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Biomedical subjects

C C Miller

Publications and source records attributed to C C Miller.

At least 109 records · Page 6Linked to original sources
PubMed1995

Anticardiolipin antibody in patients on maintenance hemodialysis and its association with recurrent arteriovenous graft thrombosis.

To investigate the relationship between dialysis access thrombosis (arteriovenous grafts [AVG] and arteriovenous fistulas [AVF]) and the presence of elevated concentration of immunoglobulin G-anticardiolipin antibody (IgG-ACA), we conducted a cross-sectional study of all patients, in a single dialysis facility, who had a minimum of 6 months of uninterrupted hemodialysis. Episodes of thrombosis of AVGs and AVFs in the preceding 30 months were documented and each patient's IgG-ACA titer was determined. Sixteen of 74 patients with AVGs (22%) had a raised titer of IgG-ACA compared with only one of 17 patients (6%) with AVFs. In the patients with AVGs the odds ratio for patients with raised IgG-ACA titer to have experienced two or more episodes of thrombosis, compared with none or only one episode, was 3.7 (95% confidence interval, 1.2 to 11.8; P < 0.04). No events of AVF thrombosis were encountered during the same period. We conclude that in end-stage renal disease patients undergoing hemodialysis, there is a greater prevalence of elevated IgG-ACA titer in patients with AVGs than in patients with AVFs, and this in turn is associated with increased odds of having had recurrent AVG thrombosis.

Adult↗
PubMed1995

Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac arrest.

STUDY OBJECTIVE: End-tidal CO2 (ETCO2) measurement can be used to predict death in prehospital cardiac arrest patients with pulseless electrical activity (PEA). DESIGN: A prospective, observational study. SETTING: An urban and rural emergency medical services system in northwestern Washington state. PARTICIPANTS: Ninety consecutive victims of prehospital cardiac arrest with PEA. INTERVENTIONS: Patients were intubated in the field and treated using standard advanced cardiac life support protocols with online medical control. In addition, all patients were evaluated using mainstream ETCO2 monitoring. In this study, a hypothetical decision was made to cease resuscitative efforts based on an ETCO2 level of 10 mm Hg or less after 20 minutes of advanced cardiac life support. RESULTS: The study included 90 patients (61 were men) with a mean age of 67.6 +/- 13.6 years (range, 27 to 95 years). The initial ETCO2 averaged 11.7 +/- 6.6 mm Hg in nonsurvivors (range, 5 to 50 mm Hg) and 10.9 +/- 4.9 mm Hg in survivors (range, 5 to 24 mm Hg) (P > .672 [NS]). After 20 minutes of advanced cardiac life support, ETCO2 averaged 3.9 +/- 2.8 mm Hg (range, 0 to 12 mm Hg) in patients in whom the theoretical decision was made to cease field resuscitation. In contrast, survivors' ETCO2, just before restoration of circulation, averaged 31 +/- 5.3 mm Hg (range, 16 to 35 mm Hg) (P < .0001). Using an ETCO2 of 10 mm Hg or less as a theoretical threshold to predict death in the field successfully discriminated between the 16 survivors to hospital admission (those that achieved return of spontaneous circulation) and 75 prehospital deaths. Of the 16 survivors to hospital admission, 9 died in the hospital, and 7 were discharged from the hospital alive. In 13 of the 16 survivors, the first evidence of return of spontaneous circulation, before a palpable pulse or blood pressure, was a rising ETCO2. The logistic-regression parameters for the model are 4.4391 + ETCO2*-0.3624 (P < .0001). Sensitivity was 97.3%; specificity 100%; positive predictive value 100%; and negative predictive value 88.9%. CONCLUSION: This study suggests that a low ETCO2 (10 mm Hg or less) can be used to predict irreversible death in patients with pulseless electrical activity undergoing prehospital advanced cardiac life support. If future studies validate this model, use of ETCO2 may allow for triage decisions in the field.

Adult↗
PubMed1995

Effect of recurrent episodic hypocapnic, eucapnic, and hypercapnic hypoxia on systemic blood pressure.

