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1.
Int J Psychophysiol ; 98(1): 95-111, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26166440

ABSTRACT

Whilst a number of previous studies have been conducted in order to investigate functional brain changes associated with eyes-closed meditation techniques, there is a relative scarcity in the literature with regards to changes occurring during eyes-open meditation. The current project used magnetoencephalography (MEG) to investigate differences in spectral power and functional connectivity between 11 long-term mindfulness meditators (LTMMs) with >5 years of experience and 12 meditation-naïve control participants both during baseline eyes-open rest and eyes-open open-monitoring (OM) mindfulness meditation. During resting with eyes-open, prior to meditating, greater mean alpha power was observed for LTMMs in comparison to controls. However, during the course of OM meditation, a significantly greater increase in theta power was observed over a broad fronto-centro-parietal region for control participants in comparison to LTMMs. In contrast, whole-head mean connectivity was found to be significantly greater for long-term meditators in comparison to controls in the theta band both during rest as well as during meditation. Additionally, mean connectivity was significantly lower for long-term meditators in the low gamma band during rest and significantly lower in both low and high gamma bands during meditation; and the variance of low-gamma connectivity scores for long-term meditators was significantly decreased compared to the control group. The current study provides important new information as to the trait functional changes in brain activity associated with long-term mindfulness meditation, as well as the state changes specifically associated with eyes-open open monitoring meditation techniques.


Subject(s)
Brain Mapping , Brain Waves/physiology , Brain/physiology , Mindfulness/methods , Anxiety/physiopathology , Anxiety/rehabilitation , Cluster Analysis , Electroencephalography , Eye , Female , Fourier Analysis , Humans , Longitudinal Studies , Magnetoencephalography , Male , Middle Aged , Rest , Surveys and Questionnaires
2.
Eur J Neurosci ; 39(8): 1363-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24528168

ABSTRACT

Stop-signal paradigms operationalize a basic test of goal-directed behaviour whereby an overarching stop goal that is performed intermittently must be maintained throughout ongoing performance of a reaction time go task (go goal). Previous studies of sustained brain activation during stop-signal task performance in humans did not observe activation of the dorsolateral prefrontal cortex (DLPFC) that, in concert with the parietal cortex, is known to subserve goal maintenance. Here we explored the hypothesis that a DLPFC and parietal network has a key role in supporting ongoing stop-signal task performance. We used a blocked functional magnetic resonance imaging design that included blocks of trials containing typical stop-signal paradigm stimuli that were performed under three conditions: Stop condition, which required reaction time responding to go stimuli and inhibition of cued responses upon presentation of a stop signal; Go condition, identical except that the tone was ignored; and Passive condition, which required only quiescent attention to stimuli. We found that, whereas a distributed corticothalamic network was more active in Stop compared with Go, only the right DLPFC and bilateral parietal cortex survived after masking that contrast with Stop compared with Passive. These findings indicate that sustained activation of a right dominant frontoparietal network supports stop goal processes during ongoing performance of the stop-signal task.


Subject(s)
Brain Mapping , Parietal Lobe/physiology , Prefrontal Cortex/physiology , Psychomotor Performance , Adult , Female , Goals , Humans , Male
3.
J Evol Biol ; 26(11): 2359-68, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24016035

ABSTRACT

Evolutionary change in the timing of dormancy enables animals and plants to adapt to changing seasonal environments and can result in ecological speciation. Despite its clear biological importance, the mechanisms underlying the evolution of dormancy timing in animals remain poorly understood because of a lack of anatomical landmarks to discern which phase of dormancy an individual is experiencing. Taking advantage of the nearly universal characteristic of metabolic suppression during insect dormancy (diapause), we use patterns of respiratory metabolism to document physiological landmarks of dormancy and test which of the distinct phases of the dormancy developmental pathway contribute to a month-long shift in diapause timing between a pair of incipient moth species. Here, we show that divergence in life cycle between the earlier-emerging E-strain and the later-emerging Z-strain of European corn borer (ECB) is clearly explained by a delay in the timing of the developmental transition from the diapause maintenance phase to the termination phase. Along with recent findings indicating that life-cycle differences between ECB strains stem from allelic variation at a single sex-linked locus, our results demonstrate how dramatic shifts in animal seasonality can result from simple developmental and genetic changes. Although characterizing the multiple phases of the diapause developmental programme in other locally adapted populations and species will undoubtedly yield surprises about the nature of animal dormancy, results in the ECB moth suggest that focusing on genetic variation in the timing of the dormancy termination phase may help explain how (or whether) organisms rapidly respond to global climate change, expand their ranges after accidental or managed introductions, undergo seasonal adaptation, or evolve into distinct species through allochronic isolation.


