Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration

Objectives: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). Design and setting: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. Patients: Sis critically ill patients with acute renal failure on CVVHDF. Interventions: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 lih of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter,. Measurements and results: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg .h l(-1). Conclusions: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.

Revision of Australian Clistoabdominalis (Diptera : Pipunculidae)

The 29 Australian species of Clistoabdominalis Skevington are revised and a phylogenetic analysis is presented. The following 23 new species are proposed: Clistoabdominalis ancylus, C. angelikae, C. capillifascis, C. carnatistylus, C. collessi, C. colophus, C. condylostylus, C. danielsi, C. dasymelus, C. digitatus, C. exallus, C. gaban, C. gremialis, C. lambkinae, C. lingulatus, C. mathiesoni, C. nutatus, C. octiparvus, C. scalenus, C. scintillatus, C. tasmanicus, C. tharra, and C. yeatesi. Pipunculus picrodes Perkins is proposed as a junior synonym of C. trochanteratus (Becker). Diagnoses and an illustrated key to species are provided. A summary of host records for all Australian species of Pipunculidae is presented to clarify confusion in the literature. Pipunculidae are documented hilltopping for the first time. This mating strategy is used by many species of Clistoabdominalis and patterns of hilltopping within the genus are examined.

Phylogenetic classification of Eudorylini (Diptera: Pipunculidae)

The phylogenetic relationships of members of Eudorylini (Diptera: Pipunculidae: Pipunculinae) were explored. Two hundred and fifty-seven species of Eudorylini from all biogeographical regions and all known genera were examined. Sixty species were included in an exemplar-based phylogeny for the tribe. Two new genera are described, Clistoabdominalis and Dasydorylas. The identity of Eudorylas Aczél, the type genus for Eudorylini, has been obscure since its inception. The genus is re-diagnosed and a proposal to stabilize the genus and tribal names is discussed. An illustrated key to the genera of Pipunculidae is presented and all Eudorylini genera are diagnosed. Numerous new generic synonyms are proposed. Moriparia nigripennis Kozánek & Kwon is preoccupied by Congomyia nigripennis Hardy when both are transferred to Claraeola, so Cla. koreana Skevington is proposed as a new name for Mo. nigripennis.

Phylogenetic revision of Australian members of the Allomethus genus group (Diptera : Pipunculidae)

The Australian species of Allomethus and Claraeola are revised and include one described species, Claraeola erinys (Perkins), and five new species: Allomethus unicicolis sp. n., Claraeola cyclohirta sp. n., C. sicilis sp. n., C. spargosis sp. n., and C. yingka sp. n.. Claraeola hylaea (Perkins) is proposed to be a synonym of C. erinys (Perkins). A key to species is provided and male and female genitalia are illustrated. The Australian species are placed phylogenetically into a world context using available taxa within the Allomethus genus group. The phylogenetic relationships are discussed in light of a cladistic analysis involving 22 taxa and 60 characters.

History of the events leading to the formulation of the apoptosis concept

Histological studies of ischaemic liver injury performed between 1962 and 1964 distinguished two types of cell death: classical necrosis, and a process involving conversion of scattered cells into small round masses of cytoplasm that often contained specks of condensed nuclear chromatin. Enzyme histochemistry demonstrated rupture of lysosomes in the former, but preservation of lysosomes in the latter. Similar small round masses were also observed sparsely in normal liver. Electron microscopy showed that the small round bodies resulted from cellular condensation and budding, that they were bounded by membranes and contained intact organelles, and that they were phagocytosed and digested by resident tissue cells, including epithelial cells. In work done in association with Jeffrey Searle, the process was found to occur spontaneously in a variety of malignant tumours and to be enhanced in squamous cell carcinomas of skin responding to radiotherapy. During 1971-1972, I collaborated with Andrew Wyllie and Alastair Currie while on sabbatical leave in Scotland. The newly defined type of cell death was shown to be regulated by hormones in the adrenal cortex and in breast carcinomas. Further, review of published electron micrographs of the cell death known to play an essential role in normal development revealed the same morphological pattern. We proposed that this distinctive phenomenon subserves a general homoeostatic function and suggested it be called apoptosis. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Effect of manual hyperinflation on hemodynamics, gas exchange, and respiratory mechanics in ventilated patients

