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J Gates

Publications and source records attributed to J Gates.

At least 19 recordsLinked to original sources
PubMed2006

Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model.

The purpose of this study was to evaluate the effect of continuously released BDNF on peripheral nerve regeneration in a rat model. Initial in vitro evaluation of calcium alginate prolonged-release-capsules (PRC) proved a consistent release of BDNF for a minimum of 8 weeks. In vivo, a worst case scenario was created by surgical removal of a 20-mm section of the sciatic nerve of the rat. Twenty-four autologous fascia tubes were filled with calcium alginate spheres and sutured to the epineurium of both nerve ends. The animals were divided into 3 groups. In group 1, the fascial tube contained plain calcium alginate spheres. In groups 2 and 3, the fascial tube contained calcium alginate spheres with BDNF alone or BDNF stabilized with bovine serum albumin, respectively. The autocannibalization of the operated extremity was clinically assessed and documented in 12 additional rats. The regeneration was evaluated histologically at 4 weeks and 10 weeks in a blinded manner. The length of nerve fibers and the numbers of axons formed in the tube was measured. Over a 10-week period, axons have grown significantly faster in groups 2 and 3 with continuously released BDNF compared to the control. The rats treated with BDNF (groups 2 and 3) demonstrated significantly less autocannibalization than the control group (group 1). These results suggest that BDNF may not only stimulate faster peripheral nerve regeneration provided there is an ideal, biodegradable continuous delivery system but that it significantly reduces the neuropathic pain in the rat model.

Animals↗
PubMed2003

Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone.

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.

Animals↗
PubMed2001

Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome.

PURPOSE: Vagus nerve stimulation (VNS) is approved for use for refractory partial seizures. Nevertheless, information regarding VNS therapy for special populations, including Lennox-Gastaut syndrome (LGS) is limited. We discuss the effectiveness, tolerability, and safety of VNS therapy in patients with LGS. METHODS: A six-center, retrospective study evaluated the effectiveness of VNS therapy in patients with LGS at 3 and 6 months and compared preimplant and postimplant seizure frequency. Adverse effects and quality of life (QOL) were included as secondary measures. RESULTS: Fifty patients, median age 13 years, with medically refractory epilepsy, were implanted. Median age at onset of seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been tried before implantation. Data-collection forms were designed for retrospectively gathering data on each patient's preimplant history, seizures, implants, device settings, QOL, and adverse events. Median reductions in total seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most common adverse events reported were voice alteration and coughing during stimulation. Other uncommon adverse events included increased drooling and behavioral changes. Investigators noted that QOL had improved for some patients in the study. CONCLUSIONS: VNS is an effective treatment for medically refractory epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.

Adolescent↗
PubMed2001

Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study.

This six-center, retrospective study evaluated the effectiveness, tolerability, and safety of vagus nerve stimulation in children. Data were available for 125 patients at baseline, 95 patients at 3 months, 56 patients at 6 months, and 12 patients at 12 months. The typical patient, aged 12 years, had onset of seizures at age 2 years and had tried nine anticonvulsants before implantation. Collected data included preimplant history, seizures, implant, device settings, quality of life, and adverse events. Average seizure reduction was 36.1% at 3 months and 44.7% at 6 months. Common adverse events included voice alteration and coughing during stimulation. Rare adverse events, unique to this age group, included increased drooling and increased hyperactivity. Quality of life improved in alertness, verbal communication, school performance, clustering of seizures, and postictal periods. We concluded that vagus nerve stimulation is an effective treatment for medically refractory epilepsy in children.

Adolescent↗
PubMed2001

Telemedicine for the delivery of professional development for health, education and welfare professionals in two remote mining towns.

Over a two-year period, telemedicine was used to deliver training and development services for health, education and welfare staff in two remote towns in South Australia - Roxby Downs and Coober Pedy. Both are mining towns but they have different profiles in terms of the community's mental health needs. The services were provided by the Child and Adolescent Mental Health Services (CAMHS) from the Women's and Children's Hospital in Adelaide, South Australia. The media used were videoconferencing, telephone, video-tapes, the Internet and printed material. During 1998-9, professional staff in the two locations participated in structured videoconferencing seminars that addressed important mental health topics, chosen in response to surveys of the needs of the participants. The videoconferencing sessions were sometimes used to discuss specific patient cases. Each remote town was also supported via videoconferencing by a nominated office of the CAMHS: Roxby Downs by the suburban office at Port Adelaide and Coober Pedy by the office in the industrial town of Port Pirie. This customized support was an important factor in the success of the professional development network.

