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Biomedical subjects

M A Miller

Publications and source records attributed to M A Miller.

At least 235 records · Page 13Linked to original sources
PubMed1995

Insulin-like growth factor 1 and parathyroid hormone effects on the growth of fetal rat metatarsal bones cultured in serum-free medium.

Insulin-like growth factor 1 (IGF-1) has roles in bone growth, and parathyroid hormone (PTH) is suspected of having effects on bone, perhaps mediated by IGF-1. The purpose of this study was to determine the individual and combined effect of PTH and IGF-1 on fetal long bone metabolism. Three medial metatarsal bones were dissected from Sprague-Dawley rat fetuses harvested at the 19th day of gestation, then grown in serum-free MEM. IGF-1 (group II) or PTH (group PP) were added at the dose of 100 ng/ml for 8 days. In a third group (PI), bones were preincubated for 4 days with PTH followed by a 4-day incubation with IGF-1. Both hormones stimulated endochondral (longitudinal) growth, the highest effect was observed with IGF-1 (II: 3.11 +/- 0.06 vs. 2.16 +/- 0.08 mm in controls). The length elicited by the PI treatment ranged between those measured with IGF-1 (II) and PTH (PP) given alone (PI: 2.80 +/- 0.04 mm; PP: 2.57 +/- 0.06 mm). In addition, both hormones enhanced periosteal growth (endomembranous ossification), as measured by the width of bones (II: 0.39 +/- 0.02 mm; PP: 0.34 +/- 0.02 mm; PI: 0.38 +/- 0.02 vs. 0.29 +/- 0.01 mm in controls). On the other hand, IGF-1 but not PTH caused a significant increase in 35S incorporation (as an indicator of sulfated proteoglycan synthesis in cartilage (percent of incorporating activity; II: 0.18 +/- 0.04%; PI: 0.09 +/- 0.01 vs. 0.03 +/- 0.01% in controls). Nevertheless, both IGF-1 and PTH enhanced osteoblastic activity as shown by increased alkaline phosphatase activity in treated bones (II: 1.18 +/- 0.00 mumol/bone; PP: 0.50 +/- 0.00 vs. 0.28 +/- 0.00 mumol/bone). In conclusion, IGF-1 had the greatest effects on growth in bone length (endochondral osteogenesis) and bone width (intramembranous osteogenesis) and appeared to stimulate both chondrogenesis and osteogenesis. It also increased growth but appeared to have greater effects on osteogenesis than on chondrogenesis. Pretreatment with IGF-1 followed by PTH produced effects that were intermediate between the groups treated with IGF-1 and PTH alone.

Animals↗
PubMed1995

Reduction of salt intake during converting enzyme inhibitor treatment compared with addition of a thiazide.

A moderate reduction in salt intake lowers blood pressure in individuals with hypertension and improves blood pressure control in those taking a converting enzyme inhibitor. However, it is unclear how effective reduction of salt intake is compared with addition of other drugs, in particular, thiazide diuretics. We directly compared the separate effects on blood pressure of reducing sodium intake or adding a thiazide diuretic in the pressure of a converting enzyme inhibitor in a double-blind, randomized, crossover study. We studied 11 subjects with essential hypertension who had been taking 25 mg captopril twice daily for at least 1 month. In the double-blind study, after 1 month of captopril alone, supine blood pressure was 151 +/- 5/95 +/- 4 (SEM) mm Hg. With the addition of 25 mg hydrochlorothiazide once daily for 1 month, blood pressure fell to 137 +/- 5/87 +/- 3 mm Hg. When a moderate reduction in salt intake (from 206 +/- 26 to 109 +/- 20 mmol urinary sodium/24 h) was added to captopril for 1 month, blood pressure was reduced by a similar amount (to 137 +/- 4/90 +/- 3 mm Hg). Plasma potassium fell during the diuretic treatment (3.9 +/- 0.1 to 3.7 +/- 0.1 mmol/L, P < .05) but increased nonsignificantly during salt reduction (3.9 +/- 0.1 to 4.1 +/- 0.2 mmol/L). These results clearly demonstrate that moderate salt reduction, which can be easily achieved, is as effective as a thiazide diuretic in lowering blood pressure in the presence of a converting enzyme inhibitor and has the particular advantage that plasma potassium does not decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Cutaneous melanocytomas in 10 young cattle.

