Angiogenic and angiostatic chemokines in idiopathic pulmonary fibrosis and granulomatous lung disease.

BACKGROUND: Angiogenesis-angiostasis balance and leukocyte recruitment are influenced by different concentrations of distinct chemokines. OBJECTIVE: To investigate the relative contribution of angiogenic and angiostatic CXC chemokines to the pathogenesis of idiopathic pulmonary fibrosis (IPF) and granulomatous lung diseases, we examined the in vitro production of an angiogenic chemokine (IL-8), and 2 angiostatic chemokines (IP-10 and MIG) by alveolar macrophages. METHODS: Alveolar macrophages from 16 patients with granulomatous lung diseases [8 with sarcoidosis, 8 with extrinsic allergic alveolitis (EAA)], 16 patients with IPF, and 8 control subjects were cultured for 24 h. IL-8, IL-18, IP-10 and MIG in the culture supernatants were measured by a fluorescent bead-based multiplex technique. RESULTS: In IPF patients, IL-8 was increased and correlated with bronchoalveolar lavage (BAL) neutrophils, whereas the levels of IP-10 and MIG were normal. In sarcoidosis and EAA patients, IL-8, IP-10, and MIG were all increased and IP-10 and MIG correlated with IL-18, a Th1 cytokine, and the percentage and number of BAL lymphocytes. CONCLUSIONS: The difference in the expression of CXC chemokines and a Th1 cytokine may contribute to the different immunopathogenesis, clinical course and responsiveness to treatment of these diseases.

Thiopental inhibits lipopolysaccharide-induced tissue factor expression.

BACKGROUND: During Gram-negative sepsis, lipopolysaccharide (LPS) stimulates toll-like receptor 4, resulting in an activation of the immune system and the expression of tissue factor on monocytes. As a consequence, intravascular coagulation, ischemia, and multiorgan dysfunction may occur. Because thiopental has been described to modulate the immune system, we tested the hypothesis that thiopental alters the LPS-induced tissue factor expression. METHODS: (i) Citrated whole blood samples were incubated with thiopental (0, 0.25, 0.5, 1 mg/mL) and LPS (100 microg/mL) for 4 h. After recalcification, clotting time (CT) was determined by rotational thrombelastometry. (ii) The mechanism of the LPS-induced shortening of CT was investigated using the tissue factor blocker active-site inhibited factor VIIa and the protein synthesis inhibitor cycloheximide. (iii) A concentration response curve for the effect of tissue factor on CT was generated. RESULTS: LPS shortened CT from 618 +/- 122 s to 192 +/- 33 s (n = 6; P < 0.05). Shortening of CT was mediated by synthesis of tissue factor, because both inhibition of protein synthesis and blockade of tissue factor effects abolished this effect of LPS. Thiopental markedly inhibited the LPS-induced shortening of CT (372 +/- 86 s; n = 6; P < 0.001). Comparison of CT with a tissue factor standard curve demonstrated that thiopental reduced the LPS-induced tissue factor activity up to 86%. A direct effect of thiopental on coagulation was excluded, because tissue factor-induced CT was not affected by the barbiturate. CONCLUSIONS: Thiopental markedly inhibits the LPS-induced tissue factor expression in whole blood samples.

Intravenous lidocaine after tracheal intubation mitigates bronchoconstriction in patients with asthma.

