Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin.

We compared the pharmacokinetics and the serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Fifteen healthy volunteers received 1 g of cefpirome, ceftazidime, and ceftriaxone intravenously, 500 mg of imipenem-cilastatin intravenously, and 500 mg of ciprofloxacin orally. High-performance liquid chromatographic assays were used to quantitate unchanged antibiotic in plasma and urine. Serum bactericidal activities were determined against six clinical isolates each of Staphylococcus aureus, Enterobacter cloacae, and Pseudomonas aeruginosa by using a modified microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977). Overall, cefpirome exhibited pharmacokinetics similar to those of ceftazidime: half-life (t1/2), 1.95 h; concentration at 1 h (C1h), 47 to 49 micrograms/ml for both antibiotics. Ceftriaxone displayed the longest t1/2 (7.65 h) and the highest C1h (137.8 micrograms/ml), while we observed the shortest t1/2 (1.05 h) and the lowest C1h (19.85 micrograms/ml) with imipenem. At 1 h, cefpirome and, even more so, imipenem showed significantly better serum bactericidal activities against S. aureus (1:273 and 1:80) than did the other antibiotics (P less than 0.0005; analysis of variance with randomized block design and Bonferroni correction). Against E. cloacae, we observed the highest serum bactericidal titers at 1 h with cefpirome, and this superiority vis-à-vis the other antibiotics tested was maintained for up to 8 h after dosing. Ceftazidime remained the most active agent tested against P. aeruginosa (serum bactericidal activity titers, 1:43 at 1 h) up to 8 h. In summary, the study showed that cefpirome and imipenem provide more potent serum bactericidal activities than do broad-spectrum cephalosporins against S. aureus; thus, both of these antibiotics should be adequate against serious S. aureus infections. In addition, cefpirome appears to be a promising alternative for treatment of infections caused by E. cloacae and P. aeruginosa.     

In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral vectors

Hematopoietic stem cell (HSC) gene transfer has been attempted almost entirely ex vivo and has been limited by cytokine-induced loss of self-renewal capacity and transplantation-related defects in homing and engraftment. Here, we attempted to circumvent such limitations by injecting vectors directly into the bone marrow (BM) to transduce HSCs in their native environment. Simian virus 40 (SV40)-derived gene delivery vectors were used because they transduce resting CD34+ cells very efficiently. Rats received SV-(Nef-FLAG), carrying FLAG marker epitope--or a control recombinant SV40 (rSV40)--directly into both femoral marrow cavities. Intracellular transgene expression by peripheral blood (PB) or BM cells was detected by cytofluorimetry. An average of 5.3% PB leukocytes expressed FLAG for the entire study--56 weeks. Transgene expression was sustained in multiple cell lineages, including granulocytes (average, 3.3% of leukocytes, 20.4% of granulocytes), CD3+ T lymphocytes (average, 0.53% of leukocytes, 1% of total T cells), and CD45R+ B lymphocytes, indicating gene transfer to long-lived progenitor cells with multilineage capacity. An average of 15% of femoral marrow cells expressed FLAG up to 16.5 months after transduction. Thus, direct intramarrow administration of rSV40s yields efficient gene transfer to rat BM progenitor cells and may be worthy of further investigation.     

Computer equipment used in patient care within a multihospital system: recommendations for cleaning and disinfection

Computer hardware has been implicated as a potential reservoir for infectious agents. Leaders of a 22-hospital system, which spans North America and serves pediatric patients with orthopedic or severe burns, sought to develop recommendations for the cleaning and disinfection of computer hardware within its myriad patient care venues. A task force comprising representatives from infection control, medical affairs, information services, and outcomes management departments was formed. Following a review of the literature and of procedures within the 22 hospitals, criteria for cleaning and disinfection were established and recommendations made. The recommendations are consistent with general environmental infection control cleaning and disinfection guidelines, yet flexible enough to be applicable to the different locales, different computer and cleaning products available, and different patient populations served within this large hospital system.     

Imaging thromboembolism with fibrin-avid 99mTc-peptide: evaluation in swine.

