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Biomedical subjects

G Gardner

Publications and source records attributed to G Gardner.

At least 55 records · Page 3Linked to original sources

Clozapine treatment of schizophrenia: implications for forensic psychiatry.

Clozapine, a new antipsychotic medication, is now the first-line treatment for neuroleptic refractory schizophrenia. Preliminary observations on its efficacy in treating schizophrenic patients with co-morbid substance abuse and, particularly, schizophrenic patients with persistent aggressive behaviour suggests that clozapine may provide a useful treatment option in forensic patient populations. Potential applications of clozapine and management considerations that are relevant to the forensic setting are discussed.

Journal Article↗

Disease-modifying antirheumatic drugs. Potential effects in older patients.

Disease-modifying antirheumatic drugs (DMARDs) are frequently used in rheumatoid arthritis. A number of physiological changes occur in the elderly which may modify the use of these medications. The most commonly used DMARDs are antimalarial drugs (particularly hydroxychloroquine), sulfasalazine and methotrexate. The principal mechanism of action of the antimalarials relates to the fact that they change intracellular pH, which downregulates numerous immune functions. Hydroxychloroquine is metabolised to 3 metabolites and has a very low clearance. It is moderately effective in dosages up to 6.4 mg/kg/day. While it is not the most effective of the DMARDs, it is the least toxic. Sulfasalazine is a prodrug which is enzymatically split in the bowel to form sulfapyridine (the principal active metabolite) and 5-aminosalicylic acid. The metabolism of sulfasalazine is complex and, to some extent, genetically determined. The mechanism of action of the drug is not well understood, but involves decreased production of cytokines and decreased proliferative response of lymphocytes. It may slow the rate of bony damage associated with rheumatoid arthritis. Nearly 50% of the patients who are prescribed sulfasalazine continue to receive the drug for up to 4 years. Sulfasalazine is not as well tolerated as hydroxychloroquine. Gastrointestinal toxicity, in particular, seems to be a problem in elderly patients taking this medication. Methotrexate is presently the most popular of the DMARDs for the treatment of rheumatoid arthritis. Methotrexate inhibits dihydrofolate reductase and adenosine release and has a secondary effect on cytokines and polymorphonuclear chemotaxis. It is highly metabolised within cells and remains there for prolonged periods. Up to 70% of patients who are prescribed methotrexate continue treatment for 5 years. Methotrexate treatment is associated with gastrointestinal, hepatic, cutaneous and, possibly, pulmonary adverse effects. The use of azathioprine, penicillamine and gold compounds is briefly reviewed in this article. Elderly patients have an increased incidence of rashes when using penicillamine, relative to young patients. There are no age-related differences in the efficacy and tolerability of azathioprine or gold therapy. The poor absorption and renal toxicity associated with cyclosporin, the new 'salvage' therapy in rheumatoid arthritis, make it generally unsuitable for use in the elderly, except under specialists' supervision.

Aged↗

Teenage health.

Explore the source record for details and available documents.

Adolescent↗

Blastomycotic cranial osteomyelitis.

This is the second case report of a temporal bone osteomyelitis caused by Blastomyces dermatitidis, which presented as a chronic serous otitis media. The presenting serous otitis media was refractory to conventional medical and surgical management and progressed to a temporal bone osteomyelitis prior to diagnosis. B. dermatitidis is a rare fungal pathogen that causes a systemic pyogranulomatous disease that primarily manifests itself in the skin, bones, pulmonary, and genitourinary systems. If left untreated it is associated with a high rate of mortality. The otologic presentation of this rare disease is emphasized, while the clinical and therapeutic features are reviewed.

Adult↗

The discovery of novel auxin transport inhibitors by molecular modeling and three-dimensional pattern analysis.

Molecular modeling techniques and three-dimensional (3D) pattern analysis have been used to investigate the chemical and steric properties of compounds that inhibit transport of the plant hormone auxin. These compounds bind to a specific site on the plant plasma membrane characterized by its affinity for the herbicide N-1-naphthylphthalamic acid (NPA). A 3D model was derived from critical features of a set of ligands for the NPA receptor, a suggested binding conformation is proposed, and implications for the topographical features of the NPA receptor are discussed. This model, along with 3D structural analysis techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the criteria of the model, 77 representative molecules were evaluated for their ability to compete for the binding of [3H]NPA to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, representing chemical classes not included in the original compound set, were also found to inhibit polar auxin transport through corn coleoptile sections. Thus, this study demonstrates that 3D analysis techniques can identify active, novel ligands for biochemical target sites with concomitant physiological activity.

Binding Sites↗

Aryl-Substituted alpha-Aminooxycarboxylic Acids: A New Class of Auxin Transport Inhibitors.

Certain herbicidal aminooxyisovalerate analogs were noted in whole plant phytotoxicity bioassays to cause disoriented roots. Since this symptom is often characteristic of interference with the transport of the plant hormone auxin, the ability of several of these compounds to compete for the N-1-naphthylphthalamic acid (NPA) binding site in corn (Zea mays L.) coleoptile membranes was measured. Significant NPA binding activity was found, expecially for the 2,4-dichlorophenyl analog. Application of structure-activity principles from traditional auxin transport inhibitors to this new class of molecules led to the synthesis of the naphthyl analogue. This molecule was extremely active in competing for NPA binding and in eliciting whole plant growth regulator effects. Possible relationships between these molecules and the mode of auxin transport are discussed.