BACKGROUND: Although prophylactic IV administration of lidocaine attenuates the response to a variety of inhalation challenges, its effect on airway resistance after endotracheal intubation in patients with asthma is unclear. We tested the hypothesis that IV lidocaine attenuates intubation-evoked bronchoconstriction in patients with asthma. METHODS: Thirty patients with asthma (age 49.1 +/- 15.6 yr [mean +/- sd]) undergoing intubation after standardized anesthetic induction (etomidate 0.3 mg/kg, fentanyl 5 microg/kg, rocuronium 0.6 mg/kg, 50% nitrous oxide) were studied. Airway resistance was measured immediately after intubation and 5, 10, and 15 min later. Five minutes after intubation, either lidocaine (2 mg/kg IV for 5 min, followed by 3 mg x kg(-1) x h(-1) for 10 min) or saline was administered. RESULTS: Airway resistance immediately after intubation averaged 23 +/- 12 cm H2O x s x L(-1). Airway resistance further increased (+38%) after administration of saline, but decreased (-26%, P < 0.004) to less than the initial values after lidocaine. CONCLUSIONS: IV lidocaine given after endotracheal intubation mitigates bronchoconstriction in patients with asthma.

Longitudinal study on the relationship between symptomatology of dementia and levels of subjective burden and depression among family caregivers in memory clinic patients.

The objective was to evaluate the course and severity of dementia-related symptoms and their relationship to caregivers' subjective burden and depression over time. Forty-five patients with dementia and their caregivers were followed over a period of 2 years. Patients' cognition, function, and behavioral/psychological symptoms were assessed by the Mini Mental State Examination, Syndrome Kurz Test, Geriatric Depression Screening scale, Instrumental Activities of Daily Living Scale, Physical Self Maintenance Scale, Behavioral Abnormalities in Alzheimer's Disease Rating Scale, and Nurses Observation Scale for Geriatric Patients. Caregivers' depression and subjective burden were evaluated by the Geriatric Depression Screening scale or Beck Depression Inventory and the Caregiver Burden Interview. Global dementia severity, functional impairment, and behavioral disturbances increased significantly over the 2-year observation period. Caregivers' burden remained stable, and severe depression decreased over time. There were significant associations between burden and dementia-related symptoms. For deficits in activities of daily living as well as behavioral disturbances, these associations became stronger over time. It was concluded that stage of dementia, functional deficits, and behavioral disturbances are important factors when evaluating the relationship between patients' symptoms and caregivers' well-being.

No effects of a combination of caregivers support group and memory training/music therapy in dementia patients from a memory clinic population.

OBJECTIVES: To evaluate the impact of a combination of caregiver support group and memory training/music therapy in dementia patients on behavioural and psychological symptoms (BPSD) and caregiver burden compared to a control group. METHOD: Eighteen patient-carer-dyads in the treatment group and 18 patient-carer-dyads as controls were studied in the setting of a memory clinic of a psychiatric university hospital over a period of 2 years. Controls were matched for age, gender, diagnosis, dementia severity, living arrangement and medication. The interventions were conducted once per week for 1 hour run by a clinical psychogeriatric team. Outcome measures were patients' cognitive and functional status as well as BPSD and caregivers subjective burden and depression measured by validated scales. Data were obtained 6, 12 and 24 months after baseline. RESULTS: There were no significant differences between the intervention and control group neither after 6, 12 nor after 24 months treatment. CONCLUSIONS: The lack of a positive impact in alleviating caregiver burden or BPSD after intensive psychological interventions may result from extensive care in the routine clinical management including individual counselling for patients and families. The effect of 'treatment as usual' needs to be taken into account when comparing an intervention and control group, as well as the dosage of the intervention.

Lung function under high thoracic segmental epidural anesthesia with ropivacaine or bupivacaine in patients with severe obstructive pulmonary disease undergoing breast surgery.

