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Biomedical subjects

R Lew

Publications and source records attributed to R Lew.

At least 55 records · Page 3Linked to original sources

Histopathologic differences in the photoaging process in facial versus arm skin.

We used clinical criteria to study skin biopsy specimens with mild to moderate photoaging taken from the face and dorsal forearms of 74 Caucasian volunteers between the ages of 30 and 50. Facial skin had a greater number of granular cell layers, a higher degree of keratinocytic atypia, and more often showed a compact stratum corneum than arm skin. Furthermore, the dermis of facial skin had a more extensive perivascular and perifollicular lymphocytic infiltrate, more perifollicular fibrosis, a greater number of mast cells and melanophages, and thinner vascular walls than forearm skin. This study demonstrated that the photoaging process is different for face and arm skin. Appreciation of these differences should permit more refined studies of photoaging and the development of more efficient therapies.

Adult↗

Relationship between serum total cholesterol, infarct size, and early clinical outcome following acute myocardial infarction.

Strategies designed to decrease coronary heart disease (CHD) associated morbidity and mortality have focused primarily on established risk factors, including hypercholesterolemia, systemic hypertension, and cigarette smoking. Indeed, primary and secondary intervention trials have provided evidence for cholesterol lowering as an efficient method of CHD risk reduction. To test the hypothesis that serum total cholesterol influences the clinical outcome following acute myocardial infarction, infarct size, left ventricular ejection fraction, infarct-related vessel patency, and in-hospital cardiac events were determined in 106 consecutive patients given thrombolytic therapy within 5 h of symptom onset. Cumulative 48-hour creatine kinase (CK) release, peak CK, and calculated infarct size did not differ significantly between patients with an admitting serum total cholesterol level less than 200 mg/dl (group 1) and those with a cholesterol level greater than 250 mg/dl (group 2). Total cholesterol did not correlate with either cumulative CK release, peak CK, infarct size, vessel patency, or left ventricular ejection fraction. The vessel patency correlated inversely with cumulative CK release (r = -0.27; p = 0.03) and directly with left ventricular ejection fraction (r = 0.24; p = 0.03). The incidence of in-hospital cardiac events including recurrent infarction, congestive heart failure, and death was 6.9, 13.9, and 2.6%, respectively, and did not differ significantly between patient groups. Thus, although serum total cholesterol has been shown to influence CHD incidence, morbidity, and overall mortality, the findings of our study suggest that it does not impact directly on infarct size, left ventricular function, or in-hospital clinical outcome among patients sustaining acute myocardial infarction.

Cholesterol↗

Trends in prevalences of behavioral risk factors: recent Hawaiian experience.

Recent time trends were studied for the prevalences of behavioral risk factors in Hawaii during the 5-year period from 1986 through 1990. The presence of linear time trend was analyzed by the multiple logistic regression method on weighted data, adjusting for confounding factors. The risk factors studied were seatbelt nonuse, lack of exercise, obesity, hypertension, smoking, acute drinking, chronic drinking, and driving while intoxicated. Seatbelt nonuse showed a significant decline, from 8.6% to 4.8%, with a mean annual decrease of 0.9 percentage point. Lack of exercise and obesity increased steadily, from 48.0% to 62.4% and from 16.7% to 21.6%, respectively, with respective annual mean increases of 3.3 and 1.4 percentage points.

Chronic Disease↗

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations? A randomized, double-blind study.

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.

Blood Loss, Surgical↗

Computer applications in quality assurance.

The computer is rapidly becoming an essential tool for the physician. Proper use of computers in practice will help physicians achieve both higher levels of quality and greater consistency in patient care. Only with computers can physicians rapidly access and process all the data now needed to best address the needs of their patients. As computer use in practice becomes the standard, the inability to use these tools will be incompatible with quality care. The computer is rapidly becoming essential to modern medical management strategies that demand efficiency, accuracy, and cost effectiveness in response to patient demands for assurance that quality care is being delivered.

Computer Systems↗

Dopamine transporter: deglycosylation with exo- and endoglycosidases.

