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Biomedical subjects

C Hamilton

Publications and source records attributed to C Hamilton.

At least 19 recordsLinked to original sources
PubMed1998

Do inflammatory processes contribute to radiation induced erythema observed in the skin of humans?

BACKGROUND: Two prospective trials were designed to determine whether there may be a role for inflammatory mediators in human skin erythema at both high and low doses per fraction and for 'out of field' effects. METHODS: Trial 1. Effects of topical indomethacin (1%) and hydrocortisone (1%) applied before and during radiotherapy were compared for erythema induced by 20 Gy in four fractions (n = 26, 6 MV). Trial 2. Effects of topical hydrocortisone (1 %) applied before and during radiotherapy and no medication were compared for erythema induced by 1, 3, 5 and 7 Gy in five fractions (n = 21, 120 kV). Erythema was measured using reflectance spectrophotometry (RFS) and laser Doppler (LD) on a weekly basis. RESULTS: Trial 1. A bi-phasic reaction time course was suggested in two-thirds of the cases. The first phase did not appear to be influenced by hydrocortisone cream but the second was significantly attenuated. Indomethacin had no effect on either reaction phase. Erythema measured several centimetres outside of the field was reduced by hydrocortisone but not by indomethacin. Trial 2. Trial 2 confirmed the presence of measurable erythema, invisible to the eye, that coincided in its time course to the first phase of erythema noted in trial 1. This reaction was more intense than predicted by the LQ formula and was non-significantly attenuated by topical hydrocortisone. RFS readings proved to be less subject to inter- and intra-patient variations than the LD unit used. CONCLUSION: Inflammatory responses may play a role in the mediation of the erythematous response to radiation in human skin. Further studies are warranted.

Aged↗
PubMed1998

Determinants of tissue estradiol levels and biologic responsiveness in breast tumors.

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10-50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.

Animals↗
PubMed1998

How should we introduce high-dose chemotherapeutic strategies into the adjuvant management of high-risk breast cancer in Australasia?

BACKGROUND: Development of bone marrow support techniques has altered the standard chemotherapeutic management of haematological malignancies, and these techniques are now being increasingly utilized in solid tumours. In breast cancer, survival benefits have resulted from conventional dose adjuvant chemotherapy, but outcomes remain poor in many women with high-risk disease. Improved response rates with high-dose chemotherapy (HDC) in metastatic disease have led to the investigation of these techniques in adjuvant therapy of high-risk localized disease. In some high-risk patient subgroups survival is extremely poor, with 5-year rates below 30%. Improved adjuvant strategies for patients in these subgroups are therefore urgently required. In Australasia, oncology departments are currently considering accrual of women with high-risk disease into the International Breast Cancer Study Group (IBCSG) 15-95 Trial investigating HDC/stem cell transplantation. METHODS: The present paper reviews the available data on the efficacies and toxicities of currently available high-dose chemotherapeutic strategies; discussing methodological considerations relevant to their introduction and safe use in the adjuvant setting in Australia and New Zealand. RESULTS: Although response rates with HDC in metastatic disease are encouraging, the clinical effectiveness of current HDC regimens in adjuvant management has not been established and is limited by significant toxicity. CONCLUSIONS: The introduction of HDC strategies for high-risk breast cancer in Australia encounters difficulties both in trial design and potential clinical practice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Does waiting time affect the outcome of larynx cancer treated by radiotherapy?

