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PubMed2006

Detection of Anaplasma platys and Babesia canis vogeli and their impact on platelet numbers in free-roaming dogs associated with remote Aboriginal communities in Australia.

OBJECTIVE: To detect Anaplasma platys and Babesia canis vogeli infection, using polymerase chain reaction (PCR)-based assays, in free-roaming dogs associated with eight Aboriginal communities in remote areas of Australia and to determine the impact of infection through the assessment of platelet numbers. PROCEDURES: Blood samples from 215 dogs were screened by PCR for A platys and B canis vogeli using established genus-specific DNA primers for the 16S and 18S rRNA genes respectively. Both A platys DNA and B canis vogeli DNA were confirmed from the screening PCR either by sequencing or by the use of species-specific primers. Peripheral blood films from 92 of the 215 dogs were used to estimate platelet numbers through an indirect method. RESULTS: Of 215 dogs, 69 (32%) were positive for A platys, 22 (10%) for B canis vogeli and 24 (11%) for both. The two organisms were detected singularly and as coinfection in all communities. For the 92 dogs in which peripheral blood films were examined, the mean estimated platelet counts for the non-infected dogs was 318 x 10(9)/L, those infected with A platys alone was 256 x 10(9)/L, those with B canis vogeli alone was 276 x 10(9)/L and those infected with both parasites was 169 x 10(9)/L. In young dogs, infection produced significantly decreased mean platelet counts when compared to uninfected dogs. Thrombocytopenia (< 200 x 10(9)/L) was detected in 18 (51%) dogs infected with A platys alone, 3 (33%) dogs infected with B canis vogeli alone, 13 (72%) dogs coinfected, and 8 (27%) uninfected dogs. CONCLUSIONS: A platys and B canis vogeli infection, either singularly or together, was widespread in free roaming dogs associated with remote Aboriginal communities in the Northern Territory and north-western New South Wales. Moreover, both A platys and B canis vogeli infections were associated with a reduction in mean platelet numbers in dog populations, particularly in young dogs. The fact that 51% of dogs infected with A platys alone and 72% dogs coinfected were thrombocytopenic compared to 27% of uninfected dogs suggests that the organism alone or in combination with B canis vogeli has the potential to cause thrombocytopenia and perhaps contribute to a clinical bleeding disorder in infected dogs.

Anaplasma↗
PubMed2004

Postoperative hypoxemia exacerbates potential brain injury after deep hypothermic circulatory arrest.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA) is often used in infants undergoing the Norwood procedure. These infants are hypoxic after surgery. Previous investigations into the cerebral metabolic response and oxygen utilization after DHCA examined animals with normal arterial oxygenation. This study reports the cerebral metabolic consequences if hypoxemic conditions are present after DHCA. METHODS: Eighteen neonatal piglets were randomly assigned to three groups. The control group was ventilated; the cardiopulmonary bypass group underwent 60 minutes of normothermic cardiopulmonary bypass, and the DHCA group underwent cardiopulmonary bypass and 60 minutes of DHCA (16 degrees to 18 degrees C) followed by rewarming. Hemodynamic and cerebral perfusion data were measured at an arterial partial pressure of oxygen (PaO2) of 150 to 250 mm Hg, and then at moderate hypoxemia (PaO2, 50 to 60 mm Hg) and severe hypoxemia (PaO2, 25 to 35 mm Hg). RESULTS: Cerebral oxygen delivery decreased by 44% from PaO2 150 to 250 mm Hg to severe hypoxemia (p < 0.001). Cerebral oxygen extraction increased from moderate hypoxemia to severe hypoxemia in the control (57.9% +/- 3.7% to 71.8% +/- 3.8%; p = 0.002) and cardiopulmonary bypass groups (61.2% +/- 2.6% to 70.6% +/- 1.2%; p = 0.035); however, the cerebral oxygen extraction of the DHCA group did not increase under these conditions (82.8% +/- 1.8% to 77.9% +/- 4.3%; p = 0.32). The cerebral metabolic rate of oxygen consumption of the DHCA group decreased from PaO2 150 to 250 mm Hg to severe hypoxemia (1.86 +/- 0.20 to 0.99 +/- 0.24 mL O2 x 100 g(-1) x min(-1); p = 0.02), whereas the cerebral metabolic rate of oxygen consumption did not change under these conditions in the control and cardiopulmonary bypass groups. CONCLUSIONS: Under hypoxemic conditions cerebral metabolic rate of oxygen consumption deteriorates after DHCA. Infants exposed to DHCA may be at greater risk of brain injury when postoperative hypoxemia is present. Because maximal cerebral oxygen extraction after DHCA occurs at moderate hypoxemia, techniques that increase cerebral oxygen delivery may reduce the risk of hypoxic brain injury.

