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Biomedical subjects

A Clifford

Publications and source records attributed to A Clifford.

17 recordsLinked to original sources

Studies on itraconazole delivery and pharmacokinetics in mallard ducks (Anas platyrhynchos).

Avian aspergillosis is commonly treated with itraconazole (ITZ). This paper describes two studies using mallard ducks (Anas platyrhynchos). The first study evaluated in vivo release of ITZ from subcutaneously injected controlled-release gel formulations and the second study compared pharmacokinetic parameters for two ITZ oral suspensions. ITZ-A suspension was prepared by mixing contents of commercially available capsules with hydrochloric acid and orange juice. ITZ-B suspension was prepared by dispersing the complex of the drug with hydroxypropyl-beta-cyclodextrin in water. Concentrations of ITZ and its active metabolite, hydroxyitraconazole (OH-ITZ), in plasma and tissue samples were measured using high-performance liquid chromatography. In the second study, drug concentrations in plasma samples were also analyzed using a bioassay. After administration of two ITZ controlled-release formulations, plasma and tissue concentrations of ITZ and OH-ITZ were either very low (< or = 52 ng/mL) or undetectable. Exceptions included skin, subcutaneous fat, and muscle adjacent to the injection site. The drug from ITZ-A and ITZ-B suspensions was absorbed after oral administration. ITZ pharmacokinetic parameters for both suspensions in mallard ducks were similar and the bioassay successfully measured ITZ equivalents in plasma samples from ducks.

Administration, Oral↗

Intravenous and subcutaneous pharmacokinetics of florfenicol in sheep.

Pharmacokinetic parameters of florfenicol were determined in 10 adult sheep (five wethers and five ewes) after a single 40 mg/kg intravenous (i.v.) dose, and three daily subcutaneous (s.c.) doses of 40 mg/kg of a commercial preparation (Nuflor((R))). The concentration of florfenicol in serum samples was assayed using a proprietary HPLC assay method, and pharmacokinetic parameters derived for individual animal data by each route using compartmental and noncompartmental approaches. Two animals (one male and one female) were excluded due to observed i.v. dosing problems, and a biexponential model was found to fit the i.v. data well for six of the other eight animals. Data from two males showed prolonged low concentrations of florfenicol in serum and were better fit by a three-compartment model. The mean +/- SD for the half-lives of the distribution and elimination phases for the six sheep best fit with a two-compartment model were 0.069 +/- 0.018 and 1.01 +/- 0.09 h respectively, and for the V(d(ss)) and clearances were 0.503 +/- 0.035 L/kg and 366 +/- 53 mL/h/kg respectively. The data collected during the s.c. multiple dose study were analyzed using noncompartmental methods only. The bioavailability (F%) after s.c. dosing was calculated in three ways to compare estimation methods as steady-state had not been reached and single dose s.c. data were not obtained past 24 h. Using the AUC(0--24) and AUC(0--> infinity ) from the first dose, the F% values averaged 27 and 40% respectively. Using the AUC(0--> infinity ) for all doses, the F% was 65%. Calculations of the mean time during which the serum concentration exceeded 0.5 and 1.0 microg/mL were 105 +/- 3.9 and 74.7 +/- 12.2 h respectively.

Animals↗

Influence of bone invasion and extent of mandibular resection on local control of cancers of the oral cavity and oropharynx.

The aim of this paper was to evaluate the influence of bone invasion on treatment outcome among patients with cancers of the oral cavity and oropharynx and to determine whether or not outcome was influenced by the extent of mandibular resection. A review of 127 prospectively documented patients who were treated with marginal or segmental resection for oral (n = 110) and oropharyngeal (n = 17) cancers was undertaken. There were 97 males and 30 females with a median age of 61 years. Clinical T stages were: T1 17 patients, T2 33, T3 22, T4 55. Median followup was 4 years. A total of 94 patients underwent marginal resections and 33 underwent segmental resections. Histological bone invasion was present in 17 patients (16%) in the marginal resection group and 21 patients (64%) in the segmental group (P<0.05). Soft tissue surgical margins were positive in 11 patients (12%) in the marginal group and in seven patients (21%) in the segmental group (P=not significant). Local control did not correlate significantly with T stage, the extent of mandibular resection or the presence of histological bone invasion, but was significantly influenced by positive soft tissue margins (P<0.01). Among patients with bone invasion, the local control rate was higher following segmental resection when compared to marginal resections (87% vs 75%) but this was not statistically significant. Survival was significantly influenced by positive soft tissue margins but not bone invasion or the type of resection. We conclude that bone invasion alone did not predict for local control or survival rates among patients with oral and oropharyngeal cancers. Involved soft tissue margins were highly predictive of local recurrence and decreased survival. Conservative resection of the mandible is safe as long as marginal mandibulectomy does not lead to compromise of soft tissue margins. Segmental resection should be reserved for patients extensive bone invasion or those with limited invasion in a thin atrophic mandible.