AIM: To determine the impact of waiting for radiotherapy on local control in early larynx cancer treated by radiotherapy alone. METHODS: Records of patients with T1 and T2, N0-2 larynx cancer were examined at three radiotherapy centres. Waiting time was defined in three ways, (1) time from biopsy to radiotherapy, (2) time from presentation to radiation department to start of radiotherapy and (3) the minimum of (1) and (2). Time to relapse was the major end point. RESULTS: There were 581 patients with a median follow-up of 6.8 years. Stage distribution was as follows: T1, 370; T2a, 106; T2b, 94; T2 unspecified, 11; N0, 563; N+, 18. Median times from biopsy, presentation and minimum time to treatment were 24, 16 and 15 days, respectively. Ninety percent of minimum waiting times were < or = 31 days. The median dose was 61 Gy in a median of 30 fractions over a median 46 days. Local recurrence occurred in 126 patients. The actuarial recurrence free rate at 5 years was 77% (SE 2%). In a multivariate analysis the significant predictors of relapse were higher T stage, longer treatment duration and increasing field area. Waiting time was not significantly associated with local relapse. CONCLUSION: This study did not show longer waiting time to be a significant predictor of relapse in early larynx cancer. Other end-points which are relevant, such as quality of life, have not been examined. Longer treatment times were significantly associated with relapse.

Adult↗
PubMed1997

Normal variation in cutaneous blood content and red blood cell velocity in humans.

This study was designed to determine normal variations in cutaneous blood content, red blood cell content and skin thickness in healthy human volunteers. The blood content (BC) of human skin and the velocity of red blood cells (RBV) has been comprehensively mapped over 30 anatomical sites in 28 volunteers between the age of 7 and 77 years using reflectance spectrophotometry (RFS) and laser Doppler (LD) techniques respectively. Total skin thickness, which may have a relationship with blood content, has been mapped at the same anatomical sites in six of the volunteers using two-dimensional array, 12 MHz ultrasound equipment. The major determinant of BC and RBV was found to be anatomical site. Regardless of age, gender or prior sun exposure, anatomical sites above the waist produced higher readings than below. BC and RBV were found to be dependent on age and gender at most sites with higher readings being observed in males and younger volunteers. The largest difference was seen in males under 55 years whose RFS readings above the waist were significantly higher than in older males or females of any age. Heavy prior sun exposure and skin thickness could not be demonstrated to impact on either RFS or LD readings independently of the effects of anatomical site, gender or age. In general, RFS and LD readings paralleled one another and correlated linearly at most anatomical sites. While RFS readings tended to decrease in the cranio-caudal direction, LD readings were relatively uniform across the body except for the head and groin where they were higher, and the abdomen where they were lower. The site-to-site variations in RFS readings observed in this study correspond well to capillary density variations noted in previous studies.

Adolescent↗
PubMed1997

Estrogen production via the aromatase enzyme in breast carcinoma: which cell type is responsible?

Studies of breast tumor homogenates from women with breast cancer have demonstrated the synthesis of estrogens in situ through the enzyme aromatase. The present series of investigations sought to determine which cell type within the tumor is responsible for local estrogen biosynthesis, and whether or not the amount produced is biologically important. Accordingly, we utilized an indirect immunohistochemical scoring method (H-score) to determine the relative amount of enzyme present in tumor epithelial and stromal cells. This revealed a value of 13 for tumor stromal cells and 4.8 for the epithelial component. Contributing to this difference is the fact that a greater percentage of cells in the tumor were stromal (45%) than epithelial (37%). To obtain direct evidence that tumor stromal cells could synthesize estrogens, we isolated and grew these cells in tissue culture. Stromal cells originating from within the tumor could be stimulated by known enhancers of transcription to produce nearly as much aromatase as is found in placental microsomes. Stromal cells isolated from benign tissue distal to the tumor exhibited properties similar to those of the tumor stroma. Epithelial cells, in contrast, did not respond to these enhancers and had low levels of aromatase basally. To obtain proof of the principle that local estrogen synthesis can be biologically meaningful, we measured tumor tissue estradiol levels and growth rates in aromatase-transfected MCF-7 cells implanted into nude mice. Local synthesis resulted in tumor levels ranging from 300 to 800 pg/g and growth rates substantially higher than in non-aromatase-containing tumors. These data suggest that tumor stromal cells contribute the major portion of estrogen synthesized in tumors, and that this local synthesis can increase tumor estradiol levels and growth rates.