Animals↗
PubMed2003

Identification of severe acute respiratory syndrome in Canada.

BACKGROUND: Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. METHODS: SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. RESULTS: The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. CONCLUSIONS: SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation.

Adult↗
PubMed2005

Stimulation of paracrine pathways with growth factors enhances embryonic stem cell engraftment and host-specific differentiation in the heart after ischemic myocardial injury.

BACKGROUND: Growth factors play an essential role in organogenesis. We examine the potential of growth factors to enhance cell engraftment and differentiation and to promote functional improvement after transfer of undifferentiated embryonic stem cells into the injured heart. METHODS AND RESULTS: Green fluorescent protein (GFP)-positive embryonic stem cells derived from 129sv mice were injected into the ischemic area after left anterior descending artery ligation in allogenic (BALB/c) mice. Fifty nanograms of recombinant mouse vascular endothelial growth factor, fibroblast growth factor (FGF), and transforming growth factor (TGF) was added to the cell suspension. Separate control groups were formed in which only the growth factors were given. Echocardiography was performed 2 weeks later to evaluate heart function (fractional shortening [FS]), end-diastolic diameter, and left ventricular wall thickness). Hearts were harvested for histology (connexin 43, alpha-sarcomeric actin, CD3, CD11c, major histocompatability complex class I, hematoxylin-eosin). Degree of restoration (GFP-positive graft/infarct area ratio), expression of cardiac markers, host response, and tumorigenicity were evaluated. Cell transfer resulted in improved cardiac function. TGF-beta led to better restorative effect and a stronger expression of connexin 43, alpha-sarcomeric actin, and major histocompatability complex class I. TGF-beta and FGF retained left ventricular diameter. FS was better in the TGF-beta, FGF, and embryonic stem cells-only group compared with left anterior descending artery-ligated controls. Growth factors with cells (TGF-beta, FGF) resulted in higher FS and smaller end-diastolic diameter than growth factors alone. CONCLUSIONS: Growth factors can promote in vivo organ-specific differentiation of early embryonic stem cells and improve myocardial function after cell transfer into an area of ischemic lesion. TGF-beta should be considered as an adjuvant for myocardial restoration with the use of embryonic stem cells.

Animals↗
PubMed2005

Travel patterns and risk behaviour of HIV-positive people travelling internationally.

BACKGROUND: International travel is associated with an increased risk of enteric, vector-borne, sexually transmitted and blood-borne infections. These risks are even higher among immunocompromised people, such as those with HIV infection. We conducted a study to determine HIV-positive people's travel patterns and risk behaviours while abroad. METHODS: We conducted an anonymous survey of HIV-positive people attending an HIV clinic in a tertiary care hospital in Toronto about their travel activities and pretravel precautions as well as their burden of illness and risk exposure during travel. We compared the characteristics of respondents who had travelled outside Canada and the United States (international travellers) with those of respondents who had not travelled internationally. RESULTS: Of 290 HIV-positive people who participated in the study, 133 (45.9%) indicated that they had travelled internationally in the 5 years before the survey. These people were predominantly men (93.2%) and well educated (60.0% had a university level education), and they had travelled mostly for personal reasons (89.5%) on trips that lasted 3.6 weeks on average. Only 58 (43.6%) sought health advice before travelling, and only 17 (12.8%) sought advice from a travel clinic. Five (3.8%) had received live vaccines before travel, and 9 (6.8%) had taken malaria chemoprophylaxis. Of the 119 international travellers who were taking antiretroviral therapy; 35 (29.4%) reported either discontinuing their medications or being poorly compliant with the therapy while travelling. Thirty-one (23.3%) of the 133 international travellers reported having had casual sexual activity with new partners while travelling, and only 18 (58.1%) of them reported always using a condom. Twenty-one (15.8%) of the 133 reported having had risky exposure to sharps. Twenty-four (18.0%) said they had become ill enough while travelling to require medical attention. INTERPRETATION: Only one-fifth of HIV-positive people surveyed who travelled internationally sought advice from a health professional before their trip. Their travel was associated with poor adherence to antiretroviral therapy, risky sexual practices and risky exposure to sharps.

Adult↗
PubMed2006

Results of concomitant aortic valve replacement and coronary artery bypass grafting in the VA population.

