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Biomedical subjects

L Collins

Publications and source records attributed to L Collins.

At least 19 recordsLinked to original sources
PubMed2006

Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer.

It has been demonstrated that the Phellinus linteus (PL) mushroom, which mainly consists of polysaccharides, possesses antitumour activity. The mechanisms of PL against malignant growth remain unknown. The anticancer drug doxorubicin (Dox) has been shown to induce apoptosis via initiating a caspase cascade. In this investigation, we tested the effect of PL on Dox-induced apoptosis in prostate cancer LNCaP cells. We showed that PL or Dox, at relatively low doses, does not induce apoptosis in the cells. However, combination treatment with low doses of PL and Dox results in a synergistic effect on the induction of apoptosis. In this apoptotic process, caspases 8, 3 and BID are cleaved, and the addition of caspase inhibitor z-VADfmk completely blocks apoptosis. In addition, JNK is activated in response to PL or the combination treatment in LNCaP cells. The suppression of JNK partially inhibits the induction of apoptosis elicited by the co-treatment. These findings indicate that PL has a synergistic effect with Dox to activate caspases in prostate cancer LNCaP cells. Our study also suggests that PL has therapeutic potential to augment the magnitude of apoptosis induced by antiprostate cancer drugs.

Agaricales↗
PubMed2006

Multicentric Castleman's disease in a patient with HIV.

Multicentric Castleman's disease (MCD) was originally described in non-HIV patients. It is a rare lymphoproliferative disorder, which is more commonly seen in HIV-positive patients and is associated with human herpes virus-8 (HHV-8). We describe a patient with advanced HIV who responded well to conventional highly active antiretroviral treatment. She was diagnosed with MCD soon after her diagnosis of HIV. She presented with multiple flares of her MCD. The case illustrates the difficulty of differentiating between episodes of septicaemia and a flare of MCD. The patient was treated with various chemotherapy regimens, which included several cycles of liposomal doxyrubicin and etoposide. There is currently no consensus on the treatment of MCD and various therapies are described in the literature, which include chemotherapy. Chemotherapy must be chosen with the immunosuppressive effects of the treatment being considered with caution. Both doxyrubicin and etoposide are well tolerated and successfully controlled the symptoms of MCD in our patient.

Adult↗
PubMed2005

A remarkable permeability of canalicular tight junctions might facilitate retrograde, non-viral gene delivery to the liver via the bile duct.

AIMS: To establish the extent of retrograde bile duct infusion at an ultrastructural level, as a preliminary step before evaluating the efficacy of gene delivery to the rat liver via a branch of the bile duct. METHODS: The extent of retrograde infusion into the biliary tree was established by light and electron microscopy, following infusion of 10 nm gold particles into the right lateral lobe. Canalicular permeability was further assessed by the infusion of a 67 kDa protein. For gene delivery, both naked DNA and a synthetic peptide vector system were evaluated. Because canalicular tight junction permeability can be compromised in damaged livers, both normal rats and rats recovering from the hepatotoxin D-galactosamine were studied. RESULTS: The gold particles penetrated the peripheral one third of the hepatic lobules and, surprisingly, reached the space of Disse in normal rats. Equally surprisingly, blood levels of a 67 kDa protein were identical after bile duct infusion and portal vein injection. Gene delivery with peptide/DNA complexes was much more effective in rats treated with D-galactosamine. However, gene delivery with naked DNA was equally effective in normal and damaged livers. Localisation of gene expression showed a scattering of positive hepatocytes restricted to the right lateral lobe. CONCLUSIONS: Retrograde infusion into the bile duct advances well into the hepatic lobule and reveals a remarkable permeability of the canalicular or cholangiole tight junctions in normal rats. It is an effective approach for delivering genes to a small population (approximately 1%) of hepatocytes.

Animals↗
PubMed2005

Recommendations for a technical quality control program for diagnostic X-ray equipment.

This position paper was produced by a working party set up by the Radiology Special Interest Group of the ACPSEM in 2001. It is designed to give the consensus view of College members in Australia and New Zealand on the nature and frequency of tests which should be performed on diagnostic x-ray equipment to maintain adequate quality control of imaging performance and radiation safety. Tests on mammographic equipment have been excluded having been covered in a previous ACPSEM position paper (Australas Phys Eng Sci Med, 24(3):107-131, 2001). Detailed descriptions of test procedures are not given but it is intended that a series of workbooks should be produced giving College recommended test methods for each imaging modality. The recommendations are produced here in an easy-to-read, tabular form giving the nature and purpose of each test and the implications of non-compliance with regard to image quality and radiation safety.

