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Biomedical subjects

B A Davis

Publications and source records attributed to B A Davis.

At least 19 recordsLinked to original sources
PubMed2000

Long-term outcome of continuous 24-hour deferoxamine infusion via indwelling intravenous catheters in high-risk beta-thalassemia.

The optimal regimen of intravenous deferoxamine for iron overload in high-risk homozygous beta-thalassemia is unknown because only short-term follow-up has been described in small patient groups. We report the outcome over a 16-year period of a continuous 24-hour deferoxamine regimen, with dose adjustment for serum ferritin, delivered via 25 indwelling intravenous lines for 17 patients. Treatment indications were cardiac arrhythmias, left ventricular dysfunction, gross iron overload, and intolerability of subcutaneous deferoxamine. Cardiac arrhythmias were reversed in 6 of 6 patients, and the left ventricular ejection fraction improved in 7 of 9 patients from a mean (+/- SEM) of 36 +/- 2% to 49 +/- 3% (P =.002, n = 9). The serum ferritin fell in a biphasic manner from a pretherapy mean of 6281 +/- 562 microg/L to 3736 +/- 466 microg/L (P =.001), falling rapidly and proportionally to the pretreatment ferritin (r(2) = 0.99) for values >3000 microg/L but falling less rapidly below this value (at 133 +/- 22 microg/L/mo). The principal catheter-related complications were infection and thromboembolism (1. 15 and 0.48 per 1000 catheter days, respectively), rates similar to other patient groups. Only one case of reversible deferoxamine toxicity was observed (retinal) when the therapeutic index was briefly exceeded. An actuarial survival of 61% at 13 years with no treatment-related mortality provides evidence of the value of this protocol. (Blood. 2000;95:1229-1236)

Actuarial Analysis↗
PubMed2000

Metabolism and pharmacokinetics, in the rat, of (R)-N-(2-Heptyl)Methyl-propargylamine (R-2HMP), a new potent monoamine oxidase inhibitor and antiapoptotic agent.

(R)-N-(2-Heptyl)-N-methylpropargylamine (R-2HMP) is a monoamine oxidase inhibitor and putative antiapoptotic agent analogous to (R)-deprenyl. In the rat, the major amine metabolites of R-2HMP have been identified as (R)-N-2-heptylmethylamine (R-2HMA), (R)-N-2-heptylpropargylamine (R-2HPA), and (R)-2-heptylamine (R-2HA). After R-2HMP was administered s.c. to male Wistar rats, it was observed that the greatest concentration was of the original drug followed in decreasing order by R-2HMA, R-2HPA, and R-2HA in brain, liver, and plasma at all times after administration. The greatest concentrations of the three metabolites were found in brain followed by liver and plasma, and the peak concentrations occurred between 15 and 30 min after administration. After oral administration, the liver contained the greatest concentrations of drug and metabolites, and, again, the peak concentrations occurred at about 15 min. In all cases, depropargylation appears to occur at a faster rate than demethylation. After s.c. administration, R-2HMP and its metabolites exhibited biexponential redistribution and elimination losses. Half-lives of the compounds in brain for the redistribution phase were: R-2HMP, 10 min; R-2HMA, 11 min; R-2HPA, 16 min; and R-2HA, 15 min.

Administration, Oral↗
PubMed1999

Femoral neck stress fracture presenting as gluteal pain in a marathon runner: case report.

A case is described of a 50-year-old man with a femoral neck stress fracture presenting as gluteal pain. An operative pinning procedure of the femoral neck was performed for stabilization. Femoral neck stress fractures are often misdiagnosed early in their presentation. The signs and symptoms can mimic those of more commonly seen disorders. Appropriate physiatric history and physical examination, along with indicated studies, will help prevent misdiagnosis and potentially serious complications associated with musculoskeletal pathology.

Athletic Injuries↗
PubMed1999

Inversion of selectivity of N-substituted propargylamine monoamine oxidase inhibitors following structural modifications to quaternary salts.

