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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

At least 91 records · Page 5Linked to original sources
PubMed2000

Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats.

Parathyroid hormone (PTH) is an effective bone anabolic agent, but it must be administered parenterally. An orally active anabolic agent would provide a valuable alternative for treating osteoporosis. NPS 2143 is a novel, selective antagonist (a "calcilytic") of the parathyroid cell Ca(2+) receptor. Daily oral administration of NPS 2143 to osteopenic ovariectomized (OVX) rats caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density. Concurrent oral administration of NPS 2143 and subcutaneous infusion of 17beta-estradiol also resulted in increased bone turnover. However, the antiresorptive action of estrogen decreased the extent of bone resorption stimulated by the elevated PTH levels, leading to an increase in bone mass compared with OVX controls or to either treatment alone. Despite the sustained stimulation to the parathyroid gland, parathyroid cells did not undergo hyperplasia. These data demonstrate that an increase in endogenous PTH secretion, induced by antagonism of the parathyroid cell Ca(2+) receptor with a small molecule, leads to a dramatic increase in bone turnover, and they suggest a novel approach to the treatment of osteoporosis.

Animals↗
PubMed2000

Retrospective study of 338 canine oral melanomas with clinical, histologic, and immunohistochemical review of 129 cases.

Diagnostic records from 338 canine oral melanomas in 338 dogs received at the Veterinary Medical Diagnostic Laboratory (1992-1999) were reviewed. Of these tumors, 122 plus an additional 7 metastatic melanomas of unknown origin were selected for clinical follow-up, histologic review, and immunohistochemistry. Chow Chow, Golden Retriever, and Pekingese/Poodle mix breeds were overrepresented, whereas Boxer and German Shepherd breeds were underrepresented. There was no gender predisposition and the average age at presentation was 11.4 years. Forty-nine dogs were euthanized due to recurrence or metastasis. The average postsurgical survival time was 173 days. The gingiva and the labial mucosa were the most common sites. Most tumors were composed of either polygonal cells (27 cases, 20.9%), spindle cells (44 cases, 34.1%), or a mixture of the two (polygonal and spindle) (54 cases, 41.9%). Clear cell (3 cases, 2.3%) and adenoid/papillary (1 case, 0.8%) patterns were uncommon. The metastases of 6/6 oral melanomas had morphologic and immunohistochemical features similar to those of the primary tumors. Immunohistochemically, Melan A was detected in 113/122 oral (92.6%) and 5/7 (71.9%) metastatic melanomas. Only 4/163 nonmelanocytic tumors were focally and weakly positive for Melan A. Antibodies against vimentin, S100 protein, and neuron-specific enolase stained 129 (100%), 98 (76%), and 115 (89.1%) of 129 melanomas, respectively. Antibodies against other melanocytic-associated antigens (tyrosinase, glycoprotein 100) did not yield adequate staining. We conclude that Melan A is a specific and sensitive marker for canine melanomas.

Animals↗
PubMed2000

Glucagonoma in a jaguar (Panthera onca).

An obese adult jaguar (Panthera onca) was euthanized because of progressive lameness. Two 3-cm-diameter pancreatic nodules were identified as islet cell tumors, which were positive with immunohistochemical stains for glucagon, neuron-specific enolase, chromogranin A, and synaptophysin. The jaguar did not present clinical evidence of hyperglucagonemia.

Animals↗
PubMed2000

Laboratory aspects of rheumatologic disease.

Assessment of laboratory values is an important function of nursing practice. Rheumatologic laboratory assessment, in particular, can be complex because few findings are actually pathognomonic. This article provides a perspective on an interpretive approach to laboratory assessment of rheumatologic disease. In conjunction with the patient's clinical status, these values can provide helpful information for monitoring or predicting the course of disease.

Acute-Phase Proteins↗
PubMed2000

Demands of illness in people treated for colorectal cancer.

