Effect of SARS-CoV-2 and Toxoplasma gondii co-infection on IFN-γ and TNF-α expression and its impact on disease severity.

The symptomatology of COVID-19 is dependent on the immune status and the cytokine response of the host. The cytokine level of the host is influenced by the presence of chronic persistent or latent infections with co-pathogens. Parasitic diseases are known to induce host immune-modulation which may impact the response to co-infection. Toxoplasmosis is a widespread protozoal infection that remains quiescent in its latent form to be re-activated during states of immune depression. Clinical data on the relation between toxoplasmosis and COVID-19 cytokine profile and symptomatology are still insufficient. Seventy-nine subjects were included in this study. Patients were diagnosed with COVID-19 by PCR. Serological testing for toxoplasmosis was performed by the detection of anti-Toxoplasma IgG antibodies, in addition to IgG avidity testing. IFN-γ and TNF-α levels were determined by RT-PCR. Among patients diagnosed with COVID-19, 67.1% were seronegative for anti-Toxoplasma IgG, while 32.9% were seropositive. High avidity was found in 10 cases (40% of seropositive cases), 4 of whom required ICU administration, while low avidity was found in 15 cases (60%), 7 of which were administered to the ICU. TNF-α and INF-γ levels were significantly higher in COVID-19 patients than in healthy control subjects. No significant association was found between the seroprevalence of toxoplasmosis and the presence of COVID-19 and its severity. Cytokines were significantly higher in both seropositive and seronegative COVID-19 patients than in their control counterparts. The high prevalence of toxoplasmosis merits further exploration of its relation to COVID-19 by mass studies.

Evaluation of serum levels of Irisin as a marker of endothelial dysfunction in patients with type 2 diabetes mellitus.

INTRODUCTION: Insulin resistance and obesity have been associated with irisin, a protein in fat cells. The levels of irisin in patients with type 2 diabetes mellitus (T2DM) were significantly lower than those in non-diabetics. This study aimed to examine the relationship between serum irisin levels and endothelial dysfunction in patients with T2DM. METHODS: There were 90 participants in this study. We matched 65 patients with T2DM with 25 healthy control participants. A series of tests were performed on the participants, including fasting blood glucose, 2 hours postprandial blood glucose, glycated haemoglobin, triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), TG/HDL-C ratio and albumin/creatinine ratio. In addition to measuring high-sensitivity C-reactive protein (hs-CRP). Enzyme-linked immunosorbent assay (ELISA) technique was used for estimating irisin concentrations. RESULTS: Flow-mediated dilation (FMD) was significantly lower in patients with T2DM; however, there was a non-statistically significant difference between healthy controls and patients with T2DM regarding serum Irisin level. CRP and LDL levels were inversely correlated with circulating irisin levels. In a stepwise regression analysis, only the hs-CRP and LDL were statistically significant in predicting irisin level. CONCLUSIONS: In patients with T2DM, serum levels of irisin were inversely correlated with hyperglycaemia, body mass index and per cent body fat; this suggests that detecting irisin levels early can prevent cardiovascular diseases from progressing. According to the study results, serum irisin serves as a predictive marker for early cardiovascular disease, thus preventing the disease from progressing. There is a need for further research in order to understand how irisin contributes to the development of atherosclerosis and the development of diabetic complications.

Evaluation of Serum Visfatin as a Biomarker of Lupus Nephritis in Egyptian Patients with Systemic Lupus Erythematosus.

