Arterial base deficit in pulmonary embolism is an index of severity and diagnostic delay

In acute pulmonary embolism, patients free from circulatory failure usually present a blood gas pattern consistent with respiratory alkalosis. We investigated whether the appearance of arterial base deficit in these patients indicates disease severity and diagnostic delay. Twenty-four consecutive patients with pulmonary embolism were retrospectively evaluated. Twelve patients had arterial base excess ≥0 mmol/L (Group 1), and 12 patients arterial base deficit <0 mmol/L (Group 2). No patient showed signs of circulatory failure. Group 1 was characterized by a mean base excess of 2.2 ± 1.7 mmol/L, while in Group 2, the mean base deficit was −1.9 ± 0.7 mmol/L (p < 0.0001). At 1 week since the embolism, 11 patients of Group 1 and 6 of Group 2 received a PE diagnosis (p < 0.05). The vascular obstruction index was more severe in Group 2 than in Group 1 (48 ± 12 vs. 36 ± 17%, respectively, p < 0.05). In Group 2, the PaCO₂ was lower (33 ± 3 vs. 36 ± 5 mmHg, respectively, p < 0.05), the arterial pH was decreased (7.442 ± 0.035 vs. 7.472 ± 0.050, respectively, p = 0.097), the Pv₅₀ was lower (28.3 ± 1.7 vs. 29.8 ± 1.6 mmHg, respectively, p < 0.05), the aHCO₃ ⁻ was lower (22.5 ± 0.7 vs. 26.1 ± 1.6 mmol/L, respectively; p < 0.0001), while between the Groups, O₂ delivery, O₂ mixed venous saturation, and O₂ extraction ratio were equivalent. Despite no signs of circulatory failure, an arterial Base deficit develops in patients with respiratory alkalosis subsequent to more severe pulmonary vascular obstruction. Diagnostic delay favors a base deficit. Depending on the degree of hypocapnia, there may be limitation of peripheral O₂ uptake despite adequate O₂ availability. Progressive bicarbonate deficit suggests an increased risk for underlying conditions such as cardio-respiratory disorders or cancer, and requires close control and treatment.     

Analysis of the association of IL1B (C+3954T) and IL1RN (intron 2) polymorphisms with dental implant loss in a Brazilian population

Background: Although dental implants have a high success rate, failures occur, in spite of adequate clinical conditions. Together with the observation that multiple implant losses occur in certain groups of individuals (clusterization phenomenon), this suggests that host response may influence implant failure. Little is known about the influence of genetic susceptibility on implant loss. Interleukin (IL)-1β and IL-1ra are believed to play a key role in the immune-inflammatory response, and polymorphisms IL1B (C+3954T) and IL1RN (intron 2) are shown to alter the coding proteins expression.
Objectives: The aim of this study was to investigate the association between dental implant loss and polymorphisms IL1B (+3954) and IL1RN (intron 2).
Material and methods: The study population ( n =266) was divided into Test group (T) – 90 subjects with implant loss, and Control group (C) – 176 subjects without any implant failure. Genotyping was performed by PCR-RFLP.
Results: The number of present teeth was observed to influence implant loss. No differences in genotype and allele frequencies between C and T were found for IL1B (+3954) and IL1RN (intron 2) polymorphisms. However, the analysis of the whole study population (control and test groups) showed that genotype 2/2 was significantly more frequent in individuals with multiple implant losses ( n =35) than in individuals that lost up to a single implant ( n =231) (OR: 3.07, IC: 1.13–8.34, P =0.027).
Conclusion: It was observed that number of teeth and edentulism were associated with implant loss. Genotype 2/2 of IL1RN polymorphism was significantly more frequent in patients who presented multiple losses, which suggests that the clusterization phenomenon has a genetic basis.     