Subject(s)
Biological Evolution , Moths/physiology , Seasons , Torpor , Adaptation, Physiological , Animals , Energy Metabolism , Moths/growth & development , Time Factors
4.
Int J STD AIDS ; 23(3): 182-4, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22581871

ABSTRACT

Implementing HIV voluntary counselling and testing (VCT) in bathhouses is a proven public health strategy for reaching high-risk men who have sex with men (MSM) and efficiently identifying new HIV cases. However, some bathhouse managers are concerned that VCT programmes could adversely affect business. This study examined whether offering VCT on the premises of a bathhouse changed patterns of patron visits. A collaborating bathhouse provided electronic anonymized patron data from their entire population of attendees. VCT was offered on premises with varying frequencies over the course of three years. Club entrances and exits were modelled as a function of intensity of VCT programming. Club entrances did not differ as a function of how many days per week testing was being offered in a given month. Additionally, club entrances did not decrease, nor did club exits increase, during specific half-hour time periods when testing was offered. Implementing bathhouse-based VCT did not have any demonstrable impact on patronage. Public health officials can leverage these results to help alleviate club managers' concerns about patron reactions to providing testing on site, and to support expanding sexual health programmes for MSM in these venues.


Subject(s)
Clinical Laboratory Techniques/methods , Counseling/methods , HIV Infections/diagnosis , HIV Infections/prevention & control , Homosexuality, Male , Mass Screening/methods , Public Facilities , Health Services Research , Humans , Male , Steam Bath
5.
Tech Coloproctol ; 14(2): 113-23, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20422436

ABSTRACT

BACKGROUND: A meta-analysis of published literature comparing J-pouch with side to end anastomosis after anterior resection (AR) for rectal cancer. METHODS: Electronic databases were searched from January 1980 to March 2009. A systematic review was performed to obtain a summative outcome. RESULTS: Four randomized controlled trials involving 273 patients were analysed. One hundred and thirty-eight patients were in the J-pouch and 135 in the side to end anastomosis (STEA) group. No significant difference in surgically related outcomes was established (hospital stay, operative time, estimated blood loss, overall morbidity and mortality). Resting pressures at 24 months post-operatively were lower in J-pouch group compared with STEA and approached statistical significance [random effects model: SMD = -1.23, 95% CI (-2.47, -0.01), z = -1.94, P = 0.053]. No statistical difference was found in volumetric parameters (Volume at which the patient first experiences a sensation to defaecate and maximal tolerable volume). No statistical difference except urgency at 6 months [P < 0.05] was elicited in functional outcomes (use of enemas, bowel medications, pads, incomplete defaecation and stool frequency) between J-pouch and STEA groups. CONCLUSIONS: J-pouch or STEA are acceptable and safe options after AR for rectal cancer. Either approach may be considered according to surgeon choice. A randomized controlled trial including a larger number of patients is required to strengthen the evidence.


Subject(s)
Anastomosis, Surgical/methods , Colonic Pouches , Proctocolectomy, Restorative , Rectal Neoplasms/surgery , Humans , Rectal Neoplasms/pathology , Rectal Neoplasms/physiopathology , Treatment Outcome
6.
Int J STD AIDS ; 21(1): 19-22, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20029062

ABSTRACT

HIV prevalence estimates from bathhouse testing programmes differ widely, ranging from 3% to 11%. The observed difference may be a consequence of whether the programme was part of a research project or a community-based programme. A research-funded testing programme was offered at a bathhouse between May 2001 and December 2002. A local community-based organization began a testing programme in July 2006 at the same bathhouse; the data for this analysis cover the period July 2006 through December 2007. County-wide HIV prevalence estimates were available across the two time periods (i.e. 2001-2002 and 2006-2007). The research-funded testing programme recruited fewer men but identified more positive individuals (10.7% of those testing in the research programme) than were identified among men who tested in the area clinics (3.8% of those men who have sex with men [MSM] testing throughout the county in the same time period). However, the community-based testing programme identified about the same proportion of positive MSM (2.6%) as county clinics (2.7%) in the same time period. In conclusion, results confirmed that even in the same venue, a community-based HIV testing programme identified a similar proportion of positive MSM as the area clinics; however, the research-funded programme identified appreciably more. Incentives may contribute to the difference.


