Elektrophysiologischer Nachweis des quadratischen Differenztons am Menschen

Ohne Zusammenfassung     

Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin

Pregnancy is a major risk factor for venous thromboembolism (VTE), and low-molecular weight heparin (LMWH) seems to be safe and effective in pregnant women. Normal pregnancy is accompanied by a state of hypercoagulability, indicated by an increase in markers of coagulation activation. In a prospective cohort study, we followed 61 women who received LMWH thromboprophylaxis throughout pregnancy because of a history of VTE, hereditary thrombophilia and/or previous pregnancy-related complications. The control group consisted of 113 healthy pregnant women without antithrombotics. D-Dimer, prothrombin fragment F1+2 (F1+2) and the resistance to activated protein C (APC-ratio) were measured in all women during the first, second and third trimester. Patients and controls did not significantly differ with regard to baseline characteristics and pregnancy outcome. A (recurrent) VTE was seen in one patient despite LMWH. D-Dimer levels significantly increased among patients and controls during pregnancy (p < 0.0001), and were significantly higher among patients compared with the controls (p <0.0001) [395 ng/ml (95% CI 340-458) and 249 ng/ml (95%CI 234-266); 710 ng/ml (95% CI 602-838) and 475 ng/ml (95% CI 431-523); 1089 ng/ml (95% CI 931-1273) and 822 ng/ml (95% CI 741-911); respectively]. Levels of F1+2 significantly increased while the APC-ratio significantly decreased during pregnancy among patients and controls. Despite LMWH, pregnancy is accompanied by a substantial activation of the coagulation system.     

Effect of intranasal histamine challenge on Eustachian tube function

OBJECTIVE: To show a relationship between intranasal histamine challenge, the development of middle ear effusion and Eustachian tube (ET) dysfunction in a rat model. METHODS: Non-allergic Sprague-Dawley rats weighing between 450-600 g were randomly assigned to receive an intranasal infusion of 16 microl of 10% histamine or normal saline. ET function was assessed by using the forced-response test to measure passive and active opening and closing pressures at time intervals of 6, 10, 14, 18, 22, and 26 min and 24 h post-infusion. Mucociliary clearance times (MCCTs) of the tubotympanum at 18 min post-infusion were measured by timing the transit of dye from the middle ear to the nasopharynx. Outcome measures were ET dysfunction and evidence of clinical effusion. RESULTS: Intranasal histamine caused acute ET dysfunction when introduced into the nasopharynx demonstrated by significant elevations in passive and active opening and closing pressures (P < or = 0.001) compared to controls. The largest difference was seen at 26 min post-infusion. Furthermore, MCCTs were 2.4 times longer after infusing intranasal histamine than after saline infusion. No clinically significant effusions were evident in either group at any time interval. CONCLUSION: These data demonstrate a successful development of an intranasal histamine rat model, in addition to a relationship between intranasal histamine challenge and development of acute ET dysfunction.     

Oxygen saturation as a screening test for critical congenital heart disease: a preliminary study

The aim of this study was to assess the utility of arm and leg oxygen saturation as a candidate screening test for the early detection of ductal-dependent left heart obstructive disease. We measured arm and leg oxygen saturation in 2876 newborns admitted to well baby nurseries and 32 newborns with congenital heart disease. Fifty-seven newborns in the well baby nurseries (0.02%) had an abnormal test (leg saturation less than 92% in room air or 7% lower saturation in the leg than in the arm). Four of the 57 had critical congenital heart disease, including 1 with coarctation of the aorta. Of the 32 newborns with congenital heart disease, 11/13 (85%) with left heart obstructive disease had abnormal oxygen saturation tests, as did 15/19 (79%) with other forms of congenital heart disease. Pulse oximetry deserves further study as a screening test for critical congenital heart disease.     

Prostate carcinoma knowledge, attitudes, and screening behavior among African-American men in Central Harlem, New York City

BACKGROUND: Although the benefits of prostate carcinoma screening in reducing mortality rates have not been proven or shown to be cost-effective, screening, particularly using prostate specific antigen (PSA) tests, is widespread. A better understanding of screening behavior, knowledge of prostate carcinoma risk, and attitudes toward screening among men at high risk, such as African-American men, would be valuable. METHODS: A prevalence survey was conducted using 2 samples of African-American men, aged 50-74 years: a clinic sample drawn from all clinics in Central Harlem (n = 404) and a random-digit dial sample from the same geographic region (n = 319). The prevalence of self-reported PSA screening was estimated using a cognitive survey methodology based on the internal consistency of answers to four different questions. Prevalence estimates were adjusted to take into account the high proportion of nontelephone residences. RESULTS: The clinic sample, representing a poorer, more ill population (as determined by MOS Physical Function Scores, was less likely to report PSA screening than the community sample (11.1% in clinic sample vs. 25.5% in community). The prevalence of PSA testing in Central Harlem overall in this age group by using two different techniques was estimated to be 24%. In multiple logistic models, self-reported PSA screening was associated with age, education, favorable attitudes toward screening, and knowing someone who had prostate carcinoma. However, the association between these factors and the likelihood of self-reported PSA screening differed between clinic and community samples. CONCLUSIONS: The prevalence of self-reported PSA screening in Central Harlem was lower than that reported for other populations. These findings may be useful in the design of health education campaigns and for counseling innercity, low-income African-American patients appropriately about the disease.     

