentamidine aerosolized as three different salts.

Aerosolized pentamidine isoethionate is retained in the lung and appears to prevent Pneumocystis carinii pneumonia (PCP) in many AIDS patients. We evaluated alternative formulations of pentamidine that might reduce the airway irritation associated with aerosolized pentamidine isoethionate. Specifically, we assessed the biodistribution, histologic response, and lung retention of the isoethionate, gluconate, and lactate salts of pentamidine after aerosol administration to mice. For each of the three aerosolized salts tested, greater than 50% of the pentamidine initially recovered from the lungs after one dose was still retained there 14 days later. Thus, significant levels of pentamidine, aerosolized as three different salts, are retained in the lung for at least 2 wk after a single dose. The three salts of pentamidine each produced high lung to extrapulmonary drug ratios, the converse of that produced by intravenous injection of pentamidine isoethionate. At very high aerosol doses, the ability of the lung to retain pentamidine appeared saturable. Even aerosolized daily for 2 wk at very high doses, none of the three pentamidine salts produced histologic evidence of organ toxicity. A Phase 1 trial of aerosolized pentamidine gluconate in AIDS-PCP patients is now in progress to determine if this approach can reduce airway irritation.

Aerosols

Polymorphic N-acetylation of sulfamethazine and benzidine by human liver: implication for cancer risk?

Extensive epidemiologic studies have indicated a relationship between bladder cancer in populations exposed to arylamines and the slow phenotype for acetylation of arylamines (e.g., sulfamethazine) and aryl hydrazides (e.g., isoniazid). In human liver preparations, we have examined the association between the capability for sulfamethazine acetylation and that for the human bladder arylamine carcinogen, benzidine. By the usual criteria for polymorphic acetylation, we classified the 10 donor subjects as four rapid and six slow acetylators of sulfamethazine. Concurrent tests of benzidine acetylation in the same liver preparations yielded capacities to acetylate benzidine that were directly and significantly correlated with those for sulfamethazine acetylation (r = 0.672; P less than 0.05). We suggest that acetylation of these two compounds is directly related and knowledge of the human acetylator phenotype may be a useful indicator of possible risk for bladder cancer due to exposure of certain arylamines and, perhaps for other cancers in man.

Acetylation