Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4‐h intravenous infusion of LPS (total dose: 2 ng kg^?1). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh‐cuff deflation‐induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh‐cuff deflation caused a MAP reduction of 16 (13–20) % at baseline and 18 (16–20) % after LPS, while the MAP reduction was 12 (11–13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31–0·49) s^?1 at baseline to 0·58 (0·36–0·74) s^?1 after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36–0·52) s^?1; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh‐cuff deflation failed to induce sufficient MAP reductions in patients.     

Hospitalisation of and mortality from bleeding peptic ulcer in Sweden: a nationwide time-trend analysis

Aliment Pharmacol Ther 2011; 33: 578–584

Summary

Background Time‐trend analyses of incidence and mortality in bleeding peptic ulcer show divergent results. Aim To conduct a detailed national analysis of hospitalisation of and mortality from bleeding peptic ulcer in Sweden. Method Data from all hospitalisations at departments with primary responsibility for patients with bleeding ulcer in Sweden, with main diagnosis or co‐diagnosis of bleeding ulcer from 1987 to 2005 were retrieved from the Hospital Discharge Register. A validation study was performed due to an uncertainty in diagnostic setting after the introduction of ICD‐10 in 1997. Annual hospitalisation rates per 100 000 inhabitants in relation to gender, age and ulcer location were calculated as well as age‐standardised 30‐day mortality rates. Results Hospitalisations for bleeding ulcer decreased from 63.9 to 35.3 per 100 000 inhabitants per year during the study period. The decrease was greater among men (men: from 80.4 to 40.9; women: from 47.7 to 29.7) and in younger age groups. Bleeding gastric ulcer decreased in both genders, and bleeding duodenal ulcer decreased most among men, but was stable in a subgroup of elderly women. Median age increased from 70 to 76 years. Standardised 30‐day mortality increased from 5.3% to 6.2%. The increased mortality was found in those aged more than 65 years and with duodenal ulcer disease, whereas mortality remained unchanged in those with bleeding gastric ulcer. Conclusion Hospitalisation rates for bleeding peptic ulcer have markedly decreased in Sweden in all age groups. The 30‐day mortality is low compared with other nationwide studies in the western world, but has increased among patients with duodenal ulcer disease.     

The effects of sertindole on sensory gating, sensorimotor gating, and cognition in healthy volunteers

Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders. There is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Some recent studies have investigated the effects of antipsychotic medications on gating in healthy volunteers exhibiting low levels of gating, rather than in patients. Therefore, the current study investigated the influence of sertindole versus placebo in two separate experimental sessions, on PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and high baseline gating levels. Sertindole increased PPI and P50 suppression in healthy subjects exhibiting low baseline PPI and low baseline P50 suppression, respectively, while sertindole attenuated gating in subjects exhibiting high baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategies in a spatial working memory task. These findings suggest that mixed D(2)/5-HT(2) receptor antagonists enhance both PPI and P50 suppression in a way that enhances it in healthy subjects exhibiting low baseline gating. Furthermore, the results militate in favor of the concomitant assessment of PPI, P50 suppression and cognitive measures while investigating the effect of antipsychotic medication in healthy subjects.     

Penetrating Missile Injuries During the Iraqi Insurgency

INTRODUCTION

Since the invasion of Iraq in 2003, the conflict has evolved from asymmetric warfare to a counter-insurgency operation. This study investigates the pattern of wounding and types of injuries seen in casualties of hostile action presenting to a British military field hospital during the present conflict.

PATIENTS AND METHODS

Data were prospectively collected on 100 consecutive patients either injured or killed from hostile action from January 2006 who presented to the sole coalition field hospital in southern Iraq.

RESULTS

Eighty-two casualties presented with penetrating missile injuries from hostile action. Three subsequently died of wounds (3.7%). Forty-six (56.1%) casualties had their initial surgery performed by British military surgeons. Twenty casualties (24.4%) sustained gunshot wounds, 62 (75.6%) suffered injuries from fragmentation weapons. These 82 casualties were injured in 55 incidents (mean, 1.49 casualties; range 1–6 casualties) and sustained a total 236 wounds (mean, 2.88 wounds) affecting a mean 2.4 body regions per patient. Improvised explosive devices were responsible for a mean 2.31 casualties (range, 1–4 casualties) per incident.

CONCLUSIONS

The current insurgency in Iraq illustrates the likely evolution of modern, low-intensity, urban conflict. Improvised explosive devices employed against both military and civilian targets have become a major cause of injury. With the current global threat from terrorist bombings, both military and civilian surgeons should be aware of the spectrum and emergent management of the injuries caused by these weapons.     

Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For this reason, it is both misleading and unhelpful to perpetuate the current practice of reporting association results for these trials one gene at a time, ignoring the fact that multiple gene-by-phenotype tests are being carried out on the same data set. On the other hand, suggestive associations in such trials may lead to new hypotheses that can be tested through both replication efforts and biological experimentation. The appropriate handling of these forms of data therefore requires dissemination of association statistics without undue emphasis on select findings. Here we attempt to illustrate this approach by presenting association statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21 pharmacogenetic phenotypes. On current evidence it is impossible to know which of these associations may be real, although in total they form a valuable resource that is immediately available to the scientific community.     

