The effect of tidal volume and peep on CO2 and oxygenation during resuscitation of very premature lambs

Background: Over-ventilation causing low arterial carbon dioxide levels (PaCO2) has been associated with the development of neonatal chronic lung disease and adverse outcomes. This may occur very soon after birth. Aim: To investigate the effect on PaCO2 and oxygenation of very premature lambs resuscitated with different tidal volumes and PEEP. Methods: Anaesthetised lambs delivered at 126 days gestation were randomised to 15 min resuscitation with 3 regimes: (1) Laerdal resuscitation bag (B) with 100% oxygen and no PEEP, (2) fixed tidal volume (VT) of 5 mL/kg, or (3) VT of 10 mL/kg, both delivered with a Babylog 8000 ventilator in volume guarantee mode with 8 cm H2O PEEP and variable FiO2. Frequent blood gases were measured and VT, mean airway pressure (Paw), minute volume (MV), ventilation rate (VR), respiratory system compliance (Crs) and alveolar/arterial oxygen difference (AaDO2) were recorded. Results: Twenty lambs were studied. B (1) was associated with more variable VT and peak inspiratory pressures (PIP) compared to fixed tidal volumes (2 and 3). The lambs ventilated with 10 mL/kg were over-ventilated, those ventilated with 5 mL/kg were slightly under-ventilated. Those ventilated with the Laerdal bag had a mean VT of 7.5 mL/kg and were normocarbic. The different tidal volumes had little effect on oxygenation. PEEP improved oxygenation. The table shows the values at 15 minutes expressed as mean and SEM. TABLE. No caption av... TABLE. No caption av... Image Tools Conclusion: Very premature lambs can be effectively resuscitated from birth using volume guarantee ventilation. Within minutes of birth different tidal volumes had a large effect on PaCO2 and no effect on oxygenation. Studies are needed to determine the appropriate tidal volume for resuscitating very premature infants to maintain acceptable levels of PaCO2. © International Pediatrics Research Foundation, Inc. 2004. All Rights Reserved.

Porphyrin-phospholipid interaction and ring metallation depending on the phospholipid polar head type

The interaction between a hydrophobically modified 5,10,15,20-tetrakis(4-N-tetradecyl-pyridyl) porphyrin and three phospholipids: two negatively charged, DMPA (the sodium salt of dimyristoyl-sn-glycero-phosphatidyl acid) and DMPG (the sodium salt of 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]) and a zwitterionic DMPC (dimyristoyl-sn-glycero-phosphatidylcholine), were studied by means of surface pressure isotherms and spectroscopic methods. The interaction results in partial or total metallation of the porphyrin with zinc ions in the presence of negatively charged phospholipids, as attested by UV-vis and luminescence spectroscopy of the transferred films. In the presence of the zwitterionic phospholipid no insertion of zinc ion in the porphyrin ring is detected. These results are relevant for the understanding of photosensitizer-lipid-carrier binding for use in photodynamic therapy. (C) 2010 Elsevier Inc. All rights reserved.

Effects of tidal volume and positive end-expiratory pressure during resuscitation of very premature lambs

Background: Guidelines recommend neonatal resuscitation without controlling tidal volume or positive end-expiratory pressure (PEEP). However, these may improve gas exchange, lung volume and outcome. Aim: To investigate resuscitation of very premature lambs with a Laerdal bag without PEEP versus volume guarantee ventilation with PEEP. Methods: Anaesthetized lambs (n = 20) delivered at 125 d gestation were randomized to three groups receiving 15 min resuscitation: (1) Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm H2O PEEP; (3) ventilation with 10 ml/kg and 8 cm H2O PEEP. They were then all ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H2O PEEP. Ventilation parameters and blood gases were recorded. Results: Different tidal volumes affected PaCO2 within minutes, with 10 ml/kg causing severe hypocarbia. PEEP had little effect on PaCO2. Oxygenation improved significantly with PEEP of 8 cm H2O, irrespective of tidal volume. Conclusion: Very premature lambs can be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal volumes affected PaCO2 within minutes but had little effect on oxygenation. PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature babies with controlled tidal volumes and PEEP might improve their outcome.

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine`s potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 mu g naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals. Cancer Gene Therapy (2009) 16, 598-608; doi:10.1038/cgt.2009.9; published online 6 February 2009

Cancer detection and mammogram volume of radiologists in a population-based screening programme

This study investigates the relationship between the number of screening mammograms read by radiologists and the screening breast cancer detection rate. Cancer detection rates for incident screens (all women aged >= 40 years) were compared by increasing categories of reader volume using Poisson regression. Data from New South Wales (NSW) for a 2 year period (2000-2001) were obtained from the BreastScreen NSW programme. Cancer detection rates increased with the number of mammograms read in the programme, reaching a plateau of approximately 40 per 10,000 after 1375 mammograms per year. No significant differences in cancer detection were evident above 875 mammograms (compared to below 875 mammograms) per year (RR = 0.79, 95% CI 0.63-0.99). (c) 2005 Elsevier Ltd. All rights reserved.