BACKGROUND: Because general anesthesia with tracheal intubation can elicit life-threatening bronchospasm in patients with bronchial hyperreactivity, epidural anesthesia is often preferred. However, segmental high thoracic epidural anesthesia (sTEA) causes pulmonary sympathetic and respiratory motor blockade. Whether it can be safely used for chest wall surgery as a primary anesthetic technique in patients with chronic obstructive pulmonary disease or asthma is unclear. Furthermore, ropivacaine supposedly evokes less motor blockade than bupivacaine and might minimize side effects. To test the feasibility of the technique and the hypotheses that (1) sTEA with ropivacaine or bupivacaine does not change lung function and (2) there is no difference between sTEA with ropivacaine or bupivacaine, the authors studied 20 patients with severe chronic obstructive pulmonary disease (forced expiratory volume in 1 s [FEV1] = 52.1 +/- 17.3% of predicted [mean +/- SD]) or asthma who were undergoing breast surgery. METHODS: In a double-blind, randomized fashion, sTEA was performed with 6.6 +/- 0.5 ml of either ropivacaine, 0.75% (n = 10), or bupivacaine, 0.75% (n = 10). FEV1, vital capacity, FEV1 over vital capacity, spread of analgesia (pin prick), hand and foot skin temperatures, mean arterial pressure, heart rate, and local anesthetic plasma concentrations were measured with patients in the sitting and supine positions before and during sTEA. RESULTS: Segmental high thoracic epidural anesthesia (segmental spread C4-T8 [bupivacaine] and C5-T9 [ropivacaine]) significantly decreased FEV1 from 1.22 +/- 0.54 l (supine) to 1.09 +/- 0.56 l (ropivacaine) and from 1.23 +/- 0.49 l to 1.12 +/- 0.46 l (bupivacaine). In contrast, FEV1 over vital capacity increased from 64.6 +/- 13.5 to 68.2 +/- 14.5% (ropivacaine) and from 62.8 +/- 12.4 to 66.5 +/- 13.6% (bupivacaine). There was no difference between ropivacaine and bupivacaine. Skin temperatures increased significantly, whereas arterial pressure and heart rate significantly decreased indicating widespread sympathetic blockade. All 20 patients tolerated surgery well. CONCLUSIONS: Despite sympathetic blockade, sTEA does not increase airway obstruction and evokes only a small decrease in FEV1 as a sign of mild respiratory motor blockade with no difference between ropivacaine and bupivacaine. Therefore, sTEA can be used in patients with severe chronic obstructive pulmonary disease and asthma undergoing chest wall surgery as an alternative technique to general anesthesia.

Psychometric properties of Clock Drawing Test and MMSE or Short Performance Test (SKT) in dementia screening in a memory clinic population.

OBJECTIVE: To evaluate five different scoring methods of the Clock Drawing Test (CDT) and to examine whether a combination of Mini Mental State Examination (MMSE) or Short Performance Test (Syndrom Kurz Test, SKT), respectively, with CDT can be used for cognitive screening. METHODS: Retrospective blinded analysis of clock drawing performance using five scoring methods (Shulman et al. (1986), Sunderland et al. (1989), Wolf-Klein et al. (1989), Watson et al. (1997), Manos (1997)). A Memory Clinic at an academic psychiatric hospital (University of Frankfurt am Main, Germany). 123 consecutive patients (79 dementia patients, 44 controls). Inter-rater reliability and correlation of five different scoring methods of the CDT with established psychometric tests. Sensitivity and specificity of all five CDT's using the original and modified cut-off scores. Sensitivity, specificity and positive and negative predictive value of a combination of the CDT with MMSE and SKT, respectively. RESULTS: All scoring methods of the CDT showed a highly significant interrater reliability (0.82 to 0.94). Correlation with the MMSE and the SKT was also significant (p < 0.01) for all five CDTs. Highest sensitivity was achieved by the Shulman scoring method (81% sensitivity, specificity 79%). Sensitivity of all scoring methods could be improved up to 89% by modifying the originally proposed cut-off scores at the cost of lower specificity. By combining the CDT with the MMSE or the SKT, respectively, the sensitivity of each of the tests could be improved to 92% (SKT and Shulman scale). In patients with mild dementia (GDS 3), a combination of the Shulman Scale with the SKT (92%) and the MMSE (75%) achieved the highest sensitivity. CONCLUSIONS: The CDT in combination with the MMSE or SKT is an easily administered, non threatening and highly sensitive screening test for dementia in the setting of a memory clinic.