Effect of ABT-627 (A-147627), a potent selective ETA receptor antagonist, on the cardiopulmonary profile of newborn lambs with surgically-induced diaphragmatic hernia

1. Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right-to-left shunting. 2. Endothelins (ETs) are potent vasoconstrictors and pro-mitogenic peptides. Strong evidences support their participation in CDH and in the etiology of PH via the activation of ET(A) receptors (ET(A)-Rs). 3. Evaluation of the effect of ABT-627, a selective non-peptidic ET(A)-R antagonist, given from -15 to 210 min post-delivery (1 mg kg(-1) bolus +0.01 mg kg(-1) h(-1) infusion, i.v.), was conducted in the lamb model of CDH. 4. Severity of CDH was assessed in comparison to untreated controls (n=5). Untreated CDH lambs (n=7) had a higher mean pulmonary arterial pressure (MPAP; P<0.0001), lower mean blood pressure (MBP; P=0.0004), higher MPAP / MBP ratio (P<0.0001), lower arterial pH (P<0.0001), higher paCO(2) (P<0.0001), lower paO(2) (P<0.0001) and lower post-ductal pulsatile SaO(2) (P<0.0001) than untreated controls. 5. Treated controls (n=7) showed a higher MPAP, lower MBP, higher MPAP/MBP ratio, lower arterial pH, higher paCO(2), lower paO(2), lower post-ductal pulsatile SaO(2) and lower plasmatic ir-ET ratios compared to untreated controls (P<0.0001). 6. Treated CDH lambs (n=8) showed a higher MBP (P<0.0001), lower MPAP / MBP ratio (P<0.0001), higher arterial pH (P<0.0001), lower paCO(2) (P<0.0001), higher paO(2) (P=0.0228), higher post-ductal pulsatile SaO(2) (P=0.0016) and lower plasmatic ir-ET ratios (P=0.0247) when compared to untreated CDH lambs. 7. These observations revealed that, although acute perinatal treatment with a selective non-peptidic ET(A)-R antagonist had some adverse effects in controls, it attenuated the progressive cardiopulmonary deterioration that occurred after birth in CDH lambs.     

Mediastinal lymphadenectomy influences postoperative immune response after lung cancer surgery

The aim of the study was to calculate the amount of surgical injury caused by systematic lymphadenectomy of mediastinum in patients operated on due to non-small cell lung cancer,with uneventful postoperative course.The study group consisted of 11 patients with cancer of the right lung(Group 1).The control group consisted of 12 patients with left lung cancer(Group 2).In patients with right lung cancer systematic lymphadenectomy,while in patients with left lung cancer systematic sampling was performed.Serum IL-6 and IL-1ra concentration was measured before and after surgery,and on postoperative day 1,3,and 7,as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1,by ELISA test.Peripheral blood lymphocyte(PBL) count was measured with flow cytometry.Time of surgery was higher in patients with right than left lung cancer(154.1±31.29) vs(119.6±24.81) min;P=0.008) .The number of resected mediastinal lymph nodes was higher in patients with right than left lung cancer(27.6±7.6) vs(11.1 ±8.1);P=0.00006) .Postoperative decrease of PBL was significantly higher in group 1 than 2(1.25±0.37) vs(1.75 ±0.64) ×103/μL;P=0.04) .No significant differences were found in serum,pleural fluid and sputum concentration of IL-6 and IL -1ra between groups.Negative correlation between concentration of these cytokines in pleural fluid and number of resected mediastinal lymph nodes was found(Spearman test for IL-6:r=-0.723;P<0.001;for IL-1ra:r=-0.768;P<0.001).Number of "positive" N2 lymph nodes did not correlate with pleural fluid concentration of cytokines.Systematic lymphadenectomy of the mediastinum causes immunosuppression,as measured by decreased count of PBL and a negative correlation between number of resected mediastinal lymph nodes and concentration of cytokines in pleural fluid.     

Systemic and local myotoxicity induced by snake venom group II phospholipases A2: comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue.