PURPOSE/OBJECTIVES: To describe the most common and most intense demands of illness in people with colorectal cancer. DESIGN: Descriptive, comparative. SETTING: People with colorectal cancer were accrued through weekly online computer postings. SAMPLE: 121 people (68 men and 53 women) from 35 states (n = 106) and six other countries (n = 15) who were treated for colon, rectal, or anal cancer. METHODS: Mailed questionnaires included a 125-item, self-report instrument with seven subscales (Demands of Illness Inventory (DOII) and a 14-item demographic form. MAIN RESEARCH VARIABLES: Demands of illness, time since treatment, perception of illness state, activity level, and age. FINDINGS: Demands of illness were greatest in the personal meaning domain, with more than 93% of subjects reporting that they thought about the value of life and how long they might live. More than 85% reported uncertainty in six similar areas. The 10 most intense demands were predominately psychosocial and existential concerns. Respondents in the youngest age group (< 45 years) reported significantly greater demands in six of seven domains of the DOII than the middle and older groups. Three variables (time since treatment, perception of illness, activity level) accounted for 45% of the variance in DOII scores. CONCLUSIONS: Colorectal cancer imposed significant psychosocial and existential concerns on respondents, especially the youngest age group. IMPLICATIONS FOR NURSING PRACTICE: Nurses should address these concerns with patients while continuing to identify and scientifically test creative strategies to minimize psychosocial morbidity.

Adaptation, Psychological↗
PubMed2000

Suburban versus urban: does it matter where the residency interview begins?

Geographic location is an important factor in students' ranking of residency programs. Our program's inner city location has a negative impact on our recruitment efforts. In an attempt to assess the impact of geography, we started half of the residency interview days at our suburban community medical center and then measured the effect on the applicant's perception of the program. During the 1998-1999 residency interview season we alternated the site at which the day began. Students were randomly assigned based on interview date requests to starting the day at the urban hospital or at the community hospital. At the conclusion of the day the students completed a questionnaire regarding various components of the interview day and how their perception of the program was influenced by the experience. Of 206 students asked to complete the questionnaire, 188 (91%) completed the survey. The degree to which the students' perception of the program was affected was remarkably similar regardless of where the interview day began; however, significant differences were found between the Chairman's Talk, the Teaching Session, and talking with current residents when compared by univariate analysis. We concluded that students' perception of the program at the conclusion of the interview day was similar regardless of whether the interview day began at an urban or suburban medical center.

Career Choice↗
PubMed1999

Galanin antagonizes vasopressin-stimulated flank marking in male golden hamsters.

Microinjection of vasopressin (VP) into the anterior hypothalamus (AH) of golden hamsters induces a rapid bout of flank marking, a stereotyped scent marking behavior used for olfactory communication. In rats, VP is colocalized with galanin (GAL) in several brain regions. GAL has been shown to antagonize the postsynaptic actions of other cosecreted neurotransmitters including acetylcholine and norepinephrine; however, the ability of GAL to modulate the postsynaptic actions of VP has not been assessed. Here, we report that coadministration of GAL can block VP-induced flank marking in golden hamsters in a dose dependent manner. These findings provide the first evidence in any species that GAL can antagonize the central actions of VP. Using slice binding and receptor autoradiography, we have identified GAL binding sites in the AH and two other regions implicated in flank marking behavior (the lateral septum and central grey). These findings raise the possibility that endogenous GAL may function as an inhibitory modulator of this stereotypic scent marking behavior.

Animals↗
PubMed1999

Leptin binding in the arcuate nucleus is increased during fasting.

The arcuate nucleus (ARC) mediates the anorexic effects of leptin and expresses the long form (Ob-Rb) of the leptin receptor. To determine whether ARC leptin binding increases when plasma leptin levels are low during fasting, [125I]-leptin specific binding to rat brain slices was measured by quantitative autoradiography. [125I]-leptin specific binding was dense in the ARC and increased 2-fold after a 48-h fast (P<0.001). These findings suggest that leptin receptor binding in the ARC is upregulated during fasting and that fasting changes the sensitivity of the ARC to leptin.

Animals↗
PubMed1999

Absence of vasopressin expression by galanin neurons in the golden hamster: implications for species differences in extrahypothalamic vasopressin pathways.

