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Biomedical subjects

R Lew

Publications and source records attributed to R Lew.

At least 37 records · Page 2Linked to original sources

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

The autoradiographic distribution of substance P binding sites in guinea-pig vas deferens is altered by capsaicin pretreatment.

The distribution of binding sites for [125I]Bolton-Hunter substance P (BHSP) was investigated in vasa deferentia from normal, capsaicin-pretreated and vehicle-pretreated guinea-pigs, using qualitative and quantitative autoradiography. Dense binding of BHSP was seen over the outer longitudinal muscle with less over the inner longitudinal muscle. Very low specific binding occurred to the circular muscle and was absent in the mucosa. Characterization in slide-mounted sections showed that binding was saturable and of high affinity, with equilibrium dissociation constant (KD) 91 +/- 15 pM. BHSP was displaced by substance P greater than neurokinin A greater than neurokinin B, suggesting binding to NK-1 receptors. Capsaicin pretreatment had no effect on the lengthwise distribution of binding sites but significantly altered their relative distribution between the different smooth muscle layers. There was a very marked increase in BHSP binding over the inner longitudinal muscle and the inner part of the circular muscle layer, whereas binding was virtually abolished over the outer longitudinal muscle, compared with vehicle control. Capsaicin-sensitive binding sites over the outer longitudinal muscle may be located presynaptically on capsaicin-susceptible primary afferent sensory neurons. In contrast, the increase in number of binding sites associated with the inner longitudinal muscle may be due to receptor upregulation resulting from loss of sensory innervation, and suggests that these binding sites are postsynaptic.

Animals

Dopamine transporter: solubilization from dog caudate nucleus.

3H-GBR 12935 was used to label the digitonin-solubilized dopamine transporter from dog caudate nucleus. Specific binding to soluble fractions was observed in dog caudate but was absent in rat cerebellum. Binding to the solubilized transporter sites was saturable and of high affinity (Bmax = 2.57 +/- 0.60 pmol/mg protein, KD = 23.42 +/- 2.24 nM, n = 4). Heating or addition of trypsin abolished specific binding in the soluble fractions. In competition studies, soluble 3H-GBR 12935 binding was inhibited by mazindol, GBR 12909, nomifensine, dimethocaine, dopamine, (-) cocaine, and (+) cocaine in a manner typical of binding to the dopamine transporter. As expected, tomoxetine and citalopram, inhibitors of norepinephrine and serotonin uptake, respectively, were weak competitors of 3H-GBR 12935 binding.

Animals

Serum thyrotropin concentrations are more highly correlated with serum triiodothyronine concentrations than with serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats.

To assess the relative role of circulating T4 and T3 in the regulation of serum TSH, we have measured serum T4, T3, and TSH concentrations in normal and thyroidectomized rats, some of which were chronically infused with T3 or T4. Serum T3, T4, and TSH concentrations were measured 7 and 14 days after surgery. Some groups of infused rats were mildly hypothyroid, as judged by elevated serum TSH concentrations. At both 7 and 14 days, there was a significant inverse correlation between serum T3 and serum TSH concentrations (day 7, r = 0.65, P less than 0.01; day 14, r = 0.71, P less than 0.01). The coefficients for the inverse correlations between serum T4 and TSH concentrations were 0.37 on day 7 (P less than 0.05) and 0.37 (P less than 0.05) on day 14. Linear regression analysis was performed using TSH as the dependent variable for outcome and serum T3 and T4 concentrations as the independent predictor variables. This analysis revealed that after controlling for T3, TSH and T4 were no longer significantly correlated (P = 0.14). The correlation between T3 and TSH remained highly significant. These results suggest that in the euthyroid and mildly hypothyroid rat, serum T3 has a greater inhibitory effect on TSH secretion than does serum T4.

Animals

Dopamine transport sites selectively labeled by a novel photoaffinity probe: 125I-DEEP.

The dopamine transporter was labeled using a photosensitive compound related to GBR-12909, 125I-1-[2-(diphenylmethoxy)ethyl]-4-[2- (4-azido-3-iodophenyl)ethyl]piperazine (125I-DEEP). 125I-DEEP bound reversibly and with high affinity to the dopamine transport protein in the absence of light and could be covalently attached to the protein following exposure to UV light. In rat striatal homogenates, 125I-DEEP was found to incorporate covalently into a protein with apparent molecular weight of 58,000 Da. The properties of this binding protein were characteristic of the dopamine transporter since covalent attachment could be inhibited by dopamine-uptake blockers with the proper pharmacological rank order of potencies. Covalent binding was also inhibited in a stereospecific manner by (+) and (-) cocaine, as well as other cocaine analogs. The protein was not found in the cerebellum. The dopamine transporter appears to exist in a glycosylated form since photoaffinity-labeled transport sites could adsorb to wheat germ-agglutinin and could be specifically eluted from the column by beta-N-acetylglucosamine.

Affinity Labels

Reduction of sternal infection by application of topical vancomycin.

Sternal or mediastinal infection after heart operations occurs infrequently but carries a high cost in money, morbidity, and mortality. At our hospital, Staphylococcus nonaureus causes most of these infections and is uniformly sensitive to vancomycin. In a prospective study of 416 patients having cardiac operations, randomized by hospital record number, topical vancomycin was applied to the cut sternal edges in 223 patients (group V) and was omitted in the control group (C) of 193 patients. The vancomycin was applied in a hemostatic paste of topical thrombin and powdered absorbable gelatin; in the control group only the hemostatic paste was applied. All patients received prophylactic systemic antibiotics for 2 days. Sternal infection occurred in one patient in group V (0.45%) and in seven patients in group C (3.6%) (p = 0.02). Infection also correlated with longer operative times (p = 0.027). By multivariate testing, vancomycin (p = 0.013) and shorter operative times (p = 0.014) independently predicted reduced infection rates. In the one patient with an infection in group V, Staphylococcus aureus was cultured; this organism was also cultured in two patients in group C, with Staphylococcus nonaureus being the culprit in the other five patients with sternal infections in group C. Topical vancomycin applied to the cut sternal edges reduces the risk of postoperative sternal infection.

Administration, Topical

Should prophylactic anticonvulsants be administered to patients with newly-diagnosed cerebral metastases? A retrospective analysis.

We analyzed a retrospective series of 195 patients with documented intracerebral metastases (ICM) to assess the frequency of late seizure development and the impact of prophylactic anticonvulsants. Eighteen percent of the patients presented with seizures. Of the remaining patients, 40% received prophylactic anticonvulsants (diphenylhydantoin [DPH] in greater than 90%). Ten percent developed late seizures at an interval from the diagnosis of ICM ranging from 1 to 59 weeks. No patient with a posterior fossa lesion developed seizure; conversely, patients with evidence on initial examination of cerebral hemispheric dysfunction had a higher incidence of late seizure development. The incidence of seizure was virtually identical in patients who received DPH compared with those in whom it was withheld, although two thirds of patients who developed seizure while on DPH had a serum anticonvulsant level that was subtherapeutic. Based on the above findings and until prospective data become available, we recommend that anticonvulsants be withheld in newly-diagnosed patients with ICM until the first seizure.

Adult

The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: a double-blind randomized study.

Sixty patients scheduled for elective coronary artery bypass graft operations were randomly assigned to receive epsilon-aminocaproic acid or placebo to test whether antifibrinolytic therapy would decrease postoperative bleeding. A small but significant decrease in bleeding was observed in the treated group without complications resulting from treatment with epsilon-aminocaproic acid.

Aminocaproates