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Biomedical subjects

K A Baker

Publications and source records attributed to K A Baker.

At least 19 recordsLinked to original sources
PubMed2005

Prolonged local neurotrophin-3 infusion reduces ipsilateral collateral sprouting of spared corticospinal axons in adult rats.

The corticospinal tract is widely used to study regeneration and is essential for voluntary movements in humans. In young rats, corticospinal axons on the uninjured side sprout and grow into the denervated side. Neurotrophin-3 (NT-3) induces such crossed collateral sprouting in adults. We investigated whether local intraspinal NT-3 infusions would promote collateral sprouting of spared corticospinal terminals from within a partially denervated side, as this would be more appropriate for enhancing function of unilateral and specific movements. Adult rats received a partial bilateral transection of the pyramids, leaving approximately 40% of each tract intact. Vehicle or vehicle plus NT-3 (3 or 10 microg/day) was infused for 14 days into the left side of the cervical (C5/6) or lumbar (L2) cord. The corticospinal processes on the left side were anterogradely traced with cholera toxin B (CTB; which labeled gray matter processes more robustly than biotinylated dextran amine) injected into the front or hind limb area of the right sensorimotor cortex, respectively, 3 days before analysis. Unexpectedly, approximately 40% fewer CTB-labeled corticospinal processes were detectable in the cervical or lumbar gray matter of NT-3-treated rats than in vehicle-infused ones. Vehicle-infused injured rats had more corticospinal processes in the center of the cord than normal rats, evidence for lesion-induced collateral sprouting. NT-3 caused sprouting of local calcitonin gene-related peptide-positive fibers. These results suggest that NT-3 reduces collateral sprouting of spared corticospinal axons from within the denervated regions, possibly because of the injury environment or by increasing sprouting of local afferents. They identify an unexpected context-dependent outgrowth inhibitory effect of NT-3.

Animals↗
PubMed2002

A sequential intrastriatal dopaminergic graft strategy in the rodent model for Parkinson's disease: implications for graft survival and targeting.

Optimal placement of intrastriatal dopaminergic grafts is likely crucial to optimize clinical recovery in Parkinson's disease (PD). The target sites of dopaminergic grafts vary among clinical trials and may partially explain the variable results in clinical efficacy reported thus far. In this study we hypothesized that a subsequent dopaminergic graft may promote functional recovery following a suboptimal initial graft. To test this hypothesis, rats with unilateral 6-hydroxydopamine lesions of the right nigrostriatal pathway were randomly divided into three groups. The first group received 900,000 fetal nigral cells in the medial striatum only (n = 6). The second group received 900,000 cells in both the medial and lateral striatum simultaneously (1.8 million total; n = 8). The final group received a second graft of 900,000 cells in the lateral striatum 6 weeks following initial transplantation of a medial graft (n = 6). Amphetamine-induced circling behavior was significantly reduced in both simultaneous and sequential graft groups at 9 and 12 weeks following transplantation of the initial graft. However, no recovery was noted in the single medial graft group at those time points. Furthermore, increased survival of dopaminergic cells was observed in the lateral graft of sequentially grafted animals compared with the medial graft. We conclude that a well-positioned subsequent graft can restore function in animals with a suboptimal initial graft and that the initial graft may improve survival of the second graft. These results are further discussed in relation to their important clinical implication for neural transplantation in PD.

Animals↗
PubMed2001

Enhancement of sensorimotor behavioral recovery in hemiparkinsonian rats with intrastriatal, intranigral, and intrasubthalamic nucleus dopaminergic transplants.

One of the critical variables that influences the efficacy of clinical neural transplantation for Parkinson's disease (PD) is optimal graft placement. The current transplantation paradigm that focuses on ectopic placement of fetal grafts in the striatum (ST) fails to reconstruct the basal ganglia circuitry or normalize neuronal activity in important basal ganglia structures, such as the substantia nigra (SN) and the subthalamic nucleus (STN). The aim of this study was to investigate a multitarget neural transplantation strategy for PD by assessing whether simultaneous dopaminergic transplants in the ST, SN, and STN induce functional recovery in hemiparkinsonian rats. Forty-six female Wistar rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were randomly divided into eight groups and received lesions only or injections of 900,000 embryonic rat ventral mesencephalic cells in the (1) ST, (2) SN, (3) STN, (4) ST and SN, (5) ST, SN, and STN, (6) ST and STN, or (7) SN and STN. The number of cells transplanted was equally divided among grafting sites. Animals with two grafts received 450,000 cells in each structure, and animals with three grafts received 300,000 cells per structure. Recovery was assessed by amphetamine-induced rotations and the stepping tests. Graft survival was assessed using tyrosine hydroxylase immunohistochemistry. At 8 weeks after transplantation, simultaneous dopaminergic transplants in the ST, SN, and STN induced significant improvement in rotational behavior and stepping test scores. Intrastriatal transplants were associated with significant recovery of rotational asymmetry, whereas SN and STN transplants were associated with improved forelimb function scores. These results suggest that restoration of dopaminergic activity to multiple basal ganglia targets, such as the ST and SN, or the ST and STN, promotes a more complete functional recovery of complex sensorimotor behaviors. A multitarget transplant strategy aimed at optimizing dopaminergic reinnervation of the basal ganglia may be crucial in improving clinical outcomes in PD patients.