Journal Article↗

Hemolytic uremic syndrome following cisplatin, bleomycin, and vincristine chemotherapy: a report of a case and a review of the literature.

This report describes a patient who developed the hemolytic uremic syndrome while undergoing chemotherapy with cisplatin, bleomycin, and vincristine, for metastatic squamous cell cancer of the floor of the mouth. In spite of dialysis and plasmapheresis, the patient died. This complication has rarely been reported in association with cisplatin, bleomycin, or vincristine therapy. The etiology of this syndrome is uncertain but may be related to scleroderma-like endothelial injury and vasospasm caused by bleomycin combination chemotherapy. It is notable that the development of the hemolytic uremic syndrome in conjunction with this combination of agents has been fatal in all patients over the age of 50 with squamous cell cancers.

Antineoplastic Combined Chemotherapy Protocols↗

Shunt surgery in Meniere's disease: a follow-up report.

Between December 1969 and May 1986, 140 patients were treated for Menière's disease using the endolymphatic sac subarachnoid shunt. The technique and results are contrasted with an earlier report. The surgical technique described includes modifications of the originally described procedure. A microcomputer was used for the storage and manipulation of data based upon 1972 Academy criteria. Control of vertigo was accomplished in 83% of patients; 51% of patients were graded class A or B, according to the 1972 Academy criteria. No serious complications occurred. Problems included the potential for serious complications, the lack of specific criteria for patient selection, and the continued deterioration of hearing with the passage of time. Comparison of data with those presented in 1973 indicates a lower overall success rate, but continued success in the management of vertigo and imbalance. The endolymphatic sac subarachnoid shunt is worthy of consideration in the management of Menière's disease when surgery is indicated and retention of hearing is desirable.

Adult↗

Inhibition of phytochrome synthesis by the transaminase inhibitor, 4-amino-5-fluoropentanoic Acid.

Gardner and Gorton (1985 Plant Physiol 77: 540-543) demonstrated that the transaminase inhibitor gabaculine (5-amino-1,3-cyclohexadienyl-carboxylic acid) inhibits the initial synthesis and resynthesis of spectrophotometrically detectable phytochrome in vivo. Another mechanism-based transaminase inhibitor, 4-amino-5-fluoropentanoic acid (AFPA), is examined in this report for its effects on phytochrome synthesis in developing etiolated seedlings. Preemergence treatment with AFPA was found to inhibit initial phytochrome synthesis in peas (Pisum sativum L.), corn (Zea mays L.), and oats (Avena sativa L.). In general, reduction in phytochrome correlated with reduction in chlorophyll. However, the extent of inhibition of phytochrome synthesis was not as great as that of chlorophyll synthesis. These results confirm those with gabaculine, indicating that both initial synthesis and resynthesis of phytochrome require de novo synthesis of chromophore as well as apoprotein. AFPA was a more effective inhibitor of both chlorophyll and phytochrome synthesis than was gabaculine, suggesting that AFPA may be the preferred tool with which to probe the physiological consequences of the inhibition of phytochrome biosynthesis.

Journal Article↗

Silk gland-specific tRNA(Ala) genes are tightly clustered in the silkworm genome.

To understand the basis for tissue-specific production and accumulation of alanine tRNA in silkworms, we have examined the organization of the genes that code for silk gland-specific and constitutive alanine tRNAs. We have found that all of the silk gland-specific tRNA(Ala) genes (approximately 20) appear to be tightly clustered at a single locus in the Bombyx genome. These genes are arranged in tandem at intervals of approximately 150 base pairs. In contrast to the arrangement of the silk gland-specific tRNA(Ala) genes, most of the 20 to 30 constitutive tRNA(Ala) genes are dispersed in the genome. Silk gland-specific tRNA(Ala) genes are not amplified or grossly rearranged in the silk gland. Thus it is likely that differential transcription, rather than changes in gene number or structure, accounts for the tissue-specific accumulation of tRNA(Ala).

Animals↗

The subarachnoid shunt for Menière's disease: sixteen years' experience.

One hundred forty patients have been treated at the Baptist Memorial Hospital in Memphis, Tennessee for Menière's disease over a 16-year period, using an endolymphatic sac-subarachnoid shunt. Emphasis was placed on surgical methods, including compression of the sigmoid sinus with bone wax during surgery, facial nerve identification, and coverage of the sac with vein tissue. Satisfactory follow-up was accomplished in 66% of patients. Results were reported according to the criteria of the American Academy of Ophthalmology and Otolaryngology (1972). Control of attacks was accomplished in 83% of cases; median pure tone average (PTA) was 49 dB preoperatively and 54 dB postoperatively. Speech discrimination was 78% preoperatively and 69% postoperatively. Sixty-eight patients (51%) were graded as class A or B. Sixty-six (49%) were class C or D. Twenty-three patients (17%) were A+. Absence of nasal allergy and the presence of fluctuation of hearing appeared to indicate a more favorable outcome.

Adult↗