Traumatic Brain Injury and Suicidal Ideation Among U.S. Operation Enduring Freedom and Operation Iraqi Freedom Veterans

Traumatic brain injury (TBI) is associated with suicidal behavior among veterans, and gender differences in the strength of associations may exist. Almost all research has been limited to Veterans Health Administration (VHA) patients, and it is unclear if findings generalize to veterans who do not use VHA services. We examined gender‐ and VHA‐user‐specific associations between TBI related to deployment and postdeployment suicidal ideation in a U.S. national sample of 1,041 female and 880 male Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans. Path analysis was used to estimate TBI and suicidal ideation association, and examine PTSD and depression symptomatology in these associations. TBI was associated with suicidal ideation among male VHA users, OR = 3.64, 95% CI [2.21, 6.01]; and male and female nonusers, OR = 2.24, 95% CI [1.14, 4.44] and OR = 2.65, 95% CI [1.26, 5.58], respectively, in unadjusted analyses. This association was explained by depression symptoms among male and female nonusers. Among male VHA users an association between TBI and suicidal ideation remained when accounting for depression symptoms, OR = 2.50, 95% CI [1.33, 4.71]. Our findings offered evidence of an association between TBI and suicidal ideation among male OEF/OIF VHA users.     

Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults

STUDY OBJECTIVE: To determine the steady-state, extracellular, and intracellular pulmonary disposition of moxifloxacin (MXF), levofloxacin (LEVO), and azithromycin (AZI) relative to that of the plasma over a 24-h dosing interval. DESIGN: Randomized, multicenter, open-label investigation. PATIENTS: Forty-seven older adults (mean [+/- SD] age, 62 +/- 13 years) undergoing diagnostic bronchoscopy. INTERVENTIONS: Oral administration of MXF, 400 mg, LEVO, 500 mg daily for five doses, or AZI, 500 mg for one dose, then 250 mg daily for four doses. BAL and venipuncture were completed at 4, 8, 12, or 24 h following the administration of the last dose. MEASUREMENTS AND RESULTS: Steady-state MXF, LEVO, and AZI concentrations were determined in the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs). The concentrations of all three agents were greatest in the AMs followed by the ELF compared to the plasma. Plasma concentrations were similar to those previously reported with these agents. The mean ELF concentrations at 4, 8, 12, and 24 h were as follows: MXF, 11.7 +/- 11.9, 7.8 +/- 5.1, 10.5 +/- 3.7, and 5.7 +/- 6.3 micro g/mL, respectively; LEVO, 15.2 +/- 4.5, 10.2 +/- 6.7, 6.9 +/- 4.4, and 2.9 +/- 1.7 micro g/mL, respectively; and AZI, 0.6 +/- 0.4, 0.7 +/- 0.4, 0.9 +/- 0.5, and 0.9 +/- 0.7 micro g/mL, respectively. The AM concentrations at 4, 8, 12, and 24 h were as follows: MXF, 47.7 +/- 47.6, 123.3 +/- 126.4, 26.2 +/- 19.4, and 32.8 +/- 16.5 micro g/mL, respectively; LEVO, 28.5 +/- 30.2, 26.1 +/- 15.7, 28.3 +/- 12.6, and 8.2 +/- 6.1 micro g/mL, respectively; and AZI, 71.8 +/- 50.1, 73.8 +/- 75.3, 155.9 +/- 81.3, and 205.2 +/- 256.3 micro g/mL, respectively. CONCLUSIONS: The intrapulmonary concentrations of MXF, LEV, and AZI were superior to those obtained in the plasma. The AM concentrations of all agents studied were more than adequate relative to the minimum concentration required to inhibit 90% of the organism population (MIC(90)) of the common intracellular pathogens (< 1 micro g/mL). These data indicate that attainable extracellular concentrations of AZI are insufficient to reliably eradicate Streptococcus pneumoniae, based on the agent's current minimum inhibitory concentration profile, whereas the mean concentrations of MXF and LEVO in the ELF exceed the MIC(90) of the S pneumoniae population. Moreover, MXF concentrations exceeded the S pneumoniae susceptibility breakpoint (1.0 micro g/mL) at all time points, while 2 of 15 concentrations (13%) failed to maintain LEVO concentrations above the breakpoint (2.0 micro g/mL) throughout the dosing interval.     