Australasia↗
PubMed2004

Case of cryptic malaria.

We report a case of falciparum malaria in a renal transplant patient with no history of foreign travel. Three weeks previously she had been a hospital inpatient with cellulitis and had stayed on the same ward as a man with falciparum malaria acquired in Nigeria. There were no cases of malaria in other patients on the ward at the same time. The parasites from the two cases were genotypically indistinguishable. Despite a thorough investigation, reviewed by an expert external panel, no clear route of infection between the cases was identified. Patients with malaria should be considered highly infectious by the parenteral route. They should be managed with the infection control precautions used for patients with bloodborne virus infections. Our case reinforces the need for high levels of compliance with universal infection control procedures.

Adult↗
PubMed2003

Predictive, pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000.

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.

Adolescent↗
PubMed2001

In vivo gene delivery via portal vein and bile duct to individual lobes of the rat liver using a polylysine-based nonviral DNA vector in combination with chloroquine.

The objective of this study was to evaluate a bifunctional synthetic peptide as a DNA vector for regional gene delivery to the rat liver by the portal vein and bile duct routes. The 31-amino-acid peptide (polylysine-molossin) comprises an amino-terminal chain of 16 lysines for electrostatic binding of DNA, and the 15 amino acid integrin-binding domain of the venom of the American pit viper, Crotalus molossus molossus. Initial in vitro evaluation demonstrated that polylysine-molossin/DNA complexes were much smaller (approximately 50-100nm versus 500-1300nm), more positively charged, and more stable in isotonic dextrose in comparisons with salt-containing solutions. However, polylysine-molossin/DNA complexes in any solution other than complete culture medium were ineffective for gene delivery in vitro. Vector localization studies demonstrated that both the portal vein and bile duct routes provided excellent access of polylysine-molossin/DNA complexes to the liver. However, complexes delivered by the portal vein were rapidly lost (<15 min) following re-establishment of the portal circulation, whereas complexes delivered by the bile duct persisted much longer. Polylysine-molossin/DNA complexes in various isotonic solutions were delivered to the right lateral lobes either by perfusion through a branch of the portal vein or by infusion into appropriate branches of the bile duct. Two or three hours before gene delivery, rats were given a single injection of chloroquine. We report that the polylysine-molossin vector is much more effective (>10-fold) when delivered by the bile duct route with all isotonic solutions evaluated, and that polylysine-molossin/DNA complexes in isotonic dextrose are much more effective (>10-fold) than complexes in salt-containing solutions.

Animals↗
PubMed2001

A probabilistic atlas and reference system for the human brain: International Consortium for Brain Mapping (ICBM).

Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four-dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono- and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post-mortem tissue to determine the probabilistic distribution of microscopic cyto- and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo, provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro- and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.

Adult↗
PubMed2001

Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis.

BACKGROUND: Controlled trials in lupus nephritis have demonstrated that cyclophosphamide therapy is superior to corticosteroid therapy alone. The long-term effectiveness and side-effect profiles of pulse immunosuppressive regimens warrant further study. OBJECTIVE: To define the long-term risk and benefit of monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both. DESIGN: Extended follow-up (median, 11 years) of a randomized, controlled trial. SETTING: U.S. government research hospital. PATIENTS: 82 patients with proliferative lupus nephritis. MEASUREMENTS: Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events. RESULTS: In an intention-to-treat survival analysis, the likelihood of treatment failure was significantly lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002) groups than in the methylprednisolone group. Combination therapy and cyclophosphamide therapy alone did not differ statistically in terms of effectiveness or adverse events. Of patients who completed the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combination group than in the cyclophosphamide group (relative risk, 0.095 [95% CI, 0.01 to 0.842]). CONCLUSION: With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide and methylprednisolone appears to provide additional benefit over pulse cyclophosphamide alone and does not confer additional risk for adverse events.