One of the most significant consequences of systemic lupus erythematosus (SLE) is lupus nephritis (LN). Visfatin, an adipokine that is significantly expressed in visceral fat and is a marker of endothelial dysfunction in chronic kidney disease, has multiple proinflammatory actions. We aimed to evaluate the state of serum visfatin in SLE patients and to detect its possible correlation with the disease's activity and effects on the kidney affection. Fifty patients with active LN, 50 patients with inactive lupus, and 50 healthy people had their serum visfatin levels tested. Chemical and immunological markers of SLE and LN were measured. The SLE Disease Activity Index (SLEDAI) was used to measure the disease's activity. Renal biopsies from the LN subgroup were collected and classified using the modified classification of the World Health Organization. The serum visfatin of patients with active LN was significantly greater than that of inactive lupus patients and the healthy controls (20.56 ± 1.07 ng/mL, 16.77 ± 1.02 ng/mL, and 9.96 ± 1.46 ng/mL, P <0.001). SLEDAI and serum visfatin levels were shown to be significantly correlated (P = 0.000057). Serum visfatin levels were likewise significantly correlated with the index of histological activity in the active group (P <0.00001). Serum visfatin was raised in individuals with active LN and was related to the SLEDAI and disease severity scores. Serum visfatin could be utilized as a noninvasive biomarker for evaluating the severity of LN and risk stratification of the risk.

Platelets' morphology, metabolic profile, exocytosis, and heterotypic aggregation with leukocytes in relation to severity and mortality of COVID-19-patients.

Roles of platelets during infections surpass the classical thrombus function and are now known to modulate innate immune cells. Leukocyte-platelet aggregations and activation-induced secretome are among factors recently gaining interest but little is known about their interplay with severity and mortality during the course of SARS-Cov-2 infection. The aim of the present work is to follow platelets' bioenergetics, redox balance, and calcium homeostasis as regulators of leukocyte-platelet interactions in a cohort of COVID-19 patients with variable clinical severity and mortality outcomes. We investigated COVID-19 infection-related changes in platelet counts, activation, morphology (by flow cytometry and electron microscopy), bioenergetics (by Seahorse analyzer), mitochondria function (by high resolution respirometry), intracellular calcium (by flow cytometry), reactive oxygen species (ROS, by flow cytometry), and leukocyte-platelet aggregates (by flow cytometry) in non-intensive care unit (ICU) hospitalized COVID-19 patients (Non-ICU, n=15), ICU-survivors of severe COVID-19 (ICU-S, n=35), non-survivors of severe COVID-19 (ICU-NS, n=60) relative to control subjects (n=31). Additionally, molecular studies were carried out to follow gene and protein expressions of mitochondrial electron transport chain complexes (ETC) in representative samples of isolated platelets from the studied groups. Our results revealed that COVID-19 infection leads to global metabolic depression especially in severe patients despite the lack of significant impacts on levels of mitochondrial ETC genes and proteins. We also report that severe patients' platelets exhibit hyperpolarized mitochondria and significantly lowered intracellular calcium, concomitantly with increased aggregations with neutrophil. These changes were associated with increased populations of giant platelets and morphological transformations usually correlated with platelets activation and inflammatory signatures, but with impaired exocytosis. Our data suggest that hyperactive platelets with impaired exocytosis may be integral parts in the pathophysiology dictating severity and mortality in COVID-19 patients.

The potential use of urinary transferrin, urinary adiponectin, urinary Retinol Binding Protein, and serum zinc alpha 2 glycoprotein levels as novel biomarkers for early diagnosis of diabetic nephropathy: A case-control study.

BACKGROUND AND AIMS: The level of albuminuria is used to evaluate diabetic nephropathy (DN). However, to detect or predict the early stages of DN, better biomarkers are needed. METHODS: This study is a case-control observational study. 80 Egyptians participated in the study: 60 patients with type 2 diabetes mellitus (T2DM) were divided into three groups (20 patients each), and 20 healthy subjects with matched age and gender were used as controls. Demographic and laboratory data were analyzed. An enzyme-linked immunosorbent assay was used to determine the levels of four biomarkers of DN; urinary adiponectin (ADP), urinary transferrin, serum Zinc Alpha 2 Glycoprotein (ZAG), and urinary Retinol Binding Protein (RBP). RESULTS: The levels of DN biomarkers urinary ADP, transferrin, RBP, and serum, ZAG were significantly higher in patients with T2DM than in controls. The ROC curve of the validity of the simultaneous use of all four biomarkers in predicting albuminuria indicates a sensitivity of 90% and a specificity of 90%. The Area Under the Curve (AUC) was 0.948, the 95% confidence interval was 0.998-0.897, and the p-value was 0.001. CONCLUSIONS: In patients with T2DM, urine adiponectin, transferrin, RBP, and serum ZAG concentration may be useful biomarkers in the early diagnosis of DN. A further longitudinal prospective study is required to explore the potential utility of these biomarkers.

Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality.

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1-35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors' HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan-Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 µM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

The role of autonomy-connectedness in stress-modulating effects of social support in women: An experimental study using a virtual Trier Social Stress Test.

Social support is associated with mental well-being and favorable therapy outcomes. As autonomy-connectedness, the capacity for self-governance in interpersonal context, may affect reliance on others, we investigated whether stress-modulating effects of social support are moderated by autonomy-connectedness. Ninety-seven undergraduates completed measures on autonomy-connectedness and trait social anxiety, and attended a laboratory session with a friend (support) or alone (control). All underwent a virtual Trier Social Stress Test and completed anxiety, cortisol and heart rate (variability) measures. Preregistered analyses revealed that social support reduced anxiety reactivity and delayed heart rate variability decreases, but not heart rate. Contrary to hypotheses, autonomy-connectedness did not predict stress-reactivity or interact with condition. Exploratory analyses suggested effects of social support on cortisol reactivity and indicated that reported support quality varied by trait anxiety and self-awareness. Our findings underline the stress-modulating effects of social support and suggest that social support can benefit individuals with varying levels of autonomy-connectedness.

New-onset Type 1 Diabetes Mellitus with Diabetic Ketoacidosis and Pancreatitis in a Patient with COVID-19.

Coronavirus Disease 2019 (COVID-19) had struck the world with health and economic catastrophes and recently with unusual autoimmune presentations, including new-onset Type 1 Diabetes. Herein we present a 17-year-old male patient who presented to the outptient clinic with fever, palpitation, and cough of four-week duration; he was referred to the emergency room and was found to have DKA. CT of the chest showed ground-glass opacities suggestive of COVID-19 pneumonia, and abdominal cuts showed dilated intrahepatic biliary radicles with pancreatic loculations suggestive of pancreatitis. The patient was admitted to the ICU, started on intravenous fluids and insulin infusion then COVID-19 PCR returned positive. We hypothesize that SARS-CoV-2 has a vital role in eliciting an autoimmune response triggering type 1 diabetes, and further studies are needed to confirm this hypothesis. SARS-CoV-2 may cause pancreatitis, and the first presentation could be high blood sugar or DKA.

Neutrophil-mediated Oxidative Stress and Albumin Structural Damage Predict COVID-19-associated Mortality

Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 25 patients who were followed up for a median of 12.5 days (1-35 days), among them 14 had died. Analyzing blood samples from patients and healthy individuals (n=10), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance (EPR) spectra of spin labelled fatty acids (SLFA) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10-11). Non-survivors HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and greater S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Stratified at the means, Kaplan-Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W<0.16, 80% (9/12) vs. S/W>0.16, 20% (2/10), p=0.008; plasma [H2O2]>7.1 M, 83.3% (5/6) vs. 16.7% (1/6), p=0.049). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (< 0.0253) predicted mortality with 100% accuracy (100% (6/6) vs. 0% (0/6), logrank{chi} 2 = 12.01, p = 5x10-4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements.

Multi-modal responses to the Virtual Reality Trier Social Stress Test: A comparison with standard interpersonal and control conditions.

The Trier Social Stress Test (TSST) is a reliable social-evaluative stressor. To overcome limitations of the in vivo TSST, a standardized virtual reality TSST (VR-TSST) was developed. The present study compares the emotional (anxiety) and physiological (heart period and variability) response to a VR-TSST with an in vivo TSST and a control condition. Participants took part in either an in vivo TSST (N = 106, 64% female), VR-TSST (N = 52, 100% female), or a control TSST (N = 20, 40% female). Mixed linear modeling examined response profile differences related to TSST type. While there was an equivalent anxiety response to the in vivo TSST as the VR-TSST, we found a smaller heart period and heart rate variability response in VR-TSST compared to the in vivo TSST, especially in response to the math part of the test. The present findings demonstrate that social evaluative stress can be successfully induced in a VR setting, producing similar emotional and slightly attenuated cardiovascular responses.