We have described a rat model that responds to chronic (8 h/day, 35 days) repetitive nonapneic episodic (cycled every 30 s) hypocapnic hypoxia with sustained increase in systemic blood pressure. Because the usual blood gas change of apnea is mildly increased CO2, we hypothesized that episodic hypoxia ranging from eucapnea to hypercapnia might cause a greater chronic increase in blood pressure than hypocapnic hypoxia in this model. Five groups of male Sprague-Dawley rats were studied: unhandled group received no treatment, sham group received compressed air in their chambers, hypocapnic hypoxic group received episodic hypoxia for 35 days, eucapnic hypoxic group received the same level of hypoxia but with 7-10% inspired fraction of CO2, and hybercarbic hypoxic group received hypoxia with 11-14% inspired fraction of CO2. Mean arterial blood pressure was measured in unrestrained conscious animals at baseline and after 35 days under their respective study conditions. Neither episodic eucapnic nor hypercarbic hypoxia had any additional effect on the changes in chronic diurnal blood pressure compared with hypocapnic hypoxia. These results suggest that the sympathetic nervous system or other neurohumoral systems contributing to chronic diurnal blood pressure elevation may be maximally stimulated by hypoxia or there may be some protective mechanism limiting the blood pressure response to asphyxia in this rat model.

Animals↗
PubMed1995

Acute systemic blood pressure elevation in obstructive and nonobstructive breath hold in primates.

Phasic blood pressure (BP) response during obstructive apnea (OA) in human sleep has been previously described as consisting of a slow incremental increase in BP to the point of apnea termination followed by a rapid rise and then fall in BP at the resumption of respiration. This rise in BP has been attributed to postapneic augmentation of cardiac output resulting after release of the marked negative intrathoracic pressure (NIP) of obstructed inspiration. Via an endotracheal tube, we created obstructed and nonobstructed breath hold (apnea) in chloralose-anesthesized baboons consisting of fixed-duration (30, 45, and 60 s) single OAs (mechanical obstruction) and nonobstructive (paralysis, ventilator cessation) apneas of matched duration and arterial desaturation. Systemic BP was measured before apnea (T0), during the last 5 s of apnea (T1), and during the first 5 s after resumption of respiration (T2). Despite wide fluctuations in NIP and BP during the T0 to T1 phase of OA, BP elevation in OA and nonobstructive apnea at T0, T1, or T2 did not differ for any duration apnea. At the release of obstruction, when resolution of NIP changes could theoretically increase cardiac output and accentuate BP, there was no difference in T1 and T2 pressures between the two conditions. We conclude that in this anesthesized animal model, mechanical (NIP) changes do not play a major role in overall maximum BP response to OA. Because of physiological differences between natural sleep in humans and the anesthetized state in animals, care must be taken in extrapolating these results to human sleep apnea.

Airway Obstruction↗
PubMed1995

The visual appearance and somatic cell count of mammary secretions collected from primigravid heifers during gestation and early postpartum.

Mammary secretions, obtained before and after calving, were examined for visual appearance, SCC, and bacteriology as part of a larger study determining the prevalence of IMI in 1588 primigravid heifers. Appearance of secretions was categorized into five groups: thin and watery, honey-like, serumy, milky, or thickened colostrum. Precalving secretions were further characterized as low viscosity (thin and watery, serumy, or milky) or high viscosity (honey-like and thickened colostrum). Postcalving secretions were further characterized as normal (milky, thickened colostrum) or abnormal (thin and watery, serumy, or honey-like). Infected precalving quarters (81%) had low viscosity secretions. Quarters that were uninfected precalving (75%) had high viscosity secretions. Greater than 90% of all postcalving milk samples appeared to be normal, regardless of geographic location, season, or bacterial infection status. Only 77% of the samples from quarters infected with contagious and noncontagious mastitis pathogens had normal appearance. Precalving SCC from bacteriologically negative quarters were lower than SCC from infected quarters. Similarly, postcalving SCC were lower from the bacteriologically negative quarters than from the infected quarters. Infected quarters had higher mean SCC than the uninfected quarters during both pre- and postcalving periods.

Animals↗
PubMed1994

Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection.

The ability of conjugated linoleic acid to prevent endotoxin-induced growth suppression was examined. Mice fed a basal diet or diet with 0.5% fish oil lost twice as much body weight after endotoxin injection than mice fed conjugated linoleic acid. By 72 hours post injection, mice fed conjugated linoleic acid had body weights similar to vehicle injected controls; however, body weights of basal and fish oil fed mice injected with endotoxin were reduced. Conjugated linoleic acid prevented anorexia from endotoxin injection. Splenocyte blastogenesis was increased by conjugated linoleic acid.