Psychosocial adjustment in children of mothers with breast cancer

Thirty-five children of 28 mothers diagnosed with breast cancer during the previous year were compared to 34 children of 24 mothers with recent benign breast biopsies. Mothers and children, ages 8-16, completed questionnaires about mood, behavior problems and social functioning to assess whether children of mothers with breast cancer were at increased risk for adjustment problems. Significant differences were not found between children in the breast cancer group and the comparison group on any of the measures, even though mothers with breast cancer reported more psychological distress than mothers with benign biopsies. In addition, children in both groups were functioning better than normative samples on some adjustment measures. Variables measuring the mother's illness and treatment were not significantly related to children's adjustment in the breast cancer group. Findings suggested that some adolescents whose mothers had breast cancer did better in social and academic activities when their mothers were more distressed, while adolescents whose mothers had benign biopsies did less well when their mothers were distressed. The study's small sample size limits conclusions that can be drawn; however, clinical and research implications are discussed, given other reports that some children of parents with cancer may experience adjustment problems.     

Pharmacokinetics of a glycine site antagonist (gavestinel) following multiple dosing in patients with acute stroke

OBJECTIVE: The objective of this study was to characterize the pharmacokinetics of gavestinel in patients with acute stroke. METHODS: Gavestinel was administered as an 800-mg loading dose and followed by either 100-, 200-, or 400-mg maintenance doses given every 12 h for five doses. Blood and urine samples were collected for pharmacokinetic evaluation. The pharmacokinetics of gavestinel were determined using compartmental analysis. RESULTS: The mean clearance (CL) and central (Vc) and steady-state (Vss) volumes of distribution across the dose groups were 0.31-0.40 l x h(-1), 3.3-3.9 l, and 9.8-17 l, respectively. The mean terminal half-life ranged from 29 h to 56 h. Gavestinel was extensively bound to plasma protein (median percentage free <0.01). During gavestinel administration, some patients exhibited elevated levels of bilirubin, which may be the result of shared mechanisms of elimination (glucuronide conjugation and excretion in bile). CONCLUSIONS: This study characterized the pharmacokinetics of gavestinel following multiple doses in acute stroke patients and showed that the pharmacokinetics are similar for increasing maintenance doses. The high protein binding of gavestinel was confirmed in acute stroke patients. A pharmacokinetic interaction between gavestinel and bilirubin may contribute to the increase in bilirubin.     

The mechanism of acute cytotoxicity of triethylphosphine gold(I) complexes. III. Chlorotriethylphosphine gold(I)-induced alterations in isolated rat liver mitochondrial function

Chlorotriethylphosphine gold(I) (TEPAu) is an organo-gold compound that has therapeutic activity in animal models of rheumatoid arthritis. Initial studies have suggested that TEPAu is a potent cytotoxic compound in vitro against a variety of cultured cell types and isolated hepatocytes. Mitochondrial dysfunction induced by this compound has been suggested as a primary biochemical alteration which may result in lethal cell injury in isolated hepatocytes. The purpose of this study was, therefore, to determine the mechanism of TEPAu-induced dysfunction of isolated rat liver mitochondria. TEPAu induced a rapid, concentration-related collapse of the mitochondrial inner membrane potential (EC50 = 24.7 +/- 2.5 microM) which was potentiated in Ca2+ loaded mitochondria (EC50 = 11.3 +/- 3.8 microM). TEPAu-induced collapse of the membrane potential was partially inhibited in the presence of ruthenium red or EGTA. TEPAu caused the rapid release of mitochondrially sequestered Ca2+ which was not inhibited by ruthenium red and, thus, was not via a reversal of the Ca2+ uniporter. TEPAu caused mitochondrial swelling, increased permeability of the inner membrane, and the oxidation/hydrolysis of endogenous mitochondrial pyridine nucleotides. Addition of exogenous ATP slightly reversed the effects of TEPAu on pyridine nucleotides. TEPAu-induced mitochondrial alterations were reversed or inhibited by exposure to the sulfhydryl reducing agent, dithiothreitol. Also, the TEPAu-induced collapse of the mitochondrial membrane potential was partially inhibited by dibucaine, a non-specific inhibitor of phospholipases. These data suggest that TEPAu-induced mitochondrial dysfunction is sulfhydryl dependent. TEPAu-induced mitochondrial dysfunction results in dissipation of the potential difference across the inner mitochondrial membrane which inhibits mitochondrial oxidative phosphorylation. The mechanism by which TEPAu induces the collapse of the membrane potential may be mediated by a sulfhydryl-dependent increase in permeability of the inner membrane to protons.