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Biomedical subjects

C Hamilton

Publications and source records attributed to C Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

New methods showing in vitro changes of platelets.

INTRODUCTION: In vitro methods for assessing stored platelets are time consuming and variably correlate with in vivo survival. We used the ADVIA 120 and the Thromboelastogram (TEG) to assess changes during storage to determine a correlation of the results with those of other commonly used measures. METHODS: Platelet concentrates were tested at 1 and 5 days of storage. In vitro test included platelet count, aggregation response, the hypotonic shock response (HSR), The Kunicki morphology score (KMS) and platelet activation using CD62. The ADVIA was used to measure the platelet density and the granule content. The TEG measured the kinetics of clot formation. RESULTS: The platelet count and HRS did not change during storage. Aggregation decreased 50% by day 5. The KMS dropped from 307 at day 2-170. The MPC fell below 200g/l. There was slight platelet activation; the rate of clot formation decreased. CONCLUSIONS: Standard measures of in vitro platelet function indicated alterations during storage. A MPC of less than 200 corresponded to a Kunicki morphology score of less than 200. The TEG results correlated will with the KMS. These measurements may prove useful in predicting platelet survival and recovery.

Blood Platelets↗
PubMed2006

MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.

In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on "prefrontal" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.

Adolescent↗
PubMed2005

Effects of minocycline and tetracycline on retinal ganglion cell survival after axotomy.

In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold. The presence of activated microglia was confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve axotomy produced RGC death and increased activation of microglia. No significant RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss occurred at 7 and 14 days, respectively. Examination of the effects of tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized control) compared with vehicle-only (52% of control) and tetracycline-treated (58% of control) animals. The densities of RGCs (RGCs/mm2+/-S.D.) for control, vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996+/-81, 1029+/-186, 1158+/-190 and 1497+/-312, respectively. The neuroprotective effect of minocycline seen at 7 days was transient, since RGCs present in minocycline-treated animals at 14 days post-axotomy (281+/-43, 14% of control) were not significantly different to vehicle-treated animals (225+/-47, 11% of control). OX-42 staining of activated retinal microglia was reduced in tetracycline- and minocycline-treated axotomized animals compared with axotomized animals receiving vehicle-only. These results demonstrate that systemic administration of the second-generation tetracycline derivative, minocycline, delays the death of axotomized RGCs by a mechanism that may be associated with inhibition of microglia activation. The neuroprotective efficacy of minocycline following optic nerve axotomy was superior to that of tetracycline.

Animals↗
PubMed2004

SARS Surveillance Project--Internet-enabled multiregion surveillance for rapidly emerging disease.

INTRODUCTION: On March 15, 2003, CDC requested health-care and public health agencies to conduct surveillance for severe acute respiratory syndrome (SARS). The SARS Surveillance Project (SARS-SP) was established to rapidly implement multiregional SARS surveillance in emergency departments (EDs) by using existing Internet-based tools. OBJECTIVES: The objectives of SARS-SP were to 1) disseminate and update SARS screening forms for ED triage, 2) establish surveillance for SARS syndrome elements by using Regional Emergency Medicine Internet (REMI), 3) expand surveillance to multiple regions, and 4) evaluate the usefulness of Internet tools for agile surveillance during a rapidly emerging global epidemic. METHODS: SARS-SP developed, distributed, and updated an Internet-based triage form to identify patients for infection control and public health reporting. EDs then were invited to report visit frequencies with various SARS syndrome elements to local public health authorities by using the REMI Internet application (first in one metropolitan area, and later in four). After pilot-testing in one metropolitan area, the surveillance system was implemented in three others. RESULTS: Active syndromic surveillance was established by health departments in Milwaukee, Wisconsin; Denver, Colorado; Akron, Ohio; and Fort Worth, Texas. A total of 27 EDs reported syndrome frequencies from >146,000 patient encounters. CONCLUSIONS: ED and public health partners reported being satisfied with the system, confirming the usefulness of Internet tools in the rapid establishment of multiregion syndromic surveillance during an emerging global epidemic.

Communicable Diseases, Emerging↗
PubMed2004

All delays before radiotherapy risk progression of Merkel cell carcinoma.

