Plasma cytokines do not reflect expression of pro- and anti-inflammatory cytokine mRNA at organ level after cardiopulmonary bypass in neonatal pigs

BACKGROUND: Plasma concentrations of inflammatory markers are increased in response to the trauma of cardiac surgery and cardiopulmonary bypass (CPB). It is, however, unknown whether the plasma cytokine levels and cytokine mRNA expression at organ level reflect each other. METHODS: Twenty-six piglets (17-19 days) were allocated to the sham-group (sternotomy only, n = 13) or to the CPB-group (sternotomy, 120 min CPB procedure with 60-min aortic cross-clamp, n = 13). The pigs were observed for 0.5 h or 4 h post-CPB. Plasma levels of IL-1beta, IL-6, IL-8 and IL-10 and mRNA expression of TNF-alpha, IL-1beta, IL-6, IL-8, IL-10 and iNOS in organs were registered with concomitant changes in oxygenation index (OI) and expiratory nitric oxide (NO). RESULTS: In pigs killed 0.5 h post-CPB there was a significant increase in IL-10 mRNA in the lungs and kidneys compared with the sham-group. IL-1beta mRNA was detectable in the kidneys and lungs of the CPB-pigs, while IL-6 mRNA was up regulated only in lungs. In pigs killed 4 h post-CPB a significantly higher IL-6 mRNA was found in heart tissue and a lower IL-10 mRNA was found in lungs of CPB pigs compared with the sham-group. There was a concomitant significant increase in OI and increased plasma IL-8 and IL-10 concentrations in the CPB-pigs compared with the sham-pigs. CONCLUSION: The cytokine mRNA expression pattern was very different for the pigs killed already 0.5 h after the CPB procedure compared with the pigs killed 4 h post-CPB. The plasma cytokine levels poorly reflected mRNA expression of the pro- and anti-inflammatory cytokines.     

Dead regions in the cochlea: implications for speech recognition and applicability of articulation index theory

Dead regions in the cochlea have been suggested to be responsible for failure by hearing aid users to benefit from apparently increased audibility in terms of speech intelligibility. As an alternative to the more cumbersome psychoacoustic tuning curve measurement, threshold-equalizing noise (TEN) has been reported to enable diagnosis of dead regions. The purpose of the present study was first to assess the feasibility of the TEN test protocol, and second, to assess the ability of the procedure to reveal related functional impairment. The latter was done by a test for the recognition of low-pass-filtered speech items. Data were collected from 22 hearing-impaired subjects with moderate-to-profound sensorineural hearing losses. The results showed that 11 subjects exhibited abnormal psychoacoustic behaviour in the TEN test, indicative of a possible dead region. Estimates of audibility were used to assess the possible connection between dead-region candidacy and ability to recognize low-pass-filtered speech. Large variability was observed with regard to the ability of audibility to predict recognition scores for both dead-region and no-dead-region subjects. Furthermore, the results indicate that dead-region subjects might be better than no-dead-region subjects at recognizing speech of marginal audibility.     

Dependence of cadmium-metallothionein nephrotoxicity on glutathione.

Acute cadmium-metallothionein (CdMT) injection is frequently used as a model to study the mechanism of chronic Cd-induced nephrotoxicity. The purpose of this study was to investigate the relationship between glutathione (GSH) status and the ability of CdMT, either administered as a bolus dose or infused over a 24-h period by an osmotic minipump, to cause nephrotoxicity. GSH levels were modulated by pretreatment with either buthionine sulfoximine (BSO) or GSH. BSO enhanced while GSH suppressed acute CdMT nephrotoxicity. An infused dose of CdMT (150 microg Cd/kg) that was well tolerated when delivered over a 24-h period became nephrotoxic when GSH synthesis was inhibited by BSO. With depletion of GSH, as little as 0.4 microg Cd/g renal cortex was sufficient to cause nephrotoxicity after an acute dose of CdMT. While BSO had no effect on renal Cd accumulation, pretreatment with GSH reduced renal cortical Cd accumulation by 36%. CdMT nephrotoxicity was enhanced by depleting renal GSH, but without increasing renal Cd accumulation, which suggests that intracellular GSH is directly involved in protection against CdMT nephrotoxicity. Reduced Cd accumulation in the renal cortex following GSH pretreatment suggests an additional extracellular mechanism of GSH protection. It is concluded that GSH status is an important determinant of CdMT nephrotoxicity, with low GSH levels enhancing and high GSH levels reducing its toxicity, and that the mechanism appears to involve both intracellular and extracellular sites.     