BACKGROUND AND AIM OF THE STUDY: Concomitant aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) is an established risk factor for diminished postoperative survival. Results from a VA population were reviewed in order to determine factors influencing early and late survival. METHODS: Between 1993 and 2003, a total of 401 patients underwent AVR at the authors' institution. Of these patients, 249 (62%; mean age 70.6 years) had combined AVR and CABG. Surgical indications were primarily aortic valve pathology (group A: n = 168; 68%), primarily coronary artery disease (CAD) (group B: n = 55; 22%), and both severe aortic and coronary disease (group C: n = 26; 10%). In total, 177 patients (71%) received a bioprosthesis, and 72 (29%) received a mechanical valve. Short- and long-term outcomes were explored using univariate and multivariable hazard analyses. RESULTS: Overall operative mortality was 6.4%; mortality for groups A, B and C was 4.8%, 9.1% and 11.5%, respectively. On multivariable analysis, significant factors associated with early-phase mortality were NYHA class IV, diabetes, bioprosthetic valve and combined severe aortic and coronary disease. Survival at one and five years was 86% and 62%, respectively. Five-year survival for groups A, B and C was 71%, 63% and 54%, respectively. Significant associated factors for late-phase mortality were the presence of preoperative peripheral vascular disease (PVD) and cerebrovascular disease (CVD). Factors such as age, prior cardiac surgery, number of grafted coronary arteries, and/or effective orifice area index (EOAI) had no significant effect on outcome. CONCLUSION: Combined AVR/CABG is a marker for decreased survival. Pre-existing factors such as diabetes, PVD and CVD, as well as poor preoperative NYHA functional status, affected survival. Further investigation is needed to assess the influence of the severity of CAD and EOAI on survival. Thoughtful consideration of all these factors is essential for an accurate prediction of survival, and to determine the appropriate type of aortic prosthesis to be used.

Age Factors↗
PubMed2001

Mechanisms of intestinal failure in Crohn's disease.

PURPOSE: The purpose of this study was to determine the mechanisms by which patients with Crohn's disease develop intestinal failure and, in particular, to assess the relative importance of severe primary disease, repeated uncomplicated elective small intestine resection, and resection performed as a consequence of intra-abdominal septic surgical complications. METHODS: This was a retrospective analysis of 41 patients with Crohn's disease referred to a specialized intestinal failure unit between January 1987 and September 1998 for permanent home parenteral nutrition. To compare the surgical activity in patient groups, a resection index was calculated by dividing the number of intestinal resections by the interval in years between the first resection for Crohn's disease and referral for management of intestinal failure. RESULTS: Extensive primary Crohn's disease was responsible for intestinal failure in 7 cases (17 percent). The remainder (n = 34, 83 percent) developed intestinal failure after intestinal resection. Nine of the "surgical" Crohn's patients developed intestinal failure after uncomplicated sequential resection, (median small-bowel length 65 (range, 60-120) cm) after a median of 3 (range, 2-8) operations over a median of 17 (range, 3-27) years. By contrast, the other 25 surgical Crohn's patients developed intestinal failure after multiple unplanned laparotomies for intra-abdominal sepsis (median small-bowel length 70 (range, 60-200) cm), with a median of 4 (range, 2-7) laparotomies performed over a median of 0.5 (range, 0.1 to 1.5) years (P < 0.001). The resection index for the 25 Crohn's patients undergoing laparotomies for intra-abdominal sepsis was significantly greater than that of the 9 patients who had planned sequential resections (2.1 (0.27-25) vs. 0.23 (0.1-1.0); P < 0.002, Mann-Whitney U test). CONCLUSION: Intestinal failure develops in Crohn's disease primarily as a result of complications of surgical treatment. The largest group of patients at risk consists of those who are undergoing multiple unplanned laparotomies to control intra-abdominal sepsis.

Adult↗
PubMed2006

A comparison of adenosine A2A agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits.

