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Biomedical subjects

D W Lee

Publications and source records attributed to D W Lee.

At least 127 records · Page 7Linked to original sources

The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis.

PURPOSE: To develop a strategy to identify cases of endogenous subclinical hyperthyroidism and free triiodothyronine (free T3) thyrotoxicosis in otherwise healthy ambulatory patients. PATIENTS AND METHODS: In a retrospective study we reviewed the records of ambulatory patients who had thyroid stimulating hormone (TSH) levels determined between October 1, 1991 and August 31, 1992. Each patient also had a simultaneous free thyroxine (free T4) measurement. Patients were excluded from consideration if they had active, concurrent non-thyroidal illness, psychiatric disease, known hypothalamic/pituitary lesions, were under treatment for hyper- or hypothyroidism, were on drugs known to affect TSH levels, or were pregnant. Patients without exclusions were diagnosed with free T3 toxicosis if they had: (1) a markedly subnormal TSH level (less than or equal to 0.1 mU/L), (2) a normal free T4, (3) a normal total T3, (4) evidence of a primary thyroid abnormality (e.g., autonomous function on a thyroid scan), and (5) an elevated free T3 level by tracer equilibrium dialysis. Patients meeting conditions 1-4, but with normal free T3 levels, were considered to have subclinical hyperthyroidism. RESULTS: One thousand twenty-five patients had TSH and simultaneous free T4 determinations, and 148 of these had markedly subnormal TSH but normal free T4 levels. Three patients met the criteria for free T3 toxicosis and three had subclinical hyperthyroidism. All six patients had either multinodular glands or a single nodule on thyroid exam. Four patients were treated with radioactive iodine or surgery, resulting in reversal of the TSH suppression in three cases. CONCLUSION: Apparently healthy ambulatory patients with subnormal TSH levels should be worked up with measurements of free T4 and total T3. If these are normal, a T3 level (by tracer equilibrium dialysis) be obtained to distinguish subclinical hyperthyroidism from overt free T3 toxicosis. A thyroid scan and radioiodine uptake measurement can be obtained to substantiate the diagnosis. Some patients with these conditions will benefit from treatment.

Adult↗

Milia en plaque.

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Adolescent↗

Reading speed and prose memory in older and younger adults.

A method is described for determining the minimum amount of time required to read a proposition in the context of a sentence. This threshold reading time was reliable, stable, and significantly longer for older adults than for younger adults. Prose memory was assessed for texts presented at varying speeds determined by the threshold reading time measure and by a whole-text reading time measure. Recall from these paced conditions was compared with recall from a self-paced condition. In general, age differences in recall tended to increase as the amount of time allowed for processing increased. The results of regression analyses suggest that although the basic speed of processing for a single sentence accounts for substantial variance in prose recall, processes that operate across sentence boundaries are also important and require further specification.

Adult↗

Regulation of intracellular pH by immortalized human intrahepatic biliary epithelial cell lines.

We have produced continuous cell lines using retroviral transduction of SV40 large T antigen into human intrahepatic biliary epithelial (IBE) cells from three different normal individuals. These IBE cell lines grow in a hormone-supplemented medium in the presence of NIH/3T3 fibroblast coculture. These cells maintain their epithelial appearance and are positive for the biliary-specific markers cytokeratins 7 and 19 and gamma-glutamyl transpeptidase while being negative for the hepatocyte markers albumin and asialoglycoprotein receptor. To evaluate ion transport pathways in IBE cell lines, we utilized intracellular pH (pHi) measurements obtained using the intracellular fluorescent indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. In the absence of HCO3(-)-CO2, an amiloride-sensitive Na(+)-H+ exchanger participated in the regulation of basal pHi. In the presence of HCO3(-)-CO2, a 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-sensitive, Na-, Cl-, and HCO3(-)-dependent acid extrusion mechanism accounted for approximately 60% of pHi recovery from acidic pHi; this mechanism is most consistent with the presence of a Na-dependent Cl-HCO3- exchanger (Na+HCO3(-)-Cl-H+). Under basal conditions, Cl- depletion revealed a DIDS-sensitive alkalinization consistent with a Na-independent Cl(-)-HCO3- exchanger. These model systems will allow the opportunity to study the normal mechanisms of IBE function and to study the pathobiology of IBE processes in disease states.