Ten melanocytomas from 10 cattle were diagnosed by histopathologic examination of biopsy specimens submitted to the Veterinary Medical Diagnostic Laboratory, University of Missouri, between 1 January 1986 and 31 December 1993. One tumor was congenital; the others were first noticed between 2 months and 2 years of age (means = 9.9 months). Six tumors occurred in purebred (3) or crossbred (3) Angus cattle; one tumor each occurred in a Holstein, a Shorthorn, a Simmental, and a beef calf of unrecorded breed or coat color. Five calves were female, and five were male. Five tumors occurred in truncal dermis or subcutis (three in abdominal skin), four occurred on a limb, and one occurred on the jaw. Tumors varied in histologic appearance, but all were pigmented and all had few mitotic figures. Outcome was known for 8/10 cattle. In four cattle followed for at least 1 year, the tumor did not recur after surgical excision. Another heifer had residual gray tissue at the tumor site after surgery but remained in the herd without regrowth of the tumor 30 months after excision. Three other calves were slaughtered within 6 months of excision without apparent recurrence of the tumor.

Animals↗
PubMed1995

Comparison of argyrophilic nucleolar organizer regions (AgNORs) and mitotic index in distinguishing benign from malignant canine smooth muscle tumors and in separating inflammatory hyperplasia from neoplastic lesions of the urinary bladder mucosa.

Staining for argyrophilic nucleolar organizer regions (AgNORs) has proven useful in differentiating recurrent or malignant neoplasms from less aggressive or benign ones. We applied this stain to benign and malignant smooth muscle tumors and to hyperplastic and carcinomatous lesions in the urinary bladder of dogs in an effort to determine its utility in diagnostic situations. The stain was simply performed, and the results were repeatable for different staining intervals and between staining batches. For smooth muscle tumors, enumeration of AgNORs in 100 nuclei was about as efficient as mitotic index in correctly categorizing histologically benign and malignant neoplasms. The mean number of AgNORs/100 nuclei for leiomyomas was significantly less than that obtained for leiomyosarcomas and significantly greater than that obtained for normal smooth muscle. Counts for smooth muscle tumors correlated with the mitotic indexes. Counts by an individual observer were repeated without introducing significant variation, but there was variability between observers, particularly in AgNOR counts for leiomyosarcomas. AgNORs were not useful in separating hyperplastic or polypoid cystitis from transitional cell carcinoma, misclassifying both. Mean AgNOR counts for these 2 conditions did not differ at the 5% level of significance; mitotic index was more efficient at separating the 2 conditions. There was no correlation between mitotic index and AgNOR in urinary tract mucosal specimens. This easily prepared stain may be useful in separating benign and malignant smooth muscle tumors, although AgNORs were less contributory to diagnosing mucosal lesions of the urinary bladder of dogs.

Analysis of Variance↗
PubMed1995

Sex difference in coexpression by galanin neurons accounts for sexual dimorphism of vasopressin in the bed nucleus of the stria terminalis.

Vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) are steroid sensitive and sexually dimorphic. The number of VP messenger RNA (mRNA)-expressing neurons is larger in male than in female rats. This initial observation suggested that sexual dimorphism resulted from enhanced proliferation and/or survival of VP neurons after gonadal hormone exposure during the critical perinatal period. However, galanin (GAL) and VP mRNAs were recently reported to be coexpressed in the BNST of adult male rats, and GAL gene expression, unlike VP gene expression, is not sexually dimorphic. These findings are consistent with the hypothesis that the sex difference in VP cell number in the BNST results from a sex difference in the number of GAL neurons dedicated to express the VP gene. To test this hypothesis, double in situ hybridization histochemistry was performed for GAL and VP mRNAs in the BNST of adult male and female rats. For quantification, the posterior BNST was divided into its two anatomical regions: medial (BSTM) and lateral (BSTL) divisions. Extending previous results for the whole BNST, the number of GAL-expressing cells in either the BSTM or the BSTL was not sexually dimorphic. A significant sex difference was found in the number of GAL cells coexpressing VP in the BSTM (mean +/- SE, male, 124 +/- 8; female, 56 +/- 6; P < or = 0.0001), but not in the BSTL (male, 80 +/- 9; female, 83 +/- 15). Accordingly, the number of cells expressing GAL mRNA only was significantly lower (P < or = 0.002) in the BSTM of male (43 +/- 5) than in female (85 +/- 9) rats. Evidence is provided that the reduced incidence of coexpression of VP by GAL neurons in the BSTM of female rats may account for the reported sex difference in VP cell number in the entire BNST. The results suggest that gonadal hormones in the perinatal period may not influence the proliferation and/or survival of VP neurons in the BNST per se but influence, instead, the capacity of GAL neurons to synthesize VP.