Animals↗
PubMed1994

Ultraviolet B injury increases prostaglandin synthesis through a tyrosine kinase-dependent pathway. Evidence for UVB-induced epidermal growth factor receptor activation.

To study the signal transduction mechanisms by which ultraviolet B (UVB) leads to increased prostaglandin E2 (PGE2) synthesis, human epidermal cultures were irradiated with 30 mJ/cm2 UVB and assayed for 6-h cumulative PGE2. Supernatants from irradiated cultures showed a 4-fold increase in PGE2 synthesis (113.6 +/- 26.8 pg/mg protein) when compared to supernatants from sham-irradiated cultures (25.6 +/- 3.9 pg/mg protein). Pretreatment of irradiated cultures with genistein (10 micrograms/ml) or tyrphostin-23 (50 microM), inhibitors of tyrosine kinases, blocked UVB-stimulated PGE2 synthesis. Treatment of nonirradiated cultures with epidermal growth factor (EGF), which acts through the receptor tyrosine kinase EGF-R, produced a 4-fold increase in PGE2 synthesis. However, addition of EGF to irradiated cultures did not further enhance their PGE2 synthesis, indicating irradiation rendered them refractory to EGF stimulation. In contrast, irradiated cultures could still significantly increase their PGE2 synthesis in response to the calcium ionophore A23187 or the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate, suggesting that the lack of response to EGF was selective. Furthermore, anti-phosphotyrosine immunoblot analysis revealed UVB-induced phosphorylation of tyrosine residues of EGF-R, an indicator of receptor activation. Phosphorylation was maximal 30-60 min after irradiation and was blocked by the tyrosine kinase inhibitors, genistein and tyrphostin. The antioxidant N-acetylcysteine decreased UVB-induced EGF-R tyrosine phosphorylation and PGE2 synthesis to near-basal levels. Conversely, treatment of unirradiated cultures with the potent oxidant tert-butyl-hydroperoxide (100 microM) increased both PGE2 synthesis and EGF-R phosphorylation. Collectively, these data suggest that antioxidant depletion induced by UV results in tyrosine phosphorylation and activation of the EGF-R. This activation may subsequently activate epidermal phospholipase at early time points after UVB exposure.

Calcimycin↗
PubMed1994

Large-scale isolation of equine zonae pellucidae.

A simple and rapid method is described for the large-scale isolation of cumulus cell-free, zona pellucida-intact equine oocytes. Aspiration of palpable antral follicles present on frozen-thawed equine ovaries was accomplished using a constant vacuum source. The resultant follicular fluid, oocytes, and particulate matter were then filtered through a series of nylon screens of alternating mesh openings in combination with sodium citrate-containing buffer to a final volume of approximately 20 ml. This fluid was transferred to scored Petri dishes and a stereomicroscope was used to locate the oocytes for futher processing or storage. The methodology described is inexpensive, time-efficient, and the recovery rate is similar to or better than other methods previously described for equine oocyte recovery. Collected oocytes are adequate for biochemical evaluation of the equine zona pellucida (EZP) as well as sperm-egg binding assays.

Journal Article↗
PubMed1994

Evidence against the induction of immunological tolerance by feeding antigens to chickens.

A series of studies was conducted to determine whether oral tolerance shown to be inducible in rodents can be induced in chickens. A preliminary study was performed with male juvenile Sprague-Dawley rats to ascertain the ability of ELISA to detect oral tolerance induction. Two groups of six rats were provided water with or without 2 mg/mL BSA for 14 consecutive d to induce tolerance. Eight days following water treatment, the rats were challenged i.m. with 1 mg BSA. Serum collected from the rats 20 d later showed decreased (P < .01) anti-BSA ELISA titers in the group given BSA in the water relative to those given ordinary water. Three experiments were conducted to determine whether oral tolerance could be induced in chickens. Birds were given daily oral doses of 25 mg BSA for 14 d (Experiment 1), or fed 5% casein in their diet for 14 d (Experiment 2), or 1 mL of a 50% suspension of SRBC for 10 d (Experiment 3). All birds were challenged with the same antigen after oral dosing. Birds orally dosed with BSA prior to challenge with BSA had titers similar to birds not fed BSA prior to challenge with BSA. When chickens were fed casein (P < .05) or orally gavaged with SRBC (P < .1), titers were enhanced. These observations suggest that feeding antigens prior to injection with the same antigen leads to an enhanced humoral immune response in birds and not tolerance.