3T3 Cells↗

Front-loaded infusion therapy of rT-PA during active menstruation. A case report.

The authors report use of intravenous (IV) tissue plasminogen activator (TPA) to treat acute anterior wall myocardial infarction in a forty-two-year-old woman during the active menstrual period. The patient received the TPA with the front-loading system with excellent result. Hemoglobin remained unchanged. This case demonstrates that TPA infusion can be used in a menstruating woman without causing a dangerous hemorrhage.

Adult↗

Physician responses to Medicare payment reform: an update on access to care.

This paper updates previous research on physician-based measures of access to care for Medicare beneficiaries following the implementation of Medicare payment reform in 1992. Using data collected in spring 1993, the results show that the majority of physician-based access indicators did not change significantly from 1992 levels. Those indicators that did change generally offset reductions in access identified immediately after the implementation of Medicare physician payment reform.

Attitude of Health Personnel↗

Modulation of cytochrome P-450 induction by long-term food restriction in male rats.

The influence of food restriction (FR) on the induction of liver microsomal cytochrome P-450 (P-450) was examined in rats, FR by 40% for 6 weeks caused increase in the levels of P-450, cytochrome b5 (b5), NADPH P-450 reductase, NADH b5 reductase, P-450 dependent testosterone 6 beta-, 16 alpha- and 16 beta-hydroxylases (P < 0.05). Treatment of 3-methylcholanthrene (MC) to food restricted rats (FR rats) induced more P-450, but phenobarbital (PB) induced it less. MC-inducible P-450 from FR rats did not increase its specific ethoxycoumarin O-deethylase activity but it increased testosterone 2 alpha-hydroxylase activity, and the maximum absorption of its CO complex was shifted from 448 nm to 450 nm. PB-inducible P-450 showed less increase in the activities of its specific benzphetamine N-demethylase and it rather significantly decreased testosterone 16 alpha-hydroxylase activity (P < 0.05). These results indicate that the drugs did not induce their unique types of P-450 in FR rats. Such alterations in P-450 induction in FR rats seem to be closely related to the level of P-450 and its related components enhanced by FR, and it could result in modulation of mixed function oxidase system.

Animals↗

Short-term, intermediate-term, and long-term memories.

This paper focuses on the temporal dimension of memory formation and storage. Is the usual two-fold separation between short-term memory (STM) and long-term memory (LTM) sufficient to encompass all the phenomena of memory? The traditional view is that STM grades into LTM. Evidence for an intermediate-term memory (ITM) has been proposed by some investigators. We have used both rats and chicks to investigate the stages of memory formation. In this paper, the advantages of chicks for this type of research are briefly discussed. Using a paradigm that produces weak training, the retention function for control chicks appears to be made up of four successive components which we have interpreted as representing the memory buffer, STM, ITM, and LTM. In experiments using a variety of kinase inhibitors, we have obtained evidence that ITM and LTM depend on different classes of protein kinase activities. Agents that act on calcium/calmodulin kinase cause amnesia in the ITM range--15 to 30 min post-training. Another class of inhibitors act on one or more of the kinases PKA, PKC, or PKG and cause amnesia by 60 min post-training, so we interpret this group of inhibitors as inhibiting the formation of LTM. However, the three-stage model of memory may be over-simple. For example some agents including [Leu]enkephalin and MK801 cause amnesia 4 or more h after training.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effect of subchronic administration of antioxidants against cigarette smoke exposure in rats.