Combination chemotherapy (M-2) protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone) for Waldenstrom macroglobulinemia: preliminary report

Fourteen consecutively referred, symptomatic patients with Waldenstrom's macroglobulinemia (ages 52-87 yr) have been treated with the 5-drug M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Three patients were previously treated and 11 patients were untreated. The majority of patients were symptomatic from hyperviscosity. All patients have responded to therapy. Two patients have achieved complete remissions and 12 patients partial remissions to date. None of the patients with symptomatic hyperviscosity has required plasmapheresis since therapy with the M-2 has been initiated. Lymphadenopathy, hepatosplenomegaly, and anemia have also responded to treatment. Follow-up data are limited, with survival from initiation of therapy with the M-2 ranging from 2+ to 35% mo (median 17+ mo) 2+-40+ mo from time of diagnosis). Combination chemotherapy for Waldenstrom's macroglobulinemia with the M-2 protocol appears to increase the response rate in patients with symptomatic disease. Further survival analysis will be carried out.     

Healing of mat mutations and control of mating type interconversion by the mating type locus in Saccharomyces cerevisiae

Homothallic yeasts switch cell types (mating types a and α) at high frequency by changing the alleles of the mating type locus, MATa and MATα. We have proposed in the cassette model that yeast cells contain silent MATa and MATα blocs (“cassettes”), copies of which can be substituted at the mating type locus for the resident information. The existence of silent cassettes was originally proposed to explain efficient switching of a defective MATα locus (matα) to a functional MATα locus. We report here that this “healing” of mat mutations is a general property of the mating type interconversion system and is not specific to the class of matα mutations studied earlier: a defective MATa (mata1) switches readily to MATa and various matα loci switch readily to MATα. These observations satisfy the prediction of the cassette model that all mutations within MATa and MATα be healed. These studies also identify MAT functions that control the switching process: the same functions known to promote sporulation and prevent mating in a/α cells also inhibit the switching system in a/α cells. Finally, we present additional characterization of a natural variant of MATα, MATα-inc [Takano, I., Kusumi, T. & Oshima, Y. (1973) Mol. Gen. Genet. 126, 19-28] that is insensitive to switching. Our observation that MATα-inc acts in cis suggests that it may be altered in a site concerned with excision of MATα-inc or its replacement by another cassette.     

Effects of angiotensin II on membrane current in cardiac Purkinje fibers

We studied the actions of the octapeptide hormone angiotensin II (AII) on isolated cardiac Purkinje fibers. AII (1 to 75 nm) increased the height and duration of the plateau phase of the action potential and increased the strength of contraction in these preparations. These effects were not blocked by propranolol (10^?6m). A two-microelectrode voltage clamp technique combined with simultaneous tension measurements was used to study the AII-induced changes in membrane current and contractile activation. AII enhanced peak tension and promoted an inward shift in the net membrane current-voltage relation at test voltages between ?40 and 0 mV. The inward shift in current was maintained for the duration of the 500 ms test voltage step. The AII-induced current shift was reduced or abolished when external calcium concentration was decreased from 5.4 mm to 1.8 mm, and was inhibited by the calcium antagonist D600.     

Maximal exercise test as a predictor of risk for mortality from coronary heart disease in asymptomatic men

Exercise testing in asymptomatic persons has been criticized for failing to accurately predict those at risk for coronary heart disease (CHD). Previous studies on asymptomatic subjects, however, may not have been large enough or long enough to provide reliable outcome measures. This study examines the ability of a maximal exercise test to predict death from CHD and death from any cause in a population of asymptomatic men. This is a prospective longitudinal study performed between 1970 and 1989, with an average follow-up of 8.4 years. The subjects are 25,927 healthy men, 20 to 82 years of age at baseline (mean 42.9 years) who were free of cardiovascular disease and who were evaluated in a preventive medicine clinic. The main outcome measures are CHD mortality and all-cause mortality. During follow-up there were 612 deaths from all causes and 158 deaths from CHD. The sensitivity of an abnormal exercise test to predict coronary death was 61%. The age-adjusted relative risk of an abnormal exercise test for CHD death was 21 (6.9 to 63.3) in those with no risk factors, 27 (10.7 to 68.8) in those with 1 risk factor, 54 (21.5 to 133.7) in those with 2 risk factors, and 80 (30.0 to 212. 5) in those with >/=3 factors. A maximal exercise test performed in asymptomatic men free of cardiovascular disease does appear to be a worthwhile tool in predicting future risk of CHD death. An abnormal exercise test is a more powerful predictor of risk in those with than without conventional risk factors.