Animals↗
PubMed1995

Cocaine's effects on food-reinforced pecking in pigeons depend on food-deprivation level.

Four pigeons deprived to 80% of their laboratory free-feeding weights pecked keys under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. Components alternated strictly with 15-s timeouts separating them; each was presented six times. When rates of pecking were stable, 2 pigeons' weights were reduced to 70%, and the other 2 pigeons' weights were increased to 82.5% to 85% of free-feeding levels. Cocaine (1.0, 3.0, 5.6, and 10.0 mg/kg and saline) was administered 5 min prior to sessions. When each dose had been tested twice, pigeons' weights were adjusted to the level that they had not yet experienced, and cocaine was tested again. Cocaine reduced response rates in a dose-dependent manner under the fixed-ratio schedule and under the fixed-interval schedule at high doses, and increased rates under the fixed-interval schedule at low low doses. Reductions in pecking rates occurred at lower doses under both schedules in 3 of 4 pigeons when they were less food deprived compared to when they were more food deprived. Low doses of cocaine increased low baseline rates of pecking in the initial portions of the fixed-interval schedules by a greater magnitude when pigeons were more food deprived. Thus, food-deprivation levels altered both the rate-decreasing and rate-increasing effects of cocaine. The implications of these results for the mechanisms by which food deprivation increases cocaine self-administration and for the dependence of cocaine's effects on the baseline strength of operant behavior are discussed.

Animals↗
PubMed1995

An epizootic of hemorrhagic disease in white-tailed deer (Odocoileus virginianus) in Missouri: necropsy findings and population impact.

An epizootic occurred among white-tailed deer (Odocoileus virginianus) from July through October 1988 in Missouri (USA). From late July through September, nine necropsied deer had lesions of the peracute or acute forms of hemorrhagic disease (HD) or no apparent lesions, whereas two deer necropsied in October had lesions of the chronic form of HD. Epizootic hemorrhagic disease virus was isolated from two necropsied deer. Based on changes in population indices, there is evidence that deer populations declined in seven of Missouri's 57 deer management units from 1987 to 1990. Based on a deterministic model designed to simulate deer populations in management units, it appeared that summer and fall 1988 mortality ranging from 6% to 16% accounted for the population decreases in deer management units with population declines. Heavily hunted areas where high deer mortality was not reported in the summer and fall of 1988 did not have population declines. Based on these results, we believe that HD mortality was high and resulted in deer population declines in parts of Missouri when combined with hunting harvest.

Animals↗
PubMed1995

Patient-focused care from a materials manager perspective.

In one year, Cedars-Sinai Medical Center (Los Angeles, CA) implemented patient-focused care on 32 nursing units. Through utilizing a continuous quality improvement (CQI) model of which patient-focused care was one operative, successful implementation was completed. The key concept was teamwork, and Materials Management Services proved to be a valuable member at all levels in the process whether at the oversight, design, or specialty task force level. Materials Management Services provided a consistent, efficient, streamlined service while following the guiding principles of patient-focused care: managed demand, redesigned work, and empowered employees.

Hospital Restructuring↗
PubMed1995

Effects of papaverine and vasointestinal polypeptide on penile and vascular cAMP and cGMP in control and diabetic animals: an in vitro study.

Adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) mediate penile erection. We have previously established that adenylate and guanylate cyclase activity is elevated in the diabetic rat penis and aorta. This study investigates the action of papaverine and vasoactive intestinal polypeptide (VIP) on these cyclases. The aortae and penes of Sprague Dawley rats (n = 7) were stimulated with VIP and papaverine. Diabetes mellitus (DM) was induced in Sprague Dawley rats (n = 7) with streptozotocin and the penile and aortic tissues were treated with VIP. The penes, aortae and carotid arteries of New Zealand White rabbits were similarly processed. cAMP and cGMP generation was measured by radioimmunoassay. In all tissues: VIP stimulated cAMP synthesis; VIP did not increase cGMP levels; papaverine was without effect on either cAMP or cGMP synthesis. VIP-stimulated cAMP was significantly enhanced in the diabetic rat penis and aorta; there was also a significant elevation in the basal levels of cGMP in these tissues. These data: (1) consolidate that cAMP is a mediator of penile erection, (2) indicate that papaverine and VIP elicit erection by different mechanisms, (3) suggest that an enhanced penile capacity to generate cAMP in DM may constitute an adaptive response to counteract the previously reported reduction in VIP content and VIP receptors, and (4) indicate that the penile and vascular tissues of the rabbit respond in a similar manner to VIP and papaverine.