Animals↗
PubMed1996

Factors affecting motion characteristics of frozen-thawed stallion spermatozoa.

Five experiments were conducted to evaluate damage incurred in each processing step for cryopreservation of stallion spermatozoa. In Experiment 1, semen was centrifuged for 9 centrifugation times and the percentage of spermatozoa recovered after each treatment was calculated and spermatozoal motion characteristics analysed. Recovery of spermatozoa was > or = 80% when spermatozoa were centrifuged for > or = 10 min. Experiment 2 evaluated spermatozoa cryopreserved at 5 different concentrations in each of 2 extenders (skim milk-egg yolk-glycerol, SM-EYG; and lactose-EDTA, LAC). In SM-EYG, TMOT and PMOT were higher at spermatozoal concentrations of 20, 200 and 400 x 10(6)/ml (51%/41%, 52%/44%, 50%/43%, respectively) than for samples frozen at > or = 800 x 10(6) spermatozoa/ml (41%/35%, 32%/27%; P < 0.05). Spermatozoa frozen in LAC at a concentration of 20 x 10(6)/ml resulted in the highest TMOT and PMOT (43% and 30%, respectively, P < 0.05). The effect of freezing rate on motion characteristics of spermatozoa was evaluated in Experiment 3. The VCL of spermatozoa frozen in SM-EYG was the only parameter affected by freezing rate (P < 0.05). Experiment 4 evaluated motion characteristics after cryopreservation of spermatozoa in different sized straws (0.5 or 2.5 ml) in each of 2 extenders (SM-EYG and LAC). In SM-EYG, PMOT (38%) and VCL (109 microns/s) were highest when spermatozoa were frozen in 0.5 ml straws (P < 0.05). In Experiment 5, spermatozoa thawed immediately after cryopreservation or thawed after storage in liquid nitrogen for 24-48 h were evaluated. There was no effect of length of storage in liquid nitrogen on spermatozoal motion characteristics (P < 0.05). Experiment 6 evaluated the effects of cooling time to 5 degrees C (0, 2.5 and 5 h) on motion characteristics of spermatozoa cryopreserved in 2 extenders (SM-EYG and LAC). TMOT and PMOT were effected by cooling time, and there was a cooling-time-by-extender interaction (P < 0.05). In SM-EYG, TMOT and PMOT were higher if spermatozoa were cooled to 5 degrees C prior to initiation of freezing than if freezing was initiated at 20 degrees C (P < 0.05). A suggested protocol for cryopreservation of stallion spermatozoa would include: 1) centrifugation at 400 g for 14 to 16 min; 2) extension at 23 degrees C with SM-EYG to 400 x 10(6) spermatozoa/ml; 3) cool to 5 degrees C for 2.5 h; 4) package in 0.5 ml straws at 5 degrees C; 5) freeze in liquid nitrogen vapour at -160 degrees C; and 6) thaw for 30 s in 37 degrees C water.

Animals↗
PubMed1995

Oxidized-LDL induced changes in membrane physico-chemical properties and [Ca2+]i of bovine aortic endothelial cells. Influence of vitamin E.

The effects of 3 days' exposure to native and oxidatively modified human low density lipoprotein (LDL and Ox-LDL) on cultured bovine aortic endothelial cell cholesterol content, membrane microviscosity and intracellular free calcium concentration ([Ca2+]i) were studied. Free cholesterol content increased by 35% and 100% in LDL and Ox-LDL treated cells, respectively, these effects being reversed by vitamin E; esterified cholesterol, which rose by 110% in the Ox-LDL group only, was not affected by vitamin E. Membrane microviscosity, measured as the fluorescence polarization of the trimethylammonium derivative of diphenyl-hexatriene, increased by 9% in Ox-LDL treated cells only. This effect was also reversed by vitamin E. Using the calcium sensitive fluorescent dye fura 2-AM, increases in basal [Ca2+]i of 36% in LDL and 81% in Ox-LDL treated cells were observed. The bradykinin mediated increase in [Ca2+]i was enhanced in both the LDL and, to a greater extent, the Ox-LDL group. Vitamin E reversed the effects of LDL on [Ca2+]i but had no influence in the Ox-LDL group. The lipoproteins affected all parameters measured in this study. Oxidized LDL produced reversible and irreversible alterations to the membrane and the [Ca2+]i. All changes associated with LDL were abolished by vitamin E. Such modifications in the physicochemical properties of the membrane and [Ca2+]i could be involved in the initiation of the atherosclerotic process.