OBJECT: Steroid agents remain the lone pharmacological treatment in widespread use for acute spinal cord injury (SCI), although their utility remains in dispute in the neurotrauma literature. Adenosine A2A receptor activation with ATL-146e, a selective A2A agonist, has shown potential benefit in treating SCI; however, it has not been compared with the gold standard, methylprednisolone. The authors of this study evaluated ATL-146e and methylprednisolone for their ability to preserve neuronal viability and motor function in experimental SCI. METHODS: New Zealand White rabbits sustained SCI or sham injury via the Allen weight-drop technique. Ten minutes postinjury, animals received ATL-146e (ATL group, 0.06 microg/kg/min intravenously for 3 hours), methylprednisolone (steroid group, 30 mg/kg intravenously), or saline (trauma control group). Hindlimb motor function was recorded every 12 hours using the Tarlov motor grading scale (0, paralysis-5, normal hop). At 48 hours, fixed spinal cord tissue was evaluated for neuronal viability. Hindlimb motor function in animals treated with ATL-146e was equivalent to that of sham-injured animals and was significantly better than that of trauma control animals at all time points and that of steroid-treated animals at 12 hours (p = 0.05). Motor function in steroid-treated animals was worse than in those given ATL-146e and better than that of trauma control animals at later time points, but was not statistically significant (both p > 0.05). Neuronal viability (measured in neurons/hpf) was significantly higher in both treatment groups compared with the trauma control group (12.1 +/- 1.4 neurons/hpf for the ATL and 13.3 +/- 1.4 neurons/hpf for the steroid group compared with 7.5 +/- 1.5 neurons/hpf for the trauma control group; both p < 0.04). Neuronal viability did not differ among ATL-146e-treated, steroid-treated, and sham-injured groups. CONCLUSIONS: The use of ATL-146e is at least as effective as methylprednisolone in preserving function and is equivalent to methylprednisolone in preserving the structure of spinal cord tissue after blunt SCI. Adenosine A2A receptor activation may be an effective treatment for acute SCI while avoiding the adverse effects of steroid agents.

Animals↗
PubMed2005

EUS-guided fine needle tissue acquisition by using high negative pressure suction for the evaluation of solid masses: a pilot study.

BACKGROUND: The capability of obtaining tissue samples for histologic examination during EUS has theoretical advantages over cytology alone. The objective was to evaluate the feasibility and the yield of EUS-guided FNA tissue acquisition (EUS-FNTA) by using high negative pressure suction. METHODS: The study design is a prospective, observational pilot study set at a tertiary referral center. Twenty-seven patients with a solid mass amenable to sampling with EUS were included in the study. FNA with a 22-gauge needle was used for a total of 5 passes. An additional pass with the same needle was performed by applying continuous high negative pressure suction using the Alliance II inflation system. The main outcome measurements were the rate of tissue acquisition and the diagnostic accuracy of EUS-FNTA. OBSERVATIONS: Tissue samples were obtained in 26 of the 27 patients (96%). Malignancy was detected in 20 of the 26 biopsy specimens obtained by FNTA and in 20 of the 27 FNA specimens. In 3 patients, EUS-FNTA failed to disclose malignancy, which in two of the patients was diagnosed by FNA. Conversely, EUS-FNTA diagnosed a recurrent malignant thymoma and a schwannoma in two FNA-negative patients. In 3 patients with both FNTA and FNA negative for malignancy, a definitive diagnosis could not be established. Overall, diagnostic accuracy was 76.9% for both EUS-FNTA and EUS-FNA. When combined, a correct diagnosis was achieved in 84.6% of the patients. Immunostaining of the retrieved tissue allowed characterization of the primary tumor in 5 cases and the diagnosis of a schwannoma and two neuroendocrine tumors. Limitations of the study were small sample size and a pilot study. CONCLUSIONS: EUS-FNTA has a high yield for the retrieval of core tissue samples. Further studies in which EUS-FNTA is performed before FNA and with variable number of passes are needed to better define its diagnostic role and performance characteristics.

Adrenal Gland Neoplasms↗
PubMed2004

The evolution of ischemic spinal cord injury in function, cytoarchitecture, and inflammation and the effects of adenosine A2A receptor activation.

OBJECTIVE: Spinal cord ischemia/reperfusion injury involves multiple factors that may be modulated by adenosine A 2A receptor activation. This study defines injury progression in terms of function, cytoarchitecture, and inflammation and assesses whether adenosine A 2A receptor activation by ATL-146e limits injury progression. METHODS: Mature swine were divided into 3 groups: sham thoracotomy, IR (30 minutes of ischemia followed by reperfusion), and ATL (ischemia/reperfusion with ATL-146e administration for the first 3 hours of reperfusion). Subgroups were killed at 0, 3, 6, 12, 24, and 48 hours after reperfusion. Function was followed up with Tarlov scores. Spinal cord tissue was evaluated for neuronal viability, microtubule-associated protein-2 immunohistochemistry, and neutrophil sequestration (myeloperoxidase assay). Spinal cord tissue, cerebrospinal fluid, and serum were evaluated for tumor necrosis factor-alpha by enzyme-linked immunosorbent assay. RESULTS: Function was significantly impaired at 24, 36, and 48 hours in the IR group compared with the sham and ATL groups ( P < .05). Neuronal viability and microtubule-associated protein-2 staining were significantly preserved in the sham and ATL groups compared with the IR group at 24 and 48 hours ( P < .05). Spinal cord myeloperoxidase levels were significantly higher in the IR group than in the sham and ATL groups at 24 and 48 hours. Although negligible in serum and cerebrospinal fluid, tumor necrosis factor-alpha levels in the spinal cord peaked significantly higher in the IR group compared with the sham and ATL groups at 6 and 24 hours ( P < .05). CONCLUSIONS: Spinal cord ischemia/reperfusion induced changes in neutrophil sequestration, microtubule-associated protein-2 expression, and neuronal viability within 24 hours of reperfusion. Spinal cord tumor necrosis factor-alpha increased significantly by 6 to 12 hours after reperfusion. Adenosine A 2A receptor activation attenuates spinal cord inflammation, which may be critical for the preservation of neuronal function and cytoarchitecture after ischemia/reperfusion.