In golden hamsters, there is a complete absence of the small diameter vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BST) and medial amygdala (Me) which have been shown to exhibit steroid dependency and sexual dimorphism in many other rodent species. In rats, VP in the BST/Me is always colocalized with the neuropeptide galanin (GAL) and the sex difference in VP cell number appears to result from a sex difference in the number of GAL neurons which coexpress VP. Likewise, we reasoned that the species difference in extrahypothalamic VP pathways present in the golden hamster could result from a reduced coexpression of VP by GAL neurons in these regions. Here, we used in situ hybridization histochemistry to determine whether GAL mRNA expressing neurons are present in the BST and Me of golden hamsters despite the absence of VP expression in these regions. In addition, we have used slice binding and receptor autoradiography to identify specific GAL binding sites in the lateral septum, a probable target region of BST/Me neurons, and in situ hybridization to confirm that some of these binding sites correspond to the GALR1 GAL receptor subtype. Our findings indicate that the absence of VP expression in the BST/Me of golden hamsters results from a failure of extrahypothalamic GAL neurons to express the VP phenotype. Because GAL is expressed in the extended amygdaloid complex and GAL receptors are present in the septum of golden hamsters, GAL may play a role in modulating functions previously attributed to BST/Me pathways.

Amygdala↗
PubMed1999

An FDA review of sulfamethazine toxicity.

Recently, changes have been proposed in the criteria historically used in the evaluation of the applicability to humans of some of the results obtained from the rodent carcinogenicity bioassay data. These questions center on the suitability of the rodent model for agents that exert their toxic effects via specific enzyme interactions and endocrine mechanisms which appear to be inoperative within humans. Within the U.S. Food and Drug Administration (FDA), this issue has been brought to the forefront of concern with the recent application for a New Animal Drug Application for sulfamethazine (SMZ). A panel of FDA experts from the National Center for Toxicological Research (NCTR), the Center for Veterinary Medicine (CVM), and the Center for Food Safety and Applied Nutrition has reviewed the sum of the scientific evidence available on the toxicology of SMZ. They noted that, in previous feeding studies at NCTR, high doses of SMZ were associated with significant incidences of thyroid tumors in mice and rats. The panel also notes that the tumorigenic activity of SMZ in rodents was due to its goitrogenic activity, resulting in constant stimulation of the thyroid by TSH. Humans, on the other hand, were found to be insensitive to the SMZ-like inhibition of thyroid function. Further, apart from X-irradiation and radioactive iodine, there are no other physical or chemical agents known to cause thyroid tumors in humans. Thus, the expert panel concludes that the best scientific information available indicates that elevated levels of TSH and the consequent thyroid tumors would not be produced under approved use conditions of SMZ. This conclusion is in agreement with recommendations made by three other panels, viz. the World Health Organization, the U.S. Environmental Protection Agency, and CVM, which also evaluated the public health risk of SMZ.

Animals↗
PubMed1999

Cause of in-hospital death in 12,232 consecutive patients undergoing percutaneous transluminal coronary angioplasty. The Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Some deaths after percutaneous coronary angioplasty (PTCA) occur in high-risk situations (eg, shock), whereas others are unexpected and related to procedural complications. To better describe the epidemiologic causes of death after PTCA, we undertook a systematic review of all in-hospital PTCA deaths in Northern New England from 1990 to 1993. METHODS: The medical records of 121 patients who died during their acute hospitalization for PTCA were reviewed with a standardized data extraction tool to determine a mode of death (eg, low output failure, arrhythmia, respiratory failure) and a circumstance of death (eg, death attributable to a procedural complication, preexisting acute cardiac disease). Any death not classified as a procedural complication was reviewed by a committee and the circumstance of death assigned by a majority rule. RESULTS: Low-output failure was the most common mode of death occurring in 80 (66.1%) of 121 patients. Other modes of death included ventricular arrhythmias (10.7%), stroke (4.1%), preexisting renal failure (4.1%), bleeding (2.5%), ventricular rupture (2.5%), respiratory failure (2.5%), pulmonary embolism (1.7%), and infection (1.7%). The circumstance of death was a procedural complication in 65 patients (53.7%) and a preexisting acute cardiac condition in 41 patients (33.9%). Women were more likely to die of a procedural complication than were men. CONCLUSION: Procedural complications account for half of all post-PTCA deaths and are a particular problem for women. Other deaths are more directly related to patient acuity or noncardiac, comorbid conditions. Understanding why women face an increased risk of procedural complications may lead to improved outcomes for all patients.

Age Factors↗
PubMed1999

Platelet sodium/hydrogen exchanger activity in normotensives and hypertensives.