Animals↗
PubMed1995

In vitro formation, disposition and toxicity of N-acetoxy-sulfamethoxazole, a potential mediator of sulfamethoxazole toxicity.

Variation in the formation and disposition of the hydroxylamine of (SMX-HA) is thought to play an important role in the pathogenesis of sulfamethoxazole (SMX)-induced idiosyncratic adverse drug reactions. We hypothesized that, in analogy to carcinogenic arylamines, SMX-HA might be further converted to an electrophilic N-acetoxy metabolite which could play a role in mediating SMX toxicity. Accordingly, we chemically synthesized N-acetoxy-SMX, and examined the characteristics of its formation, metabolism, cytotoxicity and mutagenicity in human and bacterial test systems. The human arylamine N-acetyl-transferases, (NAT)1 and NAT2, were capable of converting SMX-HA to N-acetoxy-SMX. NAT1 and NAT2 possessed similar affinities for SMX-HA (apparent Km values of 650 and 520 microM, respectively), but the apparent maximal velocity of the NAT1-mediated acetylation was higher than that of NAT2. (1332 vs. 37 nmol/min/U of immunoreactive NAT protein). Human peripheral blood mononuclear cells 12,000 x g supernatant fractions converted N-acetoxy-SMX mainly back to SMX-HA, and also to a lesser extent to SMX, at clinically relevant concentrations. Similar pathways were observed in human hepatic cytosolic fractions. In a cytotoxicity assay, N-acetoxy-SMX was significantly more toxic to human peripheral blood mononuclear cells than SMX-HA (16.6 vs. 11.5% dead cells at a concentration of 300 microM). N-acetoxy-SMX was weakly mutagenic to the Salmonella typhimurium TA100 strain in the Ames test. These data suggest that the N-acetoxy metabolites of sulfonamides could potentially play a role in mediating sulfonamide idiosyncratic adverse drug reactions.

Acetyltransferases↗
PubMed1995

Propionibacterium acnes endocarditis.

Propionibacterium acnes endocarditis is a rare disease. A case of prosthetic valve endocarditis involving P acnes complicated by multiple mycotic aneurysms is reported. A brief review of the literature is presented.

Aortic Valve↗
PubMed1995

Tumor necrosis factor-induced necrosis: a monocyte-mediated hypercoagulable effect.

The mechanisms by which tumor necrosis factor (TNF) exerts its necrotic effects are somewhat obscure. We hypothesize that TNF, by monocyte activation, produces the procoagulant tissue factor, thus leading to a state of hypercoagulability with resultant thrombotic vascular occlusion and tissue necrosis. To test this hypothesis, modified recalcification time values (in minutes +/- standard deviation) were obtained on aliquots of blood with A) 20 microL of albumin, B) 20 microL of saline containing endotoxin, and C) 20 microL of albumin with 450 units of TNF. No differences were noted if the samples were not incubated. We conclude that TNF, can cause tumor (tissue) necrosis, and since incubation is required, TNF alone (without monocyte activation) has no procoagulant activity.

Blood Coagulation↗
PubMed1995

Safety and immunogenicity of PRP-T combined with DTP: excretion of capsular polysaccharide and antibody response in the immediate post-vaccination period.

OBJECTIVE: To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic. DESIGN: Randomized clinical trial. SETTING: Suburban New Orleans pediatric population. PARTICIPANTS: Convenience sample of 150 healthy infants. METHODS: Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197 (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide. RESULTS: The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01). CONCLUSIONS: Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.

Antibodies, Bacterial↗
PubMed1995

A novel method for isolating and quantifying urine pathogens collected from gel-based diapers.

BACKGROUND: Given that children often present to physicians with a wet gel-based diaper, a method for using this diaper for a urine specimen was studied. METHODS: A blinded clinical laboratory trial was conducted in the microbiology laboratory. The sampling technique involved the use of oval gynecologic forceps as a template and sterile scissors to cut out samples of diapers. Each diaper sample was then vortexed in 20 mL of sterile saline and the supernatant quantitatively cultured. Diaper sample supernatant cultures with simulated infected urines (suspensions of Escherichia coli) were used. RESULTS: Weight measurements of the diaper samples soaked with 20 mL or more of saline yielded reproducible results (0.703 g; 95% confidence interval [CI], 0.52 to 0.88 g). Culture results (colony-forming units per liter [CFU/L] of supernatant) from diapers soaked with 25 mL of various concentrations of E coli (10(6), 10(7), 10(8), 10(9) CFU/L) showed excellent correlation with the inoculum used, and no effect of a 2-hour delay in culturing the wet diapers. CONCLUSIONS: Our technique provides accurate and reliable estimates of bacterial concentrations in the usual range for infected urine from gel-based diapers soaked with solutions of E coli. Further evaluation of clinical implementation is needed.