A number of N-substituted-propargylamines are well known mechanism-based MAO inhibitors. Clorgyline and deprenyl in fact represent archetypal MAO-A and MAO-B inhibitors respectively. In the present study several ring-substituted deprenyl structural analogues were synthesized and alterations of selectivity and potency towards MAO-A and MAO-B activities were found. When deprenyl and its structural analogues were further modified to their corresponding quaternary ammonium salts. i.e. by attaching either an extra propargyl or a methyl group to the nitrogen atom, the potency of inhibition of MAO-B activity was drastically reduced and inhibition of MAO-A activity substantially increased. Such a complete inversion of selectivity may be related to a hydrophilic and electrophilic region seemingly present only in the MAO-A but not in the MAO-B molecule. The results also suggest that at least three sites are required for the selectivity and mechanism-based action of an inhibitor towards MAO.

Amino Acid Sequence↗
PubMed1999

Patient satisfaction with nursing care in a rural and an urban emergency department.

This descriptive study was designed to describe and compare the level of patient satisfaction and explore differences and relationships of demographic variables with patient satisfaction in two emergency department patient populations in Victoria, Australia. The sample consisted of 103 rural and urban emergency patients. Tests for differences demonstrated that urban patients were more satisfied with nurse teaching behaviours (P = 0.017), with female patients at the urban hospital more satisfied with nurse caring behaviours (P = 0.026). An item, 'The nurse performed his/her duties with skill' scored highest and had the lowest variability. Qualitative analysis of two open-ended questions regarding what respondents liked best about the experience and what could have made the experience better, produced four and six themes, respectively. Conclusions indicated the need for more research comparing rural and urban emergency patients and patients of different cultures.

Adolescent↗
PubMed1999

Patient satisfaction with emergency department triage nursing care: a multicenter study.

This descriptive, correlational study examines relationships between (1) individual patient and nurse characteristics and (2) patient satisfaction with triage nursing care, patient satisfaction with the triage nurse, and patient's intention to return to a specific Emergency Department. The convenience sample consisted of Urgent/Delayed patients (N = 378) triaged in an urban academic medical center, a public hospital in a small city, and a Catholic hospital in a small city. Analysis of variance revealed significantly higher levels of patient satisfaction at the academic medical center, whereas higher levels of intent to return were reported by subjects from the Catholic-affiliated hospital. Educational preparation of the triage nurse was identified as a significant predictor of both patient satisfaction with triage nursing care and loyalty to a specific.

Adult↗
PubMed1999

Litter effects on caries in rats and implications for experimental design.

The purpose of this study was to obtain quantitative estimates of litter effects on caries development in rats and to examine the implications for design of rat caries experiments. Twelve female Sprague-Dawley rats, aged 60 days, were bred with 4 male rats. Nine of the 12 dams had litters in close proximity. The litters were culled to 10 pups. One pup from each litter was placed with each of the other dams for nursing, leaving 2 pups from each litter with the birth dam. This design allowed the litter effect to be separated into a prenatal component, reflecting the shared genetic makeup and in utero environment of littermates, and a postnatal component reflecting a shared environment from shortly after birth to weaning. Pups were infected with Streptococcus sobrinus and fed Diet 2000 and 10% (w/v) sucrose water for 5 weeks. There was no significant evidence of a postnatal litter effect for smooth surface caries (p = 0.37) or sulcal caries (p = 0.43). The prenatal litter effect was significant for both smooth surface caries and sulcal caries (p<0. 01). When litter effects are present, the statistical power of caries studies is improved if animals from the same litter are divided evenly among experimental groups. In addition, if litter effects are present but not allowed for in data analysis, incorrect statistical inferences may be drawn. Based on our results and other reports of litter effects, we recommend planning for litter effects in the design and analysis of rat caries studies.

Animals↗
PubMed1998

Collagenase and tissue plasminogen activator production in developing rat calvariae: normal progression despite fetal exposure to microgravity.

Exposure to zero gravity has been shown to cause a decrease in bone formation. This implicates osteoblasts as the gravity-sensing cell in bone. Osteoblasts also are known to produce neutral proteinases, including collagenase and tissue plasminogen activator (tPA), which are thought to be important in bone development and remodeling. The present study investigated the effects of zero gravity on development of calvariae and their expression of collagenase and tPA. After in utero exposure to zero gravity for 9 days on the NASA STS-70 space shuttle mission, the calvariae of rat pups were examined by immunohistochemistry for the presence and location of these two proteinases. The ages of the pups were from gestational day 20 (G20) to postnatal (PN) day 35. Both collagenase and tPA were found to be present at all ages examined, with the greatest amount of both proteinases present in the PN14 rats. At later ages, high amounts were maintained for tPA but collagenase decreased substantially between ages PN21 to PN35. The location of collagenase was found to be associated with bone-lining cells, osteoblasts, osteocytes, and in the matrix along cement lines. In contrast, tPA was associated with endothelial cells lining the blood vessels entering bone. The presence and developmental expression of these two proteinases appeared to be unaffected by the exposure to zero gravity. The calvarial thickness of the pups was also examined; again the exposure to zero gravity showed little to no effect on the growth of the calvariae. Notably, from G20 to PN14, calvarial thickness increased dramatically, reaching a plateau after this age. It was apparent that elevated collagenase expression correlated with rapid bone growth in the period from G20 to PN14. To conclude, collagenase and tPA are present during the development of rat calvariae. Despite being produced by the same cell in vitro, i.e., the osteoblast, they are located in distinctly different places in bone in vivo. Their presence, developmental expression, and quantity do not seem to be affected by a brief exposure to zero gravity in utero.

Aging↗
PubMed1998

Structural characterization of the rat cysteine-rich intestinal protein gene and overexpression of this LIM-only protein in transgenic mice.

Cysteine-rich intestinal protein (CRIP) has a double zinc-finger motif called the LIM domain. The most elementary member of the Group 2 LIM-only protein family, CRIP was initially identified as a developmentally regulated intestinal gene. Subsequently, it was found to be highly expressed in immune cells. The structural portion of the rat CRIP gene is comprised of five exons extending over i.8 kb, with the two zinc-finger motifs of the LIM domain being divided among the first three exons. In addition to transcriptional regulatory elements previously identified in the promoter, consensus sequences for AP-1, AP2, Sp-1, and a glucocorticoid response element are located within the first intron. We have developed a line of transgenic mice that overexpress the rat CRIP gene with an expression profile that mirrors that of the endogenous gene. Driven by the homologous rat CRIP promoter, expression increased threefold to sevenfold in intestine, thymus, spleen, and lung over endogenous levels. The transgenic mice had only about 50% of the white blood cell count found in nontransgenic animals. Differential leukocyte counts showed transgenic animals had proportionately fewer lymphocytes and more monocytes, eosinophils, neutrophils. Flow cytometry data suggested that mice overexpressing CRIP have more CD4+/CD8+ thymic lymphocytes. These data suggest that CRIP plays a significant role in differentiation or maturation of cells with rapid turnover such as those found in the intestine and immune system.

Amino Acid Sequence↗
PubMed1998

The reliability of monopolar and bipolar fine-wire electromyographic measurement of muscle fatigue.

Bipolar intramuscular wire electrodes and spectral analysis of the electromyographic signal have been used to measure fatigue in muscles that cannot be studied with surface electrodes. Intramuscular electrodes can detect a greater range of frequencies from muscle, obtain a less distorted signal, and are therefore felt to be more sensitive to detecting fatigue. To determine the reliability and sensitivity of electrode placement (with a fixed distance) for assessing muscle fatigue, we placed three intramuscular electrodes in and two surface electrodes on the biceps brachii of 30 healthy male subjects. With these electrodes, we devised eight configurations that were analyzed separately for reliability. Subjects performed four, 30-s isometric fatiguing contractions divided between two testing sessions. Mean and median frequency of the power density spectrum were plotted against time. Linear regression was performed to obtain slopes, which were used as indicators of fatigue. The bipolar surface electrode configuration displayed mean and median frequency intrasession and mean frequency intersession reliability for slope. All four bipolar fine-wire configurations had mean and median frequency intrasession reliability (P < or 0.05). Only three of the four bipolar fine-wire configurations approached mean frequency intersession reliability, and none fo the four displayed median frequency intersession reliability. the configuration with distal bipolar intramuscular electrodes placed 1 cm apart was the most reliable intramuscular technique. The bipolar fine-wire configuration studied showed a trend toward better reliability than monopolar fine-wire configurations. No intramuscular technique, however, was reliable enough for clinical use in the study of fatigue.

Adolescent↗
PubMed1998

Effect of expressing the water channel aquaporin-1 on the CO2 permeability of Xenopus oocytes.