Animals↗
PubMed2006

In vitro and in vivo MMP gene expression localisation by In Situ-RT-PCR in cell culture and paraffin embedded human breast cancer cell line xenografts.

BACKGROUND: Members of the matrix metalloproteinase (MMP) family of proteases are required for the degradation of the basement membrane and extracellular matrix in both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type-1-MMP) expression is higher in more invasive human breast cancer (HBC) cell lines, whilst in vivo its expression has been associated with the stroma surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised around invasive cells of breast tumours in vivo. As MMPs are not stored intracellularly, the ability to localise their expression to their cells of origin is difficult. METHODS: We utilised the unique in situ-reverse transcription-polymerase chain reaction (IS-RT-PCR) methodology to localise the in vitro and in vivo gene expression of MT1-MMP, MMP-1 and MMP-3 in human breast cancer. In vitro, MMP induction was examined in the MDA-MB-231 and MCF-7 HBC cell lines following exposure to Concanavalin A (Con A). In vivo, we examined their expression in archival paraffin embedded xenografts derived from a range of HBC cell lines of varied invasive and metastatic potential. Mouse xenografts are heterogenous, containing neoplastic human parenchyma with mouse stroma and vasculature and provide a reproducible in vivo model system correlated to the human disease state. RESULTS: In vitro, exposure to Con A increased MT1-MMP gene expression in MDA-MB-231 cells and decreased MT1-MMP gene expression in MCF-7 cells. MMP-1 and MMP-3 gene expression remained unchanged in both cell lines. In vivo, stromal cells recruited into each xenograft demonstrated differences in localised levels of MMP gene expression. Specifically, MDA-MB-231, MDA-MB-435 and Hs578T HBC cell lines are able to influence MMP gene expression in the surrounding stroma. CONCLUSION: We have demonstrated the applicability and sensitivity of IS-RT-PCR for the examination of MMP gene expression both in vitro and in vivo. Induction of MMP gene expression in both the epithelial tumour cells and surrounding stromal cells is associated with increased metastatic potential. Our data demonstrate the contribution of the stroma to epithelial MMP gene expression, and highlight the complexity of the role of MMPs in the stromal-epithelial interactions within breast carcinoma.

Animals↗
PubMed1993

Birefringence changes associated with isometric contraction and rapid shortening steps in frog skeletal muscle fibres.

1. Muscle birefringence, the difference between the refractive indices of light polarized parallel and perpendicular to the muscle fibre axis, was measured at 3 degrees C in intact single fibres isolated from frog muscle. Resting birefringence was 2.20 +/- 0.02 x 10(-3) (mean +/- S.E.M., n = 44) at sarcomere length 2.4-2.7 microns and 2.35 +/- 0.03 x 10(-3) (n = 19) at 3.5-3.8 microns. 2. Birefringence decreased during isometric twitch or tetanic contractions. The peak change in a twitch at sarcomere length 2.6 microns, determined by two independent methods, was 0.150 +/- 0.017 x 10(-3) (mean +/- S.E.M., n = 6). The corresponding value after 0.4 s of tetanic stimulation was 0.167 +/- 0.012 x 10(-3) (n = 6). 3. The birefringence change had a shorter latency than tension and reached its half-maximum value earlier than tension. The difference in time to half-maximum in tetani was 11.5 +/- 1.3 ms (mean +/- S.E.M., n = 6) at 3 degrees C. After stimulation birefringence recovered to its pre-stimulus baseline more slowly than tension. 4. The birefringence decrease after 0.4 s of tetanic stimulation was linearly related to the expected degree of overlap between actin and myosin filaments in the sarcomere length range 2.6-3.6 microns. The amplitude of the birefringence decrease at full filament overlap (sarcomere length 2.2 microns) was estimated to be 0.235 +/- 0.015 x 10(-3). 5. Birefringence changes associated with shortening steps of 0.9% fibre length at sarcomere length 2.6 microns exhibited four phases corresponding to those of the tension transient. There was no consistent birefringence change during the length step itself. During the rapid tension recovery birefringence increased by 0.014 +/- 0.001 x 10(-3) (n = 3), measured from the end of the length step to 2 ms later. Birefringence continued to increase as tension recovery slowed, reaching a peak about 10 ms after the step, then recovered with a rate similar to that of the final tension recovery. 6. These birefringence changes are likely to be caused by axial rotation of the head domain of the myosin cross-bridge. During isometric contraction heads bind to actin with their long axes more perpendicular to the fibre axis than in resting muscle, although there is likely to be a wide range of head orientations during contraction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Immediate extubation and epidural analgesia allow safe management in a high-dependency unit after two-stage oesophagectomy. Results of eight years of experience in a specialized upper gastrointestinal unit in a district general hospital.