Subject(s)
AIDS Serodiagnosis/statistics & numerical data , Delivery of Health Care/statistics & numerical data , HIV Infections/diagnosis , Program Evaluation , California/epidemiology , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , Prevalence , Risk Factors
7.
J Vet Pharmacol Ther ; 32(3): 271-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19646092

ABSTRACT

Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injured and control horses. The possible role of anti-inflammatory agents in musculoskeletal injuries of Thoroughbred race horses was investigated by comparing the apparent concentrations of NSAIDs in injured horses to concentrations in control horses. The plasma concentrations of phenylbutazone and flunixin were higher in injured horses than in control horses. Most injured and control horses did not have a detectable level of naproxen in their plasma samples. Further studies must be carried out to determine whether horses with higher plasma concentrations of NSAIDs have an altered risk of musculoskeletal injuries compared with other horses.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/blood , Athletic Injuries/veterinary , Horses/blood , Horses/injuries , Musculoskeletal System/injuries , Animals , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Athletic Injuries/blood , Athletic Injuries/epidemiology , Case-Control Studies , Chromatography, High Pressure Liquid/veterinary , Euthanasia, Animal , Kentucky/epidemiology , Phenylbutazone/adverse effects , Phenylbutazone/blood , Risk Factors , Sports
8.
Acta Chir Belg ; 109(1): 98-100, 2009.
Article in English | MEDLINE | ID: mdl-19341206

ABSTRACT

BACKGROUND: Retroperitoneal abscess, extending to the groin as an isolated tender lump, is rare as the first manifestation of Crohn's disease. CASE PRESENTATION: This report describes a young, fit and healthy 22 year-old woman with no previous history of gastrointestinal disorder, who presented with an isolated, tender lump in her right groin as the initial presentation of Crohn's disease. The patient, after a conventional incision and drainage of the abscess, was readmitted with enterocutaneous fistula at the right groin. After radiological investigations, she underwent a laparotomy, which showed jejunal perforation through ileocaecal mesentery producing retrocaecal abscess. There was also a suspicious fistulous connection between jejunum and ileo-caecal junction. A segmental small bowel resection and a limited right hemicolectomy with primary anastomoses were performed. The patient made an uneventful post-operative recovery and was discharged home on the fifth post operative day. CONCLUSION: Crohn's disease could manifest as an isolated, tender groin lump which has not been described in the published literature so far. Since retroperitoneal abscess remains a rare but serious complication of Crohn's disease, aggressive operative therapy should be ensued without delay in order to remove the source of the abscess. Groin abscess could conceal surprises and should always be investigated radiologically before proceeding to incision and drainage.


Subject(s)
Crohn Disease/complications , Crohn Disease/diagnosis , Psoas Abscess/etiology , Colectomy/methods , Crohn Disease/surgery , Female , Groin , Humans , Intestinal Fistula/etiology , Intestinal Fistula/surgery , Magnetic Resonance Imaging , Psoas Abscess/surgery , Retroperitoneal Space , Young Adult
9.
J Vet Pharmacol Ther ; 32(1): 66-78, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19161458

