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Biomedical subjects

T Miller

Publications and source records attributed to T Miller.

At least 181 records · Page 10Linked to original sources
PubMed1991

Cholecystokinin antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors.

The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of greater than 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor.

Animals↗
PubMed1991

Differences in cerebral blood flow between alpha-stat and pH-stat management are eliminated during periods of decreased systemic flow and pressure. A study during cardiopulmonary bypass in rabbits.

Prior reports suggest cerebral blood flow (CBF) responses to changing bypass (systemic) flow rates may differ between alpha-stat and pH-stat management. To compare the effect of blood gas management upon CBF responses to changing systemic flow and pressure, 15 New Zealand White rabbits, anesthetized with fentanyl and diazepam, underwent nonpulsatile cardiopulmonary bypass at 25 degrees C. One group of animals (n = 8) was randomized to alpha-stat blood gas management that maintained arterial carbon dioxide tension (PaCO2) approximately 40 mmHg when measured at 37 degrees C. A second group (n = 7) was managed with pH-stat technique, maintaining PaCO2 approximately 40 mmHg when corrected to the animal's actual temperature. Bypass was initiated at a flow rate of 100 ml.kg-1.min-1 and, after approximately 20 min, control hemodynamic and CBF measurements (radioactive microspheres) were made. Thereafter, bypass flow rate was changed in random order at 15-min intervals to 50, 70, and 100 ml.kg-1.min-1. CBF and hemodynamic measurements were repeated at the end of each period of altered bypass flow. Groups differed significantly with respect to both pHa and PaCO2. There were no significant differences between groups with respect to bypass flow rate, mean arterial pressure (MAP), central venous pressure, temperature, hematocrit, arterial oxygen tension (PaCO2), or bypass duration at any measurement point. MAP decreased significantly, from approximately 80 to approximately 65 mmHg with decreasing bypass flow (P = 0.0001). Over the entire range of bypass flows, CBF decreased with decreasing bypass flow (P = 0.001), and the degree of change was equivalent among regions and between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

A case of multiple pilar tumors and pilar cysts involving the scalp and back.

The case of a patient with multiple proliferating trichilemmal tumors and trichilemmal cysts of the scalp and back is discussed. The multicentric presentation of this tumor is unusual and, to our knowledge, has not been described previously. The appearance of trichilemmal cysts in association with multiple proliferating trichilemmal tumors suggests a common histogenesis of these two neoplasms. The typical presenting features, histologic description, and recommended treatment for these tumors are reviewed.

Back↗
PubMed1991

Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus.

The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained greater than 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P less than 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P less than 0.05) higher when dogs consumed the LF diet vs the IF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P less than 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1990

Epidermal growth factor gene expression in human breast cancer biopsy samples: relationship to estrogen and progesterone receptor gene expression.

This paper addresses the expression of the epidermal growth factor (EGF) gene by human breast tumor biopsy samples. Northern analysis was used to demonstrate the presence of an approximately 5-kilobase mRNA which specifically hybridized with radiolabeled human EGF complementary DNA in some human breast tumor biopsy samples. Quantitation of EGF mRNA in 60 human breast tumor biopsies using the RNase protection assay revealed that 83% of tumors contained detectable EGF mRNA. Estrogen receptor (ER) and progesterone receptor (PgR) mRNAs were similarly quantitated in the same samples. It was found that 89.4% of the ER mRNA-positive breast tumor biopsies had detectable EGF mRNA, whereas only 58.3% of the ER mRNA-negative tumors had detectable EGF mRNA. Furthermore, whereas 90.5% of the PgR mRNA-positive tumors contained EGF mRNA, only 60% of the PgR mRNA-negative tumors contained EGF mRNA. chi 2 analysis indicated that the increased percentage of tumors expressing EGF in the receptor-positive groups was statistically significant (P less than 0.01). It was also found that the mean relative level of EGF mRNA in those tumors which were ER and PgR negative [9.8 +/- 5.6 (SEM) relative units] was significantly lower than those tumors which were ER and PgR positive (40.5 +/- 6.4 relative units, P less than 0.05) or ER positive and PgR negative (68.4 +/- 19.9 relative units, P less than 0.005). These observations suggest that the EGF-expressing tumors probably arose originally from hormonally responsive cell types and that EGF expression in a large proportion of human breast tumors in vivo may also be hormonally responsive.

Biomarkers, Tumor↗
PubMed1990

Inhibition of T lymphocyte heparanase by heparin prevents T cell migration and T cell-mediated immunity.

Previously we reported that activated T lymphocytes express a heparanase enzyme that degrades the heparan sulfate moiety of the proteoglycan of the extracellular matrix (ECM). Expression of the heparanase enzyme was found to be associated with the ability of activated T lymphocytes to penetrate blood vessel walls and accumulate in target organs. We recently found that relatively low doses of heparin administered to mice or rats inhibited T cell-mediated immune reactions. In the present study we investigated the effects in vitro and in vivo of the heparanase inhibitor, heparin, on the expression of T lymphocyte heparanase and on the ability of T lymphocytes to mediate a delayed-type hypersensitivity (DTH) reaction. We found that heparanase was induced by immunizing mice with antigen in vivo or by activating T lymphocytes with concanavalin A in vitro. Relatively low doses of heparin administered once daily in vivo (5 micrograms) or present in vitro (0.1 microgram/ml) inhibited the expression of heparanase induced by immunization or by concanavalin A incubation. Higher or lower doses of heparin did not have these effects. The same doses of heparin that inhibited expression of heparanase also inhibited the ability of the lymph node cells to migrate to a site of antigen and adoptively produce a DTH reaction. These findings suggest that modulation of cell-mediated immune reactions may be achieved by relatively low doses of heparin which inhibit expression of T lymphocyte heparanase.