Increased activity of sodium/hydrogen exchange provides a potentially important mechanism for the development of hypertension. The aims of this study were to compare platelet sodium/hydrogen exchanger activity and renal acid-base excretion in normotensives and hypertensives of Caucasian origin. Platelet intracellular pH (pHi) was measured using the fluorescent dye BCECF to monitor intracellular pH. Sodium/hydrogen exchanger activity was estimated from the recovery of pHi clamped to 6.25 with nigericin. Normotensives had supine blood pressures of < 140 and < 90 mmHg; those with essential hypertension had blood pressures > 150/95 mmHg with no known secondary cause. Measurements of platelet pHi and sodium/hydrogen exchanger activity were made on 26 normotensives (ten female, sixteen male) and 25 hypertensives (five female, twenty male). All subjects were on their usual dietary sodium intake. Statistical analysis was by two-way analysis of variance for gender and blood pressure status. Group values are expressed as means+/-SD and a P value of < 0.05 was taken as being statistically significant. There were no significant differences in platelet pHi between the normotensive (n = 26) and the hypertensive (n = 25) group: pHi 7.21+/-0.14 and 7.18+/-0.16, respectively. The pHi recovery after acidification was sodium-dependent and inhibited by N-hexamethylene amiloride. Comparison of kinetic constants showed no significant differences between the normotensive and the hypertensive groups: values for rate constants and initial velocities were 0.24+/-0.04 s(-1), 0.16+/-0.03 dpHi/s for the normotensives and 0.25+/-0.05 s(-1), 0.16+/-0.03 dpHi/s for the hypertensives, respectively; there were also no significant differences in proton fluxes. The inability to find raised platelet sodium/hydrogen exchanger in the hypertensives contrasts with previous observations using other methods for the measurement of this exchanger in platelets and this raises important methodological issues in the assessment of platelet sodium/hydrogen exchanger activity.

Adult↗
PubMed1999

Health implications of residues of veterinary drugs and chemicals in animal tissues.

The animal drug approval process in the United States is based upon the premise that the presence of drug residues in meat and poultry above tolerance is a public health hazard. Tolerances represent the maximum level of concentration of antimicrobials permitted in animal tissues at the time of slaughter. The tolerances are intended to ensure that residual drugs will have no harmful effects if ingested. The purpose of this article is to present existing evidence of the acute and chronic health consequences that may occur because of food of animal origin contaminated with illegal residues above the tolerance. The impact of food-borne drug residues on the gut microflora, residue detection limitations, and the responsibility of the veterinary practitioner in ensuring food safety is discussed.

Abnormalities, Drug-Induced↗
PubMed1999

Lack of transmission of vancomycin-resistant enterococci in three long-term-care facilities.

Three patients colonized with vancomycin-resistant Enterococcus were admitted to one or more of three long-term-care facilities. Six point-prevalence surveys revealed no transmission of vancomycin-resistant Enterococcus after a total of 234 days of exposure during which moderately strict infection control measures were implemented. Four of 116 environmental cultures were positive.

Aged↗
PubMed1999

Spiritual well-being and demands of illness in people with colorectal cancer.

The purpose of this descriptive correlational study was to identify the relationship between subjects' spiritual well-being and the demands of illness (DOI) imposed by colorectal cancer. Potential subjects were notified about the study through computer networks. Those who met the criteria and wished to participate in the study used e-mail to request a study packet, which included an explanation of the study, the Demands of Illness Inventory (DOII), the Spiritual Well-Being Scale (SWBS), a demographic form, and a stamped return-reply envelope. Of the 170 packets requested, 121 (71%) were returned complete. More than half of the respondents were men and were of a Christian faith. Most respondents reported physical symptoms, but were able to carry on normal activity. Demands of illness were greater among men, the youngest subjects, those who received treatment in the previous 2 months, and those who reported decreased activity, metastatic disease, and/or terminal status. Women reported significantly greater spiritual well-being than men. Subjects who reported higher levels of spiritual well-being indicated significantly lower DOI related to physical symptoms, monitoring symptoms, and treatment issues. Findings indicate that a greater degree of spiritual well-being may help to mitigate the DOI imposed by colorectal cancer.

Adaptation, Psychological↗