Animals↗
PubMed1995

A rapid diagnostic and treatment center for patients with chest pain in the emergency department.

STUDY OBJECTIVE: To evaluate a comprehensive diagnostic 9-hour evaluation (Heart ER Program) for patients with possible acute ischemic coronary syndromes. DESIGN: Retrospective review of consecutive patients. SETTING: Urban tertiary care emergency department. PARTICIPANTS: A total of 1,010 patients with symptoms suggestive of acute ischemic coronary syndrome was enrolled in the Heart ER Program over the first 32 months of operation. Patients with history of coronary artery disease, hemodynamic instability, acute ST-segment elevation or depression of more than 1 mm, or a clinical syndrome consistent with unstable angina were directly admitted to the hospital. INTERVENTION: Patients underwent serial testing for creatine kinase (CK-MB) on presentation to the Heart ER and 3, 6, and 9 hours later with continuous 12-lead ECGs/serial ST-segment trend monitoring for 9 hours. Two-dimensional echocardiography and graded exercise testing were performed in the ED after the 9-hour evaluation period. RESULTS: Of 1,010 patients, 829 (82.1%) were released home from the ED; 153 (15.1%) required admission for further cardiac evaluation. Fifty-two of 153 (33.9%) admitted patients were found to have a cardiac cause for their symptoms; 43 had acute ischemic coronary syndromes (12, acute myocardial infarction; 31, angina or unstable angina). CONCLUSION: The Heart ER program provides an effective method for evaluating low- to moderate-risk patients with possible acute ischemic coronary syndrome in the ED setting.

Adult↗
PubMed1995

Workload and use factor of medical linear accelerators in radiotherapy.

An important factor in the design of primary protective barriers is the use factor. The present study was aimed at obtaining historical data on the use factor of two dual modality linear accelerators in a radiotherapy department. Gantry angle, field size, and beam modifiers were recorded for all radiation qualities in use at two medical linear accelerators with 6 MV and 18 MV x-rays and multiple electron energies ranging from 4 MeV to 20 MeV. The data for one year of clinical use was extracted from a record and verifying system and an estimate of the physics workload on the machines was obtained by going through the quality assurance records and machine log books. Of the total dose of approximately 37,000 Gy delivered in one year at isocenter on each unit 80% was given as 6 MV x-rays. As can be expected, most x-ray beams were directed at the four cardinal gantry angles with the angular distribution for 6 MV and 18 MV x-rays being very similar. Electron fields were broadly distributed around the gantry pointing down position. Less than 25% of all clinical x-ray treatment fields extended beyond a field size of 200 cm2.

Blood Component Transfusion↗
PubMed1994

Peptides related to thyrotrophin-releasing hormone (TRH) in human prostate and semen.