The dopamine transporter from rat caudate-putamen was photolabeled with [125I]DEEP as previously described. Treatment of photolabeled membranes with neuraminidase and N-glycanase reduced the molecular weight of the [125I]DEEP photolabeled dopamine transporter complex, whereas treatment with alpha-mannosidase had no effect. The solubilized [125I]DEEP photolabeled dopamine transporter complex readily bound to wheat-germ agglutinin but not to concanavalin-A sepharose columns. These results suggest that the carbohydrate moiety of the dopamine transporter is N-linked and contains significant quantities of sialic acid but not high mannose residues. A DEEP binding protein was readily detectable in other brain regions including the nucleus accumbens and olfactory tubercle, but not in the prefrontal cortex, olfactory bulb or hypothalamus under similar conditions. The DEEP binding protein in the other brain regions was similar to that in the striatum.

Animals↗

Broadband ultrasound attenuation of the calcaneus predicts lumbar and femoral neck density in Caucasian women: a preliminary study.

Recent studies have demonstrated the ability of ultrasound techniques to differentiate normal and osteoporotic women. To define the ability of broadband ultrasound attenuation (BUA) of the calcaneus to predict axial bone mass, the ultrasound value was correlated with lumbar vertebral and femoral neck density in 22 Caucasian women. The three measures of bone mass inversely correlated with age: lumbar density (r = 0.54), femoral neck density (r = 0.65), and BUA (r = 0.73). BUA correlated with lumbar (r = 0.83) and femoral neck (r = 0.87) density. Lumbar vertebral density predicted femoral neck density with a standard error of estimate (SEE) of 0.07 g/cm2, and femoral neck density predicted lumbar density with a SEE of 0.09 g/cm2. BUA of the calcaneus was as effective as either axial bone mass measure in predicting the other value: the SEE for lumbar density was 0.09 g/cm2 while that for femoral neck density was only 0.06 g/cm2. The results of this preliminary study indicate that this rapid, radiation-free technique can accurately predict axial bone mass, and may be of value as an initial procedure to discriminate those women warranting more extensive radiologic evaluations.

Aged↗

A rapid binding assay for solubilized dopamine transporters using [3H]WIN 35,428.

The cocaine analog [3H]WIN 35,428 was used to label digitonin-solubilized dopamine transporters from dog caudate nucleus. The assay consists of incubation of extracts with the ligand followed by separation of free from bound ligand by centrifugation after adding activated charcoal. Specific binding was observed in dog caudate but was absent in dog cerebellar extracts. Binding was linear with tissue, saturable, and of high affinity (Kd = 16 nM). In competition studies, soluble [3H]WIN 35,428 binding was inhibited strongly by mazindol, GBR 12909, and (-)-cocaine but only weakly by citalopram, desipramine, and (+)-cocaine; this is typical of binding to the dopamine transporter. Compared to assays using [3H]GBR 12935, (-)-cocaine was relatively more potent, suggesting that the cocaine and GBR 12935 binding sites are somewhat different. When soluble extract was chromatographed on a wheat germ agglutinin-Sepharose column, [3H]WIN 35,428 binding activity was eluted with N-acetylglucosamine in a manner similar to photoaffinity-labeled dopamine transporters.

Adsorption↗

Heparin pharmacokinetics and in vitro anticoagulant activity in patients receiving nonionic radiographic contrast media.