BACKGROUND: The perioperative management of two-stage oesophagectomy has not been standardized and the prevailing practice regarding the timing of extubation after the procedure varies. This audit has evaluated the outcome, in particular the respiratory morbidity and mortality, after immediate extubation in patients who have had thoracic epidural analgesia. METHODS: All the patients who underwent two-stage oesophagectomy by a single specialist upper gastrointestinal surgeon were recorded both retrospectively (1993-1999) and prospectively (1999-2001). Physical characteristics, comorbid factors, anaesthetic management and postoperative events were recorded on a computer database. Analysis was undertaken to evaluate the morbidity and mortality, in particular the need for reventilation and transfer to the ITU. RESULTS: Seventy-six patients underwent two-stage oesophagectomy between 1993 and 2001. Seventy-three (96%) patients were extubated in theatre and transferred to a high-dependency bed. Three were ventilated electively and extubated within 36 h and made an uncomplicated recovery. Seven (10%) of the immediately extubated patients subsequently needed admission to the ICU and reventilation. Sixty-seven patients had effective epidural analgesia and nine needed i.v. morphine by patient-controlled analgesia. The 30-day or in-hospital mortality was 2.6% (2 of 76). A further two patients died within 90 days, but after discharge. Respiratory complications were responsible for half of the overall morbidity (44.7%). Respiratory failure occurred in 6.5% (5 of 76) and acute respiratory distress syndrome in 2.6% (2 of 76). Both the in-hospital deaths occurred in patients requiring reventilation and resulted from respiratory complications. The following factors were found to be significant in the reventilated patients: duration of one-lung ventilation; forced expiratory volume in the first second; and ratio of forced expiratory volume in the first second/forced vital capacity. CONCLUSIONS: Immediate extubation after two-stage oesophagectomy in patients with thoracic epidural analgesia is safe and associated with low morbidity and mortality. Patients can be managed in a high-dependency unit, thus avoiding the need for intensive care. This has cost-saving and logistical implications.

Adult↗
PubMed2004

Adenosine A2A analogue reduces long-term neurologic injury after blunt spinal trauma.

BACKGROUND: ATL-146e is an adenosine A(2A) agonist that has recently been demonstrated to improve neurological outcome in spinal cord injury in animals. In the current study, we extended the treatment paradigm and tested neurobehavioral functioning out to 1 week after injury to assess if early neurological improvement is sustained long term by an adenosine analogue. MATERIALS AND METHODS: New Zealand White rabbits (3.0-3.5 kg) sustained mid-thoracic blunt spinal cord injury using a weight-drop model (10 g weight dropped from 6 cm directly onto dura). Animals received either (1) 3 h iv infusion of saline carrier (Trauma, N = 21); (2) 3 h iv infusion of 0.06 microg/kg/min ATL-146e followed by intraperitoneal bolus of 10.8 microg/kg ATL-146e at 3 h postinjury (ATL, N = 14); or (3) 3 h iv infusion of 0.06 microg/kg/min ATL-146e followed by intraperitoneal bolus injection of 10.8 microg/kg ATL-146e at 3, 12, and 24 h postinjury (ATL-PLUS, N = 11). Fourteen animals underwent sham injury. Hemodynamic parameters were monitored and hind limb motor functioning was assessed by Tarlov scores (0 = paralyzed to 5 = normal hop) for 7 days after injury. RESULTS: ATL-146e significantly improved Tarlov scores of ATL-146e groups compared with saline-treated controls (P < 0.01 12, 24, 36, and 48 h). Control animals, severely neurologically impaired at 48 h (Tarlov 1.61 +/- 0.35), were euthanized early due to ethical concerns, thus not permitting later statistical comparisons. Early neurological improvements in both ATL-146e-treated groups were sustained longer term (7 day mean Tarlov, SHAM 4.9 +/- 0.30, ATL 5.0 +/- 0, ATL-PLUS 4.25 +/- 0.31). CONCLUSIONS: ATL-146e given immediately after blunt spinal cord trauma significantly improves neurological outcome, which is sustained through 7 days. Early adenosine A2A receptor agonism may be critical since additional IP administration afforded no further neurological improvement. The current data further support the potential clinical utility of adenosine A(2A) agonists in the treatment of spinal cord injury.