The patterns of myotoxicity induced in mice by crotoxin, crotoxin B and a Lys49 phospholipase A(2) (PLA(2)) homologue were compared. Lys49 PLA(2)-induced local myotoxicity is reflected by creatine kinase (CK) loss in injected gastrocnemius muscle, and by a profile of CK increase in plasma characterized by a rapid increment and drop after intramuscular injection, and by a lack of CK increase in plasma after intravenous injection. In contrast, crotoxin and crotoxin B, which induce local and systemic myotoxicity, provoked a more prolonged increment in plasma CK activity upon intramuscular injection, and induced increments in plasma CK after intravenous injection. The three toxins promoted a similar extent of local myotoxicity, assessed by the loss of CK in injected gastrocnemius. A method for the quantitative assessment of the ability of toxins to induce systemic myotoxicity is proposed, based on the estimation of the ratio between the area under the curve in the plasma CK activity (total myotoxicity) to the loss of CK in injected gastrocnemius (local myotoxicity). The highest ratio corresponded to crotoxin, and the lowest corresponded to Lys49 PLA(2), the former being a systemic myotoxin and the latter a local myotoxin. Neutralization by antivenoms also differed between the toxins: a drastic reduction in plasma CK, with very poor neutralization of local CK loss, was achieved in the case of crotoxin B when antivenom was injected intravenously, whereas no neutralization was achieved in the case of Lys49 PLA(2). When tested in undifferentiated myoblasts in culture, Lys49 PLA(2) induced cytotoxicity, whereas crotoxin and crotoxin B did not, evidencing that the latter are devoid of widespread cytolytic activity. Molecular modeling analysis showed that Lys49 PLA(2) has a conspicuous cationic face, which is likely to interact with diverse membranes. In contrast, crotoxin B, despite its overall basic pI, has a lower density of positively charged residues at this molecular region. It is suggested that Lys49 PLA(2)s homologues interact, through this cationic face, with many different cell types, thus lacking specificity for muscle cells. In contrast, crotoxin B has a more selective interaction with targets in the muscle cell membrane. This selectivity might be the basis for the ability of crotoxin and crotoxin B to induce systemic myotoxicity.     

Drug-induced skin, nail and hair disorders.

Drug eruptions are among the most common adverse drug reactions, affecting approximately 3% of hospitalised patients. Although the rate of severe cutaneous adverse reactions to medications is low, these reactions can affect anyone who takes medication, and can result in death or disability. Two general patterns can be distinguished, depending on the type of onset of these cutaneous adverse drug reactions: acute or chronic. Acute-onset events are usually rather specific cutaneous 'syndromes' that constitute emergencies and should therefore be promptly recognised and treated, while chronic-onset events often present as dermatological diseases. The challenge is therefore to recognise the drug aetiology in front of a 'classical' dermatosis such as acne, lichen or pemphigus. Therefore, clinicians should carefully evaluate the signs or symptoms of all adverse reactions thought to be drug related, and discontinue the offending agent when feasible. Erythematous drug eruptions are the most frequent and less severe acute immune drug-induced rashes, and are sometimes difficult to differentiate from viral eruptions. On the other hand, acute urticaria and angioedema are sometimes life-threatening eruptions for which a drug aetiology must be investigated. Photosensitivity, vasculitis and skin necrosis belong to the acute onset reactions, which are not always drug-induced, in contrast to fixed drug eruptions. The early recognition of acute generalised exanthematous pustulosis, DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, Stevens-Johnson syndrome and toxic epidermal necrolysis are of high importance because of the specific mechanisms involved and the different prognosis of each of these diseases. Chronic onset drug-induced disorders include pigmentary changes, drug-induced autoimmune bullous diseases, lupus, pseudo lymphoma and acneiform eruptions; these are discussed, along with specific data on drug-induced hair and nail disorders. As the disorders are numerous, the mechanisms and the drugs involved in the development of these various reactions are multiple. The list of drugs discussed in relation to the different disorders are as accurate as possible at the time of preparation of this review, but will need updating as new drugs emerge onto the market. We emphasize the clinical recognition, pathophysiology and treatment of skin, hair and nail adverse drug reactions, and the role of each doctor involved in the management of these patients in the notification of the adverse drug reaction to health authorities, using the minimal requirement for notification proposed.     