Intranasal oxytocin and the stress-buffering effects of social support during experimentally induced pain: The role of attachment security.

BACKGROUND: This study examined whether intranasal oxytocin enhances the stress-buffering effects of social support during experimentally induced pain, taking into account the role of individual differences in attachment security. METHODS: Female participants (N = 193) were randomly assigned to oxytocin (24 IU intranasal) or placebo and to receive support or no support from a friend (2 × 2 factorial design with repeated measures)). Participants underwent the Cold Pressor Task (CPT) and were monitored for heart rate variability (HRV: RMSSD) and heart rate and reported pain levels. The Experiences in Close Relationships Questionnaire was used to measure attachment. RESULTS: Oxytocin reduced RMSSD (p = 0.003, partial ɳ2 = 0.03) and increased heart rate (p = 0.039, partial ɳ2 = 0.03) in individuals who received support, possibly reflecting an enhanced attentional state. Oxytocin did not enhance beneficial effects of social support on perceived pain, but increased pain intensity in avoidantly attached individuals who were supported by a friend (p = 0.009, partial ɳ2 = 0.06). LIMITATIONS: Only female participants were examined. Future studies are needed to determine sex differences in how oxytocin shapes stress-buffering effects of support. CONCLUSIONS: Oxytocin may enhance the salience of social proximity and may be a mechanism underlying previously reported social influences on cardiovascular and mental health. However, oxytocin effects depend on interpersonal insecurities and may trigger discomfort in avoidantly attached individuals. Caution about oxytocin's therapeutic promise is warranted.

Evaluation of serum presepsin, procalcitonin, copeptin, and high-sensitivity C-reactive protein for differentiating bacterial infection from disease activity in Egyptian patients with systemic lupus erythematosus.

OBJECTIVES: Several biological markers have been studied for the differentiation of infection from disease activity in systemic lupus erythematosus (SLE) patients with discrepant results. We aimed to evaluate the role of serum presepsin, hs-CRP, procalcitonin (PCT), and copeptin (CPP) in differentiating bacterial infections from disease activity in SLE patients. METHODS: This study is a cross-sectional observational study in which 94 Egyptian patients were recruited from June 2017 to January 2018. Our patients were divided into two groups: group (1) included 48 patients with active SLE hospitalized with any sort of lupus activity and group (2) included 46 patients with active SLE admitted with a proven bacterial infection. Hs-CRP, presepsin, PCT, and CPP were measured using enzyme-linked immune sorbent assay technique. RESULTS: Hs-CRP, presepsin, PCT, and CPP were highly significantly higher among group (2) patients compared to group (1) patients (p < 0.001). Serum presepsin expressed higher specificity than hs-CRP (87.5% vs 60.4%) but the same sensitivity (80.4%) in the detection of bacterial infection in SLE patients. Serum PCT expressed higher specificity than hs-CRP (100% vs 60.4%) but lower sensitivity (73.9% vs 80.4%). Serum CPP expressed higher specificity than hs-CRP (65.9% vs 60.4%) but lower sensitivity (65.9% vs 80.4%). CONCLUSION: Our study suggests that increased serum levels of hs-CRP, presepsin and PCT levels are useful in differentiating bacterial infections from disease activity in SLE patients. Serum CPP could be used as an adjunct with more specific inflammatory biomarkers in making better diagnostic judgments. KEY POINTS: • The increased serum levels of hs-CRP, presepsin and PCT levels are useful in differentiating bacterial infections from disease activity in SLE patients. • Serum Presepsin expressed higher specificity than hs-CRP but the same sensitivity in the detection of bacterial infection in SLE patients. • Serum CPP expressed higher specificity than hs-CRP but lower sensitivity.

Oxytocin effects on resting-state heart rate variability in women: The role of childhood rearing experiences.

