Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Lipopolysaccharide binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide. Implications for cytokine production in normal and injured lungs.

A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli O111B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNF alpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNF alpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pHi or [Cai++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNF alpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNF alpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNF alpha expression by alveolar macrophages within the lungs.

Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) is characterized by lung injury and damage to the alveolar type II cells. This study sought to determine if endogenous surfactant is altered in ARDS. Bronchoalveolar lavage was performed in patients at-risk to develop ARDS (AR, n = 20), with ARDS (A, n = 66) and in normal subjects (N, n = 29). The crude surfactant pellet was analyzed for total phospholipids (PL), individual phospholipids, SP-A, SP-B, and minimum surface tension (STmin). PL was decreased in both AR and A (3.48 +/- 0.61 and 2.47 +/- 0.40 mumol/ml, respectively) compared to N (7.99 +/- 0.60 mumol/ml). Phosphatidylcholine was decreased in A (62.64 +/- 2.20% PL) compared to N (76.27 +/- 2.05% PL). Phosphatidylglycerol was 11.58 +/- 1.21% PL in N and was decreased to 6.48 +/- 1.43% PL in A. SP-A was 123.64 +/- 20.66 micrograms/ml in N and was decreased to 49.28 +/- 21.68 micrograms/ml in AR and to 29.88 +/- 8.49 micrograms/ml in A. SP-B was 1.28 +/- 0.33 micrograms/ml in N and was decreased to 0.57 +/- 0.24 micrograms/ml in A. STmin was increased in AR (15.1 +/- 2.53 dyn/cm) and A (29.04 +/- 2.05 dyn/cm) compared to N (7.44 +/- 1.61 dyn/cm). These data demonstrate that the chemical composition and functional activity of surfactant is altered in ARDS. Several of these alterations also occur in AR, suggesting that these abnormalities occur early in the disease process.

Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome.

To determine the possible mechanism(s) promoting alveolar fibrin deposition in the adult respiratory distress syndrome (ARDS), we investigated the initiation and regulation of both fibrinolysis and coagulation from patients with ARDS (n = 14), at risk for ARDS (n = 5), and with interstitial lung diseases (ILD) (n = 8), and normal healthy individuals (n = 13). Bronchoalveolar lavage (BAL) extrinsic pathway inhibitor activity was increased in ARDS BAL compared with patients at risk for ARDS (P = 0.0146) or normal controls (P = 0.0013) but tissue factor-factor VII procoagulant activity was significantly increased in ARDS BAL compared with all other groups (P less than 0.001). Fibrinolytic activity was not detectable in BAL of 10 of the 14 patients with ARDS and low levels of activity were found in BAL of the other four ARDS patients. Depressed fibrinolysis in ARDS BAL was not due to local insufficiency of plasminogen; rather, there was inhibition of both plasmin and plasminogen activator. Plasminogen activator inhibitor 1 was variably detected and low levels of plasminogen activator inhibitor 2 were found in two ARDS BAL samples, but plasminogen activator inhibitor 2 was otherwise undetectable. ARDS BAL antiplasmin activity was, in part, due to alpha 2-antiplasmin. We conclude that abnormalities that result in enhanced coagulation and depressed fibrinolysis, thereby predisposing to alveolar fibrin deposition, occur in the alveolar lining fluids from patients with ARDS.

The impact of ulcerative colitis is greater in unmarried and young patients.