Adult↗
PubMed2001

Production of narrow but deep lesions suitable for ablation of atrial fibrillation using a saline-cooled narrow beam Nd:YAG laser catheter.

BACKGROUND AND OBJECTIVE: Lines of radiofrequency ablation for cure of atrial fibrillation are broad, and the consequent loss of atrial mass may impair atrial function and contribute to the risk of stroke. We studied whether Nd:YAG laser could produce deep but narrower lesions. STUDY DESIGN/MATERIALS AND METHODS: Laser lesions were made in ventricular myocardium of nonperfused ovine hearts and at thoracotomy in dogs. RESULTS: Lesions were well demarcated, deep, and narrow. Saline irrigation prevented crater formation for energy levels below 200 J. Lesion depth increased with increasing duration of ablation (maximum 5.3 +/- 0.8mm, P < 0.01). The depth to width ratio was >1 in all cases (maximum 2.5 +/- 1.6). The narrowest lesions were made by using high power, short duration of exposure, and intermittent delivery. CONCLUSIONS: Irrigated Nd:YAG laser can be used to make deep narrow myocardial lesions without crater formation. Laser ablation may be more suitable than radiofrequency ablation for intraoperative or catheter-based cure of atrial fibrillation.

Animals↗
PubMed2001

Selective spinal anesthesia for outpatient laparoscopy. IV: population pharmacodynamic modelling.

PURPOSE: To apply a population pharmacodynamic model to small-dose hypobaric spinal anesthesia for outpatient laparoscopy. METHODS: The level of spinal analgesia after spinal blockade with small-dose (20-25 mg) hypobaric lidocaine was assessed by means of pinprick in patients undergoing outpatient laparoscopy. In 57 patients, 385 measurements were available for analysis. We first modelled the data for each patient with a mixed-effects model described by Schnider (Model 1). The population mean parameters, inter-individual variance, and residual variance were estimated. Clinically important endpoints (time to reach T10 (onset), time to maximal level, duration and maximally attained level) of each patient were calculated based on the estimated time course of analgesia level for each patient. The model was used to predict the later data with respect to level of spinal analgesia of each patient from fits based on the observed data in the first 75 min. RESULTS: The mean +/- SD onset time was 8.3 +/- 1.9 min, time to maximal level was 20.8 +/- 5.3 min, duration of effect was 37.9 +/- 13.1 min, and mean maximal level was T5. There was a good correlation (R2 = 0.90) between the observed levels of analgesia and those predicted from the model. Data from the first 75 min predicted the later observed data for each patient moderately well (R2 = 0.38). CONCLUSION: A population pharmacodynamic model was applied to low-dose hypobaric lidocaine spinal anesthesia. Clinically important endpoints were determined and forecasting of later data with respect to level of spinal analgesia was attempted. Such an approach may be useful in the management of low-dose spinal anesthetic techniques in outpatients.

Adult↗
PubMed2001

(99m)Tc antigranulocyte monoclonal antibody imaging for the detection and assessment of inflammatory bowel disease newly diagnosed by colonoscopy in children.

OBJECTIVE: This prospective study evaluated a (99m)Tc antigranulocyte monoclonal antibody Fab' imaging agent (Sulesomab) in children with inflammatory bowel disease (IBD) newly diagnosed by colonoscopy. MATERIALS AND METHODS: Ten children (4 boys, 6 girls; mean age 14 years) with newly diagnosed Crohn's disease (n = 6) or ulcerative colitis (n = 4) were studied. Colonoscopy was performed in all of these patients. Within 24 h after colonoscopy, they underwent scintigraphy with (99m)Tc-Sulesomab. Abdominal/pelvic images were acquired at 30 min (planar) and 2-4 h (planar and SPECT) after injection of Sulesomab. Eighty bowel segments were evaluated semi-quantitatively by the investigators, using these three sets of images. The Pediatric Disease Activity (PDA) was correlated with the erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, albumin, Kirschner's score, the Sulesomab bowel segment with maximum uptake, and the sum of Sulesomab score in each segment. RESULTS: The median PDA score was 26 (range 12.5-40). Three children had normal ESR and six normal WBC counts. All patients had at least one positive mucosal biopsy for IBD. While using the Kirschner's scale, the maximal severity of colonoscopy findings was graded as none (n = 2), mild (n = 4), moderate (n = 3), or severe (n = 1). Of the 59 segments evaluated with endoscopy, 35 were found to be endoscopically abnormal. The planar images identified 17 of these abnormal segments and the SPECT images 20. Nine of these ten children had abnormal bowel uptake by scintigraphy. Thus, the sensitivity of Sulesomab per patient was 90 % and per bowel segment 57 %. The correlation coefficient between the scintigraphic score for the segment with the Sulesomab maximum activity and the PDA was 0.3 (P = 0.41). CONCLUSION: In pediatric IBD assessment, planar imaging with Sulesomab did not prove very sensitive in detecting inflammation in each bowel segment. However, SPECT detected the presence of inflammation in the majority of patients. A trial comparing (99m)Tc-HmPAO-WBC with Sulesomab in a large number of patients is required.

