Intrinsic positive end-expiratory pressure in Acute Respiratory Distress Syndrome (ARDS) Network subjects

OBJECTIVE: We tested the hypothesis that subjects randomized to the 6 mL/kg predicted body weight tidal volume study group of the National Institutes of Health Acute Respiratory Distress Syndrome (ARDS) Network study had higher levels of intrinsic positive end-expiratory pressure (PEEP) than subjects randomized to the 12 mL/kg predicted body weight tidal volume study group. DESIGN: Secondary analysis of a subgroup from a randomized controlled trial. SETTING: Hospitals located in San Francisco, CA, and Seattle, WA. PATIENTS: Eighty-four patients enrolled in the ARDS Network tidal volume trial in San Francisco, CA, and Seattle, WA, with records of measurement of intrinsic PEEP. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intrinsic PEEP was assessed a median of six times over the first 48 hrs of ARDS Network protocol ventilation in study subjects, with no significant difference in number of measurements between subjects randomized to the tidal volume protocol of 6 mL/kg compared with 12 mL/kg. We found that intrinsic PEEP was higher among subjects randomized to the 6 mL/kg protocol, with a median intrinsic PEEP of 1.3 cm H2O (interquartile range, 0-3.1 cm H2O), compared with a median intrinsic PEEP of 0.5 cm H2O (interquartile range, 0-1.5 cm H2O) among subjects randomized to 12 mL/kg (p = .029). There was no difference in total PEEP between the study groups. CONCLUSIONS: In a subgroup of ARDS Network subjects, intrinsic PEEP was statistically significantly higher in subjects randomized to the 6 mL/kg protocol than those in the 12 mL/kg study group. The amount of intrinsic PEEP was very low in both study groups, and difference of median intrinsic PEEP between the groups was <1 cm H2O. It is unlikely that the difference in intrinsic PEEP between the study groups was clinically important in the ARDS Network study of low tidal volume ventilation.     

Reversal of learning and memory impairments following lesion of the nucleus basalis magnocellularis (NBM) by concurrent noradrenergic depletion using DSP4 in the rat.

In the following study the behavioural effects of simultaneous lesion of the nucleus basalis magnocellularis (NBM) using ibotenic acid and noradrenergic depletion following a single i.p. administration of DSP4 (50 mg/kg) were examined in the rat. NBM lesion induced a deficit in acquisition of a reinforced T-maze alternation task, a working memory adaptation of a spatial navigation task in a water maze and 24 h retention in a passive avoidance task compared to sham controls. No effect of the lesion on a reference memory version of spatial navigation in a water maze task was found. Animals that received a combination of NBM lesion and DSP4 treatment showed no impairment on any of the tasks that were impaired by NBM lesion alone. This indicates a reversal of the learning and memory deficits consequent to NBM lesion by simultaneous noradrenergic depletion. NBM lesion induced a significant reduction in choline-acetyltransferase activity in the frontal cortex, and DSP4 induced a significant decrease in noradrenaline concentration in occipital cortex and hippocampus, confirming the effects of these treatments. These results suggest an interaction between central noradrenergic and cholinergic systems in learning and memory processes.     

Glomerular and tubular function in glycogen storage disease

Urinary protein and calcium excretion were assessed in 77 patients with the hepatic glycogen storage diseases (GSD): 30 with GSD-I (median age 12.4 years, range 3.2–32.9 years), 25 with GSD-III (median age 10.5 years, range 4.2–31.3 years) and 22 with GSD-IX (median age 11.8 years, range 1.2–35.4 years). Inulin (C _inulin) and para-aminohippuric acid (C _PAH) clearances were also measured in 33 of these patients. Those with GSD-I had significantly greater albumin (F=15.07,P<0.001), retinolbinding protein (RBP) (F=14.66,P<0.001),N-acetyl--d glucosaminidase (NAG) (F=9.41,P<0.001) and calcium (F=7.41,P=0.001) excretion than those with GSD-III and GSD-IX. GSD-I patients (n=18) also had significantly higherC _inulin (F=5.57,P=0.009), butC _PAH did not differ (F=0.77, NS). Renal function was normal in GSD-III and GSD-IX patients. In GSD-I,C _inulin (r=–0.51,P=0.03) and NAG excretion (r=–0.40,P=0.03) were inversely correlated with age, whereas albumin excretion was positively correlated with age (r=+0.41,P=0.03). RBP and calcium excretion were generally high throughout all age groups. Hyperfiltration in GSD-I is associated with renal tubular proteinuria that occurs before the onset of significant albuminuria. Deficiency of glucose-6-phosphatase within the proximal renal tubule may primarily cause tubular dysfunction, glomerular hyperfiltration being a secondary phenomenon.     