Adult↗

The influence of calcium to phosphate ratio on the nucleation and crystallization of apatite glass-ceramics.

The nucleation and crystallization behavior of a series of glasses based on 4.5SiO2-3Al2O3-YP2O5-3CaO-1.51CaF2 was studied. The parameter Y was varied to give calcium to phosphate ratios between one and two. All of the glasses studied crystallized firstly to fluorapatite (Ca5PO4)3F). The glass with a calcium to phosphate ratio of 1.67, corresponding to apatite, bulk nucleated to give fluorapatite (FAP). The glasses with calcium : phosphate ratios either less than that of apatite, or greater than that of apatite all exhibited surface nucleation of FAP. However, following a nucleation hold of one hour at approximately 50 K above the glass transition temperature these glasses exhibited bulk nucleation of FAP.

Journal Article↗

Life threatening laryngeal toxicity following treatment with combined chemoradiotherapy for nasopharyngeal cancer: a case report with review of the literature.

Nasopharyngeal carcinoma is a rare cancer in Western society, however there is a higher incidence in Asian. Chinese and African populations. A significant number of Asians reside in Australia, and consequently patients with nasopharyngeal carcinoma are an increasing clinical problem. Radiotherapy has been the predominant treatment in the past, but more recently multi-modality treatments have been utilised. The results of an Intergroup trial, coordinated by the Southwest Oncology Group (SWOG) demonstrated markedly superior progression free and overall survival for combined chemoradiotherapy compared to radiotherapy alone. At three years progression free survival was 24% for the radiotherapy arm and 69% for the chemoradiotherapy group (P < 0.001), and three-year survival was 47% for the radiotherapy arm compared with 78% for the combined arm (P = 0.005). There was minimum toxicity reported for either of the arms and no treatment related deaths. Based on these survival data the administration of concomitant cisplatin and radiotherapy has become standard of care for nasopharyngeal carcinoma in the USA. Our institution has also adopted a similar combined therapy protocol for patients with stage III and IV nasopharyngeal cancer and good performance status. The patients treated at our institution have experienced significant side effects. We describe the case of a woman so treated with this protocol who subsequently developed severe life threatening laryngeal necrosis.

Antineoplastic Agents↗

Testing for technical files: avoiding too little and too much.

Since 13 June 1998, it has been mandatory for all new and existing medical devices to be CE-marked according to the Medical Device Directive. However, for certain electromedical devices full compliance with the requirements of EN 60601-1 as a means of obtaining the CE mark may not be necessary. This article looks at some of these products and explains how they may still qualify for distribution in the European medical market.

Electric Stimulation↗

Role of ornithine decarboxylase in epidermal tumorigenesis.

Ornithine decarboxylase (ODC) plays a key role in the biosynthesis of polyamines, which are necessary for cell growth and differentiation. ODC expression is very tightly controlled in all normal cells; however, regulation of its expression is altered in many tumor cells resulting in much higher basal levels of ODC in tumors. To investigate the potential role of ODC overexpression in epidermal tumorigenesis, we constructed a replication-defective retroviral vector to overexpress a truncated ODC protein in epidermal cells. Stable viral infection of mouse epidermal cells dramatically increases not only the basal ODC activity but also the basal putrescine and spermidine levels. In all infected epidermal cells with high polyamine levels, DNA synthesis is increased as measured by [3H]thymidine incorporation into DNA as well as increased bromodeoxyuridine staining in the nuclei of ODC-infected epidermal cells. ODC viral infection of nontumorigenic BK-1 epidermal cells and primary cultures of mouse keratinocytes and fibroblasts from newborn mouse skin yields no tumors when injected s.c. into athymic nude mice or when transplanted as skin grafts onto nude mice. Epidermal cell lines SP-1 and 308 (which possess an activated rasHa gene) are not tumorigenic when injected s.c. into nude mice. However, following infection with the ODC virus, they form tumors filled with keratin and papilloma-like projections of hyperplastic epidermal cells displaying dysplasia and many mitotic figures. These data indicate that ODC overexpression by itself is not sufficient to induce tumors in normal cells but that increased expression of ODC enhances tumor development in initiated premalignant epidermal cells.