Effects of subchronic administration of antioxidants against pulmonary damage mediated by cigarette smoke were investigated in rats. Rats were continuously received ascorbic acid, N-acetylcysteine and ginseng extract together drinking water from day 25 after birth. After 30 days of antioxidant supplementation, rats were exposed to cigarette smoke generated from six cigarettes (11 mg tar) for 20 min per day throughout 30 days, and then several biochemical markers related to the redox status in vivo were analyzed in the respiratory system. The cigarette smoke induced mild histological changes in trachea and lungs. The activity of superoxide dismutase (SOD) in the lung was significantly increased, and catalase and glutathione peroxidase activities were increased less than SOD, but total sulfhydryl compounds (Total-SH) content was decreased by cigarette smoking. In spite of the increase in activities of antioxidant enzymes, the inhibitory capacity of lung preparations on in vitro lipid peroxidation using ox brain homogenates was decreased and the change in the capacity was not related to the changes of these intracellular enzymes activities, but with the content of Total-SH. On the other hand, the content of thiobarbituric acid reactive substances and the ratio of elastase to anti-protease in the lung homogenates were significantly increased. Supplementation of antioxidants, however, effectively attenuated all of such alterations induced by cigarette smoke. These results indicate that although cigarette smoking induces antioxidant enzymes in the lung as a self defense mechanism, it seems to be not sufficient to protect the pulmonary system, and that chronic antioxidant feeding could be effective to reduce pulmonary damage induced by free radicals.

Animals↗

Purification of a high molecular weight follicle-stimulating hormone receptor-binding inhibitor from human follicular fluid.

In a previous study we reported the presence in human follicular fluid (hFF) of a FSH receptor-binding inhibitor (hFSH-BI) with FSH agonist activity, which was immunologically similar to FSH but could be distinguished from FSH on the basis of its greater stability in acid. We have now purified hFF-derived hFSH-BI after molecular sieving on Sephracyl S-100 ion exchange chromatography using Diethyl-aminoethyl-cellulose followed by polyacrylamide gel electrophoresis (PAGE). The purified hFSH-BI had a potency approximately 12,000-fold greater than that of dialyzed hFF, based on its ability to inhibit the binding of [125I]hFSH to its membrane receptor. The purified hFSH-BI also had FSH agonist activity, stimulating estradiol synthesis in cultured rat Sertoli cells. Upon sodium dodecyl sulfate (SDS)-PAGE, hFSH-BI migrated as two bands of almost identical mobility, with an estimated mol wt of 57,000, compared with 30,000 for pituitary FSH run simultaneously. A monoclonal antibody to hFSH that also recognizes hFSH-BI was used for Western blot analysis of the SDS-PAGE fraction. The Western blot confirmed the detection of two bands with very similar mobilities and estimated mol wt of 57,000, which were clearly distinguishable from that of immunologically reactive hFSH run in parallel. The hFSH-BI bands showed similar profiles upon cyanogen bromide cleavage and had indistinguishable amino acid compositions. The amino acid composition of hFSH-BI was clearly distinct from those of hFSH, hLH, hCG, and the alpha-subunit of human inhibin. Our studies confirm the presence in hFF of a unique agonist protein which is of potential importance in the regulation of gonadal function.

Animals↗

Physician responses to Medicare physician payment reform: preliminary results on access to care.

This paper examines the impact of Medicare physician payment reform on access to care by comparing several physician-based access measures in the pre- and post-reform periods. The results suggest that the broad goals of payment reform may have been at least partially achieved: the proportion of physician revenues derived from Medicare increased for primary care physicians and decreased for nonprimary care MDs; there was little change in the absolute or relative number of visits provided to Medicare patients; and an increasing number of physicians charged no more than the Medicare payment amount. Some signs of deteriorating access were found, however. Fewer physicians were willing to treat all new Medicare patients and more physicians accepted no new Medicare patients. Furthermore, there was an increase in the proportion of physicians who reduced or stopped providing to Medicare patients certain types of services that they continued to provide to other patients.

Aged↗

Estimating the effect of new technology on Medicare Part B expenditure and volume growth: do related procedures matter?

The new Medicare Part B physician reimbursement system requires the Health Care Financing Administration to consider how medical technology contributes to growth in service volume. One estimate of this effect has been made by the Physician Payment Review Commission (PPRC), which estimated how individual new technologies have influenced volume growth. This paper extends the PPRC analysis to include both new technology services and those services that are complementary, or related to, the new technology services. The results show that adjusting for related procedures can increase the estimated cost of new technology by as much as 50 percent. In addition, related procedures can increase the estimated share of volume growth attributable to new technology by as much as 42 percent. This implies that both new and related procedures should be used when implementing physician payment reforms.

Diagnostic Imaging↗

Physician-based measures of Medicare access.