From Veterans Administration Hospital,Hines, Illinois

Red eyes are caused by foreign bodies; acute congestive, chronic simple and chronic congestive glaucoma; acute iritis; and conjunctivitis, which may be bacterial, viral or allergic in origin.

Accurate diagnosis permits early and definitive treatment of numerous potentially serious threats to vision.

Signs and symptoms of the causative conditions are described, and preferred therapy is indicated.     

The association of psychiatric medication use with adherence in patients with HIV

Over two million new cases of HIV infection will occur annually, worldwide. Triple drug anti-retroviral therapy (ART) decreases the viral load in patients with HIV, helping to stop progression of HIV infection to AIDs. Our study assessed how pharmacologic treatment for mental health issues affects medication adherence and viral load in patients with HIV. We conducted a retrospective chart review of 163 patients with HIV who had at least 2 visits at the HIV-clinic at Ascension St. John Hospital. Data were collected on demographics, medications, CD4 counts and viral loads. Data were analyzed using Student’s t-test, the χ² test, the Mann–Whitney U test and logistic regression. “Poor Compliance” was defined as at least 2 consecutive visits with a CD4 count <200?µL and/or with viral load ≥100?IU/ml. Patients taking antidepressants were less likely to have poor compliance than those not on anti-depressants (6.3% vs. 22.3%, p?=?0.04). A similar association was found for patients taking any psychiatric drug (7.0% vs. 23.5%, p?=?0.02). On multivariable analysis, the odds of poor compliance were 6.3 times higher in patients who stopped HIV therapy for greater than one week between visits (p?=?0.004) and 3.6 times lower in patients taking any psychiatric medication (p?=?0.05).     

Liquid chromatography electrospray ionization tandem mass spectrometry analysis method for simultaneous detection of trichloroacetic acid,dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine

Trichloroethylene (TCE, CAS 79-01-6) is a widely used industrial chemical, and a common environmental pollutant. TCE is a well-known carcinogen in rodents and is classified as “probably carcinogenic to humans”. Several analytical methods have been proposed for detection of TCE metabolites in biological media utilizing derivatization-free techniques; however, none of them is suitable for simultaneous detection of both oxidative metabolites and glutathione conjugates of TCE in small volume biological samples. Here, we report a new combination of methods for assessment of major TCE metabolites: dichloroacetic acid (DCA), trichloroacetic acid (TCA), S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG). First, DCA and TCA were extracted with ether. Second, the remaining aqueous fraction underwent solid phase extraction for DCVC and DCVG. Then, DCA and TCA were measured by hydrophilic interaction liquid chromatography ion exchange negative electrospray ionization tandem mass spectrometry, while DCVC and DCVG were measured by reverse phase positive electrospray ionization tandem mass spectrometry. This method was applied successfully to measure all 4 TCE metabolites in as little as 50 μl of serum from mice orally exposed to TCE (2100 mg/kg, 2 h). Serum concentrations (mean ± standard deviation) of the TCE metabolites obtained with this method are comparable or equivalent to those previously reported in the literature: DCA, 0.122 ± 0.014 nmol/ml (limit of detection: 0.01 nmol/ml); TCA, 256 ± 30 nmol/ml (0.4 nmol/ml); DCVG, 0.037 ± 0.015 nmol/ml (0.001 nmol/ml); DCVC, 0.0024 ± 0.0009 nmol/ml (0.001 nmol/ml). This method opens new opportunities to increase throughput and decrease number of animals required for mechanistic studies on TCE in rodents.     

The possible role of the kynurenine pathway in adolescent depression with melancholic features

Background: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M‐MDD and NonM‐MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro‐inflammatory cytokines via induction of the enzyme indoleamine 2,3‐dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM‐MDD adolescents, adolescents with M‐MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3‐hydroxyanthranilic acid (3‐HAA, neurotoxin) and 3‐HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. Methods: Subjects were 20 adolescents with M‐MDD, 30 adolescents with NonM‐MDD, and 22 healthy adolescents. MDD episode duration had to be ≥ 6 weeks and Children’s Depression Rating Scale‐Revised (CDRS‐R) scores were ≥ 36. Blood samples were collected at AM after an overnight fast and analyzed using high‐performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS‐R scores. Analyses were repeated excluding medicated patients. Fisher’s protected least significant difference was used for multiple comparisons. Results: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M‐MDD compared to NonM‐MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M‐MDD group between KYN and 3‐HAA/KYN and CDRS‐R. Conclusions: Findings support the notion that adolescent M‐MDD may represent a biologically distinct clinical syndrome.