The TRH-related peptide, pGlu-Glu-ProNH2, which was first identified in rabbit prostate has recently been named fertilization-promoting peptide (FPP) because of its ability to enhance the in vitro fertilizing potential of mouse epididymal spermatozoa. This study set out to examine the nature of the TRH-related peptides in human prostate and semen but, first, the optimal conditions for collection of semen samples were investigated. FPP was degraded slowly (t1/2 = 163 min, S.E. +/- 51.3, n = 6) in seminal plasma which has allowed us to measure accurately the concentrations of FPP, after extraction of the peptide in acidified acetone precisely 5 min after ejaculation. In this way, high levels of FPP (mean: 49.5 nmol/l) were detected in normal human semen, from young men, although other TRH-related peptides did not appear to be present. We have also examined the TRH-related peptides present in prostate samples from clinical patients both with and without evidence of benign prostatic hyperplasia (BPH), by ion-exchange chromatography followed by radioimmunoassay. Substantial concentrations of FPP were observed in normal (4.10 pmol/g tissue, S.E. +/- 1.46) and BPH prostate (6.27 pmol/g tissue, S.E. +/- 1.65). In addition, a second, neutral TRH-immunoreactive peptide was always detected in BPH tissue (7.40 pmol/g tissue, S.E. +/- 1.98) with only low levels generally present in normal prostate. The possibility that the presence of high levels of the neutral peptide in prostate may be used as an indicator of the onset of BPH deserves further scrutiny.

Adult↗
PubMed1994

Bioaccumulation of aromatic hydrocarbons from sediments: a dose-response study with flounder (Pseudopleuronectes americanus).

Pseudopleuronectes americanus were chronically exposed to Hibernia crude oil in sediments, for 4 months. Oil was added to sediments at five concentrations between 0.09 and 4.5 mg/g (dry weight) and was 0.10-0.90 mg/g, at the termination of the exposure. Bioaccumulation measured in terms of fluorescence or in terms of the concentration of specific aromatic targets, increased with dosage. Accumulation of hydrocarbons was observed in muscle tissue (0.22 microgram/g, dry weight), when concentration of the sum of 27 polycyclic aromatic compounds (PAC) in sediments was of 0.65 microgram/g (E-50), at the end of the 4-month period. Of the 27 parental and alkylated polycyclic aromatic compounds analyzed, alkylated naphthalenes predominated in muscle (90-100%) and in sediments (30-60%). Bioaccumulation factors were derived for 13 compounds detected in muscle, at the three higher exposures. Liver concentrations (fluorescence) were higher than in muscle, but did not display a noticeable dose-response. Several alkylbenzenes, a C-2 biphenyl and C-4 acenaphthene were also detected in muscle extracts. The development of dose-response relationships for polycyclic aromatic hydrocarbons (PAH) present in sediment, in relation to bioaccumulation in flatfish, is of major interest for evaluating the environmental effects of oil contamination.

Animals↗
PubMed1994

Determinants of low systemic vascular resistance during cardiopulmonary bypass.

Although low systemic vascular resistance occurs during normothermic and hypothermic cardiopulmonary bypass, the determinants of depressed systemic vascular resistance and its effect on outcomes are unknown. To assess the predictors and clinical effects of low systemic vascular resistance, 555 patients undergoing isolated coronary artery bypass grafting were evaluated prospectively. The extent of low systemic vascular resistance during bypass was estimated by the amount of the vasoconstrictor phenylephrine administered: group 1, 0 to 160 micrograms; group 2, 161 to 800 micrograms; group 3, more than 800 micrograms. Multivariate analysis identified bypass temperature, bypass time, and ventricular function as determinants of low systemic vascular resistance. Patients on normothermic bypass accounted for 65% of the patients in group 3 and only 34% of the patients in group 1 (p < 0.0001). The bypass time was longer in the patients in group 3 (97 +/- 28 minutes) than in the patients in group 1 (89 +/- 24 minutes; p < 0.006). Patients with a preoperative left ventricular ejection fraction of 0.40 or less required less phenylephrine during cardiopulmonary bypass (498 +/- 68 micrograms) than did patients with a fraction exceeding 0.40 (1,087 +/- 88 micrograms; p < 0.001). By multivariate analysis, advanced age and the presence of peripheral vascular disease were found to decrease the likelihood of low systemic vascular resistance during normothermic bypass. Diabetes, the left ventricular ejection fraction, the bypass time, and the total cardioplegia infused were found to influence the likelihood of low systemic vascular resistance during hypothermic bypass. Patients in group 3 had a higher cardiac index and lower-mean arterial pressure and systemic vascular resistance postoperatively. In those patients who received a left internal mammary artery graft, the incidences of the low-output syndrome (group 1, 4.9%; group 3, 2.7%; p = not significant) and myocardial infarction (group 1, 1.4%; group 3, 1.8%; p = not significant) were not influenced by the amount of phenylephrine infused during cardiopulmonary bypass. In those patients who were at high risk of suffering a stroke preoperatively, the hypotension induced by the low systemic vascular resistance and its treatment with phenylephrine was not associated with an increased incidence of stroke (group 1, 5.8%; group 3, 2.8%; p = not significant).

