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P Kaw

Publications and source records attributed to P Kaw.

9 recordsLinked to original sources

Anomalous resistivity resulting from MeV-electron transport in overdense plasma.

Laser produced hot electron transport in an overdense plasma is studied by three-dimensional particle-in-cell simulations. Hot electron currents into the plasma generate neutralizing return currents in the cold plasma electrons, leading to a configuration which is unstable to electromagnetic Weibel and tearing instabilities. The resulting current filaments self-organize through a coalescence process finally settling into a single global current channel. The plasma return current experiences a strong anomalous resistivity due to diffusive flow of cold electrons in the magnetic perturbations. The resulting electrostatic field leads to an anomalously rapid stopping of fast MeV electrons (almost 3 orders of magnitude stronger than that through classical collisional effects).

Journal Article↗

Three-dimensional particle-in-cell simulations of energetic electron generation and transport with relativistic laser pulses in overdense plasmas.

The interaction of relativistic laser light with overdense plasmas is studied by three-dimensional particle-in-cell simulations. Generation of layered current sheets and quasistatic magnetic fields is observed near the target surface owing to anisotropic laser filamentation and Weibel instabilities. Later these current sheets tear into filaments that partially merge with each other to form isolated magnetic channels penetrating into the dense plasmas. It is found that fast electron energy flow is not only inside the magnetic channels but also it is widely distributed outside the channels. This is possible because of electron anomalous diffusion across self-generated magnetic fields. Consequently, the total hot electron current exceeds a few hundred kiloamperes and is much larger than the Alfvén current. Hence a considerable amount of energy flows towards the plasma core. Significant heating of the bulk plasma electrons is also observed.

Journal Article↗

Commonly missed diagnoses in the childhood eye examination.

Early and accurate detection of eye disorders in children can present a challenge for family physicians. Visual acuity screening, preferably performed before four years of age, is essential for diagnosing amblyopia. Cover testing may disclose small-angle or intermittent strabismus. Leukocoria, which is detected with an ophthalmoscope, may indicate retinoblastoma or cataract. Children with glaucoma may have light sensitivity and enlargement of the cornea, and conjunctivitis that does not respond quickly to treatment may reflect more serious ocular inflammation. Children with serious eye injuries often present to the primary care physician. Nystagmus and many systemic conditions are associated with specific eye findings.

Amblyopia↗

Impact of the order of initiation of fluconazole and amphotericin B in sequential or combination therapy on killing of Candida albicans in vitro and in a rabbit model of endocarditis and pyelonephritis.

In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of Candida albicans to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of C. albicans to AMB and on the outcome. The contribution of FLC-induced resistance to AMB for C. albicans also was assessed. In vitro, AMB monotherapy rapidly killed each of four C. albicans strains; FLC alone was fungistatic. Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to >40 h. Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation. Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC-->AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone. This antagonistic effect persisted for at least 24 h. Simultaneous exposure of C. albicans to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of > or =1 microg/ml; antagonism was seen using an AMB concentration of 0.5 microg/ml. The in vitro findings accurately predicted outcomes in our rabbit infection model. In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB-->AMB+FLC) rapidly sterilized kidneys and cardiac vegetations. AMB+FLC(simult) and FLC-->AMB treatments were slower in clearing fungi from infected tissues. FLC monotherapy and FLC-->AMB+FLC were both fungistatic and were the least active regimens. No adverse interaction was observed between AMB and FLC for the AMB-->FLC regimen. However, FLC-->AMB treatment was slower than AMB alone in clearing fungi from tissues. Thus, our in vitro and in vivo studies both demonstrate that preexposure of C. albicans to FLC reduces fungal susceptibility to AMB. The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.

Amphotericin B↗

Pharmacodynamics of daptomycin in a murine thigh model of Staphylococcus aureus infection.

Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of daptomycin for S. aureus using in vitro methods and the Craig (W. A. Craig, J. Redington, and S. C. Ebert, J. Antimicrob. Chemother. 27[Suppl. C]:29--40, 1991) neutropenic mouse thigh infection model. In Mueller-Hinton broth, the MICs for three S. aureus isolates were 0.1 to 0.2 microg/ml. In mouse serum, the MICs were 1.0 microg/ml. The protein binding of daptomycin was 90 to 92.5% in mouse serum. Single-dose intraperitoneal (i.p.) pharmacokinetic studies with infected mice showed a linear relationship between dose versus the maximum concentration of drug in serum and dose versus the area under the concentration-time curve (AUC). The serum half-life of daptomycin in infected mice was approximately 1.8 h. In single-dose, dose-ranging studies using mice, daptomycin showed a dose-response effect described by an inhibitory sigmoid E(max) (maximum effect) curve (r = 0.974; P << 0.001). The density of S. aureus in untreated controls was 8.26 log(10) CFU/g, and the E(max) was 3.97 log(10) CFU/g. The 50% effective dose (ED(50)) was 3.7 mg/kg of body weight i.p. and the stasis dose was 7.1 mg/kg. Dose fractionation studies at schedules of Q6h, Q12h, and Q24h, for total 24-h ED(30), ED(60), and ED(80) doses of 2.5, 5.6, and 15 mg/kg i.p., showed no difference in effect at each total 24-h dose level by schedule, indicating that the AUC/MIC ratio is the dynamically linked variable.

Animals↗

Treatment of subtotal medial rectus myectomy complicating functional endoscopic sinus surgery.

During the past 2 decades, the introduction of functional endoscopic sinus surgery (FESS) has dramatically improved the treatment of sinus disorders. However, a variety of orbital complications have been reported, including optic nerve damage, hemorrhage, infection, compromise of the lacrimal drainage apparatus, and strabismus. At least 10 cases have reported damage to the medial rectus muscle. (1-8) Treatment options for such patients have been limited, especially because most are adults at risk for anterior segment ischemia after transposition of vertical rectus muscles. We describe 2 patients whose medial rectus myectomies were repaired by using nonabsorbable "hang-back" sutures in combination with a botulinum toxin (Botox) injection of the antagonist lateral rectus muscle. Good primary position alignment was achieved in both patients, and one patient was able to regain binocular function. We recommend this surgical approach, especially in patients at increased risk for anterior segment ischemia.

Adult↗

Pharmacodynamics of fluconazole in a murine model of systemic candidiasis.

In this study we defined the pharmacodynamic parameter that optimizes outcome in deep-seated Candida albicans infections treated with fluconazole. Using a murine model of systemic candidiasis, we conducted single-dose dose-ranging studies with fluconazole to determine the dosage of this drug that resulted in a 50% reduction in fungal densities (50% effective dose [ED50]) in kidneys versus the fungal densities in the kidneys of untreated controls. We found that the ED50 of fluconazole given intraperitoneally was 4.56 mg/kg of body weight/day (95% confidence interval, 3.60 to 5.53 mg/kg/day), and the dose-response relationship was best described by an inhibitory sigmoid maximal effect (Emax) curve. To define the pharmacodynamics of fluconazole, we gave dosages lower than, approximating, and higher than the ED50 of fluconazole (range, 3.5 to 5.5 mg/kg/day, equivalent to the ED16 to the ED75) to various groups of infected animals using three dose-fractionation schedules. For each total dose of fluconazole examined, the dose-fractionation schedules optimized the ratio of the area under the concentration-time curve (AUC) to the MIC (the AUC/MIC ratio), the ratio of the maximum concentration of drug in serum (Cmax) to the MIC, and the time that the drug remained above the MIC for the infecting C. albicans isolate. Similar reductions in fungal densities in kidneys were seen between groups that received the same total dose of fluconazole in one, two, or four equally divided doses. Thus, dose-fractionation studies demonstrated that the pharmacodynamic parameter of fluconazole that best predicted outcome was the AUC/MIC ratio.

Animals↗