Irbesartan-mediated reduction of renal and cardiac damage in insulin resistant JCR : LA-cp rats

Background and purpose:

Angiotensin II receptor antagonists (ARBs), originally developed for antihypertensive properties, have pleiotropic effects including direct vascular actions. We tested the hypothesis that the ARB irbesartan would be effective against micro- and macrovascular complications of the prediabetic metabolic syndrome using the obese, insulin-resistant JCR : LA-cp rat that exhibits micro- and macrovascular disease with ischaemic myocardial lesions and renal disease.

Experimental approach:

Obese male rats were treated with irbesartan (30 mg·kg⁻¹·day⁻¹, incorporated into chow) from 12 to 25 weeks of age.

Key results:

Irbesartan treatment caused no change in food intake or body weight. Fasting glycaemic control of the JCR : LA-cp rats was marginally improved, at the expense of increased plasma insulin levels (∼50%). Fasting plasma triglycerides were marginally reduced (∼25%), while cholesterol concentrations were unchanged. Elevated concentrations of adiponectin, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1 were reduced along with severity of glomerular sclerosis. Macrovascular dysfunction (aortic hypercontractile response to noradrenergic stimulus and reduced endothelium-dependent relaxation) was improved and frequency of ischaemic myocardial lesions reduced (62%).

Conclusions and implications:

Irbesartan reduces markers of inflammation and prothombotic status, improves macrovascular function and reduces glomerular sclerosis and myocardial lesions in a model of the metabolic syndrome. Unlike pharmaceutical agents targeted on metabolic dysfunction, irbesartan reduced end-stage disease without major reduction of plasma lipids or insulin. The protective effects appear to be secondary to unknown intracellular mechanisms, probably involving signal transduction pathways. Understanding these would offer novel pharmaceutical approaches to protection against cardiovascular disease.     

Vater und Sohn mit Muskelschmerzen und Kraftlosigkeit

Zusammenfassung Bei einem 48j?hrigen Patienten wurde ein periorbitales ?dem als Begleitsymptom einer r?ntgenologisch gesicherten schweren Sinusitis maxillaris et ethmoidalis interpretiert. Trotz Antibiose und kompletter Rückbildung des periorbitalen ?dems entwickelte der Patient ein schweres Krankheitsbild mit heftigsten disseminierten Myalgien, Kraftlosigkeit, Fieber und Eosinophilie im Blutbild. Eine Muskelbiopsie des M. deltoideus ergab zun?chst nur den Befund einer unspezifischen Myositis. Erst nach Untersuchung der Pr?parate in Serienschnitten zeigten sich Larven von Trichinella spiralis; somit war die Diagnose einer akuten Trichinose gesichert. Beim Sohn des Patienten bestanden ebenfalls Myalgien und Kraftlosigkeit, jedoch in deutlich milderer Form. Die Muskelbiopsie best?tigte auch bei ihm eine Trichinose. Retrospektiv war zu eruieren, da? Vater und Sohn ca. 2 Wochen vor Beginn ihrer Symptomatik unvollst?ndig durchgebratene Schweinefilets verzehrt hatten. Beide erhielten eine antihelminthische Therapie mit Mebendazol. W?hrend der Sohn beschwerdefrei ist, klagt der Vater auch 3 Jahre nach der Infektion immer noch über persistierende Myalgien und Kraftlosigkeit. Die Trichinose mu? unver?ndert in die Differentialdiagnose verschiedenster Erkrankungen einbezogen werden.     

Une pneumonie exotique à ne pas méconnaitre : la mélioïdose pulmonaire

Melioidosis is a disease that is endemic in North Australia and Southeast Asia, caused by Burkholderia pseudomallei. This Gram-negative organism can affect all organs, but presents most commonly as severe pneumonia. We report a 58-year-old man who presented with a B. pseudomallei pneumonia on his return from Thailand. Radiography revealed a complete disappearance of symptoms after a 3-week therapy with ceftazidime and doxycycline followed by 4 months of combined amoxicillin–clavulanic acid and doxycycline therapy. No relapse had occurred 18 months later.     

Thromboembolische Komplikationen – Prophylaxe und Therapie im Fokus

Cancer patients are at increased risk of thromboembolic complications, which are commonly referred to as Trousseau’s syndrome. Besides the potentially dramatic effects of the tumor on the coagulation and fibrinolytic systems, various supportive measures and more specific cancer treatments, such as surgery or chemotherapy contribute to the pathophysiology of cancer-associated venous thromboembolism (VTE). Clinical trials have shown that long-term therapy with low-molecular-weight heparin (LMWH) is superior to secondary prophylaxis with vitamin K antagonists in the treatment of patients with cancer-associated VTE. Based on currently available clinical evidence it is not clear which cancer patient should be offered primary thromboprophylaxis with LMWH. In this respect, the individual risk profile which is substantially influenced by the general condition of the patient and possible co-morbidities have to be taken into account. Recent experimental and clinical studies have suggested that LMWH affects tumor biology at various levels and may thus be potentially beneficial as an adjunct in cancer therapy.