ABSTRACT

Pyrilamine is an antihistamine used in human and veterinary medicine. As antihistamines produce central nervous system effects in horses, pyrilamine has the potential to affect the performance of racehorses. In the present study, O-desmethylpyrilamine (O-DMP) was observed to be the predominant equine urinary metabolite of pyrilamine. After intravenous (i.v.) administration of pyrilamine (300 mg/horse), serum pyrilamine concentrations declined from about 280 ng/mL at 5 min postdose to about 2.5 ng/mL at 8 h postdose. After oral administration of pyrilamine (300 mg/horse), serum concentrations peaked at about 33 ng/mL at 30 min, falling to <2 ng/mL at 8 h postdose. Pyrilamine was not detected in serum samples at 24 h postdosing by either route. After i.v. injection of pyrilamine (300 mg/horse) O-DMP was recovered at a level of about 20 microg/mL at 2 h postdose thereafter declining to about 2 ng/mL at 168 h postdose. After oral administration, the O-DMP recovery peaked at about 12 microg/mL at 8 h postdose and declined to <2 ng/mL at 168 h postdose. These results show that pyrilamine is poorly bioavailable orally (18%), and can be detected by sensitive enzyme-linked immunosorbent assay tests in urine for up to 1 week after a single administration. Care should be taken as the data suggest that the withdrawal time for pyrilamine after repeated oral administrations is likely to be at least 1 week or longer.


Subject(s)
Histamine H1 Antagonists/pharmacokinetics , Horses/metabolism , Pyrilamine/analogs & derivatives , Pyrilamine/pharmacokinetics , Administration, Oral , Animals , Biological Availability , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/veterinary , Female , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/blood , Histamine H1 Antagonists/metabolism , Horses/blood , Horses/urine , Injections, Intravenous/veterinary , Pyrilamine/administration & dosage , Pyrilamine/blood , Pyrilamine/metabolism , Pyrilamine/urine , Random Allocation
10.
Acta Chir Belg ; 108(4): 460-1, 2008.
Article in English | MEDLINE | ID: mdl-18807604

ABSTRACT

AIM: To discuss an unusual and rare complication of perforated caecal volvulus (CV) following open anterior resection. METHODS: A retrospective review of the case notes of a patient. RESULTS: CV is a well known but rare cause of bowel obstruction. Chronic constipation, distal colonic obstruction and post-operative ileus are potentially aggravating factors for the development of CV in anatomically susceptible patients. The anatomical susceptibility for CV was noticed during the first operation but prophylactic caecopexy was not performed due to lack of evidence in the literature. This patient developed CV after anterior resection and subsequently underwent a second laparotmy for right hemicolectomy. CONCLUSION: CV is a known but rare case of postoperative bowel obstruction. The role of prophylactic caecopexy could be discussed in order to avoid the development of postoperative CV in anatomically susceptible patients.


Subject(s)
Adenocarcinoma/surgery , Cecal Diseases/etiology , Colectomy/adverse effects , Colorectal Neoplasms/surgery , Intestinal Perforation/etiology , Intestinal Volvulus/etiology , Postoperative Complications , Adenocarcinoma/diagnosis , Cecal Diseases/diagnosis , Colonoscopy , Colorectal Neoplasms/diagnosis , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Ileostomy/methods , Intestinal Perforation/diagnosis , Intestinal Volvulus/diagnosis , Laparotomy/methods , Middle Aged , Rupture, Spontaneous , Tomography, X-Ray Computed
11.
Colorectal Dis ; 10(4): 352-6, 2008 May.
Article in English | MEDLINE | ID: mdl-17645570

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the effectiveness of the internet as a source of information for colorectal cancer (CRC). METHOD: Six of the most common search engines (Yahoo, Google, MSN search, Alta Vista, Excite and Lycos) were used for the search of the generic term 'CRC'. First 300 links were analysed and classified by information type, provider, readership and commercial orientation. RESULTS: The average time delay was 1.70 s before matches were located. A total of 3.2827 million matches on CRC were found using the six search engines ranging from 700 (Excite) to 1 417 000 (Lycos) websites. Approximately 50% of the links were based on information from textbooks or governmental websites. Commercial companies giving information about private hospitals and products provided over 50% of the websites on CRC. The distribution of target readers was uneven, although a majority of websites were delivering CRC information to public and patients. Readability of information was difficult to comprehend by the public. CONCLUSION: The internet is becoming an essential tool for disseminating information about CRC to consumers. Half of the links on CRC are commercially oriented, containing information on goods or private health services. Less than 1% information is being provided by professional societies. To provide relevant CRC information, key consensus criteria for evaluating healthcare-related websites have to be established. There is an urgent need for CRC information on the internet to be regulated through the establishment of government-funded organizations (e.g. NHS) or professional societies (e.g. ACPGBI).


Subject(s)
Advertising , Colorectal Neoplasms , Information Services , Internet/standards , Patient Education as Topic , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/therapy , Consumer Advocacy , Disclosure , Humans , Information Dissemination , Quality Control
12.
Bone Marrow Transplant ; 40(4): 313-8, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17563741

ABSTRACT

In Children's cancer group (CCG) 2891, newly diagnosed patients with AML were randomized between standard and intensive timing induction therapies. Patients in first remission who lacked an HLA matched family donor were randomized between an autologous bone marrow transplantation (ABMT) where marrow was purged with 4 hydroperoxycyclophosphamide and consolidation chemotherapy. One hundred and thirty seven patients received an ABMT. Myeloid and platelet engraftment occurred at a median of 44 and 42 days, respectively. Disease-free survival (DFS), relapse-free survival and overall survival at 8 years post induction were 47% (95% confidence interval (CI): 38-55), 50% (CI: 42-59) and 55% (CI: 46-63), respectively. Multivariate analysis of DFS showed WBC <50 000/microl and having received intensively timed induction therapy were associated with improved DFS. Recipients who received intensive timed induction therapy and whose WBC was less than 50 000/microl had a DFS at 8 years of 62% (CI: 49-73). Conversely, recipients who received intensive timed induction therapy patients whose WBC was > or =50 000/microl had a DFS of 33% (CI: 17-50), P=0.003. The results confirm previous studies that ABMT is effective post remission therapy for pediatric patients with AML in first remission.


Subject(s)
Bone Marrow Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Remission Induction/methods , Adolescent , Adult , Bone Marrow Transplantation/adverse effects , Child , Child, Preschool , Disease-Free Survival , Female , Graft Survival , Humans , Infant , Male , Prospective Studies , Transplantation Conditioning/methods , Transplantation, Autologous
13.
Ann R Coll Surg Engl ; 89(3): 229-32, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17394704

ABSTRACT

INTRODUCTION: The aim of this work was to assess the effect of intermittent bupivacaine infusion into rectus sheath space on postoperative opioid requirement, postoperative pain score and peak expiratory flow rate. PATIENTS AND METHODS: A prospective, randomised study involving patients undergoing midline laparotomy. Patients were randomised to receive either intermittent infusion of bupivacaine 0.25% or normal saline via catheters placed in the rectus sheath for 48 h after operation. All patients received intravenous morphine infusion on demand with a patient-controlled analgesic device (PCAD). RESULTS: Forty ASA I-III patients were studied. Nineteen were randomised to receive bupivacaine and 21 patients received normal saline. Patient characteristics and surgical variables were comparable in the two groups. The mean wound lengths were similar. There was no statistically significant difference in postoperative opioid requirement, postoperative pain score and peak expiratory flow rate between the two groups. CONCLUSIONS: Intermittent bupivacaine infusion into the rectus sheath space after midline laparotomy does not reduce postoperative opioid requirement nor does it affect postoperative pain score or peak expiratory flow rate.


Subject(s)
Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Morphine/administration & dosage , Pain, Postoperative/prevention & control , Aged , Analgesia, Patient-Controlled , Anesthesia, Rectal , Female , Humans , Infusions, Intralesional , Infusions, Intravenous , Laparotomy/methods , Male , Pain Measurement , Pain, Postoperative/etiology , Pain, Postoperative/physiopathology , Peak Expiratory Flow Rate/drug effects , Prospective Studies
14.
J R Soc Interface ; 4(13): 257-69, 2007 Apr 22.
Article in English | MEDLINE | ID: mdl-17251157

ABSTRACT

In this paper, we examine the mechanical properties of muscles in a soft-bodied arthropod under both passive and stimulated conditions. In particular, we examine the ventral interior lateral muscle of the tobacco hornworm caterpillar, Manduca sexta, and show that its response is qualitatively similar to the behaviour of particle-reinforced rubber. Both materials are capable of large nonlinear elastic deformations, show a hysteretic behaviour and display stress softening during the first few cycles of repeated loading. The Manduca muscle can therefore be considered as different elastic materials during loading and unloading and is best described using the theory of pseudo-elasticity. We summarize the basic equations for transversely isotropic pseudo-elastic materials, first for general deformations and then for the appropriate uniaxial specialization. The constitutive relation proposed is in good agreement with the experimental data for both the passive and the stimulated conditions.