A pentapeptide, Gly-Pro-Arg-Pro-Pro, with high affinity for alpha-chain-fibrin was labeled with (99m)Tc ((99m)Tc-TP850) and evaluated in swine to image experimental venous thromboembolism (deep vein thrombosis [DVT]) and pulmonary embolism (PE). METHODS: Scatchard analysis was performed to determine fibrin affinity for TP850 and the number of binding sites (receptors) per milligram of fibrin. DVT was induced in the left jugular vein and PE was induced by introducing a preformed autologous blood clot into the right atrium using a 7-French introducer sheath inserted into the right jugular vein. (99m)Tc-TP850 was injected at 4, 24, 48, 72, 96, or 120 h later. Animals were imaged for up to 4 h after injection, heparinized, and sacrificed. Lungs were extirpated, radiographed, and imaged, and the PE was removed. Other tissues, including blood and normal lungs, were harvested and, concomitantly, (99m)Tc was counted for determination of target-to-tissue ratios and the percentage injected dose per gram of tissue. RESULTS: The affinity for human fibrin was 10(-9) mol/L and there were >10(15) receptors per milligram of fibrin. DVT and PE were visualized for up to 4 h after injection with high DVT/blood (7.9-22.6), DVT/muscle (31.1-89.4), PE/blood (1-155), and PE/lung (0.8-245) ratios. Thereafter, the PEs fragmented spontaneously below the spatial resolution of the gamma-camera and, despite the high associated radioactivity, could not be localized in vivo. The fragmented clots were detectable by scintigraphy on excised lungs and provided excellent concordance with radiograms. CONCLUSION: (99m)Tc-TP850 with its modest affinity (10(-9) mol/L), rapid blood clearance, and high DVT and PE uptake is a promising agent for imaging vascular thrombosis.     

Marine anoxia linked to abrupt global warming during Earth’s penultimate icehouse

Piecing together the history of carbon (C) perturbation events throughout Earth’s history has provided key insights into how the Earth system responds to abrupt warming. Previous studies, however, focused on short-term warming events that were superimposed on longer-term greenhouse climate states. Here, we present an integrated proxy (C and uranium [U] isotopes and paleo CO₂) and multicomponent modeling approach to investigate an abrupt C perturbation and global warming event (∼304 Ma) that occurred during a paleo-glacial state. We report pronounced negative C and U isotopic excursions coincident with a doubling of atmospheric CO₂ partial pressure and a biodiversity nadir. The isotopic excursions can be linked to an injection of ∼9,000 Gt of organic matter–derived C over ∼300 kyr and to near 20% of areal extent of seafloor anoxia. Earth system modeling indicates that widespread anoxic conditions can be linked to enhanced thermocline stratification and increased nutrient fluxes during this global warming within an icehouse.

Observations and climate models indicate that the dissolved oxygen inventory of the modern ocean is decreasing, with temperature-driven decline in oxygen solubility being a key driver (1). A decline in ocean dissolved oxygen, expressed as an expanded oxygen minimum zone (OMZ), will negatively impact marine ecosystems, leading to significant loss of biodiversity in the ocean (2). This is of significant concern for the world’s largest fisheries situated in the most productive areas of global oceans, as these regions are particularly susceptible to ocean deoxygenation (3, 4). Substantial uncertainty in estimating the extent of deoxygenation over the upcoming millennia, however, drives the current focus on understanding past episodes of ocean deoxygenation.Empirical constraints on the magnitude of ocean deoxygenation during climate perturbations come predominantly from the Quaternary glacial–interglacial transitions (5, 6) or early Cenozoic rapid warming events, in particular the Paleocene–Eocene Thermal Maximum (PETM) event (7, 8). The temporal scales of warming and deoxygenation of these events differ by an order of magnitude (10⁴ vs. 10⁵ y). Constraints on ocean circulation and biogeochemical cycles across warming events in the Quaternary are more robust than in Earth’s deep past (5, 9). On the other hand, Quaternary partial pressure of CO₂ (pCO₂) and temperature shifts were gradual and the overall perturbations small in magnitude (10) relative to predicted changes for the next millennia or two. Although changes in pCO₂ during the early Cenozoic warming events (foremost, the PETM) were larger in magnitude and more rapid than carbon (C) perturbations of Quaternary glacial–interglacial transitions (11, 12), they occurred under a background greenhouse climate state characterized by high baseline atmospheric pCO₂ (∼1,000 ppm). Other periods of pre-Cenozoic C perturbations (13, 14), such as the Cretaceous and Jurassic (Toarcian) ocean anoxic events (OAEs) (15, 16), and the end-Triassic (17) and the end-Permian mass extinction events (18), also occurred during background greenhouse climates (19, 20). These greenhouse OAEs have provided constraints on and insights into how to model climate change and marine redox evolution. To date, the degree of deoxygenation and spread of anoxic conditions with warming in a glacial state is relatively unexplored.Here, we provide a perspective on global warming–induced ocean deoxygenation by documenting a 10⁵-y C-perturbation event associated with widespread oceanic anoxia, superimposed on the late Paleozoic glacial climate state. This past icehouse (with main episode between ∼340 and 290 Ma) existed under atmospheric CO₂ levels comparable to that of the past few million years (21) and was a period of dynamic and widespread glaciation in the Southern Hemisphere (Gondwana). As such, it provides unique constraints on deoxygenation with warming under a background glacial state, albeit with different paleogeographic boundary and marine and ecosystem conditions compared with those of the younger greenhouse periods of C perturbation.     

Influence of iterative reconstruction and dose levels on metallic artifact reduction: A phantom study within four CT systems

Purpose

To compare metallic artifact reduction (MAR) algorithms proposed by four vendors according to the delivered dose and iterative level using a phantom study.

Morphological Characterization of Polyanhydride Biodegradable Implant Gliadel® During in Vitro and in Vivo Erosion Using Scanning Electron Microscopy

Purpose. The objectives of the current study are to characterize the distribution of the chemotherapeutic agent carmustine (BCNU) in spray dried polyanhydride microspheres and to describe the morphological changes that occur during the in vitro and in vivo erosion of the polyanhydride implant-GLIADEL^®, which consists of BCNU distributed in the copolymer matrix of poly(carboxyphenoxy propane:sebacic acid) in a 20:80 molar ratio (p(CPP:SA, 20:80)). Methods. Scanning electron microscopy (SEM) was used to visualize the morphological changes of the polymer during the manufacturing process and in vitro and in vivo erosion. Results. This study revealed that BCNU was homogeneously distributed within spray dried polyanhydride microspheres with no phase separation. The porosity of the wafer fabricated from spray dried polyanhydride microspheres gradually increased during erosion. During the initial period following wafer implantation in the brains of rats, erosion was mainly confined to the surface layer of the wafer with the majority of the wafer remaining intact. The eroding front gradually advanced from the surface to the interior of the wafer in a layerwise fashion, creating pores and connecting channel. Eventually both the interior and exterior of the wafers were eroded and the same porous structure was seen throughout the whole wafer. Conclusions. This study provides the first visual observation of the morphological changes of the GLIADEL^® wafer during erosion of the polyanhydride matrix and release of the drug substance BCNU. The observations in this study support the conclusion that BCNU release from a polyanhydride wafer is controlled both by diffusion of the drug and erosion of the polymer matrix.     

Nonsurgical Repair of a Pseudoaneurysm in a Cynomolgus Macaque (Macaca fascicularis)

A cynomolgus macaque presented with an ecchymotic and edematous left leg approximately 1 wk after a blood sample had been collected from the left femoral vein. Ecchymosis was noted in the femoral triangle, prepuce, and scrotum. The animal was not febrile or exhibiting signs of pain or distress. Duplex Doppler ultrasound imaging was used to evaluate the area. An arteriovenous fistula between the femoral artery and vein, accompanied by a pseudoaneurysm arising from the femoral artery, was identified. Various invasive and noninvasive treatment options for the pseudoaneurysm, including surgical repair, thrombin injection, stent placement, and ultrasound-guided compression repair (UGCR), were considered. UGCR was chosen as the first option for treatment. After a total of 20 min of UGCR at the neck of the pseudoaneurysm, complete thrombosis was achieved. Subsequent imaging of the lesion revealed resolution of the pseudoaneurysm. Because of the risks involved with invasive management techniques for this vascular lesion, UGCR is a valuable noninvasive treatment option for the repair of pseudoaneurysms.Abbreviation: CDI, color Doppler imaging; UGCR, ultrasound-guided compression repairVascular malformations have been reported to occur in a wide variety of species.^{2,3,5-7,10,11,13,15-22,24,25,27-35} These abnormalities include arteriovenous fistulas, vascular shunts, hemangiomas, vascular atresias, aneurysms, pseudoaneurysms, telangectasia, and lymphangiomas, with the overwhelming majority of reports describing arteriovenous fistulas.^{2,3,5,6,11,15-19,25,27,30,33,35} Aneurysms have occurred in several primates including chimpanzees, gorillas, squirrel monkeys, howler monkeys, owl monkeys, African green monkeys, spider monkeys, patas monkeys, and capuchin monkeys.²⁴ Pseudoaneurysms are reported infrequently. Pseudoaneurysms (or false) aneurysms are the result of leakage of blood from an artery into a defined space. A pseudoaneurysm associated with the femoral artery in a black and white colobus monkey was detected 6 d after manual restraint for routine blood collection from the femoral artery.³² The pseudoaneurysm was excised, and the resulting vascular defect was closed with an autologous graft. Another report¹⁰ describes a pseudoaneurysm associated with the femoral artery in a rhesus monkey. The diagnosis was obtained interoperatively, and excision of the defect was successful. Because surgical treatment of pseudoaneurysm has inherent risks and requires considerable surgical skill for a successful outcome, a noninvasive approach would be a valuable and cost-effective treatment option. This report is the first to describe the clinical presentation, diagnosis, and nonsurgical treatment of a pseudoaneurysm in a cynomolgus macaque.