GOALS: To determine whether the perceived impact of ulcerative colitis (UC) on activities of living (illness intrusiveness) is greater for people who are not living in a married or common-law relationship. BACKGROUND: In general, social and occupational achievement is not greatly impaired by UC, yet patients, especially young adults, often have interpersonal concerns. METHODS: One hundred fifty-five outpatients with UC were assessed for disease activity, and completed self-reports of marital status, income, social support and illness intrusiveness. RESULTS: Fifty-one patients (32.9%) were single, separated or divorced, and 104 patients (67.1%) were married or in common-law relationships. Compared with those who were married or in common-law relationships, single or separated patients were younger, had a lower household income, had lived with UC for fewer years and were less satisfied with social support. Among 135 patients in remission, marital status was significantly associated with illness intrusiveness, controlling for age, income and perceived social support (F=5.73; P=0.02). Low social support (F=4.94; P=0.03) and younger age (F=7.24; P=0.008) were independently associated with illness intrusiveness. Single patients in remission reported illness intrusiveness of similar severity to that reported by patients with active disease. CONCLUSIONS: The perceived impact of UC on the lives of patients is greater in those who are not married or living in common-law relationships. Youth, single status and lower social support commonly coexist, and exert additive effects on the functional impact of UC. Resources to improve social support should be directed toward this group of patients.

Subcutaneous and mediastinal emphysema. Pathophysiology, diagnosis, and management.

Subcutaneous emphysema and pneumomediastinum occur frequently in critically ill patients in association with blunt or penetrating trauma, soft-tissue infections, or any condition that creates a gradient between intra-alveolar and perivascular interstitial pressures. A continuum of fascial planes connects cervical soft tissues with the medlastinum and retroperitoneum, permitting aberrant air arising in any one of these areas to spread elsewhere. Diagnosis is made in the appropriate clinical setting by careful physical examination and inspection of the chest roentgenogram. While the presence of air in subcutaneous or mediastinal tissue is not dangerous in itself, prompt recognition of the underlying cause is essential. Certain trauma-related causes may require surgical intervention, but the routine use of chest tubes tracheostomy, or mediastinal drains is not recommended.

Solubilized nuclear thyroid hormone receptors in circulating human mononuclear cells.

In order to assess iodothyronine receptor interactions in man, we have developed a receptor assay for T3 and T4 in solubilized nuclear extracts from circulating mononuclear cells. This assay utilizes the technique of salt solubilization to isolate nuclear receptors and employs standard saturation analysis for T3 and T4 to determine maximal binding capacity (MBC) and equilibrium dissociation constants (Kd). We have determined that 11 normal subjects had a MBC for T3 of 1.20 +/- 0.20 pmol/mg DNA (+/- SE) and a Kd of 3.4 +/- 0.2 X 10(-10) M; the T4 MBC was 8.44 +/- 1.22 pmol/mg DNA and the Kd was 2.7 +/- 0.3 X 10(-10) M. Hypothyroid patients had a mean T3 MBC of 7.32 +/- 2.28 pmol/mg DNA and a mean T4 MBC of 40.04 +/- 21.36 pmol/mg DNA (P less than 0.05 compared to normal). Obese subjects (n = 12) had a basal fed MBC that was 0.66 +/- 0.13 pmol/mg DNA for T3 (P less than 0.05 compared to normal) and was 3.58 +/- 0.56 pmol/mg DNA for T4 (P less than 0.01 compared to normal). During fasting, the average T3 MBC increased to 1.43 +/- 0.31 pmol/mg DNA and the average T4 MBC increased to 9.63 +/- 2.46 pmol/mg DNA, values that are both significantly higher than those in the fed period; the dissociation constants were unaltered in obese subjects (compared to normals) in fed and fasting states. Gel filtration with 0.5 M agarose was employed to ascertain if the physicochemical properties of the solubilized mononuclear human cell receptor were similar to those previously observed in rat and human liver and kidney receptors. The elution profile obtained was similar to that reported earlier. The major binding activity has an estimated Stokes radius of 35 A and a molecular weight ratio of approximately 50,000 daltons. These studies indicate that: 1) high affinity T3 and T4 receptors exist in human mononuclear cells and have properties similar to those for T3 and T4 described previously in rat liver; 2) T3 and T4 receptor number tends to increase in hypothyroid subjects and tend to be lower in obese patients than in normal weight control subjects; 3) fasting is associated with an increase in both T3 and T4 MBC; and 4) despite their apparent physicochemical similarity, T3 receptors in rat liver and human mononuclear cells may be regulated differently, at least during fasting since hepatic T3 receptors decrease in the fasted rat. Collectively, these observations support the concept that human white cell T3 nuclear receptor binding is capable of rapid fluctuations, suggesting a mechanism for homeostatic regulation of T3 action.