Antibodies, Monoclonal↗
PubMed2001

Cost-analysis of gym-based versus home-based cardiac rehabilitation programs.

A cost-analysis of an existing gym-based program was compared with a proposed home-based program for delivering cardiac rehabilitation services in West Moreton, Queensland. Cost and baseline data were collected on 95 cardiac rehabilitation patients living in Ipswich and West Moreton. Cost data included costs to the program funders and patients. The average cost per patient rehabilitated was $1,933 in the gym-based program and $1,169 in the home-based program. Adopting the lower cost home-based program would allow the services to be provided to many more patients. The relevance of home-based rehabilitation programs for rural patients facing barriers accessing traditional hospital- or gym-based programs is significant.

Cardiac Rehabilitation↗
PubMed2001

Small-dose selective spinal anaesthesia for short-duration outpatient gynaecological laparoscopy: recovery characteristics compared with propofol anaesthesia.

A randomized controlled trial compared recovery characteristics after selective spinal anaesthesia (SSA) or propofol general anaesthesia (GA) for short-duration outpatient laparoscopic surgery. Forty women were randomized to receive either SSA (1% lidocaine 10 mg, sufentanil 10 microg and sterile water 1.8 ml) or GA (propofol and nitrous oxide 50% in oxygen). Compared with the GA group, times to leaving the operating room, performing a straight leg raise, performing deep knee-bends and achieving an Aldrete score >9 and the time in Phase II recovery were significantly shorter (P < 0.05) in the SSA group.

Ambulatory Surgical Procedures↗
PubMed2000

Efficient gene delivery to vascular smooth muscle cells using a nontoxic, synthetic peptide vector system targeted to membrane integrins: a first step toward the gene therapy of chronic rejection.

BACKGROUND: Chronic rejection is now the major cause of allograft failure. A prominent characteristic of the histopathology is extensive intimal proliferation of vascular smooth muscle cells. Targeting vascular smooth muscle cells by gene therapy techniques offers a possible avenue for arresting or reversing chronic rejection. Defining suitable non-viral DNA vectors for this application is the objective of this study. METHODS: A 31 amino acid synthetic peptide has been evaluated as a DNA vector for primary cultures of vascular smooth muscle cells of man, rabbit, and rat. The vector comprises a 15 amino acid integrin-binding domain and a chain of 16 lysines for electrostatic binding of DNA. Three agents known to promote exit of vector/DNA complexes from endocytic vesicles were studied systematically to define optimal, non-toxic conditions for gene delivery. RESULTS: Initial binding studies on frozen sections showed that the integrin-binding domain binds strongly to vascular smooth muscle cells in all three species, thereby establishing vascular smooth muscle cells as a potential target for this receptor-targeted DNA vector system. Primary cultures of vascular smooth muscle were therefore studied. The use of chloroquine to assist endocytic exit, which works well on immortalized cell lines, was of little value because of toxicity to the primary vascular smooth muscle cells. The addition of cationic lipids to polylysine-molossin/DNA conjugates gave excellent reporter gene expression, but required mildly toxic doses of cationic lipid, and resulted in some loss of integrin specificity of the vector system. The optimal system involved the use of the amino terminal 20 amino acids of the hemagglutinin of the influenza virus. This peptide, when added to polylysine-molossin/DNA complexes at an optimal w/w ratio of 5:1:2 (polylysine-molossin/DNA/fusogenic peptide) resulted in 25-30% transfection of vascular smooth muscle cells with good levels of gene expression and no toxicity. CONCLUSION: This represents an effective and safe DNA vector, comprised entirely of small synthetic peptides, and therefore readily standardized for clinical and experimental application.