Nonionic radiographic contrast media are used frequently in diagnostic and interventional angiography. However, there is concern that they may possess thrombogenic properties, and some studies have suggested that patients receiving nonionic contrast media are difficult to systemically anticoagulate with intravenous heparin. To investigate the potential effects of nonionic contrast media on systemic anticoagulation during diagnostic cardiac catheterization, pharmacokinetics and in vitro anticoagulant activity following a 3,000 U intravenous heparin bolus were assessed in 12 patients assigned randomly to either an ionic or a nonionic contrast agent. Independent of contrast agent, all patients exhibited biphasic (nonlinear) heparin pharmacokinetics characterized by an initial rapid disappearance phase, followed by a second slower phase. Each patient achieved a therapeutic plasma heparin concentration (greater than or equal to 0.2 U/ml) within 10 min of receiving the bolus, and maintained this level throughout the procedure. Heparin anticoagulant activity, as estimated by a standard activated partial thromboplastin time (APTT) was not affected differently by nonionic as compared with ionic contrast media (p greater than 0.05). Each patient rapidly achieved a level of systemic anticoagulation commonly considered therapeutic (APTT greater than or equal to 1.5 times the control), and maintained this level throughout the procedure. In both groups, APTT correlated directly with plasma heparin concentration (r = 0.95; p less than 0.0001), and inversely with the total amount of contrast media used during the procedure (r = -0.25; p = 0.01). Plasma heparin concentration did not correlate with total contrast media (r = -0.16; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗

Effect of serum total cholesterol on hemorrhagic complications following thrombolytic therapy for acute myocardial infarction.

Despite the well-known and widely publicized adverse effects of hypercholesterolemia on the cardiovascular system, cholesterol is a vital component of cellular membranes, maintaining vascular integrity and normal platelet activatability. To test the hypothesis that a low serum total cholesterol concentration increases bleeding risk following thrombolytic therapy, a comparison of in-hospital hemorrhagic events was made between 132 patients with myocardial infarction divided into three distinct groups. Group 1 patients (n = 44) had an admitting serum total cholesterol of less than 200 mg/dl, while group 2 (n = 57) and group 3 (n = 31) patients had cholesterol levels of 200-249 and greater than or equal to 250 mg/dl, respectively. There were no significant differences between groups in either minor hemorrhagic events (p = 0.85), major hemorrhagic events (p = 0.73) or transfusion requirements (p = 0.45). In addition, the primary sites of bleeding did not differ. Over the 2-year study period, a total of four intracerebral events were identified. As with minor and other major hemorrhagic events, an association with serum total cholesterol and intracerebral hemorrhage was not observed (p = 0.29). However, advanced age (greater than 65 years; p = 0.04) and a total dose of recombinant tissue-type plasminogen activator in excess of 1.5 mg/kg body weight (p less than 0.001) were identified by multivariate analysis as risk factors for intracerebral hemorrhage. Thus, although cholesterol is vital for maintaining vascular integrity and normal hemostasis, relatively low serum levels are not a risk factor for hemorrhagic complications following thrombolytic therapy.

Aged↗

Age, sex, and serum thyrotropin concentrations in primary hypothyroidism.

We studied the relationship between age, sex, serum thyroxine concentrations, and serum thyrotropin concentrations in 202 patients with primary hypothyroidism whose ages ranged from 10 to 89 years. The results from two groups of patients were analysed, both combined and separately, by multiple linear regression analysis of the factors age, sex, group, and serum free T4 index or serum T4 concentration, to predict serum TSH. The serum free T4 index or T4 values and age were negatively correlated with the serum TSH concentrations (p less than 0.001) for all comparisons. In contrast, there was no significant relationship between sex and serum TSH concentrations in these hypothyroid patients. The age-related decline in serum TSH concentrations in hypothyroidism was apparent during adolescence and early adult life (ages 10 to 39 years) and in elderly subjects (ages 61 to 89 years). We conclude that age is a determinant of TSH secretion independent of the level of thyroid secretion.

Adolescent↗

Factors affecting the development of pneumothorax associated with thoracentesis.