A controlled comparison of light box and head-mounted units in the treatment of seasonal depression.

BACKGROUND: Patterns of response to the light box and head-mounted unit (HMUs) in seasonal affective disorder (SAD) appear to differ. The current study employed a "no light" condition to compare the response rates with the light box and HMU against a plausible placebo. METHOD: Forty-three subjects with DSM-III-R nonpsychotic, unipolar major depression, seasonal subtype, were randomly assigned, in a double-blind manner, to receive 2 weeks of active treatment with a light box (N=9) or HMU (N=12) that emitted no visible light, or 2 weeks of placebo treatment with a light box (N=12) or HMU (N=10) that emitted no visible light. Response was defined as a 50% or greater reduction in both the 17-item "typical" score and 8-item "atypical" score on the Structured Interview Guide for the Hamilton Rating Scale for Depression-SAD version (SIGH-SAD). RESULTS: Using ANOVA for repeated measures, with change in total SIGH-SAD score as the dependent measure, we found no significant main effect of light (F=0.20, p=N.S.) or unit (F=0.50, p=N.S.), and no interaction (F=0.21, p=N.S.). Using log-linear analysis, we found no significant difference in response rate between the four cells (likelihood ratio chi-square = 2.1, p=N.S.). Using chi-square analysis, we found no significant difference in response rates between patients who received light (48%) versus patients who received no light (41%; chi-square = 0.2, p=N.S.) or between patients who received the light box (38%) versus HMU (50%; chi-square = 0.62, p=N.S.). CONCLUSION: The failure to detect any significant difference in efficacy between active and placebo treatments calls into question the specificity of light in light therapy for SAD. Methodological limitations, particularly small sample size, are discussed.

Effects of prostaglandin E1 on oxygen delivery and consumption in patients with the adult respiratory distress syndrome. Results from the prostaglandin E1 multicenter trial. The Prostaglandin E1 Study Group.

We wanted to determine the long-term effects of a continuous infusion of PGE1 on DO2 and VO2 in patients with ARDS. Data were obtained from a randomized double-blind multicenter trial, which evaluated the effects of PGE1 on survival in patients with ARDS. Patients were stratified according to treatment and outcome: placebo-died (n = 8); PGE1-died (n = 12); placebo-survived (n = 9); and PGE1-survived (n = 8). In the placebo-died group, elevations occurred in VO2, which were associated with increases in O2ext and a constant DO2. In contrast, in the PGE1-died group, elevations in VO2 were associated with increases in DO2 and an unchanged O2ext. In the placebo-survived group, VO2 and DO2 decreased, whereas in the PGE1-survived group, VO2 and DO2 increased; however, O2ext decreased in both of these groups. Since impaired O2ext occurs in ARDS, PGE1-induced elevations in DO2, rather than compensatory increases in O2ext, may achieve better tissue oxygenation. We conclude that although the recently completed multicenter trial failed to show an enhancing effect of PGE1 on survival in patients with advanced ARDS, PGE1 may have important effects on oxygen transport and, therefore, may still have a role in the treatment of early manifestations of ARDS, either alone or in combination with other agents.

An early test of survival in patients with the adult respiratory distress syndrome. The PaO2/FIo2 ratio and its differential response to conventional therapy. Prostaglandin E1 Study Group.

Patients with established adult respiratory distress syndrome (ARDS) have a mortality rate that exceeds 50 percent. We analyzed the magnitude of hypoxemia as manifest by the PaO2/FIO2 ratio and its early response to conventional therapy including positive end-expiratory pressure (PEEP) in the placebo group of a large multicenter study. The PaO2/FIO2 ratio was not different at the time of diagnosis of ARDS in those patients who lived compared to those who subsequently died. After one day of conventional therapy including PEEP, those patients who survived increased their PaO2/FIO2 ratio. The nonsurvivors did not improve over a seven-day course. The difference in the PaO2/FIO2 ratio was significant throughout the seven-day observation period. We conclude that the early response to conventional therapy picks a patient population with a good prognosis and can be used as a test of likely survival from ARDS.

Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group.

Prostaglandin E1 (PGE1) was compared to placebo in a 100-patient (50 PGE1, 50 placebo) randomized, double-blind, clinical trial to determine whether PGE1 therapy enhances survival of patients with adult respiratory distress syndrome (ARDS) when infused through a central line at 30 ng/kg/min continuously for seven days. At 30 days postinfusion, 30 PGE1 and 24 placebo patients had died. Total deaths judged to be related to the syndrome were 32 and 28 in the PGE1 and placebo groups respectively at six months. We conclude that PGE1 did not enhance survival in patients with established ARDS. PGE1 augmented the hyperdynamic circulation of these patients by reducing systemic and pulmonary vascular resistance, which resulted in a reduction of blood pressures and increased stroke volume, cardiac output, and heart rate. An improvement in oxygen availability and oxygen consumption was observed with PGE1 therapy. PGE1 was associated with an increased incidence of diarrhea (six patients in the PGE1 group vs one in the placebo group, p less than 0.05). Other adverse effects included hypotension (ten patients in the PGE1 group vs seven in the placebo group), fever (six patients in the PGE1 group vs three in the placebo group), and non-fatal dysrhythmias (ten in the PGE1 group vs five in the placebo group).

Adult respiratory distress syndrome. Sequence and importance of development of multiple organ failure. The Prostaglandin E1 Study Group.

STUDY OBJECTIVE: To determine the epidemiology of multiple organ failure (MOF) in patients with the adult respiratory distress syndrome. PATIENTS: We followed up 50 patients with serial determinations of respiratory and nonrespiratory organ function for seven days after diagnosis. DESIGN: Data were stratified between patients who died and those who survived (defined as hospital discharge). MEASUREMENTS AND RESULTS: Values that did not differ at any time between the two groups of patients included oxygen availability, oxygen consumption, oxygen extraction, PaCO2, respiratory rate, heart rate, systolic blood pressure, cardiac output, stroke index, systemic vascular resistance, and temperature. Patients who died had greater defects in oxygenation (from day 1 through day 7). They also exhibited decreased arterial oxygen content (from day 1 to day 4), decreased mixed venous oxygen content (day 1), increased peak inspiratory pressure (present on day 2, persisted to day 5, reappeared on day 7), decreased diastolic blood pressure (seen on days 1 through 3, reappeared on day 7), and increased mean pulmonary artery pressure (seen on days 2 and 3). Nonsurvivors also exhibited greater degrees of thrombocytopenia (from day 1 to day 4). Decreases in pH (seen on day 1, reappeared from days 4 to 7), abnormalities in liver function (seen only on day 1), and increases in serum creatinine levels (appeared on day 7) were also observed. CONCLUSIONS: Multiorgan dysfunction (MOD) was frequently observed in both groups of patients. Alterations in organ function and the pattern of abnormalities were often subtle and would not be characterized as significant organ dysfunction by most available organ scoring systems. Adult respiratory distress syndrome is a manifestation of systemic disease produced by widespread increases in endothelial permeability; lung dysfunction dominates the early clinical course. When respiratory function is supported, it becomes evident that alterations occur in other organs. Multiorgan failure is really a misnomer; the term emphasizes end-stage changes. Multiorgan dysfunction is common and often resolves without progressing to MOF. Alternatively, MOD can progress to MOF.

Platelet-specific alpha-granule proteins and thrombospondin in bronchoalveolar lavage in the adult respiratory distress syndrome.