Subject(s)
Computer Simulation , Manduca/physiology , Models, Biological , Muscle Contraction/physiology , Rubber/chemistry , Animals , Biomechanical Phenomena , Elasticity
15.
Int J STD AIDS ; 16(9): 600-4, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16176625

ABSTRACT

The aim of this study was to examine the meaning of significantly higher proportions of positive test results through outreach HIV/sexually transmitted infection testing programmes at gay bathhouses compared with clinic programmes among high-risk men who have sex with men. We conducted a random digit dial survey of men who have sex with men in New York, Los Angeles, Chicago, and San Francisco. Half of the men in the sample did not test in the past year. Among those who did not test, a sizeable minority (17%) reported engaging in high-risk sexual behaviour with a casual or secondary partner. Over half of these non-testing, high-risk men went to bathhouses. These findings strongly support the potential value of locating outreach-testing programmes in bathhouses. Although further studies are necessary, such programmes have the potential to increase testing among the high-risk segment of the population. This is particularly noteworthy given that many men among those who do not test regularly engage in high-risk behaviours.


Subject(s)
AIDS Serodiagnosis , HIV Infections/diagnosis , Homosexuality, Male , Risk-Taking , Sexual Behavior , Sexually Transmitted Diseases/diagnosis , Adolescent , Adult , Ambulatory Care , Baths , Data Collection , Humans , Male , Middle Aged , Unsafe Sex
16.
Br J Anaesth ; 95(5): 634-42, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16155038

ABSTRACT

BACKGROUND: Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements. Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay. We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery. METHODS: This single centre, blinded, prospective controlled trial randomized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based (conventional) intraoperative fluid management. The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aiming for a CVP between 12 and 15 mm Hg. RESULTS: The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05. The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001. Doppler patients achieved significantly higher cardiac output, stroke volume, and oxygen delivery. Twenty-nine (45.3%) control patients suffered gastrointestinal morbidity compared with nine (14.1%) in the Doppler guided fluid group P<0.001, overall morbidity was also significantly higher in the control group P=0.05. CONCLUSIONS: Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay. Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity.


Subject(s)
Fluid Therapy/methods , Hypovolemia/prevention & control , Intestine, Large/surgery , Intraoperative Care/methods , Intraoperative Complications/prevention & control , Adult , Aged , Algorithms , Central Venous Pressure , Double-Blind Method , Echocardiography, Transesophageal/methods , Female , Humans , Hypovolemia/diagnostic imaging , Intestine, Large/physiopathology , Intraoperative Complications/diagnostic imaging , Length of Stay , Male , Middle Aged , Monitoring, Intraoperative/methods , Prospective Studies , Recovery of Function , Stroke Volume
17.
Leukemia ; 19(12): 2054-62, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16136168

ABSTRACT

The Children's Cancer Group (CCG) conducted three Phase III prospective clinical trials for children with de novo acute myeloid leukemia between the years 1979 and 1995. A total of 1903 eligible children ages birth to 21 years of age were enrolled on CCG 251 (n=485), CCG 213 (n=532) and CCG 2891 (n=886). Follow-up is ongoing, with medians of 7.9, 10.9 and 8.6 years, respectively. These three clinical trials developed dose- and time-intensive induction regimens based upon high-dose cytarabine and daunomycin and randomly assigned patients to allogeneic bone marrow transplantation in first remission if an HLA-matched related donor was identified. Despite dose- and time-intensive induction regimens, remission induction rates remained relatively stable at 77-78%. However, overall survival, event-free survival and disease-free survival (DFS) increased for patients receiving intensive-timing induction therapy in comparison to patients who received standard-timing induction, regardless of the type of postremission therapy. Outcomes were best for patients receiving intensive-timing induction followed by matched related donor allogeneic transplantation with DFS of 65+/-9% at 6 years. These three clinical trials have established a strong foundation for the development of future studies focusing on further risk group stratification and the development of novel, molecularly-targeted therapies.