Community Mental Health Services↗
PubMed2000

Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy.

OBJECTIVE: To compare abnormalities determined in 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and [11C]flumazenil (FMZ) PET images with intracranial EEG data in patients with extratemporal lobe epilepsy. BACKGROUND: Although PET studies with FDG and FMZ are being used clinically to localize epileptogenic regions in patients with refractory epilepsy, the electrophysiologic significance of the identified PET abnormalities remains poorly understood. METHODS: We studied 10 patients, mostly children (4 boys, 6 girls, aged 2 to 19 years; mean age, 11 years), who underwent FDG and FMZ PET scans, intracranial EEG monitoring, and cortical resection for intractable epilepsy. EEG electrode positions relative to the brain surface were determined from MRI image volumes. Cortical areas of abnormal glucose metabolism or FMZ binding were determined objectively based on asymmetry measures derived from homotopic cortical areas at three asymmetry thresholds. PET data were then coregistered with the MRI and overlaid on the MRI surface. A receiver operating characteristics (ROC) analysis was performed to determine the specificity and sensitivity of PET-defined abnormalities against the gold standard of intracranial EEG data. RESULTS: FMZ PET detected at least part of the seizure onset zone in all subjects, whereas FDG PET failed to detect the seizure onset region in two of 10 patients. The area under the ROC curves was higher for FMZ than FDG PET for both seizure onset (p = 0.01) and frequent interictal spiking (p = 0.04). Both FMZ and FDG PET showed poor performance for detection of rapid seizure spread (area under the ROC curve not significantly different from 0.5). CONCLUSIONS: [11C]flumazenil (FMZ) PET is significantly more sensitive than 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET for the detection of cortical regions of seizure onset and frequent spiking in patients with extratemporal lobe epilepsy, whereas both FDG and FMZ PET show low sensitivity in the detection of cortical areas of rapid seizure spread. The application of PET, in particular FMZ PET, in guiding subdural electrode placement in refractory extratemporal lobe epilepsy will enhance coverage of the epileptogenic zone.

Adolescent↗
PubMed2000

Perivascular graft heparin delivery using biodegradable polymer wraps.

Heparin remains the gold-standard inhibitor of the processes involved in the vascular response to injury. Though this compound has profound and wide-reaching effects on vascular cells in culture and animal models, its clinical utility has been questionable at best. It is clear that the mode of heparin delivery is critical to its potential and it may well be that routine forms of administration are insufficient to observe benefit given the heparin's short half-life and complex pharmacokinetics. When ingested orally, heparin is degraded to inactive oligomer fragments while systemic administration is complicated by the need for continuous infusion and the potential for uncontrolled hemorrhage. Thus alternative heparin delivery systems have been proposed to maximize regional effects while limiting systemic toxicity. Yet, as heparin is such a potent antithrombotic compound and since existing local delivery systems lack the ability to precisely regulate release kinetics, even site-specific therapy is prone to bleeding. We now describe the design and development of a novel biodegradable system for the perivascular delivery of heparin to the blood vessel wall with well-defined release kinetics. This system consists of heparin-encapsulated poly(DL lactide-co-glycolide) (pLGA) microspheres sequestered in an alginate gel. Controlled release of heparin from this heterogeneous system could be obtained over a period of 25 days in vitro. The experimental variables affecting heparin release from these matrices were investigated. Gel permeation chromatography (GPC) and scanning electron microscopy (SEM) were used to monitor the degradation process and found to correlate well with the release kinetics. Heparin-releasing gels inhibited growth of bovine vascular smooth muscle cells in tissue culture in a dose-dependent manner. Moreover, gel release controlled vascular injury in denuding and interposition vascular graft animal models of disease even when uncontrolled bleeding was evident with standard matrix-type release. This system may therefore provide an effective means of examining the effects of various compounds in the control of smooth muscle cell proliferation in accelerated arteriopathies and also shed light on the biologic nature of these processes.

Angioplasty, Balloon↗
PubMed2000

Numerical aberrations of chromosomes 1 and 17 correlate with tumor site in human gastric carcinoma of the diffuse and intestinal types. Fluorescence in situ hybridization analysis on gastric biopsies.