9,10-Dimethyl-1,2-benzanthracene↗

Effects of a carotene-deficient diet on measures of oxidative susceptibility and superoxide dismutase activity in adult women.

The effect of consuming a low carotene diet (approximately 60 micrograms carotene/day) on oxidative susceptibility and superoxide dismutase (SOD) activity in women living in a metabolic research unit was evaluated. The diet had sufficient vitamins A, E, and C. The women ate the diet supplemented with 1500 micrograms/day beta-carotene for 4 days (baseline), then the unsupplemented diet for 68 days (depletion), followed by the diet supplemented with > 15,000 micrograms/day carotene for 28 days (repletion). Production of hexanal, pentanal, and pentane by copper-oxidized plasma low density lipoproteins from carotene-depleted women was greater than their production of these compounds when repleted with carotene. Erythrocyte SOD activity was depressed in carotene-depleted women; it recovered with repletion. Thiobarbituric acid reactive substances in plasma of carotene-depleted women were elevated and diminished with repletion. Dietary carotene seems to be needed, not only as a precursor of vitamin A, but also to inhibit oxidative damage and decrease oxidation susceptibility.

Adult↗

A critical investigation of the measurement of the force required to dilate the human uterine cervix.

A system for objectively analysing the forces of dilation of the human uterine cervix was devised using a force sensing device linked to a BBC microcomputer. The computer program allowed easy recording, storage and analysis of force/time curves obtained from the passage of tapered dilators through the cervix. A new design of dilator gave a smoother force/time curve. These force/time curves were analysed. Six indices: peak force, end force, area to peak, area to end the ratio of the peak and end forces recorded from the passage of the two largest and two smallest dilators, were compared. Area measurement was subject to artefact and rejected. Peak and end force measurements gave the best separation between parous and nulliparous patients. The peak force was judged to be the better as it was found to be easier to define than end force.

Biophysical Phenomena↗

Isolated atherosclerotic aneurysms of the internal iliac arteries: report of two cases and review of literature.

Isolated arteriosclerotic aneurysms of the internal iliac artery are uncommon, with an incidence approaching 0.4%. Although the symptoms invariably involve the genitourinary or gastrointestinal systems, the aneurysms may be found during abdominal, rectal, or vaginal examinations. The 75% mortality associated with the rupture of an internal iliac aneurysm mandates for early surgery for these aneurysms. Operation may consist of ligation of the internal iliac artery, excision of the aneurysm, or an obliterative endoaneurysmorrhaphy. While the operative mortality has average 33.3%, there were no operative deaths in this series.

Aged↗

Giant Teflon granuloma of the larynx.

Endolaryngeal injection of Teflon paste to augment and medialize the paralyzed hemilarynx aims to improve dysphonia and relieve aspiration. After an initial short-lived inflammatory reaction in the laryngeal tissues, a foreign body granuloma forms around the Teflon. In most cases the results are good but it may occasionally be necessary to consider removal of the granuloma if too large a volume has been injected, if it is inappropriately placed, or if the paralyzed vocal cord subsequently recovers. Surgical removal is difficult and the results are unpredictable. This case illustrates, for the first time, that evaluation using both a high-resolution computed tomographic (CT) scan and endoscopy with telescopes permits satisfactory assessment before removal of Teflon.

Granuloma, Foreign-Body↗

Captured for consideration--using videotape as an aid to the treatment of the disturbed child.

The use of videotape as a clinical tool to monitor work with children is discussed with reference to a group of three emotionally disturbed children seen weekly in a paediatric assessment and treatment centre. Six particular attributes of videotape are distinguished and illustrated from clinical material: video is a vehicle for discussion; video permits detailed observation; video see things that humans do not; video has a distancing effect; video shares information and video trains in observation and handling techniques. It is suggested that the experience derived from using videotape intensively over a short period can be applied to advantage in other clinical situations.

Affective Symptoms↗