Abnormal neurotransmitter release underlying behavioral and cognitive disorders: toward concepts of dynamic and function-specific dysregulation.

Abnormalities in the regulation of neurotransmitter release and/or abnormal levels of extracellular neurotransmitter concentrations have remained core components of hypotheses on the neuronal foundations of behavioral and cognitive disorders and the symptoms of neuropsychiatric and neurodegenerative disorders. Furthermore, therapeutic drugs for the treatment of these disorders have been developed and categorized largely on the basis of their effects on neurotransmitter release and resulting receptor stimulation. This perspective stresses the theoretical and practical implications of hypotheses that address the dynamic nature of neurotransmitter dysregulation, including the multiple feedback mechanisms regulating synaptic processes, phasic and tonic components of neurotransmission, compartmentalized release, differentiation between dysregulation of basal vs activated release, and abnormal release from neuronal systems recruited by behavioral and cognitive activity. Several examples illustrate that the nature of the neurotransmitter dysregulation in animal models, including the direction of drug effects on neurotransmitter release, depends fundamentally on the state of activity of the neurotransmitter system of interest and on the behavioral and cognitive functions recruiting these systems. Evidence from evolving techniques for the measurement of neurotransmitter release at high spatial and temporal resolution is likely to advance hypotheses describing the pivotal role of neurotransmitter dysfunction in the development of essential symptoms of major neuropsychiatric disorders, and also to refine neuropharmacological mechanisms to serve as targets for new treatment approaches. The significance and usefulness of hypotheses concerning the abnormal regulation of the release of extracellular concentrations of primary messengers depend on the effective integration of emerging concepts describing the dynamic, compartmentalized, and activity-dependent characteristics of dysregulated neurotransmitter systems.     

Variability and uncertainty assessment of patulin exposure for preschool children in Flanders.

The objective of the present study was to evaluate the patulin exposure of children consuming organic, handcrafted or conventional apple juice through a probabilistic approach and to evaluate the effectiveness of several risk management options aiming to reduce the risk for children due to patulin exposure. However, a large part of the data on patulin contamination of apple juice fell under the limit of detection (LOD). Different methods were tested to deal with these so-called left censored data and a uniform distribution with uncertain bounds was selected to handle this censorship. Variability and uncertainty assessment of patulin exposure showed that 0.9% [90% confidence interval (CI): 0.3-1.8%] of the children consuming only organic apple juice exceed the tolerable daily intake (TDI). For consumers of conventional and handcrafted apple juice this was respectively 0.1% [90% CI: 0-0.3%] and 0% [90% CI: 0-0.2%]. Reduction of the patulin contamination in apple juice to concentrations below 25 microg/kg reduced the percentage of the children exceeding the TDI to 0% [90%CI: 0-0.2%] for organic apple juice. Reduction of the apple juice consumption was less effective than a reduction of the patulin concentration in apple juice and is only useful when the patulin concentration of apple juice is below 25 microg/kg.     

Repeated furunculosis in adult male with abnormal neutrophil activity

A 21 years old male suffered from repeated furunculosis in different regions of the body over the last two years. This coincided with the start of professional activities in hospital surroundings. The purulent secretions all showed growth of Staphylococcus aureus. All laboratory tests were normal except for a decrease of the neutrophil phagocytic ingestion phase. Before the diagnosis of defective phagocytosis was made, antibiotic treatment was started about 4 to 5 days after the appearance of the infectious process and the furunculosis led to abscess formation with difficult healing and cellulitis. After the diagnosis of defective phagocytosis ingestion phase, personal hygiene was intensified during and after work shifts at the hospital and antibiotic treatment was started at the first signs of folliculitis, which showed healing.