It is generally accepted that gases such as CO2 cross cell membranes by dissolving in the membrane lipid. No role for channels or pores in gas transport has ever been demonstrated. Here we ask whether expression of the water channel aquaporin-1 (AQP1) enhances the CO2 permeability of Xenopus oocytes. We expressed AQP1 in Xenopus oocytes by injecting AQP1 cRNA, and we assessed CO2 permeability by using microelectrodes to monitor the changes in intracellular pH (pHi) produced by adding 1.5% CO2/10 mM HCO3- to (or removing it from) the extracellular solution. Oocytes normally have an undetectably low level of carbonic anhydrase (CA), which eliminates the CO2 hydration reaction as a rate-limiting step. We found that expressing AQP1 (vs. injecting water) had no measurable effect on the rate of CO2-induced pHi changes in such low-CA oocytes: adding CO2 caused pHi to fall at a mean initial rate of 11.3 x 10(-4) pH units/s in control oocytes and 13.3 x 10(-4) pH units/s in oocytes expressing AQP1. When we injected oocytes with water, and a few days later with CA, the CO2-induced pHi changes in these water/CA oocytes were more than fourfold faster than in water-injected oocytes (acidification rate, 53 x 10(-4) pH units/s). Ethoxzolamide (ETX; 10 microM), a membrane-permeant CA inhibitor, greatly slowed the pHi changes (16.5 x 10(-4) pH units/s). When we injected oocytes with AQP1 cRNA and then CA, the CO2-induced pHi changes in these AQP1/CA oocytes were approximately 40% faster than in the water/CA oocytes (75 x 10(-4) pH units/s), and ETX reduced the rates substantially (14.7 x 10(-4) pH units/s). Thus, in the presence of CA, AQP1 expression significantly increases the CO2 permeability of oocyte membranes. Possible explanations include 1) AQP1 expression alters the lipid composition of the cell membrane, 2) AQP1 expression causes overexpression of a native gas channel, and/or 3) AQP1 acts as a channel through which CO2 can permeate. Even if AQP1 should mediate a CO2 flux, it would remain to be determined whether this CO2 movement is quantitatively important.

Animals↗
PubMed1997

Enantioselective gas chromatographic assay of 2-alkylamines using N-(trifluoroacetyl)prolyl derivatives and a chiral capillary column.

The chromatographic properties of (R)-(+)-N-(trifluoroacetyl)prolyl and (S)-(-)-N-(trifluoroacetyl)prolyl derivatives on a chiral gas chromatography capillary column were assessed for the measurement of enantiomeric purities of 2-butylamine, 2-pentylamine, 2-hexylamine, 2-heptylamine and 2-octylamine and their N-methyl analogues, which are used as precursors in the synthesis of some selective, specific, irreversible monoamine oxidase-B inhibitors. Using a Chirasil-Val column it was possible to separate all four diastereomers of the primary amines, and three of the four isomers of the secondary amines. Quantitation of the enantiomers is facilitated even with enantiomerically impure reagent when compared to the use of an achiral phase.

Amines↗
PubMed1997

Influence of maternal lead ingestion on caries in rat pups.

Lead is one of the most toxic and pervasive pollutants in society, and although there has been some lowering of blood lead levels in recent years, the levels continue to be of concern for African Americans, central city residents, residents in the Northeast region of the United States, persons with low income, and those with low educational attainment. Notably, these are the persons and the region where the highest prevalence of dental caries is observed. Information relating lead toxicity to oral health is sparse, but the preponderance of epidemiological data shows a relation between lead in the environment and the prevalence of dental caries. Using our well-defined rat caries model we found that pre- and perinatal exposure to lead results in an almost 40% increase in the prevalence of caries and a decrease in stimulated parotid function of nearly 30%. Levels of lead in milk from lead-treated dams were approximately 10 times as high as the corresponding blood lead levels, suggesting that lead is being concentrated by mammary glands. These findings may help in part to explain the comparatively high levels of dental caries observed in the inner cities of the United States where exposure to lead is common. Environmental sources of lead include drinking water, lead-based paint and, to a lesser extent, automobile and industrial emissions. In humans lead is accumulated and stored in bones (half-life of approximately 62 years), and even maternal exposure to lead decades before pregnancy can subsequently result in exposure of the developing fetus to elevated levels of lead. Moreover, lead concentration in maternal blood has been shown to increase during pregnancy and lactation because of mobilization of stored lead from bone, and typically, lead is found in milk at a higher concentration than the level found in maternal plasma at the same time point.

Animals↗
PubMed1997

Intracellular Cl- dependence of Na-H exchange in barnacle muscle fibers under normotonic and hypertonic conditions.

We previously showed that shrinking a barnacle muscle fiber (BMF) in a hypertonic solution (1,600 mosM/kg) stimulates an amiloride-sensitive Na-H exchanger. This activation is mediated by a G protein and requires intracellular Cl-. The purpose of the present study was to determine (a) whether Cl- plays a role in the activation of Na-H exchange under normotonic conditions (975 mosM/kg), (b) the dose dependence of [Cl-]i for activation of the exchanger under both normo- and hypertonic conditions, and (c) the relative order of the Cl-- and G-protein-dependent steps. We acid loaded BMFs by internally dialyzing them with a pH-6.5 dialysis fluid containing no Na+ and 0-194 mM Cl-. The artificial seawater bathing the BMF initially contained no Na+. After dialysis was halted, adding 50 mM Na+ to the artificial seawater caused an amiloride-sensitive pHi increase under both normo- and hypertonic conditions. The computed Na-H exchange flux (JNa-H) increased with increasing [Cl-]i under both normo- and hypertonic conditions, with similar apparent Km values ( approximately 120 mM). However, the maximal JNa-H increased by nearly 90% under hypertonic conditions. Thus, activation of Na-H exchange at low pHi requires Cl- under both normo- and hypertonic conditions, but at any given [Cl-]i, JNa-H is greater under hyper- than normotonic conditions. We conclude that an increase in [Cl-]i is not the primary shrinkage signal, but may act as an auxiliary shrinkage signal. To determine whether the Cl--dependent step is after the G-protein-dependent step, we predialyzed BMFs to a Cl--free state, and then attempted to stimulate Na-H exchange by activating a G protein. We found that, even in the absence of Cl-, dialyzing with GTPgammaS or AlF3, or injecting cholera toxin, stimulates Na-H exchange. Because Na-H exchange activity was absent in control Cl--depleted fibers, the Cl--dependent step is at or before the G protein in the shrinkage signal-transduction pathway. The stimulation by AlF3 indicates that the G protein is a heterotrimeric G protein.

Aluminum Compounds↗
PubMed1996

Immunohistochemical evidence of neuroprotection by R(-)-deprenyl and N-(2-hexyl)-N-methylpropargylamine on DSP-4-induced degeneration of rat brain noradrenergic axons and terminals.

DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] is a potent neurotoxin highly selective to the locus coeruleus noradrenaline (NA) system. Previous biochemical studies have shown that the monoamine oxidase-B (MAO-B) inhibitors, R(-)-deprenyl and (+/-)2-HxMP [N-(2-hexyl)-N-methylpropargylamine], are able to prevent DSP-4 induced NA depletion in the mouse hippocampus. It is not quite certain, however, whether this actually represents neuroprotection of NA axons or a metabolic effect due to inhibition of MAO activity. Employing dopamine-beta-hydroxylase immunohistochemical and image analysis methods, we have shown that 92% and 84% of NA nerve fibers in the rat hippocampus are spared from DSP-4 neurotoxicity by a single pretreatment dose of either R(-)-deprenyl or (+/-)2-HxMP respectively. Similar neuroprotective effects of R(-)-deprenyl and (+/-)2-HxMP were also observed in the cerebral cortex, thalamus, amygdaloid complex and cerebellum. This is the first morphological evidence demonstrating that R(-)-deprenyl and (+/-)2-HxMP can indeed protect noradrenergic axons of locus coeruleus origin against DSP-4 neurotoxicity.

Animals↗
PubMed1996

Computed tomography--guided aspiration of a ganglion cyst of the anterior cruciate ligament: a case report.

This report describes the case of a ganglion cyst of the anterior cruciate ligament in a 26-year-old man who had long-standing intermittent knee pain with locking. The cyst was successfully aspirated under computed tomography guidance, with complete resolution of symptoms. A literature review is presented along with diagnostic and treatment approaches for this uncommon finding.

Adult↗