Menkes's syndrome. Report of a patient treated from 21 days of age with parenteral copper

In an infant with Menkes's steely-hair syndrome, early treatment (from 21 days of age) with parenteral copper failed to halt the disease. In addition to urinary tract abnormalities, panlobular emphysema was present a finding not previously noted in the syndrome.     

Pet sensitivities in asthmatic children

A history of pet contact and/or apparent clinical sensitivity was obtained in 65 (55%) of 118 unselected asthmatic children. These 65 children were skin tested and their sera examined for specific IgE using the radioallergosorbent test. Those children who had apparent clinical sensitivities had larger skin test reactions and were more likely to have positive specific IgE results than those without apparent sensitivities. Positive skin tests were very common (80%), but the larger the skin test reaction (weal diameter greater than 4 mm diameter) the more likely was there to be a positive history or a positive specific IgE result. Hence a large skin test reaction can provide a helpful pointer to animal allergy of clinical importance. Commercially available animal extracts have limitations for diagnostic tests. A questionnaire survey of 150 day schools emphasized the potential opportunities for contact with animal allergens at school.     

Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.     

Temporal relation of antigenaemia and loss of antibodies to core antigens to development of clinical disease in HIV infection.

A total of 276 sequential serum samples from 34 men with antibodies to the human immunodeficiency virus (HIV) followed up for two to seven years were analysed for HIV antigen and antibodies to the viral core and envelope proteins. Results were correlated with clinical outcome and CD4 T lymphocyte count. Both antigenaemia and the disappearance of antibodies to the core protein were associated with development of the acquired immune deficiency syndrome (AIDS) or AIDS related complex and depletion of CD4 cells. Thus AIDS or AIDS related complex developed in eight out of 16 patients with antigenaemia compared with one out of 18 patients without antigenaemia. Low counts of CD4 cells (less than 0.5 X 10(9)/l) were found in 14 of the 16 patients with antigenaemia and five of the 18 without antigenaemia. Nine patients seroconverted to HIV during the study; two of these developed antigenaemia 14 and 16 months after the estimated time of seroconversion. These results show that the late stages of HIV infection are characterised by increased production of antigen and a decrease in antibodies directed against the core protein. Antigenaemia indicates a poor prognosis; and as the antigen test is simple to do and interpret, it may therefore be useful for selecting patients for antiviral treatment.     

HYPOKALEMIA IN THE ELDERLY: IS IT ALWAYS DIURETIC-INDUCED?

SUMMARY Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.     

All‐cause versus cause‐specific excess deaths for estimating influenza‐associated mortality in Denmark,Spain, and the United States

BackgroundSeasonal influenza‐associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic.MethodFor Denmark, Spain, and the United States, we estimated age‐stratified excess mortality for (i) all‐cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time‐series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017.ResultsThe respective periods of weekly excess mortality for all‐cause and cause‐specific deaths were similar in their chronological patterns. Seasonal all‐cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3–6.1) and 14.3 (13.0–15.6) per 100,000 population, for the United States; 20.3 (15.8–25.0) and 24.0 (19.3–28.7) per 100,000 population for Denmark; and 22.9 (18.9–26.9) and 52.9 (49.1–56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all‐cause estimates.DiscussionWe observed fewer influenza‐associated deaths when we examined cause‐specific death categories compared with all‐cause deaths and observed the same trends in peaks in deaths with all death causes. Because all‐cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies.