Indocyanine-green videoangiography of drusen as a possible predictive indicator of exudative maculopathy

OBJECTIVE: Recent studies have shown that indocyanine-green videoangiography (ICG-V) is useful to image occult choroidal neovascularization. The authors studied the ICG-V findings in fellow drusen eyes of patients with unilateral exudative age-related macular degeneration (AMD). The authors also studied the occurrence of exudative changes to determine whether ICG-V is useful in predicting future exudative changes in these eyes with only drusen. DESIGN: Cohort study. PARTICIPANTS: The authors studied 432 consecutive patients diagnosed with unilateral exudative AMD in whom the fellow eye had only drusen by clinical fundus examination and fluorescein angiography. All of these eyes had ICG-V performed. Follow-up data were obtained in all eyes with abnormal indocyanine-green (ICG) angiograms and randomly sampled ICG angiograms of normal eyes. MAIN OUTCOME MEASURES: The initial ICG findings were classified as showing normal or abnormal hyperfluorescence. Abnormal hyperfluorescence eyes were subdivided into focal spots (focal areas of hyperfluorescence < 1 disc area in size) and plaques (areas of hyperfluorescence > 1 disc area). The development of exudative changes in eyes with normal and abnormal hyperfluorescence was compared. RESULTS: Of the 432 fellow eyes, 386 (89%) eyes with drusen had a normal ICG-V study, whereas 46 (10 focal spots and 36 plaques) (11%) eyes had an abnormal ICG-V. Exudative changes occurred in 6 (10%) of 58 normal ICG eyes and 9 (24%) of 38 eyes with abnormal ICG findings during a mean follow-up period of 21.7 months. The difference between drusen eyes with normal ICG angiograms and those with plaques on ICG-V regarding future exudative changes (10% vs. 27%, respectively) was statistically significant (P = 0.038). CONCLUSIONS: Abnormal ICG findings were found in 11% of eyes with clinically and fluorescein angiographically nonsuspicious drusen. The subgroup of patients with plaques on ICG-V had a higher chance of having exudative changes develop. Indocyanine-green videoangiography may be a predictive indicator of future exudative changes in eyes with drusen. A much larger prospective study seems justified.     

Correlates of fatigue in older women with heart failure

OBJECTIVE: To examine the relative contribution of psychologic factors and physical symptoms to the variance in fatigue in older women with heart failure. METHODS: Eighty women who had been hospitalized in the previous 12 months for heart failure were interviewed. Fifty-seven women completed second interviews 18 months after the first interview. RESULTS: Fatigue was the most frequently occurring physical symptom at both measurement times, and it significantly increased with time. Other physical symptoms contributed uniquely to the variance in fatigue at both measurement times, but psychologic factors did not. At time 1, sleep difficulties, chest pain, and weakness each explained unique variance in fatigue. At time 2, dyspnea was the only variable that explained unique variance in fatigue (9%). Dyspnea also explained a significant portion of the variance (7%) in time 2 fatigue, when time 1 fatigue was controlled. CONCLUSIONS: Fatigue in older women with heart failure is related more to other physical symptoms than psychologic factors.     

New nonsteroidal androgen receptor modulators based on 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g] quinolinone

Typhoid fever is often associated with abnormal liver biochemical tests, but severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. There have been more than 150 cases of salmonella hepatitis reported from both developed and developing countries. The documented incidence varies widely from less than 1% to 26% patients with enteric fever. The possible associated factors for development of salmonella hepatitis are virulence of the organisms, delayed treatment and poor general health of the patients. The pathogenesis of severe hepatic involvement in salmonella infection may be multifactorial and includes endotoxin, local inflammatory and/or host immune reactions. Clinical jaundice in salmonella hepatitis usually occurs within the first 2 weeks of the febrile illness. Hepatomegaly and moderate elevation of transaminase levels are common findings. Extreme hepatic dysfunction with hepatic encephalopathy is a rare coexisting complication in salmonella hepatitis. A positive culture for salmonella from blood or stool is essential to differentiate salmonella hepatitis from other causes of acute hepatitis. Hepatic pathology is characterized by the presence of typhoid nodules with marked hyperplasia of reticuloendothelial cells. The prognosis is usually good as salmonella hepatitis responds well to a specific antibiotic therapy and juandice resolves with clinical improvement. The clinical course can be severe with a mortality rate as high as 20%, particularly with delayed treatment or in patients with other complications of salmonella infection. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance.     

Reaction products of ammonium nitrate phosphate fertilizers of varying water-soluble phosphorus content in different Indian soils

Studies were undertaken on the isolation and identification of reaction products of ammonium nitrate phosphate (ANP) fertilizers containing 30, 50 and 70 per cent water-soluble phosphorus (WSP) of total phosphorus in representative soils of the vertisol, oxisol, alfisol, entisol, mollisol and aridisol groups of India. ANP fertilizers were applied in solid form to soil, and reaction products formed at and around the site of ANP fertilizer placement were identified after six weeks incubation in moist soils by X-ray diffraction technique. DCPD (dicalcium phosphate dihydrate- CaHPO₄ · 2H₂O) was the major reaction product of ANP fertilizers containing 30 and 50 per cent WSP in vertisol, entisol, aridisol, mollisol, oxisol and alfisol, and of ANP containing 70 per cent WSP in vertisol, entisol, alfisol, aridisol and mollisol. DCP (dicalcium phosphate-CaHPO₄) was detected with ANP of 30 and 50 per cent WSP in the vertisol, alfisol, entisol, mollisol and aridisol groups of soils. In addition to DCPD, FePO₄ · 2H₂O (metastrengite) and AlPO₄ · 2H₂ O-monoclinic (metavariscite) were formed in alfisol and oxisol soils with ANP of 30 and 50 per cent WSP. FePO₄ · 2H₂O and AlPO₄ · 2H₂O (metavariscite) were identified in alfisol and oxisol soils while AlPO₄ · 2H₂O-orthorhombic (variscite) was formed in alfisol soils with ANP of 70 per cent WSP.     

Extension of IMC tuning correlations for non-self regulating (integrating) processes

The filter term of a PID with Filter controller reduces the impact of measurement noise on the derivative action of the controller. This impact is quantified by the controller output travel defined as the total movement of the controller output per unit time. Decreasing controller output travel is important to reduce wear in the final control element. Internal Model Control (IMC) tuning correlations are widely published for PI, PID, and PID with Filter controllers for self regulating processes. For non-self regulating (or integrating) processes, IMC tuning correlations are published for PI and PID controllers but not for PID with Filter controllers. The important contribution of this work is that it completes the set of IMC tuning correlations with an extension to the PID with Filter controller for non-self regulating processes. Other published correlations (not based upon the IMC framework) for PID with Filter controllers fix the filter time constant at one-tenth the derivative time regardless of the model of the process. In contrast, the novel IMC correlations presented in this paper calculate a filter time constant based upon the model of the process and the user's choice for the closed-loop time constant. The set point tracking and disturbance rejection performance of the proposed IMC tunings is demonstrated using simulation studies and a bench-scale experimental system. The proposed IMC tunings are shown to perform as well as various PID correlations (with and without a filter term) while requiring considerably less controller action.     

Temperature variation in stored maize and its effect on capture of beetles in grain probe traps

Seasonal and spatial distribution of Typhaea stercorea (L.) and Tribolium castaneum (Herbst) infesting farm-stored maize in South Carolina were studied by trapping with grain probe traps. Trap catch (numbers captured per week) and weekly mean grain temperature for each trap site were plotted against time and fitted to cubic polynomials, which adequately described seasonal trends. Spatial distribution of trap catch was examined by calculating the coefficient of variation, or dispersion (s²/m) and by constructing a contour map of trap catch values for each week. Seasonal trends in trap catch varied with species, farm, and storage season, and tended to parallel temperature trends, so that trap catch and temperature were positively correlated. Trap catch was highly aggregated except for weeks when few insects were captured. Residuals (observed-predicted values), calculated from the fitted trend curves, represent the spatial component of variation. When residuals were analyzed, the positive correlation between temperature and trap catch was usually reduced or abolished, indicating that spatial variability within any given week reflected the distribution of the population itself, rather than spatial variability in activity produced by temperature gradients. The number of insects captured by a trap is determined mainly by insect activity and the numbers present, but there are no rigorous methods for separating the immediate effect of temperature on activity from the delayed effect on population growth. However, by comparing trends in trap catch with those in temperature, it is sometimes possible to make inferences about changes in population density.     