Oxytocin is known for its stress-reducing effects and has been associated with autonomic nervous system measures (ANS) involved in the stress response, such as heart rate variability (HRV). The current study examined the effects of intranasal oxytocin on HRV among women (oxytocin N â€‹= â€‹87, placebo N â€‹= â€‹86) during rest. Results show that oxytocin reduced RMSSD and low frequency (LF)-HRV, but only in women with positive childhood rearing experiences, and not in women with negative childhood experiences. These findings suggest that oxytocin plays a role in ANS regulation and that childhood rearing experiences may influence oxytocin effects on this stress regulating system.

Intranasal oxytocin enhances stress-protective effects of social support in women with negative childhood experiences during a virtual Trier Social Stress Test.

Oxytocin is considered a biological mechanism underlying stress-protective effects of positive social interactions. It is assumed to underlie the women-specific tend-and-befriend response to stress, although few studies have tested this assertion with female samples. The aim of the present study was, therefore, to test whether oxytocin enhances stress-protective effects of social support during stress in women, taking into account the moderating role of childhood adversity. The sample consisted of 180 female undergraduate students who had reported on experiences of childhood abuse and how often their mother used love withdrawal as an insensitive disciplinary strategy. Women participated in a virtual version of the Trier Social Stress Test (TSST) and were randomly assigned to receive 24 IU oxytocin or a placebo and to receive support or no support from a female friend (sub-groups N = 45). Results showed that oxytocin reduced heart rate variability during the TSST in participants who received support, possibly indicating that oxytocin increases attention and stimulates a challenge motivational state in the presence of a friend. In addition, we found that, in the presence of a friend, oxytocin reduced state anxiety levels and cortisol levels after the TSST, but only in women with higher levels of adverse childhood experiences. Our findings may indicate that oxytocin is a neurobiological means to attain and benefit from social support under stressful circumstances, which may be particularly adaptive for women with a history of adversity. Thus, oxytocin may function as motivator for affiliative disposition during stress exposure in women with a history of childhood adversity. Results should be replicated in clinical samples.

General psychopathology factor and unresolved-disorganized attachment uniquely correlated to white matter integrity using diffusion tensor imaging.

BACKGROUND: A dimensional approach of psychopathology focuses on features and risk factors that are shared across diagnoses. In support for this dimensional approach, studies point to a general psychopathology factor (GPF) associated with risk for multiple psychiatric disorders. It is, however, unknown how GPF relates to white matter integrity (WMI). In the current diffusion tensor imaging (DTI) study, we examined how GPF relates to abnormalities in a skeleton representation of white matter tracts, taking into account a trans-diagnostic risk factor: unresolved-disorganized attachment (Ud) resulting from loss or trauma. METHODS: Unique associations between GPF, Ud, and WMI were examined in a combined sample of adolescents (N = 63) with childhood sexual abuse-related posttraumatic stress disorder (N = 18), anxiety and depressive disorders (N = 26) and without psychiatric disorder (N = 19). WMI was measured using DTI. Ud was measured using the Adult Attachment Interview. We controlled for puberty stage, gender, age, and IQ. RESULTS: Controlling for GPF, Ud was associated with reduced fractional anisotropy (FA) in the splenium and inferior fronto-occipital fasciculus (IFOF). Controlling for Ud, GPF was associated with reduced FA in the genu and body of the corpus callosum. CONCLUSIONS: Decreasing WMI in the genu and body with increasing psychopathology across diagnoses suggests demyelinization in these areas and may underlie comorbidity and presence of symptoms that transcend psychopathological diagnoses. In contrast, trauma-related WMI reductions in the splenium and IFOF may account for heterogeneity within diagnostic categories as a function of childhood trauma. These findings support the importance of a dimensional approach in addition to traditional diagnostic classifications in clinical research and practice.

As tears go by: Baby tears trigger more brain activity than adult tears in nulliparous women.

The current functional magnetic resonance imaging study examines brain activity during the perception of infant and adult tears. Infant tears evoke stronger responses in the visual cortex than adult tears, indicating that infant tears are highly salient. In addition, our study shows that infant tears uniquely activate somatosensory pain regions, which could stimulate actions directed at the elimination of the source of pain. Shedding tears may be a strong means to elicit the parent's sharing of the infant's feelings, thereby strengthening caregiver-infant bonding and securing infant survival.