Animals↗
PubMed2001

Liposomal tacrolimus administered systemically and within the donor cell suspension improves xenograft survival in hemiparkinsonian rats.

The most widely used immunosuppressant in neural transplantation is cyclosporine- A (CsA). However, CsA has significant toxic effects when administered systemically. Tacrolimus (FK506), is a more potent immunosuppressant than CsA and can be prepared in lipid micelles (LTAC). This liposomal preparation allows for the administration of tacrolimus to the site of transplantation, possibly reducing the systemic side effects of immunosuppression. In this study we investigated the ability of LTAC to promote graft survival in hemiparkinsonian rats implanted with fetal mouse xenografts when LTAC is administered systemically to the host, when added to the donor cell suspension, or in combination. Rats with unilateral 6-hydroxydopamine lesions were transplanted with 800,000 fetal mouse ventral mesencephalic (VM) cells and were randomly divided into four groups. Group 1 was not immunosuppressed; Group 2 received daily systemic injections of LTAC; Group 3 received LTAC within the cell suspensions of mouse VM cells; and Group 4 received LTAC in the cell suspensions along with daily systemic administration of LTAC. Transplanted rats were assessed for rotational behavior 3 and 6 weeks posttransplantation. Cell survival was assessed using tyrosine hydroxylase (TH) immunohistochemistry. A significant reduction in rotational scores was observed only in the group of animals receiving the combination of LTAC-treated donor cells and systemic LTAC administration. This functional improvement correlated with a significantly greater survival of TH-immunoreactive cells in this group of animals. The other groups had poor cell survival and no significant functional improvement. We conclude that a combination of systemic immunosuppression and treatment of the cell suspension with LTAC may be a superior strategy to optimize xenograft survival. This strategy may have important implications for clinical neural transplantation.

Animals↗
PubMed2001

The effect of preemptive and/or postoperative ibuprofen therapy for orthodontic pain.

The control of pain during orthodontic treatment is of vital interest to both clinicians and patients. Surprisingly, there has been limited research into the control of orthodontic pain, and there is no standard of care for controlling this discomfort. The purpose of this study was to compare the effectiveness of preemptive ibuprofen therapy, postoperative ibuprofen therapy, and a combination of the 2 therapies. Forty-one orthodontic patients aged 9 years 3 months to 16 years 11 months who were to undergo separator placement were enrolled in this prospective study. Patients were randomly assigned to 1 of 3 experimental conditions: (1) 400 mg ibuprofen taken orally 1 hour before separator placement and 400 mg ibuprofen taken orally 6 hours after the initial dose, (2) 400 mg ibuprofen taken orally 1 hour before separator placement and a lactose capsule taken orally 6 hours after the initial dose, or (3) a lactose capsule taken orally 1 hour before separator placement and 400 mg ibuprofen taken 6 hours after the initial placebo. The results revealed that preemptive ibuprofen therapy significantly decreased pain that was experienced 2 hours after separator placement and at bedtime. Beginning on day 2, there was a trend for patients who had taken both preemptive and postoperative ibuprofen doses to have lower pain scores compared with the other 2 groups. In conclusion, these data indicate that ibuprofen taken 60 minutes before separator placement alleviates pain at 2 hours and at bedtime after treatment. Further study with the use of additional postoperative doses is warranted.

Administration, Oral↗
PubMed2000

Simultaneous intrastriatal and intranigral dopaminergic grafts in the parkinsonian rat model: role of the intranigral graft.

The current transplantation strategy in experimental and clinical Parkinson's disease (PD) has been to place nigral dopaminergic grafts not in their ontogenic site (substantia nigra) but in their target area (striatum). Although intrastriatal dopaminergic grafts are capable of reinnervating the striatum, they fail to reinnervate the nigra, which may be an important factor limiting the efficacy of fetal tissue transplantation in parkinsonian patients. We have previously shown that simultaneous intrastriatal and intranigral dopaminergic grafts (double grafts) may provide a more complete restoration of the nigrostriatal circuitry (Mendez et al. [1996] J Neurosci 16:7216-7227; Mendez and Hong [1997] Brain Res 778:194-205). In the present study, we investigated the contribution of the intranigral graft to functional recovery in double-grafted hemiparkinsonian rats. Twenty Wistar rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway were divided into two groups and received either double grafts (n = 10) or intrastriatal grafts alone (n = 10). Following transplantation, both intrastriatally and double-grafted animals had a significant decrease in rotational behavior. However, only animals with double grafts exhibited a significant increase in contralateral adjusting step performance. The intranigral graft was subsequently lesioned by a second 6-OHDA injection. Following the second lesion, animals with double grafts exhibited a significant reversal of rotational behavior and a 51% reduction in contralateral adjusting step performance. The reversal in functional recovery correlated with a significant loss of intranigral grafted neurons. These results suggest that the intranigral graft has an important role in the functional recovery of double-grafted animals. Restoration of dopaminergic innervation to both the nigra and the striatum may be crucial for optimizing graft efficacy and may be a superior strategy in neural transplantation for PD.

Amphetamine↗
PubMed2000

Intrastriatal and intranigral grafting of hNT neurons in the 6-OHDA rat model of Parkinson's disease.

The clinical findings on neural transplantation for Parkinson's disease (PD) reported thus far are promising but many issues must be addressed before neural transplantation can be considered a routine therapeutic option for PD. The future of neural transplantation for the treatment of neurological disorders may rest in the discovery of a suitable alternative cell type for fetal tissue. One such alternative may be neurons derived from a human teratocarcinoma (hNT). hNT neurons have been shown to survive and integrate within the host brain following transplantation and provide functional recovery in animal models of stroke and Huntington's disease. In this study, we describe the transplantation of hNT neurons in the substantia nigra (SN) and striatum of the rat model for PD. Twenty-seven rats were grafted with one of three hNT neuronal products; hNT neurons, hNT-DA neurons, or lithium chloride (LiCl) pretreated hNT-DA neurons. Robust hNT grafts could be seen with anti-neural cell adhesion molecule and anti-neuron-specific enolase immunostaining. Immunostaining for tyrosine hydroxylase (TH) expression revealed no TH-immunoreactive (THir) neurons in any animals with hNT neuronal grafts. THir cells were observed in 43% of animals with hNT-DA neuronal grafts and all animals with LiCl pretreated hNT-DA neuronal grafts (100%). The number of THir neurons in these animals was low and not sufficient to produce significant functional recovery. In summary, this study has demonstrated that hNT neurons survive transplantation and express TH in the striatum and SN. Although hNT neurons are promising as an alternative to fetal tissue and may have potential clinical applications in the future, further improvements in enhancing TH expression are needed.

Amphetamine↗
PubMed2000

Simultaneous intrastriatal and intranigral grafting (double grafts) in the rat model of Parkinson's disease.

Experimental and clinical studies of neural transplantation in Parkinson's disease have focused on the placement of fetal dopaminergic grafts not in their ontogenic site (substantia nigra) but in the main nigral target area (striatum). The reason for this is the apparent inability of intranigral nigral grafts to extend axons for long distances reinnervating the ipsilateral striatum. This review presents previous work by our laboratory [I. Mendez, M. Hong, Reconstruction of the striato-nigro-striatal circuitry by simultaneous double dopaminergic grafts: a tracer study using fluorogold and horseradish peroxidase, Brain Res. 778 (1997) 194-205; I. Mendez, D. Sadi, M. Hong., Reconstruction of the nigrostriatal pathway by simultaneous intrastriatal and intranigral dopaminergic transplants, J. Neurosci. 16 (1996) 7216-7227] using a new transplantation strategy aimed at restoring dopaminergic innervation of the nigra and striatum by simultaneous dopaminergic transplants placed in the substantia nigra and ipsilateral striatum (double grafts) in the 6-hydroxydopamine lesioned adult rat brain. These double grafts achieve not only greater striatal reinnervation than the standard intrastriatal grafts but also produce a faster and more complete behavioural recovery six weeks after transplantation. Injection of the retrograde tracer fluorogold into the striatum and nigra resulted in fluorescent labeled cells within the intranigral graft and the intrastriatal graft and surrounding striatum, respectively suggesting that these double grafts promote at least partial reconstruction of the nigrostriatal dopaminergic pathway. This double graft strategy may have potential implications in clinical neural transplantation for Parkinson's disease.

Amphetamine↗
PubMed2000

Treatment approaches to common symptomatic oral lesions in children.

A variety of oral mucosal lesions can be symptomatic in children. This article describes the classic clinical appearance of the most common oral diseases and provides treatment recommendations that are tailored to the pediatric age group. When possible, more than one drug alternative is given for each of the different oral conditions for an improved success rate. It is essential for the clinician to understand that this article should be used as a guide for managing oral and perioral lesions in children and adolescents. Specific dosages and formularies of drugs may require modification in the young child. Consultation with a primary care physician and pharmacist often is needed to ensure the best possible outcome, especially when immunosuppressive drugs are indicated. Most importantly, oral lesions that do not respond to therapeutic protocols should be referred to the appropriate specialist for definitive diagnosis and treatment.

Adolescent↗
PubMed2000

Antibiotic prophylaxis for selected implants and devices.

Certain implants or devices are widely believed to put patients at risk from oral bacteremia. They include but are not limited to intravascular access devices, solid organ transplants, vascular grafts, coronary artery stents, breast implants, and penile prostheses. The purpose of this article is to review the risk of implant or device infection from transient bacteremia of oral origin and to provide recommendations for appropriate dental management. Since dental treatment bacteremias are a very rare cause of metastatic infections, attributing causality to dental treatment procedures can be viewed as unfounded in almost all cases.

Angioplasty, Balloon, Coronary↗
PubMed1999

Physical and biological properties of cationic triesters of phosphatidylcholine.

The properties of a new class of phospholipids, alkyl phosphocholine triesters, are described. These compounds were prepared from phosphatidylcholines through substitution of the phosphate oxygen by reaction with alkyl trifluoromethylsulfonates. Their unusual behavior is ascribed to their net positive charge and absence of intermolecular hydrogen bonding. The O-ethyl, unsaturated derivatives hydrated to generate large, unilamellar liposomes. The phase transition temperature of the saturated derivatives is very similar to that of the precursor phosphatidylcholine and quite insensitive to ionic strength. The dissociation of single molecules from bilayers is unusually facile, as revealed by the surface activity of aqueous liposome dispersions. Vesicles of cationic phospholipids fused with vesicles of anionic lipids. Liquid crystalline cationic phospholipids such as 1, 2-dioleoyl-sn-glycero-3-ethylphosphocholine triflate formed normal lipid bilayers in aqueous phases that interacted with short, linear DNA and supercoiled plasmid DNA to form a sandwich-structured complex in which bilayers were separated by strands of DNA. DNA in a 1:1 (mol) complex with cationic lipid was shielded from the aqueous phase, but was released by neutralizing the cationic charge with anionic lipid. DNA-lipid complexes transfected DNA into cells very effectively. Transfection efficiency depended upon the form of the lipid dispersion used to generate DNA-lipid complexes; in the case of the O-ethyl derivative described here, large vesicle preparations in the liquid crystalline phase were most effective.

3T3 Cells↗
PubMed1999

Structural basis for paramyxovirus-mediated membrane fusion.

Paramyxoviruses are responsible for significant human mortality and disease worldwide, but the molecular mechanisms underlying their entry into host cells remain poorly understood. We have solved the crystal structure of a fragment of the simian parainfluenza virus 5 fusion protein (SV5 F), revealing a 96 A long coiled coil surrounded by three antiparallel helices. This structure places the fusion and transmembrane anchor of SV5 F in close proximity with a large intervening domain at the opposite end of the coiled coil. Six amino acids, potentially part of the fusion peptide, form a segment of the central coiled coil, suggesting that this structure extends into the membrane. Deletion mutants of SV5 F indicate that putative flexible tethers between the coiled coil and the viral membrane are dispensable for fusion. The lack of flexible tethers may couple a final conformational change in the F protein directly to the fusion of two bilayers.

Amino Acid Sequence↗
PubMed1999

The importance of cultural sensitivity and therapist self-awareness when working with mandatory clients.

Systemic therapy emphasizes the importance of understanding each relationship in the context of its ecosystem. Considerations such as the influence of social agencies, culture, and the therapist's self-awareness are described in the literature as amplifying lenses within the therapeutic relationship. When a minority client is caught in the web of larger system agencies and is mandated to family therapy, systemic family therapy, which incorporates multiple lenses and attends to the context of social background, may provide a better understanding of the client's reality. Clinical cases show that therapists may slip into veiled racist and discriminatory attitudes with minority clients. Self-awareness, "soul searching," and appropriate supervision may be of tremendous help in learning from such experiences. A case example illustrates the application of this approach.