Urine Volume in Acute Kidney Injury: How Much Is Enough?

Eight hundred and seventy-nine patients with acute kidney injury were retrospectively studied over year and eleven months for evaluation of urine volume as a risk factor for death. They were divided into five groups, according to the 24 h urine volume (UV): anuric (UV <= 50 mL/24 h, group 1), oliguric (UV > 50 mL/24 h and < 400 mL/24 h, group 2), and non-oliguric (UV >= 400 mL/24 h). Nonoliguric group was subdivided in three subgroups: UV > 400 mL/24 h and <= 1000 mL/24 h (group 3, reference group), UV > 1000 mL/24 h and <= 2000 mL/24 h (group 4), and UV > 2000 mL/24 h (group 5). Linear tendency test (Mantel extension) pointed out a significant increase in mortality with UV decrease (p < 0.001), confirmed by multivariate analysis. Anuric and oliguric patients had increased risk of respectively 95% and 76% times for death compared to controls (p < 0.05). Patients from groups 4 and 5 presented a reduced risk for death of 50% and 70%, respectively, p = 0.004 and p = 0.001. In conclusion, urine volume was a strong independent factor for mortality in this cohort of AKI patients.

Effectiveness of the CAGE questionnaire, gamma-glutamyltransferase and mean corpuscular volume of red blood cells as markers for alcohol-related problems in the workplace

Objective: To evaluate the usefulness of gamma-glutamyltransferase (GGT) and mean corpuscular volume (MCV), as well as that of the CAGE questionnaire, in workplace screening for alcohol abuse/dependence. Methods: A total of 183 male employees were submitted to structured interviews (Structured Clinical Interview for DSM-IV 2.0 and CAGE questionnaire). Blood samples were collected. Diagnostic accuracy and odds ratio were determined for the CAGE, GGT and MCV. Results: The CAGE questionnaire presented the best sensitivity for alcohol dependence (91%; specificity, 87.8%) and for alcohol abuse (87.5%, specificity, 80.9%), which increased when the questionnaire was used in combination with GGT (sensitivity, 100% and 87.5%, respectively; specificity, 68% and 61.5, respectively). CAGE positive results and/or alterations in GGT were less likely to occur among employees not presenting alcohol abuse/ dependence than among those presenting such abuse (OR for CAGE = 13, p < 0.05; OR for CAGE-GGT = 11, p < 0.05) or dependence (OR for CAGE = 76, p < 0.0 1; OR for GGT = 5, p < 0.0 1). Employees not presenting alcohol abuse/dependence were also several times more likely to present negative CAGE or GGT results. Conclusions: The use short, simple questionnaires, combined with that of low-cost biochemical markers, such as GGT, can serve as an initial screening for alcohol-related problems, especially for employees in hazardous occupations. The data provided can serve to corroborate clinical findings. (C) 2008 Elsevier Ltd. All rights reserved.

Quality of life and neuropsychological changes in mild head trauma - Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission

Introduction: mild head trauma (MHT) is defined as a transient neurological deficit after trauma with a history of impairment or loss of consciousness lasting less than 15 min and/or posttraumatic amnesia, and a Glasgow Coma Scale between 13 and 15 on hospital admission. We evaluated 50 MHT patients 18 months after the trauma, addressing signs and symptoms of post-concussion syndrome, quality of life and the presence of anxiety and depression. We correlate those findings with the S100B protein levels and cranial CT scan performed at hospital admission after the trauma. Method: patients were asked to fill out questionnaires to assess quality of life (SF36), anxiety and depression (HADS), and signs and symptoms of post-concussion syndrome. For the control group, we asked the patient`s household members, who had no history of head trauma of any type, to answer the same questionnaires for comparison. Results: total quality of life index for patients with MHT was 58.16 (+/-5), lower than the 73.47 (+/-4) presented by the control group. Twenty patients (55.2%) and four (11.1%) controls were depressed. Seventeen patients (47.2%) presented anxiety, whereas only eight (22.2%) controls were considered anxious. Victims of MHT complained more frequently of loss of balance, dry mouth, pain in the arms, loss of memory and dizziness than their respective controls (p < 0.05). We found no correlation between the presence of these signs and symptoms, quality of life, presence of anxiety and depression with S100B protein levels or with presence of injury in the cranial CT performed at hospital admission. Conclusion: MHT is associated with a higher incidence of post-concussion syndrome symptoms, lower quality of life and anxiety than their respective controls even 18 months after the trauma. (C) 2007 Elsevier Ltd. All rights reserved.