Physician payment reforms implemented in January 1992 have dramatically changed the way payments for services are determined under the Medicare Part B program. This paper presents new measures of access using physician-level data that provide a baseline for monitoring changes in access that might occur as these payment reforms unfold and that allow us to examine recent access trends. Our results suggest that Medicare beneficiaries as a group currently have a high degree of access to care, and that access generally improved between 1986 and 1990.

Financial Management↗

Metabolism of 16 alpha-hydroxytestosterone by cytochrome P-450 in rat liver.

The metabolism of 16 alpha-hydroxytestosterone by cytochrome P-450 system was studied with two different inductions. At least 5 different metabolites with higher polarity were produced from 16 alpha-hydroxytestosterone. MT-B, one of their products, appeared to be specifically increased by 3-methylcholanthrene- and phenobarbital-inducible P-450, respectively. This suggests that monohydroxylated testosterones are further metabolized by the P-450 system and that the reactions are isozyme specific. This can contribute at least in part to the diversity of steroid metabolism by P-450.

Animals↗

On the nature of serum prolactin in two patients with macroprolactinemia.

OBJECTIVE: To further characterize the high molecular weight (MW) forms of prolactin (PRL) present in patients with macroprolactinemia. DESIGN: Case reports with laboratory investigations. SETTING: Academic medical centers. PATIENTS: Two patients with macroprolactinemia. INTERVENTIONS: Measurements of PRL concentrations before and after chromatographic separations. RESULTS: The majority of serum PRL had an estimated MW of at least 669 kd in the first patient and approximately 171 kd in the second. During a pregnancy, a new form of PRL (MW 291 kd) appeared in the first patient's serum and persisted for at least 3 years. Immunoprecipitation and polyacrylamide gel electrophoresis under reducing and denaturing conditions revealed that the largest form of PRL (MW 669 kd) was composed mostly of 25 kd glycosylated PRL; intermediate forms (171 kd and 291 kd) were composed of roughly equal portions of 25 kd glycosylated PRL and 23 kd nonglycosylated PRL, whereas "little" PRL in these patients was composed primarily of 23 kd nonglycosylated PRL. Injection of the first patient's serum into rats demonstrated that the human PRL (hPRL) immunoreactivity was cleared from the serum more slowly than the PRL from sera containing predominantly little hPRL; after stimulation with thyrotropin-releasing hormone in the second patient, serum PRL concentrations decayed more slowly than observed in normal subjects. CONCLUSIONS: Large forms of serum PRL are at least partially glycosylated. These large forms are heterogeneous, both within and among patients. Delayed clearance may account for increased serum PRL concentrations in patients with macroprolactinemia.

Adult↗

Hereditary erythrocyte adenylate kinase deficiency: a defect of multiple phosphotransferases?

Adenylate kinase (AK) modulates the interconversion of adenine nucleotides (AMP + adenosine triphosphate----2 ADP). We evaluated the fifth kindred with hereditary erythrocyte (RBC) AK deficiency. The proband had chronic hemolytic anemia. Her RBC had undetectable AK activity when measured spectrophotometrically, whereas those of her parents had half-normal AK activity. AK electrophoresis showed only AK-1 in the parents. The activities of pyruvate kinase and phosphoribosylpyrophosphate synthetase were decreased given the young age of the proband's RBC. Despite the absence of spectrophotometric AK activity, the proband's RBC were able to incorporate 14C-adenine into 14C-adenine nucleotides at 50% of the rate expected for her young RBC population, suggesting the possibility of an alternative pathway for the formation of ADP from AMP. Normal hemolysate had AMP:guanosine triphosphate (GTP) phosphotransferase activity, which produced ADP at 8% to 9% of the rate of AK (6.8 +/- 0.8 IU/mL RBC). AMP:GTP phosphotransferase activity was not detectable in the proband's or parent's hemolysates. These additional biochemical defects in the AK-deficient RBC further support the concept that AK deficiency per se may not cause hemolytic anemia. We propose that defects occur in multiple phosphotransferases in the AK-deficient RBC and that these other biochemical defects may produce deleterious lesions that promote the shortened RBC survival in AK deficiency.

Adenosine Diphosphate↗