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Biomedical subjects

J Griggs

Publications and source records attributed to J Griggs.

14 recordsLinked to original sources
PubMed2001

The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress.

Previous research indicates that the serotonergic neurons of the caudal dorsal raphe nucleus (DRN) are activated to a greater degree by inescapable shock (IS) as compared to escapable shock (ES), causing a greater release of serotonin (5-HT) in the DRN and in target regions. This differential activation is necessary for the behavioral changes that occur after exposure to IS, but not to ES (i.e. learned helplessness/behavioral depression). Although the critical role of the DRN in learned helplessness is clear, the neural inputs to the caudal DRN which result in this selective activation are unknown. One structure that may be involved in the activation of the DRN and the induction of learned helplessness/behavioral depression is the habenular complex. In experiment 1, habenula lesions eliminated the differential rise in DRN extracellular 5-HT levels in response to IS and ES exposure by severely attenuating the rise in 5-HT for both groups. In experiment 2, sham operated and habenula lesioned rats were exposed to either ES, IS or no stress (home cage control; HCC). Twenty-four hours later, sham rats previously exposed to IS exhibited longer escape latencies as compared to both ES and HCC rats (i.e. learned helplessness). The habenular lesion eliminated the differences in escape latency between groups, thus eliminating the induction of learned helplessness/behavioral depression. These results suggest that the habenula is necessary for the differential activation of the DRN and the escape deficits produced by IS.

Animals↗
PubMed2001

Combretastatin-A4 disrupts neovascular development in non-neoplastic tissue.

Combretastatin-A4 phosphate (cis-CA-4) is a tubulin-binding agent currently undergoing clinical trials as an anti-tumour drug. We have investigated whether CA-4 functions as a tumour-specific anti-vascular agent using the hyperplastic thyroid as a novel in vivo model of neovascularization. CA-4 elicited pathological changes in normal tissue, manifested as the induction of multiple, discrete intravascular thrombi. These vascular-damaging effects indicate that CA-4P does not function as a tumour-specific agent but targets neovasculature irrespective of the primary angiogenic stimulus.

Animals↗
PubMed2001

Bond strength of binary titanium alloys to porcelain.

The purpose of this study was to investigate the bond strength between porcelain and experimental cast titanium alloys. Eleven binary titanium alloys were examined: Ti-Cr (15, 20, 25 wt%), Ti-Pd (15, 20, 25 wt%), Ti-Ag (10, 15, 20 wt%), and Ti-Cu (5, 10 wt%). As controls, the bond strengths for commercially pure titanium (KS-50, Kobelco, Japan) and a high noble gold alloy (KIK, Ishifuku, Japan) were also examined. Castings were made using a centrifugal casting unit (Ticast Super R, Selec Co., Japan). Commercial porcelain for titanium (TITAN, Noritake, Japan) was applied to cast specimens. The bond strengths were evaluated using a three-point bend test according to ISO 9693. Since the elastic modulus value is needed to evaluate the bond strength, the modulus was measured for each alloy using a three-point bend test. Results were analyzed using one-way ANOVA/S-N-K test (alpha = 0.05). Although the elastic moduli of the Ti-Pd alloys were significantly lower than those of other alloys (p = 0.0001), there was a significant difference in bond strength only between the Ti-25Pd and Ti-15Ag alloys (p = 0.009). The strengths determined for all the experimental alloys ranged from 29.4 to 37.2MPa, which are above the minimum value required by the ISO specification (25 MPa).

Dental Alloys↗
PubMed2001

Targeting tumour vasculature: the development of combretastatin A4.

The requirement for neovascularisation to permit the development of solid tumours beyond a threshold size, has focused attention on the therapeutic potential of agents that prevent angiogenesis. The multistep nature of angiogenesis presents several targets for intervention, including the inhibition of the endothelial-cell migration or proliferation normally associated with developing vessels. Compounds that damage established tumour vasculature are also of potential clinical use. We review the development of one such antivascular drug, combretastatin A4. This tubulin-binding agent was originally isolated from an African shrub, Combretum caffrum. The disodium combretastatin A4 phosphate prodrug is currently undergoing phase I clinical trials in the UK and USA. This review assesses the in vitro and in vivo data for combretastatin and the prodrug, and the preliminary data that have emerged from the phase I clinical trials.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Potent anti-metastatic activity of combretastatin-A4.

The requirement for tumour vascularisation to permit the expansion of solid tumours beyond a threshold size of approximately 1 mm diameter has focussed attention on anti-vascular and anti-angiogenic agents for cancer therapy. Combretastatin-A4 (cis CA-4P) is a tubulin-binding agent that is cytotoxic for proliferating endothelial cells in vitro and causes anti-vascular effects in the established tumour vessels of some primary tumours. Preliminary data from Phase I clinical trials indicate that cis CA-4 may also be effective in targeting the vasculature of human tumours. As metastatic disease is the principal cause of mortality in cancer, we have investigated the effects of cis CA-4 on metastatic development using an in vivo model. We show that bolus or continuous administration of cis CA-4P results in potent inhibition of metastases derived from ectopic primary Lewis lung carcinomas in mice whereas the trans CA-4 isomer is without effect. These data further characterise the activity of CA-4 in vivo and suggest that the drug should be evaluated clinically as an anti-metastatic agent.

Animals↗
PubMed1994

Parental and medical over-administration of acetaminophen causing lethal hepatotoxicity in a 10-year-old.

A 10-year-old girl with acute influenza B virus disease was given repetitive doses of acetaminophen by her mother to reduce the child's fever. When finally seen by trained medical personnel, the child was experiencing abdominal pain, nausea, and vomiting, which are classic signs of acetaminophen hepatotoxicity. Despite these findings, the child was given additional acetaminophen and experienced lethal hepatotoxicity.

Acetaminophen↗
PubMed1989

The efficacy and safety of GR38032F in the prophylaxis of ifosfamide-induced nausea and vomiting.

The novel 5HT3 receptor antagonist GR38032F was evaluated in the control of emesis induced by the cyclophosphamide analogue ifosfamide. At a dose of 4 mg q 6 h, GR38032F was given to six patients receiving their first dose of ifosfamide infusion (4-6 g/m2 over 24 h); over the 42-h study period, major control of retching and vomiting was achieved in five patients. In the second phase of the study six further patients, in whom high-dose metoclopramide had failed to control emesis, were given 8 mg GR38032F q 6 h; major control of emesis was again observed in five patients. Toxicity attributed to GR38032F was minimal. This selective 5HT3 antagonist is effective and safe in the control of ifosfamide-induced emesis, even in patients resistant to high-dose metoclopramide.

Adult↗
PubMed1987

Arming against AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Pharmacokinetic study of ceftazidime in bone and serum of patients undergoing hip and knee arthroplasty.

Twenty-eight patients undergoing hip arthroplasty and 15 undergoing knee arthroplasty, received chemoprophylaxis with ceftazidime 1.0 g administered intravenously at the time of induction of anaesthesia, followed by two doses of 500 mg given intramuscularly 6 and 12 h later. The mean bone concentration in hip arthroplasty showed a general rise towards a maximum of approximately 20 mg/kg when the exposure time (interval between antibiotic injection and removal of bone sample) was 35-40 min, with values ranging from 4.4 to 21.2 mg/kg (mean 14.4 mg/kg). The patients undergoing knee arthroplasty present a complicated pharmacokinetic problem, as the use of a tourniquet limits the exposure time. Bone concentrations of ceftazidime were highest at sampling times greater than 20 min in these patients (mean level of 15.9 mg/kg for femoral bone and 13.1 mg/kg for tibial bone).

Adult↗