Aged↗
PubMed1994

Patient compliance with short-term topical aural antibiotic therapy.

Little is known about patient compliance with topical aural antibiotic regimens. The compliance of 50 patients with unilateral otitis externa attending an otolaryngology clinic was studied by comparing the weight of dispensed topical ear preparations before and after completion of a 7-day-course of treatment. A standard was obtained from controlled administration of the preparation under laboratory conditions and the performance of different delivery systems evaluated. Thirty-seven patients re-attended for review with their medication. A total of 34 of 50 patients entering the study (70%) satisfied conventional criteria for compliance. However, over-use of preparations was common and stricter criteria are proposed and applied. Compliance was significantly increased when someone other than the patient administered the preparation.

Administration, Topical↗
PubMed1993

Pharmacokinetics of the anticancer agent sulofenur in mice, rats, monkeys, and dogs.

The absorption and pharmacokinetics of sulofenur [N-(indan-5-sulfonyl)-N'-(4-chlorophenyl)urea, LY186641] and its major metabolites were examined in mice, rats, monkeys, and dogs. The compound is a diarylsulfonylurea currently being evaluated as an oncolytic agent in phase I and II trials. In all species, sulofenur was well absorbed after an oral dose, but over a prolonged period, and sulofenur exhibited a fairly long half-life of elimination from plasma. These values ranged from 6 h in rats up to 30, 110, and 200 h in mice, monkeys, and dogs, respectively, at doses (240-1000 mg/m2) within the range of those used in clinical trials. Experiments describing the high degree of binding of sulofenur to plasma proteins (consistently > 99%) help to explain these relatively long half-lives. There is, however, a large difference between these plasma half-lives in the species studied. Sulofenur was previously found to be extensively metabolized to products that are excreted primarily into the urine. In this study, its major metabolites, which are found mainly in the urine, were also minor components of the drug-related material (< 10% of the sulofenur concentrations) in the plasma of rats treated with sulofenur. The absorption, binding characteristics, and elimination of these major metabolites after their administration to rats were also compared with sulofenur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Strain gauge plethysmography for the detection of deep venous thrombosis.

Deep venous thrombosis is a widely recognized medical problem which results in significant morbidity and mortality. Venography is the current 'gold standard' diagnostic test for deep venous thrombosis; however it is costly, invasive and is unnecessarily performed in 50% of cases. This paper describes a self-contained, non-invasive system for automatic venous occlusion plethysmographic measurement and analysis. An examination of 274 symptomatic limbs was conducted using strain gauge plethysmography and a subsequent venographic examination was then performed. The plethysmographic results were then compared with venography so as to develop a means of discrimination for thrombotic and non-thrombotic limbs. Strain gauge plethysmography using the Belfast DVT Screener yielded a sensitivity of 100% and a sensitivity of 66.3% for proximal segment DVT. The efficacy of the discriminatory algorithm was then tested for the diagnosis of DVT in a further 101 symptomatic patients. A sensitivity of 94.7% and a specificity of 81.7% were observed for strain gauge plethysmography for proximal segment thrombosis in this patient group. The Belfast DVT Screener is highly sensitive for deep venous thrombosis and may be used to reduce the need for venography, which is of benefit to both the patient and clinician.

Adult↗