Nonconvulsive status epilepticus--a possible cause of mental retardation in patients with Lennox-Gastaut syndrome.

Lennox-Gastaut syndrome (LGS) is one of the most severe types of childhood epilepsy. It is usually resistant to treatment and associated with mental retardation. To delineate the risk factors associated with the outcome of LGS, we evaluated, in a retrospective and multicentre study, the course of the disease, EEG tracings, and intellectual function in 101 patients. Inclusion criteria were the presence of tonic seizures as well as slow spike and wave complexes in the EEG. The average documented observation period was 16 years (range 4-31 years). Overall, the intellectual and neurological outcome was poor. At the last follow-up, 38% of the patients could not speak, 21% were unable to walk and only 4% were free of seizures. Four independent risk factors for severe mental retardation were identified by multivariate analysis. These were in a decreasing order of importance: nonconvulsive status epilepticus (NCSE), odds ratio (OR) 25.2, a previous diagnosis of West syndrome (OR 11.6), a symptomatic etiology of epilepsy (OR 9.5), and an early age at onset of epilepsy (OR 4.7). The results highlight the association between NCSE and the severity of mental retardation in patients with LGS; this association appears to be independent of symptomatic etiology. Our data provide an indirect evidence that, at least in some of the patients, NCSE is not only a concomitant feature, but also a cause of severe mental retardation.

Steroid therapy following isolated smoke inhalation injury.

Steroids have no positive influence upon pulmonary related morbidity and mortality following combined smoke inhalation and thermal cutaneous injury (3, 4). Steroid administration following isolated smoke inhalation without concomitant thermal cutaneous injury has, however, been shown to have beneficial effects in previous animal studies (1). This potential therapeutic approach to treatment has not been examined in the clinical setting. Recent hotel fires in Las Vegas, Nevada, resulted in a large cohort of individuals with similar smoke exposures without associated injuries. Two of four hospitals in the triage system administered steroids following injury. Patients were divided into two groups, a steroid-treated, and a non-treated group. These groups were compared using multivariate and frequency analyses. There were no detectable differences in sex, signs, symptoms, and previous medical history. There were likewise no differences between groups with respect to oxyhemoglobin saturation, arterial oxygen tension, arterial pH, and pulmonary-related morbidity and mortality. These data suggest that steroid coverage has little beneficial effect upon pulmonary-related morbidity and mortality following isolated smoke inhalation injury.

Ventilation and perfusion alterations following homologous blood transfusion.

A previous study in this laboratory examined the effect of micropore ultrafiltration of blood products on pulmonary gas exchange and subsequent pulmonary dysfunction--related morbidity and death. Morbidity and death from pulmonary failure was not affected; however, gas exchange was improved following ultrafiltration with 40 micrometers filters, as reflected by lower Bohr dead-space fractions. This difference might be explained by reduction of the microaggregate load seen in the pulmonary microvasculature. The purpose of this study was to examine in more detail these gas exchange alterations, paying particular attention to the correlation of changing Bohr dead-space ventilation detected with multiple inert gas analysis with direct determinations of microaggregate size and number. Fourteen patients with isolated cutaneous thermal injury scheduled for major early burn would excision were selected for study. Following transfusion with homologous blood products, the ventilation/perfusion ratio (Va/Q) distributions determined by inert gas analysis remained essentially unchanged except for subtle changes in both high VA/Q and dead-space compartments, resulting in significantly increased Bohr dead-space fractions (P less than 0.05). This combination of gas exchange alteration is consistent with vasoactive and occlusive changes in the pulmonary microvasculature following microaggregate infusion. The correlation of changing dead-space ventilation with the total microaggregate load was poor (r = 0.15) but was significant when compared with counts of microaggregates greater than 90 micrometers in diameter (r - 0.85). These findings suggest that gas exchange alterations following blood transfusion are primarily reflected by increased dead-space ventilation secondary to vasoconstriction and occlusion of the pulmonary microvasculature with microaggregates greater than 90 micrometers in diameter.