Recent studies predict that tumor aneuploidy plays a direct role in tumor instability. The relationship between interphase cytogenetics, histology, grade, and tumor site was analyzed in 20 primary gastric carcinomas. Using fluorescence in-situ hybridization, the numerical changes of centromeric sequences of chromosomes 1, 3, 10, and 17 were directly analyzed in gastric biopsies. Polysomic copy numbers of chromosomes 1 and 17 were discovered in 63% (10 of 16) and 59% (10 of 17), respectively, of informative cancer cases. Chromosome 3 and 10 signal number changes were found in only 6% (1 of 16) and 13% (1 of 8), respectively, of informative cancer cases. There was a positive correlation between the appearance of polysomic nuclear target sites of chromosomes 1 and 17 (correlation coefficient r = 0.72; p < 0.005). Copy number changes were not significantly related to histologic subtypes of either the Laurén or WHO classifications. However, incidence of cancers having dual polysomic signal number abnormalities for both chromosomes 1 and 17 was significantly correlated to tumor location at the cardia. The data suggests that (i) human gastric cancer appears in two genomic groups that can be reliably diagnosed by fluorescence in-situ hybridization on routine biopsy sections, (ii) numerical aberrations of chromosomes 1, 3, 10, and 17 are largely independent of histologic subtypes, and (iii) polysomic copy number abnormalities of chromosomes 1 and 17 correlate to intragastric tumor site and are highest in cardia cancers, suggesting high tumor instability at this particular location.

Aged↗
PubMed2000

An enhancer trap screen for ecdysone-inducible genes required for Drosophila adult leg morphogenesis.

Although extensive studies of Drosophila imaginal disc development have focused on proliferation and patterning, relatively little is known about how the patterned imaginal discs are transformed into adult structures during metamorphosis. Studies focused primarily on leg development have shown that this remarkable transformation is coordinated by pulses of the steroid hormone ecdysone and requires the function of ecdysone-inducible transcription factors as well as proteases and components of the contractile cytoskeleton and adherens junctions. Here, we describe a genetic screen aimed at expanding our understanding of the hormonal regulation of Drosophila adult leg morphogenesis. We screened 1300 lethal P-element enhancer trap insertions on the second chromosome for a series of sequential parameters including pupal lethality, defects in leg morphogenesis, and ecdysone-induced lacZ reporter gene expression. From this screen we identified four mutations, one of which corresponds to bancal, which encodes the Drosophila homolog of hnRNP K. We also identified vulcan, which encodes a protein that shares sequence similarity with a family of rat SAPAP proteins. Both bancal and vulcan are inducible by ecdysone, thus linking the hormone signal with leg morphogenesis. This screen provides new directions for understanding the hormonal regulation of leg development during Drosophila metamorphosis.

Amino Acid Sequence↗
PubMed2000

An assistive device for the treatment of positional plagiocephaly.

An assistive device (AD) was used to treat 122 infants with moderate-to-severe positional plagiocephaly. Clinical evaluations indicate that the AD provided the most benefit when applied to 2- to 8-month-old children. Our results suggest that the AD may join molding helmets and physical therapy as a treatment for moderate-to-severe positional plagiocephaly in infants under the age of 1 year.

Craniosynostoses↗
PubMed1999

Recruitment of a hedgehog regulatory circuit in butterfly eyespot evolution.

The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes in development, but the nature of these changes is largely unknown. In butterflies, eyespots have evolved as new pattern elements that develop from special organizers called foci. Formation of these foci is associated with novel expression patterns of the Hedgehog signaling protein, its receptor Patched, the transcription factor Cubitus interruptus, and the engrailed target gene that break the conserved compartmental restrictions on this regulatory circuit in insect wings. Redeployment of preexisting regulatory circuits may be a general mechanism underlying the evolution of novelties.

Animals↗
PubMed1998

Rapid progression to invasive cervix cancer in a woman infected with the human immunodeficiency virus.

BACKGROUND: Previous studies have shown an increased risk of cervical dysplasia in women infected with human immunodeficiency virus (HIV), as well as an increased risk of progression to higher-grade lesions. It is not known whether the rate of progression is accelerated over that in immunocompetent women. CASE: During September 1991, an HIV-positive woman underwent conization of the cervix showing carcinoma in situ. The surgical margins and endocervical curettings were negative for dysplasia. Papanicolaou smears 4 and 7 months after the conization also were negative. She then presented 33 months postconization with a stage Ib2 cervical carcinoma, which proved resistant to chemotherapy and pelvic radiation. CONCLUSION: Immunosuppression caused by HIV infection may cause a more rapid progression of cervical intraepithelial lesions to carcinoma.

Adult↗
PubMed1998

Increased hematocrit and decreased transfusion requirements in children given erythropoietin before undergoing craniofacial surgery.

OBJECT: This study was undertaken to determine the efficacy of preoperative erythropoietin administration in infants scheduled for craniofacial surgery and, in so doing, to minimize problems associated with blood transfusions. METHODS: Families were offered the option of having their children receive erythropoietin injections before undergoing craniofacial surgery. The children whose families accepted this option received daily iron and 300 U/kg erythropoietin three times per week for 3 weeks preoperatively. Weekly complete blood counts with reticulocyte counts were measured and transfusion requirements were noted. Blood transfusions were administered depending on the clinical condition of the child. A case-matched control population was also evaluated to compare initial hematocrit levels and transfusion requirements. Thirty patients in the erythropoietin treatment group and 30 control patients were evaluated. The dose of erythropoietin administered was shown to increase hematocrit levels from 35.4 +/- 0.9% to 43.3 +/- 0.9% during the course of therapy. The resulting hematocrit levels in patients treated with erythropoietin at the time of surgery were higher compared with baseline hematocrit levels obtained in control patients at the time of surgery (34.2 +/- 0.5%). Transfusion requirements also differed: all control patients received transfusions, whereas 64% (19 of 30) of erythropoietin-treated patients received transfusions. CONCLUSIONS: The authors conclude that treatment with erythropoietin in otherwise healthy young children will increase hematocrit levels and modify transfusion requirements. Erythropoietin therapy for elective surgery in children of this age must be individualized according to the clinical situation, family and physician beliefs, and cost effectiveness, as evaluated at the individual center.

Blood Transfusion↗
PubMed1997

Neoadjuvant chemotherapy in stage IB2 squamous cell carcinoma of the cervix.

To determine the effects of neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically treated patients diagnosed between January 1987 and December 1993. There were 20 patients treated with preoperative neoadjuvant chemotherapy and 32 treated by primary radical hysterectomy. Mean tumor diameter was significantly larger in the neoadjuvant, compared with the primary surgery group (6.5 +/- 1.8 vs 5.4 +/- 0.7, P = 0.003). In the NAC group, 5 of 20 patients were treated with three courses of cisplatin, methotrexate, and bleomycin every 21 days, whereas 15 of 20 patients received three courses of cisplatin, vincristine, and bleomycin every 10 days. Postoperative adjuvant therapy consisting of either radiation or chemotherapy was employed in 13/20 patients (65%) in the NAC group and 20/32 patients (63%) in the primary surgical group. At a median follow-up of 52.5 months, 4/20 patients (20%) in the NAC group recurred vs 11/32 (34%) in the primary surgery group. The overall response rate to NAC was 90%, with 2/20 complete clinical responders and 16/20 partial responders. High-risk pathologic factors were less commonly observed in the NAC group when compared with the primary surgical group with the incidence of nodal metastases, positive vascular space involvement, undiagnosed parametrial disease, and > or = 75% depth of invasion observed in 10.0% vs 37.5%, 20.0% vs 46.9%, 0.0% vs 15.6%, and 30.0% vs 68.8%, respectively. No differences were noted in operative time or blood loss. Cox proportional-hazards analysis indicated that the most significant prognostic factor was depth of invasion. Although the patients who received neoadjuvant chemotherapy had significantly larger tumors at baseline, their 5-year survival rate was slightly higher than that of the primary surgery group (80.0% vs 68.7%, P = 0.162). Patients receiving neoadjuvant chemotherapy, despite having significantly larger pretreatment tumors, had fewer high-risk pathologic factors, postoperatively. Although this was a small, nonrandomized study, the relative improvement in pathologic response and long-term outcome associated with neoadjuvant chemotherapy was encouraging. This highlights the need for a prospective randomized clinical trial to establish whether neoadjuvant chemotherapy can significantly improve the long-term outcome of women with Stage IB2 squamous cell carcinoma of the cervix.

Adult↗