Adenosine A2 Receptor Agonists↗
PubMedDate not supplied

Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD.

BACKGROUND: Hyperhomocysteinemia is seen in most hemodialysis (HD) patients and is an independent risk factor for cardiovascular disease. Homocysteine metabolism via remethylation requires activated folate and vitamin B12 and metabolism via transsulfuration requires serine and vitamin B6. Prior studies have shown highly variable effects of supplemental B vitamin and folate therapy for hyperhomocysteinemia. We undertook a fully controlled trial with abnormally high doses of folic acid alone or with supplemental vitamin B6 and B12 compared with active folate alone or with serine. METHODS: Two prospective studies were undertaken in hemodialysis patients. In the first study (protocol A), hyperhomocysteinemia was treated in 77 patients with 30 or 60 mg folic acid with or without vitamins B6 and B12 for eight weeks and compared with matching placebos. In the second study (protocol B), hyperhomocysteinemia was treated in 37 patients with intravenous folinic acid given alone or with serine and compared with matching placebos. All patients received the standard of care treatment with a multivitamin tablet before and throughout the protocol to test the hypothesis that additional therapy is required over and above the routine therapy for maximum reduction in total homocysteine (tHcy). RESULTS: Normal volunteers; The mean (SD) tHcy of 128 normal subjects was 6.5 (4) micromol/L. Protocol A; Plasma folate increased significantly in the groups given folic acid at both four and eight weeks (P = 0.0001 at both time points). Plasma vitamin B12 was significantly increased at four weeks (P = 0.0018) but not at eight weeks (P = 0.064) in those given Vitamin B12. However, tHcy did not differ between treatment groups at baseline (P = 0.63), four weeks (P = 0.79) or eight weeks (P = 0.74). Protocol B: Plasma folate increased significantly at four weeks in those receiving folinic acid (P = 0.0001) but tHcy was not significantly different between groups (P = 0.92). In neither study was there any significant change in tHcy comparing before and during any treatment intervention. CONCLUSIONS: In our studies high dose oral folic acid, intravenous folinic acid, vitamins B6 and B12 and oral serine were ineffective at lowering tHcy in patients on hemodialysis when given folic acid, folinic acid serine or B vitamins in addition to routine folic acid and B vitamin supplements.

Administration, Oral↗
PubMed2006

Imaging, morphologic, and immunohistochemical correlation in gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) recently have been distinguished morphologically, immunohistochemically, and genetically from other gastrointestinal-tract spindle cell neoplasms. The objective of this study was to correlate clinical and imaging findings with morphology and immunohistochemistry to diagnose GISTs and to differentiate them from other spindle cell lesions in the gastrointestinal tract. METHODS: The authors reviewed 9 patients who had tumors that were diagnosed as GIST by image-guided and endosonographic-guided fine-needle aspiration (FNA) with or without core biopsy (7 stomach tumors and 2 intraabdominal tumors). The male:female ratio was 3:6, and the patients ranged in age from 38 years to 80 years. Onsite evaluation, preliminary cytologic evaluation, and immunohistochemistry were provided for 6 patients. Immunostains were performed, depending on sample size, on aspirates and/or core biopsies. RESULTS: On imaging studies, most tumors were smooth and homogenous, consistent with GIST. Tumors ranged in size from 1.8 cm to 22 cm. The largest neoplasm showed solid/cystic and necrotic components. Aspirates consisted of spindle cell, neoplastic proliferation arranged in fascicles that exhibited focal, nuclear palisading; indistinct, cytoplasmic borders; and no significant atypia or mitosis. Focal epithelioid changes or cytologic atypia and mitoses were observed in 2 tumors. Immunostains revealed tumor expression of CD117 and/or CD34 in 5 of 6 tumors, expression of actin in 3 of 6 tumors, and expression of desmin in 1 of 6 tumors. All tumors were diagnosed as GIST (or consistent with GIST for tumors that lacked immunochemical analysis). Five patients underwent surgical excision, and the GIST diagnosis was confirmed in 3 patients, whereas 1 tumor proved to be neurofibroma, and another tumor was leiomyoma. No surgical follow-up was available for the remaining 4 patients, who had imaging and morphologic findings consistent with GIST. CONCLUSIONS: In the setting of consistent clinical and radiologic findings, the combined use of cytomorphology and immunohistochemistry on FNA and/or core biopsy in most instances provides a reliable pathologic diagnosis of GIST. The need of sufficient material for performing ancillary studies and the usual impossibility of excluding malignancy are limitations of FNA cytology of GIST.