Prolonged waiting times for radiotherapy have resulted in many centres assigning priorities to various patient or diagnostic groups. A high risk of progression on a waiting list is one factor that would reasonably influence the priority. The present descriptive study of 27 patients with Merkel cell carcinoma (MCC) found that a median wait of 24 days for radiotherapy is associated with a high risk of progression. Eleven (41%) of 27 patients developed progressive disease, including five (45%) of 11 patients waiting for adjuvant radiotherapy. Patients treated adjuvantly also had longer waiting times prior to their initial radiotherapy consultation (median 41 days), which may have contributed to the rate of progression. Merkel cell carcinoma is an aggressive but curable malignancy and appropriate management should include efforts to minimize all potential delays prior to the commencement of radiotherapy.

Carcinoma, Merkel Cell↗
PubMed2004

Multicentre analysis of treatment planning information: technical requirements, possible applications and a proposal.

Digital data from 3-D treatment planning computers is generally used for patient planning and then never considered again. However, such data contains enormous quantities of information regarding patient geometries, tissue outlining, treatment approaches and dose distributions. Were such data accessible from planning systems from multiple manufacturers, there would be substantial opportunities for undertaking quality assurance of radiotherapy clinical trials, prospective assessment of trial outcomes and basic treatment planning research and development. The technicalities of data exchange between planning systems are outlined, and previous attempts at producing systems capable of viewing and/or manipulating imaging and radiotherapy digital data reviewed. Development of a software system for enhancing the quality of Australasian clinical trials is proposed.

Clinical Trials as Topic↗
PubMed2003

Salmonella isolated from animals and feed production in Sweden between 1993 and 1997.

This paper presents Salmonella data from animals, feedstuffs and feed mills in Sweden between 1993 and 1997. During that period, 555 isolates were recorded from animals, representing 87 serotypes. Ofthose, 30 serotypes were found in animals in Sweden for the first time. The majority of all isolates from animals were S. Typhimurium (n = 91), followed by S. Dublin (n = 82). There were 115 isolates from cattle, 21 from broilers, 56 from layers and 18 from swine. The majority of these isolates were from outbreaks, although some were isolated at the surveillance at slaughterhouses. The number of isolates from the feed industry was similar to that of the previous 5-year period. Most of those findings were from dust and scrapings from feed mills, in accordance with the HACCP programme in the feed control programme. It can be concluded that the occurrence of Salmonella in animals and in the feed production in Sweden remained favourable during 1993-97.

Animal Feed↗
PubMed2002

Health of cows, calves and young stock on 26 organic dairy herds in Sweden.

The health and housing of the stock on 26 organic dairy herds in four counties in eastern Sweden were studied for one year. The herds ranged in size from 12 to 64 cows, and their milk production from 3772 to 10,334 kg per cow per year. A large-animal practitioner visited the farms three times during the year, and a random sample of a third of the cows in each herd were examined. The calves and young stock and their housing were also studied. The calves were in good condition in all but four herds; their serum immunoglobulins varied from almost none to high levels. The young stock were in good condition and in good housing in 20 herds. No cows with clinical signs of metabolic disorders were found. Body condition scores were adequate or good except in two herds. Acetone was analysed in milk samples from individual cows three to six weeks postpartum, and only sporadic cases with high levels were found. The incidence of diseases treated by a veterinarian was lower in the organic herds than the average for the conventional herds in the local dairy association. The findings at the farm visits supported these data, and it is evident that a good standard of health and welfare can be achieved in organic dairy herds.

Acetone↗
PubMed2001

Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study.

PURPOSE: The acute and late toxicities of synchronous carboplatin, etoposide, and radiation therapy were prospectively assessed in a group of patients with high-risk Merkel cell carcinoma of the skin. PATIENTS AND METHODS: Forty patients from six different centers throughout Australia were entered into a Phase II study under the auspices of the Trans-Tasman Radiation Oncology Group. The trial was activated in 1996 and continues to accrue. Patients are eligible if they have disease localized to the primary site and nodes and are required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (area under curve [AUC] 4.5) and etoposide (80 mg/M(2) i.v.) were given on days 1-3 during weeks 1, 4, 7, and 10. The median age of the group was 67 years (43-78). RESULTS: The median duration of follow-up was 22 months (2-45). There were no treatment-related deaths. Grade 3 or 4 skin toxicity occurred in 63% of patients (95% CI 48, 78). The most serious acute effect was on neutrophils with Grade 3 or 4 (neutrophils < 1 x 10(9)/L), occurring in 60% (95% CI 45, 75) of cases. Complications from neutropenia (fever and sepsis) occurred in 16 patients (40% of cases). The median time for neutropenic complications was 27 days (9-35), and 10/16 (62%) cases of neutropenic fever occurred after the second cycle of chemotherapy. The probability of Grade 3 or 4 late effects on platelets (<50 x 10(9)/L) and hemoglobin (<8 g/dl) was 10% (95% CI 1, 20) and 6% (95% CI 2, 15), respectively. Of the 40 patients, 35 were able to complete 4 cycles of chemotherapy. There were no factors predictive for neutropenic toxicity at a p value < 0.05. CONCLUSIONS: The protocol has acceptable toxicity, and the treatment has been deliverable in a multi-institutional trial setting. Neutropenia is likely to occur with synchronous carboplatin/etoposide and radiation in this population of patients. The risk of a febrile neutropenia was greatest at the time of the second cycle of chemotherapy, when there was moist desquamation of skin or mucosal membranes that provided a portal for infection. This should be considered in the design of subsequent protocols with chemoradiotherapy.