Animals↗
PubMed1993

Enhanced keratinocyte prostaglandin synthesis after UV injury is due to increased phospholipase activity.

The possibility that increased eicosanoid synthesis in skin after ultraviolet light irradiation is due to enhanced phospholipase activity was examined. [3H]arachidonic acid-labeled human keratinocyte cultures exposed to 30 mJ/cm2 ultraviolet (UV) B were studied 6 h after injury. Bradykinin-stimulated release of [3H]arachidonic acid was increased 1.8-fold over release from control cultures by prior irradiation. In unlabeled cultures, prior irradiation produced a threefold increase in bradykinin-stimulated prostaglandin (PG) E2 synthesis as measured by immunoassay. The relative contribution of increased phospholipase vs. cyclooxygenase activity was therefore examined using stable isotope mass measurements of PGE2. By this method, prior irradiation increased bradykinin-stimulated phospholipase activity 3.5-fold, while no change in total cellular cyclooxygenase activity was observed. The effects of irradiation on phospholipase activity were then assessed in more detail. The activities of phospholipase A2, arachidonoyl-CoA synthetase, and arachidonoyl-CoA lysophosphatide acyltransferase in cell homogenates were determined. No effect of UV exposure on the activity of these enzymes was observed. These results suggest that the increase in prostaglandin synthesis produced after UV irradiation is due to increased phospholipase activity, thus enhancing arachidonate release.

Acylation↗
PubMed1993

Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression.

The ability of conjugated isomers of linoleic acid (CLA) to prevent reduced growth rate following endotoxin (lipopolysaccharide, LPS) injection was studied in two chick trials and one rat trial. Chicks (10 per treatment) were fed a corn and soybean meal-based diet with or without .5% CLA. At 21 days of age, chicks were weighed and injected i.p. with 1 mg/kg BW Escherichia coli LPS and sterile PBS. Body weights were again determined 24 h later. Antibody responses to SRBC were also determined. Rats fed .5% stearic acid or CLA for 4 wk (seven per treatment) were also injected with LPS, and BW change over a 24-h postinjection period was determined. Antibody responses to BSA, phytohemagglutinin foot pad swelling, and phagocytosis of elicited peritoneal macrophages were also determined. The CLA had no adverse effects on any immune variables measured in the chicks and rats. The CLA enhanced the phytohemagglutinin response and macrophage phagocytosis in rats. Chicks fed CLA and injected with LPS continued to grow, whereas those not fed CLA either failed to grow or lost weight following LPS injection. Both control and CLA-fed rats lost weight over the 24-h period after LPS injection; however, the loss of weight in rats fed CLA was only half of the weight loss of the control rats. Thus, CLA is effective in preventing the catabolic effects of immune stimulation.

Animals↗
PubMed1992

Targeted integration of the Ren-1D locus in mouse embryonic stem cells.

We have introduced a Ren-1D targeting vector into embryonic stem cells containing the two highly homologous mouse renin genes Ren-1D and Ren-2. Using a polymerase chain reaction (PCR) screen designed to detect targeted integration at Ren-1D and Ren-2, we isolated 15 targeted embryonic stem cell clones, all of which had undergone a gene conversion event at the Ren-1D locus. We did not isolate any clones in which the incoming DNA had recombined with Ren-2. Over the region encompassed by our transgene, Ren-1D and Ren-2 display greater than 95% homology. Our results suggest that the machinery driving gene targeting by means of homologous recombination in mammalian cells is capable of distinguishing between these two sequences. Construction of transgenic mice with the embryonic stem cells reported here carrying a mutated renin gene will permit a greater understanding of the functions of the Ren-1D and Ren-2 gene products and their relative contribution to cardiovascular homeostasis.

Animals↗
PubMed1992

Alzheimer's disease: transgenic models to test new chemicals and pharmaceuticals.

Alzheimer's disease is the most common form of senile dementia and is predicted to become even more prevalent as the proportion of elderly in the population increases over the next few decades. As yet, there are no effective treatments for the disorder. A major limitation to identifying new drugs and therapeutic targets for Alzheimer's disease has been the absence of an animal model displaying typical Alzheimer's pathology. Transgenic technology is now providing a powerful new approach for the development of animal models of Alzheimer's disease.

Alzheimer Disease↗
PubMed1992

Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea.