Urodynamic evaluation of patients with lower urinary tract symptoms and small prostate volume

Introduction: The relevance of prostate size in the pathophysiology of lower urinary tract symptoms (LUTS) is controversial. We evaluated the urodynamic findings in patients with LUTS and small prostate volumes. Materials and Methods: 84 patients aged >= 50 years with LUTS and prostates < 40 ml were evaluated. All had an International Prostate Symptom Score (IPSS) >= 8. Average age was 62.0 +/- 8.1 years. We evaluated the impact of bladder outlet obstruction (BOO) and detrusor overactivity (DO) on the voiding symptoms and urodynamic findings. Results: Mean prostate volume was 29.2 +/- 7.2 ml and mean IPSS was 13.5 +/- 4.6. BOO was the main finding, affecting 42 (50.0%) patients, followed by detrusor underactivity (DU) in 41 (48.8%) and DO in 28 (33.3%) patients. Patients without BOO were significantly older than the obstructed (64.0 +/- 8.8 and 60.1 +/- 6.9 years, respectively; p = 0.026) and had an increased prevalence of DU (76.2 and 21.4%, respectively; p < 0.001). Comparison of patients with and without DO showed reduced bladder capacity and compliance in the DO group (p < 0.001). No other comparisons were significant. Conclusion: Half of the patients with LUTS and small prostates are not obstructed and may have DO or decreased detrusor contractility as the basis for their voiding symptoms. Our results emphasize the value of urodynamics in this population, especially when invasive treatments are being considered. Copyright (c) 2008 S. Karger AG, Basel.

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

Adjuvant cisplatin-based chemoradiation improves survival in HNSCC patients presenting with risk features. ERCC1 (excision repair cross-complementation group 1) is associated with resistance to chemo- and radiation therapy and may have a prognostic value in HNSCC patients. Here we studied ERCC1 expression and the polymorphism T19007C as prognostic markers in these patients. This is a retrospective and translational analysis, where ERCC1 protein expression was evaluated by immunohistochemistry, using an H-score, and mRNA expression was determined by RT-PCR. T 19007C genotypes were detected by PCR-RFLP carried out using DNA template extracted from normal lymph nodes. A high H-score was seen in 32 patients (54%), who presented better 5-year overall survival (5-y OS: 50% vs. 18%, HR 0.43, p=0.026). Fifteen out of 45 patients (33%), with high mRNA expression, presented better 5-year overall survival (OS) (86% vs. 30%, HR 0.26, p=0.052). No OS difference was detected among T 19007C genotypes. High H-score and mRNA expression remained significant as favorable prognostic factors in a multivariate analysis. Collectively, our results suggest that high ERCC1 expression seems to be associated with better OS rates in HNSCC patients submitted to adjuvant cisplatin-based chemoradiation.

Fluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock

Background: Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Methods: Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer`s, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion (""clinical penumbra"") and from the corresponding contralateral side (""lesion`s mirror"") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Results: Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Conclusion: Both small volume hypertonic saline and large volume lactated Ringer`s blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

A computerized tomography scan method for calculating the hernia sac and abdominal cavity volume in complex large incisional hernia with loss of domain

Preoperative progressive pneumoperitoneum (PPP) is a safe and effective procedure in the treatment of large incisional hernia (size > 10 cm in width or length) with loss of domain (LIHLD). There is no consensus in the literature on the amount of gas that must be insufflated in a PPP program or even how long it should be maintained. We describe a technique for calculating the hernia sac volume (HSV) and abdominal cavity volume (ACV) based on abdominal computerized tomography (ACT) scanning that eliminates the need for subjective criteria for inclusion in a PPP program and shows the amount of gas that must be insufflated into the abdominal cavity in the PPP program. Our technique is indicated for all patients with large or recurrent incisional hernias evaluated by a senior surgeon with suspected LIHLD. We reviewed our experience from 2001 to 2008 of 23 consecutive hernia surgical procedures of LIHLD undergoing preoperative evaluation with CT scanning and PPP. An ACT was required in all patients with suspected LIHLD in order to determine HSV and ACV. The PPP was performed only if the volume ratio HSV/ACV (VR = HSV/ACV) was a parts per thousand yen25% (VR a parts per thousand yen 25%). We have performed this procedure on 23 patients, with a mean age of 55.6 years (range 31-83). There were 16 women and 7 men with an average age of 55.6 years (range 31-83), and a mean BMI of 38.5 kg/m(2) (range 23-55.2). Almost all patients (21 of 23 patients-91.30%) were overweight; 43.5% (10 patients) were severely obese (obese class III). The mean calculated volumes for ACV and HSV were 9,410 ml (range 6,060-19,230 ml) and 4,500 ml (range 1,850-6,600 ml), respectively. The PPP is performed by permanent catheter placed in a minor surgical procedure. The total amount of CO(2) insufflated ranged from 2,000 to 7,000 ml (mean 4,000 ml). Patients required a mean of 10 PPP sessions (range 4-18) to achieve the desired volume of gas (that is the same volume that was calculated for the hernia sac). Since PPP sessions were performed once a day, 4-18 days were needed for preoperative preparation with PPP. The mean VR was 36% (ranged from 26 to 73%). We conclude that ACT provides objective data for volume calculation of both hernia sac and abdominal cavity and also for estimation of the volume of gas that should be insufflated into the abdominal cavity in PPP.