This study is a retrospective survey of the variables that may influence the development of pneumothorax after thoracentesis. In a 30-month period, a computer search of hospital records identified 342 thoracenteses, of which 154 were done with conventional techniques by the clinical services, and 188 were done with sonographic guidance. Other factors surveyed included the patients' age, sex, underlying pulmonary disease, and overall clinical condition; the size of the effusion; the type of tap (diagnostic or therapeutic); the amount and type (exudate or transudate) of fluid acquired; and the size of the needles used. The technique used was the most significant single risk factor affecting the development of pneumothorax (18% for clinical vs 3% for sonography-guided thoracenteses). The incidence of pneumothorax decreased when a smaller amount of pleural fluid was aspirated (mean, 246 ml aspirated from patients who did not vs 472 ml from those who did develop pneumothorax) and when thin needles were used (4% pneumothorax with 20-gauge or smaller and 18% with larger than 20-gauge needles). The other factors surveyed did not influence the development of pneumothorax. Our results show that sonography-guided thoracentesis is complicated by pneumothorax significantly less often than is thoracentesis done with conventional techniques. Use of the smallest possible needle and aspiration of the smallest possible amount of fluid will also result in fewer cases of pneumothorax.

Adult↗

Binding characteristics of [125I]Bolton-Hunter [Sar9,Met(O2)11]substance P, a new selective radioligand for the NK1 receptor.

The selective tachykinin agonist [Sar9,Met(O2)11]substance P (Sar-SP) was radioiodinated with [125I]Bolton-Hunter reagent and the product [125I]Bolton-Hunter-[Sar9,Met(O)2)11]SP (BHSar-SP) purified using reverse phase HPLC. Autoradiographic studies showed dense specific binding of BHSar-SP over the rat submandibular gland and over several regions in rat brain, with very low nonspecific binding, identical with the pattern of binding sites seen in a parallel study with [125I]Bolton-Hunter SP (BHSP). In homogenate binding experiments, BHSar-SP bound with high affinity to a single site in membranes from rat brain (KD 261 pM) and rat submandibular gland (KD 105 pM). Comparative values for BHSP were 495 and 456 pM, i.e. of two and four fold lower affinity than BHSar-SP. Association of BHSar-SP to membranes from brain (k+1 3.7 x 10(9) M-1 min-1) was faster than to membranes from salivary gland (k+1 5.6 x 10(8) M-1 min-1). In competition studies, BHSar-SP was displaced from salivary gland membranes by substance P (SP) approximately physalaemin greater than or equal to Sar-SP approximately SP-(3-11) greater than SP-(5-11) much greater than neurokinin A (NKA) approximately eledoisin = kassinin = SP-methyl ester greater than or equal to neurokinin B (NKB) much greater than [Nle10]NKA-(4-10) greater than [MePhe7]NKB-(4-10). In brain membranes, the rank potency order was SP greater than Sar-SP greater than or equal to physalaemin greater than SP-(3-11) greater than SP-(5-11) greater than NKA greater than or equal to eledoisin much greater than NKB greater than kassinin greater than SP-methyl ester: however [MePhe7]NKB-(4-10) and [Nle10]NKA-(4-10) were ineffective competitors at concentrations up to 1 microM. Both binding patterns are consistent with BHSar-SP binding to an NK1 site. With the exception of SP, Sar-SP, SP-(3-11) and physalaemin, all competitors were 5 to 54 times less potent at BHSar-SP binding sites in brain than in salivary gland. These data reveal some differences in characteristics of NK1 binding sites in brain and submandibular gland. Although of higher affinity, BHSar-SP does not appear greatly more selective than BHSP in its ability to define NK1 binding sites.

Amino Acid Sequence↗

Health risk behaviours and ethnicity in Hawaii.

This study has examined the relationships of health-related behaviours to sociodemographic factors with special emphasis on ethnicity in Hawaii. Behavioural variables investigated were non-use of car seat belts, overweight, physical inactivity, smoking, heavier alcohol use, and driving while intoxicated. Sociodemographic factors considered were ethnicity, island, sex, age, education, employment status, marital status, and household income. Major ethnic groups studied were Caucasians, Hawaiians including part-Hawaiians, Chinese, Filipinos, and Japanese. The relationships of ethnic factors with the behavioural characteristics were studied by logistic regression after fitting significant non-ethnic sociodemographic variables. Multiple risk behaviour was investigated by canonical correlation analysis. Different behavioural factors were found to be associated with different sets of non-ethnic socioeconomic variables. There were significant ethnic differences in individual at-risk behaviours except for driving while intoxicated. Overweight was most prevalent among Hawaiians followed by Caucasians. Caucasians and Hawaiians were at higher risk for non-use of seat belts, cigarette smoking, and heavier alcohol use compared to Chinese, Filipinos, and Japanese. Orientals were physically less active than Caucasians and Hawaiians. Implications of the observed ethnic differences are discussed.