Adult↗
PubMed1999

RSV infection in infants and young children. What's new in diagnosis, treatment, and prevention?

RSV is the most important respiratory pathogen in infants and young children. About 1% of primary RSV infections result in hospitalization. The virus is spread by large droplets of secretions or contact with contaminated secretions. Infants infected with RSV may demonstrate poor feeding, rhinorrhea, apnea, lethargy, wheezing, and respiratory distress. Diagnosis may be made by clinical signs and symptoms (especially those observed during epidemics), by chest radiographs showing hyperinflation, or by rapid antigen detection with immunofluorescence of nasopharyngeal aspirates. Risk factors for severe disease accompanied by complications include chronic heart disease, chronic lung disease, immunodeficiency, HIV, and prematurity. Immunity is incomplete and of short duration, and reinfection is common. Treatment remains supportive and consists of oxygen administration, hydration, and diligent monitoring. Use of corticosteroids, bronchodilators, antibiotics, and ribavirin is controversial and is dependent largely on physician preference. Use of ribavirin should be reserved for patients who have severe underlying conditions associated with increased mortality rates. Intravenous RSV Ig has been replaced by palivizumab, which is generally recommended for infants at high risk for severe RSV, including those with a history of prematurity and those with chronic lung disease.

Anti-Bacterial Agents↗
PubMed1996

Effectiveness and toxicity of several DTPA broadening agents for biological ESR spectroscopy.

The effectiveness of a standard ESR broadening agent, potassium trioxalatochromiate (CrOx), for use with the spin-label tempone, was compared to that of diethylenetriaminepentaacetic acid (DTPA) containing an ion (Gd, Cr, Mn, Fe) with a large magnetic moment. Signal attenuation, line broadening, toxicity, and cell membrane permeability were compared. As a broadening agent, CrOx was most effective, followed by Fe-DTPA. CrOx proved mildly toxic while Gd-DTPA and Fe-DTPA were virtually non-toxic. The human red blood cell membrane was tested for permeability to Fe- and Gd-DTPA and found to be impermeable to both. In situations where toxicity to cells is critical, the DTPA chelates, particularly Fe-DTPA, may prove an acceptable substitute for CrOx.

Cell Survival↗
PubMed1996

Fluticasone propionate compared with theophylline for mild-to-moderate asthma.

BACKGROUND: The inhaled corticosteroid, fluticasone propionate, was compared with the oral bronchodilator theophylline in the maintenance treatment of asthma. OBJECTIVE: The objective of the present study was to compare the efficacy and safety of twice-daily inhaled fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, with that of theophylline in the maintenance treatment of mild-to-moderate asthma. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 353 adult and adolescent patients with asthma inadequately controlled with inhaled beta-agonist therapy alone received fluticasone propionate, 50 micrograms, or fluticasone propionate, 100 micrograms, by metered-dose inhaler; theophylline capsules; or placebo twice daily for 12 weeks. Only inhaled albuterol was permitted as needed for acute symptoms. RESULTS: Both fluticasone propionate groups had a significantly greater probability of remaining in the study (ie, meeting asthma stability criteria) than did either the theophylline or placebo group (P < or = .008); 39% and 51% in the theophylline and placebo groups, respectively, were withdrawn due to lack of treatment efficacy compared with 14% and 21% in the fluticasone propionate, 50 micrograms, and fluticasone propionate, 100 micrograms, groups. Both fluticasone propionate groups experienced significantly greater improvement in FEV1 and PEF compared with patients in the theophylline or placebo group (P < or = .004). The incidence of potentially drug-related adverse events was significantly greater in the theophylline group (25%) than in the placebo group (11%) (P = .031), while there were no differences between placebo and fluticasone propionate, 50 micrograms, (18%) or fluticasone propionate 100 micrograms, (22%). CONCLUSION: Twice daily treatment with inhaled fluticasone propionate 50 micrograms or 100 micrograms was significantly more effective than theophylline in the treatment of mild-to-moderate asthma.

Administration, Inhalation↗
PubMed1994

The management of odontogenic infections. A rationale for appropriate chemotherapy.

Odontogenic infections are one of the most frequently occurring infectious processes known to health practice. Significant changes have occurred in the use of antibiotics and antimicrobials since the use of chemotherapeutic agents became widespread. This article provides some important considerations for selecting appropriate chemotherapeutic agents during the management of odontogenic infections.

Adult↗