Adult↗
PubMed2003

The beating heart approach is not necessary for the Dor procedure.

BACKGROUND: Ventricular reconstruction using the Dor technique has been demonstrated to improve outcome in patients with dilated left ventricles. It has been suggested that a beating heart approach improves ventricular function by allowing the surgeon to palpate that part of the ventricle to exclude. METHODS: We performed a retrospective analysis of patients who underwent an endoventricular circular patch plasty (Dor procedure) between 1998 and 2001. All patients who received ventricular restoration, with or without revascularization or valve repair, were included in the analysis. Discrete left ventricular aneurysms were excluded. Patients were divided into two groups: group 1 (n = 15) underwent ventricular reconstruction with the beating heart technique, whereas group 2 (n = 38) underwent restoration with the aorta cross-clamped. Clinical and hemodynamic data were collected from medical records and computerized databases and compared between the two groups. RESULTS: Fifty-three patients underwent endoventricular circular patch plasty. All patients had enlarged ventricles (echocardiogram demonstrating unidimensional end-diastolic diameter >/= 6.0 cm) and echocardiographic evidence of severe left ventricular dysfunction (mean ejection fraction: group 1 = 21.4%; group 2 = 23.4%). No operative mortalities occurred in either group and all patients were discharged home alive (mean postoperative hospital stay 8.3 days [6 to 22 days]). All patients had improvement in left ventricular function with mean postoperative left ventricular ejection fraction of 36.9% (25% to 52%) in group 1 versus 38.1% (31% to 50%) in group 2, p = 0.081. Ventricular arrhythmias occurred in 5 of 15 group 1 patients and in 9 of 38 group 2 patients. Two patients in the entire cohort (1 patient in group 1, and 1 patient in group 2) had at least one readmission within 12 months with evidence of heart failure. The group 1 patient went on to successful transplant 11 months later, whereas the group 2 patient died 10 months later. CONCLUSIONS: These results demonstrate that the Dor technique of ventricular restoration significantly improves left ventricular function and the beating heart approach provides no additional advantage over continuous aortic cross clamping.

Aged↗
PubMed2006

Multispectral quantitative magnetic resonance imaging of brain iron stores: a theoretical perspective.

OBJECTIVES: To review published magnetic resonance imaging (MRI) iron quantification techniques in the context of quantitative MRI and MR relaxation theories. To analyze comparatively and as a function of age the simultaneous measurements of the proton density (PD), the relaxation times (T1 and T2), and the longitudinal to transverse relaxation times ratio (T1/T2) of brain regions known to accumulate iron preferentially. METHODS: Twenty-seven human subjects were scanned with the mixed turbo spin echo pulse sequence, which is multispectral in PD, T1, and T2. Quantitative MRI (Q-MRI) maps of PD, T1, T2, and T1/T2 were generated, and region of interest measurements were performed in 5 brain regions, namely, frontal white matter (WM), genu of corpus callosum, caudate nucleus, putamen, and globus pallidus. RESULTS: Relaxation time measurements are consistent with results of others and provide further confirmation to our basic understanding of the relaxation effects of iron stores in the brain. Specifically, we found that the iron-rich globus pallidus exhibits enhanced T1 and T2 relaxation relative the iron poorer gray matter tissues (caudate nucleus and putamen) and also relative to the WM matter tissues (frontal WM and genu of the corpus callosum). We also observe that under riding this hypothesis-because we do not have independent confirmation-that iron caused relaxation enhancement, are the normal brain aging patterns, which suggest that the brain tissues become wetter with increasing age. Also noted is the virtual removal of age dependence observed for the T1/T2 ratio of WM tissues, further suggesting that this ratio may become of clinical significance in the diagnosis of neoplastic processes as well as for quantifying iron in tissue. CONCLUSIONS: The theoretical underpinnings of published brain iron Q-MRI techniques have been reviewed. We also examined MR relaxation theory essentials in relation to H-proton relaxation phenomena in diamagnetic tissues as well as theoretical extensions to describe relaxation effects in tissues containing iron deposits with a focus on ferritin. Also reported are in vivo Q-MRI results of 27 human brains obtained with a multispectral technique that uses the mixed turbo spin echo pulse sequence and a model conforming Q-MRI algorithms.

Brain↗