Adult↗
PubMed2001

Inhibition of antigen-receptor signaling by Platelet Endothelial Cell Adhesion Molecule-1 (CD31) requires functional ITIMs, SHP-2, and p56(lck).

Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, CD31) is a 130-kd member of the immunoglobulin gene superfamily that is expressed on the surface of platelets, endothelial cells, myeloid cells, and certain lymphocyte subsets. PECAM-1 has recently been shown to contain functional immunoreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic domain, and co-ligation of PECAM-1 with the T-cell antigen receptor (TCR) results in tyrosine phosphorylation of PECAM-1, recruitment of Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2), and attenuation of TCR-mediated cellular signaling. To determine the molecular basis of PECAM-1 inhibitory signaling in lymphocytes, the study sought to (1) establish the importance of the PECAM-1 ITIMs for its inhibitory activity, (2) determine the relative importance of SHP-2 versus SHP-1 in mediating the inhibitory effect of PECAM-1, and (3) identify the protein tyrosine kinases required for PECAM-1 tyrosine phosphorylation in T cells. Co-ligation of wild-type PECAM-1 with the B-cell antigen receptor expressed on chicken DT40 B cells resulted in a marked reduction of calcium mobilization-similar to previous observations in T cells. In contrast, co-ligation of an ITIM-less form of PECAM-1 had no inhibitory effect. Furthermore, wild-type PECAM-1 was unable to attenuate calcium mobilization in SHP-2-deficient DT40 variants despite abundant levels of SHP-1 in these cells. Finally, PECAM-1 failed to become tyrosine phosphorylated in p56(lck)-deficient Jurkat T cells. Together, these data provide important insights into the molecular requirements for PECAM-1 regulation of antigen receptor signaling.

Amino Acid Motifs↗
PubMed2001

Temporal co-ordination of macroschizont and merozoite gene expression during stage differentiation of Theileria annulata.

The bovine parasite, Theileria annulata has a complex life-cycle involving the expression and repression of genes during development of its morphologically distinct life-cycle stages. In order to detail the molecular events that occur during differentiation of the intracellular multinucleate macroschizont to the extra-cellular uninucleate merozoite, we have isolated two genes, Tash1 and Tash2 which are differentially expressed during differentiation. Nuclear run on data show that Tash1 gene expression is controlled, at least in part, at the level of transcription. Immunofluorescence data identify the macroschizont as the location for both Tash1 and Tash2 gene products. Northern blot analysis of these genes indicated that their mRNA levels decrease during differentiation in vitro, at a time point coincident with major elevation in the mRNA levels of the merozoite antigen, Tams1, shown previously to be associated with commitment to merozoite production. Furthermore, experiments where cultures were incubated at 41 degrees C for 4 days and replaced at 37 degrees C for 2 days demonstrated that re-expression of Tash1 occurred and is probably linked to reversion to the macroschizont and decreased expression of Tams1. These results imply that the control of macroschizont and merozoite gene expression during differentiation is closely co-ordinated temporally. In addition, a comparison of Tash2 and Tams1 expression has indicated that translational or post-translational control of gene expression may operate in the undifferentiated macroschizont.

Amino Acid Sequence↗
PubMed2001

Effects of urotensin II in human arteries and veins of varying caliber.