Levels of platelet-specific alpha-granule proteins, PF, BTG, and TSP were measured in BAL fluids of patients with the ARDS, ILD, and normal healthy subjects, comprising two separate cohorts. In both groups BAL showed elevated levels of BTG and thrombospondin in ARDS patients. Low levels of PF4 were found in BAL and did not differ between ARDS and control patients. The BTG:PF4 ratio was 2:1 or greater in BAL of ARDS patients and of control subjects with other lung diseases, suggesting in vivo release. In ARDS patients, the ratio of TSP to BTG exceeded that usually found in plasma. In ARDS patients in group 2, BAL levels of TSP, BTG, and total protein correlated strongly with the composite injury scores that were used to quantitate their degree of lung injury. Elevated levels of platelet-derived proteins, which modulate chemotaxis of inflammatory cells and promote connective tissue reorganization, occur in the alveolar compartment of ARDS and ILD patients but are usually undetectable in BAL of healthy control subjects. Levels in these patients in BAL fluid are nonspecific indices of the severity of lung injury in patients with ARDS.

HA-1A in septic patients with ARDS: results from the pivotal trial.

OBJECTIVE: To evaluate the effects of HA-1A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS. DESIGN: Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1A in septic patients. PATIENTS: 63 septic patients with ARDS at the time of study entry. INTERVENTION: A single intravenous injection of HA-1A (100 mg) or placebo. RESULTS: A quantitative radiographic score, the PaO2/FIO2 ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p = 0.07). Using logistic regression, a significant independent effect of HA-1A treatment was detected upon the early survival rate at 7 days (p = 0.03) but not at 14 and 28 days. CONCLUSION: A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival.

Lung lymph flow after bone marrow injection into goats was reduced by indomethacin.

We examined the pulmonary response to bone marrow embolism in untreated and indomethacin-treated goats. Pulmonary arterial pressure increased by 15 cmH2O after bone marrow infusion, reaching a peak of 37.2 then stabilizing at greater than 30 cmH2O in the control group. In the treated group it increased by 4.3 cmH2O from a base line of 18.5 cmH2O but had returned to base line by 6 h. Lymph flow increased in the control group from a base line of 7.3 ml/h to a peak of 22.4 ml/h and remained near that level. It increased from a base line of 6.4 ml/h to a peak of 9.8 ml/h in the treated group and remained close to that value. The lymph-to-plasma protein ratio was little changed throughout the experiment. Cardiac output decreased by 1.2 l/min in the control group but was unchanged from base line in the treated group. Systemic arterial pressure was similar in both groups of animals. We conclude that indomethacin prevents the pulmonary hypertension seen after bone marrow infusion and protects against some of the increased permeability.

Neutrophil depletion does not prevent lung edema after endotoxin infusion in goats.

Neutropenia was produced in goats by injection of either nitrogen mustard, (1.5 mg/kg) or hydroxyurea (200 mg X kg-1 X day-1). A nitrogen mustard (M + E) group (n = 6), a hydroxyurea (H + E) group (n = 5), and a control (E) group (n = 7) were given 1-h infusions of endotoxin (5 micrograms/kg total dose), then monitored for up to 5 h. Postmortem extravascular lung water (EVLW) was significantly higher in the M + E group (14.2 +/- 4.4 ml/kg) and the E group (11.9 +/- 3.9 ml/kg) when compared with a normal control (6.6 +/- 1.3 ml/kg) group that did not receive endotoxin. EVLW in a group made neutropenic with nitrogen mustard (6.7 +/- 1.3 ml/kg) and the H + E (7.9 +/- 1.5 ml/kg) groups were not statistically different from each other or from normal controls. Circulating neutrophil counts averaged 32 +/- 42 cells/microliter in the M + E group and 180 +/- 210 cells/microliter in the H + E group. Only minimal histological changes were seen in the H + E group, but the E and M + E lungs had severe pulmonary edema. We conclude that neutrophils are not required for increased EVLW and decreased arterial O2 partial pressure after endotoxin infusion, and hydroxyurea prevents at least part of the pulmonary edema after endotoxin by a mechanism that is not neutrophil dependent.