We have described a rat model that responds to repetitive episodic hypoxia (12-s infusions of nitrogen into daytime sleeping chambers every 30 s, 7 h/day for 35 days) with an increase in diurnal systemic blood pressure. We hypothesized that afferent information from the peripheral chemoreceptors may be necessary to produce diurnal blood pressure elevation in this hypoxia model. Carotid body denervation (CBD) was accomplished by severing both carotid sinus nerves in two groups of male Wistar rats (250-375 g). Group 4 CBD rats were subjected to intermittent hypoxia for 35 days (3-5% nadir ambient O2) as described above, whereas group 5 CBD rats remained unhandled in their usual cages. Additional sham-operated controls included group 2 sham-"hypoxia" rats, which were housed in chambers identical to the hypoxia rats but supplied with compressed air instead of nitrogen, group 1 (not denervated) rats, which remained unhandled in their usual cages, and group 3 sham-operated rats, which were subjected to 35 days of intermittent hypoxia identical to group 4 CBD rats. Femoral arterial baseline and end-of-study blood pressures were measured in conscious rats. The group 3 rats exposed to episodic hypoxia displayed a 13-mmHg increase in mean blood pressure, whereas the other groups showed no significant change from baseline. Left ventricular hypertrophy was evident in all rats exposed to episodic hypoxia, but right ventricular hypertrophy was evident only in the group 4 rats. All CBD rats developed increased hematocrit and hemoglobin, while the group 3 rats (non-CBD, episodic hypoxia) did not. The baroreceptor reflex at baseline was not depressed in the CBD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats.

An association between chronic high blood pressure and obstructive sleep apnea has been described. We hypothesized that repetitive episodic hypoxia patterned after the hypoxia seen in sleep apnea could contribute to diurnal elevation of blood pressure. Using 12-second infusions of nitrogen into daytime sleeping chambers, four groups of male rats (250-375 g) were subjected to intermittent hypoxia (3-5% nadir ambient oxygen) every 30 seconds, 7 hours per day for up to 35 days. In one group, blood pressure was measured weekly by the tail-cuff method in conscious animals during 5 weeks of episodic hypoxia. In the other three groups, blood pressure was measured in conscious animals via femoral artery catheters at baseline and after 20, 30, or 35 days of exposure. Additional groups served as controls: two sham groups housed in identical "hypoxia" chambers received compressed air instead of nitrogen (35 days) while two other groups remained unhandled in their usual cages (35 days). Both groups challenged with 35 days episodic hypoxia showed significant increases in blood pressure compared with controls: the tail-cuff rats showed a 21 mm Hg increase in systolic pressure (p less than 0.05) and the intra-arterially measured rats a 13.7 mm Hg increase in mean arterial pressure (p less than 0.05). The 30-day exposed rats also showed a 5.7 mm Hg increase in mean pressure over baseline (p less than 0.05). Blood pressure did not change significantly from baseline in the control groups. Left ventricle-to-body weight ratio was higher in both 35-day exposed groups than in unhandled or sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Sympathetic denervation blocks blood pressure elevation in episodic hypoxia.

We have previously described a rat model that responds to repetitive episodic hypoxia (FiO2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia.

Animals↗
PubMed1992

A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.

The efficacy of nasal oxygen during sleep was evaluated in patients with COPD, episodic rapid eye movement sleep desaturation, and a daytime PaO2 greater than 60 mm Hg. The double-blind, randomized 3-yr trial used nasal oxygen versus room air in two groups of nocturnal sleep desaturating subjects. The setting was the outpatient chest clinic of a Veterans Affairs Medical Center. There were 51 patients with moderate to severe COPD, daytime PaO2 greater than or equal to 60 mm Hg: 38 with proven REM sleep desaturation and 13 without desaturation. Nocturnal oxygen at 3 L/min was delivered by concentrator to 19 desaturating subjects, and room air at 3 L/min was delivered by defective concentrator to the remaining 19 desaturating subjects. There was no gas therapy for the 13 nondesaturating subjects. The nocturnal desaturator group who received supplemental oxygen during sleep over 36 months showed a significant downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9 mm Hg). Nonvascular parameters of hypoxia, such as hemoglobin and red blood cell mass, did not differ between the sham- and oxygen-treated groups. Mortality was decidedly higher in the desaturating patients compared with non-desaturating subjects, but there was no significant difference between oxygen- and sham-treated desaturating subjects. We conclude that nasal supplemental oxygen used during sleep to reverse episodic desaturation in COPD patients whose daytime PaO2 is above 60 mm Hg has a beneficial effect in reducing pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