BACKGROUND: -Urotensin II (UII) is the ligand for the GPR14 receptor and the most potent vasoconstrictor in the cynomolgus monkey. UII also contracts rat thoracic aorta. We studied the effect of human UII (hUII) in human blood vessels Methods and Results-Small subcutaneous resistance arteries, internal mammary arteries, saphenous veins, and small subcutaneous veins were studied using standard techniques. Subcutaneous resistance arteries constricted in response to norepinephrine (maximum tension, 2.84+/-0.38 mN/mm; the concentration required to produce 50% of the maximum response [EC(50)], 0.52+/-0.07 micromol/L) and endothelin-1 (maximum tension, 4.19+/-0.93 mN/mm; EC(50), 1.6+/-0.1 nmol/L). hUII did not contract these arteries, internal mammary arteries, or either type of vein, but it was a potent vasoconstrictor in rat thoracic aorta (maximum tension, 2.36+/-0.2 mN/mm; EC(50), 1.13+/-0.36 nmol/L). CONCLUSIONS: -hUII has no vasoconstrictor action in human arteries and veins of different sizes and vascular beds. Marked species differences in the actions of UII question its importance in human cardiovascular regulation.

Adult↗
PubMed2001

Protection against vertical transmission in bovine neosporosis.

In this study we were interested to determine whether infection of cattle prior to pregnancy would afford any protection to the foetus if the dams were challenged with Neospora caninum at mid-gestation. The experiment comprised four groups of cattle: group 1, uninfected controls; group 2, inoculated with N. caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum at mid-gestation; group 3, naive cattle challenged with N. caninum at mid-gestation and group 4 were infected with N. caninum prior to mating and left unchallenged throughout pregnancy. Positive cell-mediated and humoral immune responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in groups 2, 3 and 4 following challenge at mid-gestation. However there was a marked down regulation of the cell-mediated immune response in all groups around mid-gestation. There was a significant increase in rectal temperature response in animals in group 3 compared to group 2 following challenge but no other clinical symptoms of disease were recorded and all cattle proceeded to calving. At calving, pre-colostral blood samples were negative for antibodies to N. caninum in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves born to dams in group 3 had high levels of specific antibody to N. caninum indicating that they had been exposed to the parasite in utero. At post-mortem N. caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves from group 3. All tissue samples from calves in the other 3 groups were negative for N. caninum DNA with the exception of one calf from group 2 where specific DNA was detected in a sample of spinal cord. These results suggest that the immune response generated in the dams in group 2 prior to pregnancy had protected against vertical transmission of the parasite following challenge at mid-gestation.

Animals↗
PubMed2001

A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: a Trans-Tasman Radiation Oncology Group Study.

PURPOSE: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. PATIENTS AND METHODS: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. RESULTS: The median potential follow-up time was 53 months (range, 14-101). The DFS at 5 years was 41% (95% CI, 33-50%) for ART and 35% (95% CI, 27-43%) for CRT (P=0.323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66-1.15). The 5-year disease-specific survival rates were 40% for CRT and 46% for ART (P=0.398) and the loco-regional control was 47% for CRT vs. 52% for ART (P=0.300). The respective hazard ratios were 0.88 (95% CI, 0.65-1.2) and 0.85 (0.62-1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P<0.001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P<0.05), except for the mucous membrane where late effects were similar in both arms. CONCLUSIONS: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy.

Adult↗
PubMed2001

The PANDAS subgroup: recognition and treatment.

A subgroup of patients with childhood-onset obsessive-compulsive disorder (OCD) has been identified who share a common clinical course characterized by dramatic symptom exacerbations following Group A beta-hemolytic streptococcal (GABHS) infections. The term PANDAS has been applied to the subgroup, to indicate the postulated etiology of their symptoms: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. Five clinical characteristics define the PANDAS subgroup: presence of OCD and/or tic disorder, prepubertal symptom onset, sudden onset or abrupt exacerbations (sawtooth course), association with neurological abnormalities (presence of adventitious movements or motoric hyperactivity during exacerbations), and temporal association between symptom exacerbations and GABHS infections. Post-streptococcal symptom exacerbations are typically quite dramatic, with patients reporting that their symptoms "...came on overnight" or "...appeared all of a sudden a few days after I had a sore throat." The post-streptococcal inflammatory nature of the neuropsychiatric symptoms provides novel opportunities for treatment and prevention, including immunomodulatory therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG). A recently completed placebo-controlled trial revealed that both IVIG and TPE were effective in reducing neuropsychiatric symptom severity (40% to 55% reductions, respectively) for a group of severely ill children with OCD and/or tic disorders. Further research is required to determine why the treatments are helpful, as well as to ascertain whether or not antibiotic prophylaxis can help prevent post-streptococcal symptom exacerbations.

Journal Article↗