Effect of intravenous catalase on the pulmonary vascular response to endotoxemia in goats.

Neutrophils have been implicated in the pathogenesis of acute lung injury associated with clinical and experimental sepsis. Data from in vitro systems and experimental animals have suggested that neutrophil-derived oxidants, particularly H2O2, may be primarily responsible for endothelial damage, vasoconstriction, and lung edema. With the use of endotoxin infusion as an in vivo model of sepsis we tested the hypothesis that pretreatment with catalase, a peroxide scavenger, would ameliorate the resultant changes in pulmonary vasoconstriction and lung fluid balance. Paired experiments were performed in 16 goats with chronic lung lymph fistulas. One group of animals (n = 7) received endotoxin first alone and then again, several days later, after pretreatment with Ficoll-linked catalase. As a control, identical experiments were performed in a separate group (n = 6) with Ficoll-linked albumin substituted for Ficoll-catalase. A third group (n = 3) was given endotoxin alone and then again during a continuous infusion of catalase. Plasma and lymph levels of catalase were comparable to or exceeded those previously shown to be completely protective in isolated perfused lung preparations and in vitro systems. Endotoxin caused neutropenia, pulmonary arterial hypertension, decreased cardiac output, and increases in lymph flow to approximately three times base line, with a return of all variables toward control values by 6 h. Catalase pretreatment produced no significant differences in any of these variables. These experiments do not support a role for H2O2 as a mediator of acute lung injury due to endotoxemia.

Clinical prediction of the adult respiratory distress syndrome.

The use of clinical, physiologic, and laboratory parameters in the prediction or early detection of ARDS has been reviewed. From both a clinical and research standpoint, the ability to identify patients at risk is extremely important. The selection of patients according to predisposing clinical events has been the most successful thus far. The use of physiologic variables and gauges of injury severity have been of limited value, particularly for assessing ARDS risk in the individual patient. Only a handful of the proposed mediators or markers of acute lung injury have been studied prospectively in patients at risk. Of these, factor VIII antigen, lactoferrin, and phospholipase A2 appear the most promising as laboratory tests for selecting patients at risk. In the future it may be possible by using sophisticated statistical analysis techniques to combine important clinical, physiologic, and laboratory information into a numerical ARDS risk index, essentially assigning a probability of ARDS in individual patients.

Using attachment theory to understand illness behavior.

This article examines a model of illness as a stressor that activates an individual's characteristic attachment behaviors. These behaviors are the result of the attachment system, a mammalian trait that exists in order to maximize the odds of survival of an infant born without the necessary maturation for immediate independence. Attachment concepts, such as attachment style, coherence, and reflective functioning, are briefly explained, followed by examples of their application to the psychological management of patients with medical or surgical illness. Attachment theory provides a unique, simple, and pragmatically useful model for understanding the particular ways that individuals can feel and react when stressed by illness, and how the professional may help manage that distress.

Mediators of stress effects in inflammatory bowel disease: not the usual suspects.

UNLABELLED: Empirical efforts to prove or disprove an association between stress and the course of inflammatory bowel disease (IBD) have had inconsistent results. Direct study of mediators of stress-related physiological processes may clarify this important area. METHODS: candidate mediators were selected based on evidence that they have a role in the pathophysiology of IBD. Medline searches for original articles addressing each putative mediator and psychological stress were conducted. Articles were reviewed with goals of synthesis and hypothesis generation. RESULTS: there is evidence that substance P (SP), vasoactive intestinal protein (VIP), tumour necrosis factor alpha (TNFalpha), oxidant molecules, endogenous glucocorticoids and heat shock proteins (HSPs) are involved in the stress response. DISCUSSION: two principles emerge which should inform efforts to investigate stress in IBD. First, stress effects are regulated by highly interdependent systems. Second, the effects of mediators are highly specific to the location of their activity, and so, investigations in IBD are likely to require direct investigation of inflamed and unaffected gut tissue.