Subject(s)
Antineoplastic Protocols/standards , Leukemia, Myeloid/therapy , Acute Disease , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation , Child , Child, Preschool , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Leukemia, Myeloid/mortality , Male , Remission Induction/methods , Survival Analysis
18.
Leuk Lymphoma ; 46(5): 651-63, 2005 May.
Article in English | MEDLINE | ID: mdl-16019502

ABSTRACT

Treatment-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) is a devastating complication of treatment for childhood cancer. However, the major cause of premature death of children treated for cancer remains their primary cancer. The understanding of the presentation, incidence, predisposing risk factors and pathobiology of t-MDS/t-AML is increasing. This increased understanding has not yet been translated into improved outcomes of therapy for t-MDS/t-AML. However, newer approaches are under study.


Subject(s)
Leukemia, Myeloid/etiology , Myelodysplastic Syndromes/etiology , Neoplasms, Second Primary/etiology , Acute Disease , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Female , Humans , Leukemia, Myeloid/chemically induced , Male , Myelodysplastic Syndromes/chemically induced , Neoplasms/therapy , Neoplasms, Second Primary/chemically induced , Neoplasms, Second Primary/genetics , Survivors
19.
Prep Biochem Biotechnol ; 35(2): 119-34, 2005.
Article in English | MEDLINE | ID: mdl-15881594

ABSTRACT

The cancer-testis antigen, NY-ESO-1, has been engineered into a bacterial expression plasmid which incorporates a His6-tag. The plasmid was transfected into E. coli strain BL21 and Master and Working cell banks generated from this expression system. Three 15-litre fermentations were performed under cGMP (code of Good Manufacturing Practice) conditions and the crude NY-ESO-1 tagged protein isolated as solubilised inclusion bodies. A three-step cGMP chromatography process (immobilised metal affinity, anion exchange, and hydrophobic interaction) was utilised to purify the protein. The purified NY-ESO-1 is being used in early stage human cancer vaccine trials in Australia and the U.S.A.


Subject(s)
Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/isolation & purification , Cancer Vaccines/biosynthesis , Cancer Vaccines/isolation & purification , Membrane Proteins/biosynthesis , Membrane Proteins/isolation & purification , Protein Engineering/methods , Antigens, Neoplasm/genetics , Antigens, Neoplasm/therapeutic use , Australia , Cancer Vaccines/genetics , Drug Industry/standards , Guidelines as Topic , Humans , Membrane Proteins/genetics , Membrane Proteins/therapeutic use , Protein Engineering/standards , Quality Assurance, Health Care/standards , Recombinant Proteins/biosynthesis , Recombinant Proteins/isolation & purification , Reference Standards
20.
Leukemia ; 19(6): 965-70, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15830007

ABSTRACT

We reviewed consolidation therapy results and analyzed postremission outcomes for 1464 children less than 21 years old at diagnosis in five consecutive Children's Cancer Group acute myeloid leukemia trials between 1979 and 1996. Children in remission were allocated to allogeneic bone marrow transplantation (BMT) (N=373) in first remission, if a matched family donor was available. Remaining children were assigned consolidation chemotherapy (N=688) or autologous purged BMT (N=217), or withdrew from study before assignment, or with unknown data (N=186). Overall and disease-free survival were superior for children assigned allogeneic transplants. High (>50,000/microl) diagnostic white blood cell (WBC) count was prognostic for inferior outcome, but French-American-British (FAB) subtypes were not. Inv(16) is a favorable karyotypic feature for children in first remission and t(8;21) is not. Allogeneic transplantation benefit was evident in most children, including those with high or low diagnostic WBC count, each FAB subtype, and t(8;21), but was not seen in children with inv(16). Therefore, these data suggest reserving matched related donor allogeneic transplantation for children with inv(16) for second remission, but not those with t(8;21).


Subject(s)
Antineoplastic Agents/therapeutic use , Bone Marrow Transplantation , Leukemia, Myeloid/mortality , Leukemia, Myeloid/therapy , Acute Disease , Child , Combined Modality Therapy , Humans , Karyotyping , Leukemia, Myeloid/genetics , Outcome Assessment, Health Care , Prognosis , Remission Induction , Survival Analysis , Transplantation, Autologous
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