Demography↗

Preirradiation chemotherapy of supratentorial malignant primary brain tumors with intracarotid cis-platinum (CDDP) and i.v. BCNU. A phase II trial.

Thirty patients with histologically verified malignant supratentorial gliomas were treated with a preirradiation chemotherapy protocol consisting of two courses of intracarotid (i.c.) CDDP, 90 mg/m2, followed by i.v. BCNU, 200 mg/m2. Side effects from therapy were mild and self-limiting; no irreversible retinal or neurologic toxicity could be attributed to i.c. chemotherapy. Of the 27 patients who completed the chemotherapy portion of the protocol, tumor size on postchemotherapy computed tomography (CT) was decreased by greater than 50% in 13% as compared to the postoperative CT scan; in only 4% was the CT scan unequivocally increased in size. Twenty-five (83%) patients completed the entire protocol. Median time to tumor progression and survival in patients who completed the protocol was 53 (range of 13-130+) and 61 (range of 29-130+) weeks, respectively. Twenty-four percent of patients still have not demonstrated tumor progression at intervals greater than 1 year after diagnosis as judged by clinical and radiographic criteria. Tumor recurrences were always contiguous to the original tumor bed. We conclude that preirradiation chemotherapy may be administered safely and with low morbidity. Further study to determine an optimal timing between chemotherapy and radiation therapy is warranted.

Adult↗

Dopamine transporter: biochemistry, pharmacology and imaging.

In recent years, there has been substantial progress in studying the dopamine transporter, a unique component of the functioning dopaminergic nerve terminal. The transporter has been studied by direct binding techniques using a variety of ligands which function as inhibitors of transport. Analogues of these ligands have been used as photoaffinity labels to solubilize and further characterize the transporter. While a variety of drugs bind to the transporter, it is clear that the transporter may serve as an important drug receptor, particularly for the reinforcing properties of some psychostimulants such as cocaine. An extension of the in vitro ligand-binding studies reveals that it is possible to preferentially label the transporter in vivo. The success of in vivo labeling has lead to successful positron emission tomographic scanning studies of the transporter. These studies in turn have revealed the usefulness of imaging the transporter, a measure of the presence of dopaminergic nerve terminals, as a potential diagnostic tool in Parkinson's disease.

Animals↗

Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a three-year prospective study.

The effect of dietary calcium on vertebral bone mass in women is controversial. In a randomized study we have investigated the effect of dietary modification in the form of dairy products on vertebral bone mass in 30- to 42-yr-old premenopausal women over a 3-yr period. Twenty women increased their dietary calcium intake by an average of 610 mg/day (P less than 0.03) for 3 yr, while 17 age- and weight-matched women served as controls. Calcium intake was monitored by 3-day diet histories and 24-h urinary calcium excretion. The consumption of the dairy products did not alter serum calcium or PTH levels or the fasting urinary calcium to creatinine ratio. Twenty-four-hour urinary calcium excretion increased by 28% (P less than 0.03) in the supplemented women. Dairy product intake was accompanied by increased dietary fat intake, but there were no statistically significant changes in serum cholesterol, low density lipoprotein cholesterol, or high density lipoprotein cholesterol levels. The vertebral bone density in the women consuming increased calcium did not change over the 3-yr period (-0.4 +/- 0.9%). In contrast, the vertebral bone density in the control women declined (-2.9 +/- 0.8%; P less than 0.001) and was significantly lower than that in the supplemented group at 30 and 36 months. The study suggests that dietary modification in the form of dairy products retards vertebral bone loss in premenopausal women. Therefore, increased calcium intake in estrogen-replete premenopausal women may prevent age-related bone loss.

Adult↗