Escherichia coli↗
PubMed1995

Are hypertensives hypercoagulable?

Angiotensin II is a prothrombotic vasoconstrictor. This study proves that many hypertensives are hypercoagulable and at risk for myocardial infarction. The modified recalcification time (MRT) test, used to assess hypercoagulability, incorporates the role of tissue factor in coagulation by activating the monocyte with endotoxin to release latent tissue factor. Aliquots of citrated blood obtained from hypertensives and normotensive controls were placed in two groups of vials, one with saline (group S) and one with endotoxin (group E). All vials were incubated at 37 degrees C for 2 hours, citrate neutralized with calcium chloride, and the MRT (in minutes) for group S (MRT S) and for group E (MRT E) was determined. Mean MRT S values +/- standard deviation (SD) for hypertensives (n = 25) and for controls (n = 27) were 6.4 +/- 1.2 and 6.8 +/- 1.2, respectively. The MRT E values were 4.3 +/- 1.2 and 5.7 +/- 0.9 for the hypertensives and controls, respectively. The MRT E, not the MRT S, was significant. Hypertensives had MRT E values < 4.5 minutes, and by our established criteria, were hypercoagulable. We conclude that because hypercoagulability is a risk factor for thrombosis, hypertensives with short MRT E values may be at increased risk for myocardial or other thrombotic events.

Blood Coagulation Tests↗
PubMed1995

Attitudes and beliefs of Canadian infection control decision-makers towards 'borderline' methicillin-resistant Staphylococcus aureus.

'Borderline' methicillin-resistant Staphylococcus aureus (MRSA) strains are inhibited by drug concentrations of 2 to 8 micrograms/mL. This type of resistance is usually mediated by 'hyper beta-lactamase' production which is detectable in vitro by susceptibility to combinations of a beta-lactam and a beta-lactamase inhibitor (ie, amoxicillin and clavulanic acid). A survey of Canadian infection control experts was performed to assess the knowledge, attitudes and beliefs regarding the containment requirements for borderline MRSA strains in acute health care facilities. Twenty-three of 38 Canadian infection control experts (61%) (members of the Canadian Hospital Epidemiology Committee [CHEC] or the Society for Healthcare Epidemiology of American [SHEA]) returned a questionnaire about a fictional patient with a postoperative wound infection with such a strain. Eleven respondents (48%) considered the isolate as an MRSA, 11 did not and one was unsure. All who did not believe the strain to be MRSA would not have isolated or cohorted the patient. Four in the latter group would have isolated the patient if he or she were on a neurosurgery or cardiovascular surgery unit, indicating a desire to restrict spread of this isolate on those units. Seven of the 12 individuals who had managed at least one patient with a borderline MRSA did not advocate patient isolation or cohorting, and five did. This survey has supported the belief that there are discrepancies among infection control decision-makers in Canada regarding the approach, precautions and therapy of patients infected with borderline strains of MRSA. Further data on virulence of and effective therapy for these isolates are needed to assess whether the additional cost is warranted in controlling the nosocomial spread of these isolates.

Canada↗
PubMed1994

A cation binding motif stabilizes the compound I radical of cytochrome c peroxidase.

Cytochrome c peroxidase reacts with peroxide to form compound I, which contains an oxyferryl heme and an indolyl radical at Trp-191. The indolyl free radical has a half-life of several hours at room temperature, and this remarkable stability is essential for the catalytic function of cytochrome c peroxidase. To probe the protein environment that stabilizes the compound I radical, we used site-directed mutagenesis to replace Trp-191 with Gly or Gln. Crystal structures of these mutants revealed a monovalent cation binding site in the cavity formerly occupied by the side chain of Trp-191. Comparison of this site with those found in other known cation binding enzymes shows that the Trp-191 side chain resides in a consensus K+ binding site. Electrostatic potential calculations indicate that the cation binding site is created by partial negative charges at the backbone carbonyl oxygen atoms of residues 175 and 177, the carboxyl end of a long alpha-helix (residues 165-175), the heme propionates, and the carboxylate side chain of Asp-235. These features create a negative potential that envelops the side chain of Trp-191; the calculated free energy change for cation binding in this site is -27 kcal/mol (1 cal = 4.184J). This is more than sufficient to account for the stability of the Trp-191 radical, which our estimates suggest is stabilized by 7.8 kcal/mol relative to a Trp radical in solution.

Binding Sites↗