Enhancement of the surface expression of tumor necrosis factor alpha (TNFalpha) but not the p55 TNFalpha receptor in the THP-1 monocytic cell line by matrix metalloprotease inhibitors

The monocytic cell line THP-1 can be induced to express and release tumor necrosis factor alpha (TNFalpha) and both TNFalpha receptors (p55 and p75) upon exposure to bacterial lipopolysaccharide (LPS). The broad-spectrum matrix metalloprotease (MMP) inhibitors [4-(N-hydroxyamino)-2R-isobutyl-3S-(phenylthiomethyl)succinyl]-L-p henylalanine-N-methylamide (GI-129471) and marimastat [2S-[N4(R*),2R*,3S*]]-N4[2,2-dimethyl-1-[(methylamino)carbonyl]propyl]-N 1,2-dihydroxy-3-(2-methylpropyl)butanediamide (BB-2516) were effective inhibitors of LPS-induced TNFalpha (soluble) release with IC50 values of 0.2 and 4.0 microM, respectively. Upon LPS stimulation, the expression of pro-TNFalpha (membrane associated) on the cell surface (FACS analysis) could not be observed. However, in the presence of GI-129471, a concentration-dependent increase in TNFalpha surface expression was observed. Peak expression (percentage of cells expressing pro-TNFalpha and mean fluorescence units) in the presence of GI-129471 was at 2 hr, and steadily declined to return to near control levels by 8 hr. This time course was similar to TNFalpha release, which also peaked at 2-4 hr after LPS exposure and then declined. Stimulation of THP-1 cells with LPS + phorbol myristate acetate increased the percentage of cells expressing pro-TNFalpha by 10-fold. In the presence of GI-129471, these increases were augmented further and peaked between 2 and 4 hr, but also returned to near control levels of expression by 24 hr. This was in contrast to the release of soluble TNFalpha, which continued to accumulate over a 24-hr time course. TNFalpha receptor I (p55, TNFRI) and II (p75, TNFRII) shedding was also inhibited by GI-129471 (IC50 = 1.5 and 3.1 microM, respectively) and BB-2516 (IC50 = 14 and 15 microM, respectively). Unlike pro-TNFalpha surface expression, surface expression of both TNFalpha receptors steadily increased over 72 hr. In contrast to pro-TNFalpha surface expression, TNFRI surface expression was not augmented by these MMP inhibitors in THP-1 cells after LPS stimulation. Surface expression of TNFRII was augmented by these MMP inhibitors. These results suggest that even in the continued presence of LPS stimulation and an inhibitor of TNFalpha processing, the augmented surface expression of TNFalpha is transient. The potential "deleterious" implications of high levels of surface pro-TNFalpha expression in the presence of these inhibitors may be lessened by its transient nature.     

Disposition of 14C-eptifibatide after intravenous administration to healthy men

Eptifibatide, a synthetic peptide inhibitor of the platelet glycoprotein IIb/IIIa receptor, has been studied as an antithrombotic agent in a variety of acute ischemic coronary syndromes. The purpose of the present study was to characterize the disposition of 14C-eptifibatide in man after a single intravenous (i.v.) bolus dose. 14C-Eptifibatide (approximately 50 microCi) was administered to eight healthy men as a single 135-microgram/kg i.v. bolus. Blood, breath carbon dioxide, urine, and fecal samples were collected for up to 72 hours postdose and analyzed for radioactivity by liquid scintillation spectrometry. Plasma and urine samples were also assayed by liquid chromatography with mass spectrometry for eptifibatide and deamidated eptifibatide (DE). Mean (+/- SD) peak plasma eptifibatide concentrations of 879 +/- 251 ng/mL were achieved at the first sampling time (5 minutes), and concentrations then generally declined biexponentially, with a mean distribution half-life of 5 +/- 2.5 minutes and a mean terminal elimination half-life of 1.13 +/- 0.17 hours. Plasma eptifibatide concentrations and radioactivity declined in parallel, with most of the radioactivity (82.4%) attributed to eptifibatide. A total of approximately 73% of administered radioactivity was recovered in the 72-hour period following 14C-eptifibatide dosing. The primary route of elimination was urinary (98% of the total recovered radioactivity), whereas fecal (1.5%) and breath (0.8%) excretion was small. Eptifibatide is cleared by both renal and nonrenal mechanisms, with renal clearance accounting for approximately 40% of total body clearance. Within the first 24 hours, the drug is primarily excreted in the urine as unmodified eptifibatide (34%), DE (19%), and more polar metabolites (13%).