Animals↗
PubMed1990

Effect of positions, eating, and bronchodilators on gastroesophageal reflux in asthmatics.

Gastroesophageal reflux is common in asthmatics. To determine whether bronchodilators, the supine position, or eating affect gastroesophageal reflux, we performed ambulatory 24-hr pH monitoring on 44 controls and 104 unselected adult asthmatics. All asthmatics had discrete attacks of wheezing and documented reversible airway obstruction of at least 20%. The presence or absence of gastroesophageal reflux symptoms was not used as a criterion for patient selection. Chronic bronchodilator therapy was required by 71.2% of the asthmatics, and was continued during the test. Asthmatics had significantly worse GER than controls during the 3-hr postprandial period, which continued into the nonpostprandial period up to the next meal. Significant differences were present for esophageal mucosal acid contact time, frequency of reflux episodes, and clearance times. During the nonpostprandial periods asthmatics had four times the acid reflux as controls and 19-fold the frequency of prolonged reflux episodes. There were no differences between asthmatics on bronchodilators and those not on bronchodilators in any of the reflux parameters during the upright (postprandial, nonpostprandial) period or supine (sleep) period (P = NS). We conclude that: (1) regardless of the use of bronchodilator therapy, asthmatics have significant GER when asleep and after meals that continues beyond the postprandial period to the next meal; and (2) asthmatics receiving bronchodilators have similar gastroesophageal reflux patterns after eating, in the nonpostprandial period, and when asleep as asthmatics not receiving bronchodilators.

Asthma↗
PubMed1990

Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy.

The relationship between gastroesophageal reflux and asthma has not been clearly defined. We measured the lower esophageal sphincter pressures and studied gastroesophageal reflux patterns over 24 hours using an ambulatory Gastroreflux Recorder (Del Mar Avionics, Irvine, CA) in 44 controls and 104 consecutive adult asthmatics. The presence or absence of reflux symptoms was not used as a selection criterion for asthmatics. All asthmatics had discrete episodes of diffuse wheezing and documented reversible airway obstruction of at least 20%. Patients underwent reflux testing while receiving, if any, their usual asthmatic medications: 71.2% required chronic bronchodilators and 28.8% required no bronchodilators. Compared with controls, asthmatics had significantly decreased lower esophageal sphincter pressures, greater esophageal acid exposure times, more frequent reflux episodes, and longer clearance times in both the upright and supine positions (P less than 0.0001 for all parameters tested). There were no differences in any of the measured reflux parameters between asthmatics who required bronchodilators and those who did not. Thus, the decreased lower esophageal sphincter pressures and increased levels of acid reflux in asthmatics were not entirely caused by the effects of bronchodilator therapy. Receiver-operating characteristic analysis generated reflux values that discriminated asthmatics from controls. More than 80% of adult asthmatics have abnormal gastroesophageal reflux. We conclude that most adult asthmatics, regardless of the use of bronchodilator therapy, have abnormal gastroesophageal reflux manifested by increased reflux frequency, delayed acid clearance during the day and night, and diminished lower esophageal sphincter pressures.

Adult↗
PubMed1990

Withdrawing and withholding treatment: policies in long-term care facilities.

The Task Force on Life and the Law conducted a survey of nursing homes in New York State in 1986 and 1988. The survey examined the existence of policies on decisions about life-sustaining treatment, the process to determine which residents have decision-making capacity, the prevalence of ethics committees or other vehicles to resolve disputes, and policies on advance directives such as living wills and durable powers of attorney. Comparison of responses in 1986 and 1988 shows an increase in the number of facilities that have established explicit policies and institutional vehicles to address the dilemmas associated with decisions to withdraw or withhold life-sustaining treatment.

Advisory Committees↗
PubMed1990

Atelectasis affects the rate of arterial desaturation during obstructive apnea.

Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.

Animals↗
PubMed1990

Drug relationships in violence among methadone maintenance treatment clients.

In this paper the nature, scope, and drug relatedness of violent events reported by a sample of methadone maintenance treatment clients is examined and compared with events reported by a sample of drug abusers not in treatment. The drug relatedness of events is ascertained according to a tripartite model of the drugs-violence relationship. Data derive from a study of the drugs-violence nexus among male drug users and distributors who lived in or frequented the lower east side of Manhattan. Among the major findings were that while events reported by the treatment group were less likely than those reported by the not-in-treatment group to be related to heroin, total alcohol and cocaine related dimensions of violence were similar for the two groups. There was no difference between these groups in terms of the proportion of events that were drug related or the proportion of drug related events that could be attributed to each of the three posited models of drug relatedness. The implications of our findings are discussed.

Adult↗