Animals↗
PubMed2000

Tissue-binding properties of a synthetic peptide DNA vector targeted to cell membrane integrins: a possible universal nonviral vector for organ and tissue transplantation.

BACKGROUND: Gene delivery through a nonviral, receptor-mediated system widely expressed in transplanted tissue would have important advantages in transplantation, where gene delivery is performed ex vivo. Integrins are widely expressed cell surface receptors and can be targeted for gene delivery. METHODS: A synthetic 31 amino acid DNA vector (polylysine-molossin) comprising a 15-amino acid moiety for targeting cellular integrins (derived from the snake venom, molossin) and a 16-amino acid polylysine moiety for DNA-binding, has been evaluated. The 31-amino acid vector, as well as its separate 15-amino acid integrin-binding and (lys)16 components, were individually synthesized, and a monoclonal antibody was raised to the molossin peptide for these studies. Binding to cell lines and tissue sections and capacity for gene delivery were examined. RESULTS: Flow cytometric studies with the ECV304 cell line demonstrated that the binding of polylysine-molossin and polylysine-molossin/DNA complexes involved both electrostatic and integrin-mediated interactions with the cells, with the electrostatic binding being sufficient for maximal binding. However, binding to cellular integrins was essential for successful gene transfer. Binding studies on frozen tissue sections of the rat and pig demonstrated that the molossin peptide bound to many cell types of interest in transplantation, but not to all. Among the negative tissues were vascular endothelium and pancreatic islets. Small species differences in tissue binding were noted between the rat and pig. CONCLUSIONS: This study defines the cooperative nature of the binding of this vector system to target cells and establishes the cell types most likely to be effectively targeted for DNA transfer.

Antineoplastic Agents↗
PubMed2000

In vitro investigation of factors important for the delivery of an integrin-targeted nonviral DNA vector in organ transplantation.

BACKGROUND: Polylysine-molossin is a 31 amino acid synthetic peptide that has previously been demonstrated to function as a DNA vector in vitro for cell lines and for the cornea. It incorporates the 15 amino acid integrin-binding domain of the venom of the American pit viper, Crotalus molossus molossus as the targeting moiety and a chain of 16 lysines as the DNA-binding moiety. The objective of this study was to evaluate several parameters of importance for in vivo applications. METHODS: Binding and tissue distribution of the vector/DNA complexes were followed by a monoclonal antibody to the vector, or by the use of fluorescein-labeled DNA. Standard in vitro transfections were used to monitor effective gene transfer. RESULTS: (1) Optimal DNA/vector concentration. Saturation of vector/DNA binding sites on the ECV304 cell line occurred at 6 microg/ml of DNA. The concentration of vector/DNA complexes required for optimal gene transfection was found to be 2-8 microg/ml of DNA, corresponding to the concentration needed for saturation binding. (2) Optimal target cell exposure time. Vector/ DNA complexes saturated target cell binding sites within 5 min of incubation. However, lengthy exposure times (>2-3 hr) to the transfection medium were essential for substantial gene transfer. This was a consequence of two complementary factors. First, it was important that target cells be exposed to vector/DNA complexes for approximately 1 hr at 37 degrees C. Saturation of target sites at 4 degrees C and then removal of the transfection medium was much less effective. Second, exposure to chloroquine for 8-10 hr after uptake of vector/DNA complexes was essential for optimal gene transfer. (3) Inhibitory effects of serum. Exposure of complexes to even 1% serum before transfection, markedly inhibited gene transfer. However, target cells previously saturated with vector/DNA complexes and then exposed to 10% serum showed substantial gene transfer. (4) Extravasation and binding stability in vivo. Cold ex vivo perfusion of rat hearts with vector/DNA complexes demonstrated that little, if any, complex moved out of the vascular system. After transplantation of the heart, most of the complex bound to the vasculature was lost within 30 min of reestablishing the blood circulation. CONCLUSIONS: Careful attention to several parameters of little importance in vitro need to be paid for optimal in vivo application of DNA vector systems.

Cold Temperature↗