The authors investigated the effect of manual hyperinflation (MHI) with set parameters applied to patients on mechanical ventilation on hemodynamics, respiratory mechanics, and gas exchange. Sixteen critically ill patients post-septic shock, with acute lung injury, were studied. Heart rate, arterial pressure, and mean pulmonary artery pressure were recorded every minute. pulmonary artery occlusion pressure, cardiac output, arterial blood gases, and dynamic compliance (C-dyn) were recorded pre- and post-MHI. From this, systemic vascular resistance index (SVRI), cardiac index, oxygen delivery, and partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO(2)) ratio were calculated. There were significant increases in SVRI (P < 0.05) post-MHI and diastolic arterial pressure (P < 0.01)during MHI. C-dyn increased post-MHI (P < 0.01) and was sustained at 20 minutes post-MHI (P < 0.01). Subjects with an intrapulmonary cause of lung disease had a significant decrease (P = 0.02) in PaO2:FiO(2), and those with extrapulmonary causes of lung disease had a significant increase (P < 0.001) in PaO2:FiO(2) post-MHI. In critically ill patients, MHI resulted in an improvement in lung mechanics and an improvement in gas exchange in patients with lung disease due to extrapulmonary events and did not result in impairment of the cardiovascular system.

Overseas Visitor Deaths in Australia: 1997-2000

Reassuring visitors about their health and safety is particularly important for tourist destinations since the terrorist attacks of 11 September 2001. This study examined the deaths of 1513 overseas visitors to Australia over a four-year period, and found that most deaths (76%) were due to natural causes.Among the accidental deaths, the main causes were motor vehicle crashes and water-related incidents. The study findings support a widely held view that Australia is a safe destination for overseas visitors. It also provides a safety benchmark for other tourist destinations.

Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators

The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.

Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

Age-related macular degeneration (AMD) is the major cause of blindness in the developed world. its pathomechanism is unknown and its late onset, complex genetics and strong environmental components have all hampered investigations. Here we demonstrate the development of an animal model for AMD that reproduces features associated with geographic atrophy, a transgenic mouse line (mcd/mcd) expressing a mutated form of cathepsin D that is enzymatically inactive thus impairing processing of phagocytosed photoreceptor outer segments in the retinal pigment epithelial (RPE) cells. Pigmentary changes indicating RPE cell atrophy and a decreased response to flash electroretinograms were observed in 11- to 12-month-old mcd/mcd mice. Histological studies showed RPE cell proliferation, photoreceptor degeneration, shortening of photoreceptor outer segments, and accumulation of immunoreactive photoreceptor breakdown products in the RPE cells. An accelerated photoreceptor cell death was detected in 12-month-old mcd/mcd mice. Transmission electron microscopy demonstrated presence of basal laminar and linear deposits that are considered to be the hallmarks of AMD. Small hard drusen associated with human age-related maculopathy were absent in the mcd/mcd mouse model at the ages analyzed. in summary, this model presents several features of AMD, thus providing a valuable tool for investigating the underlying biological processes and pathomechanism of AMD.

Roles of fibroblast growth factors in the inner ear

The basic biology of the fibroblast growth factor (FGF) receptors and their splice variants is first reviewed, followed by a review of the known roles of FGFs in the inner ear. They include induction of the otocyst by FGF19, followed by FGF3 in further development of the otocyst. In later development, FGF3 or FGF10 acting on FGF receptor 2b is likely to be involved in development of the walls of the cochlear spaces, while FGF receptor 3 is involved in differentiation of the pillar cells of the organ of Corti. FGF1 and FGF2 act as trophic factors for the developing cochlear nerve fibres. Copyright (C) 2002 S. Karger AG, Basel.

Localization of a novel melanoma susceptibility locus to 1p22

Over the past 20 years, the incidence of cutaneous malignant melanoma (CMM) has increased dramatically worldwide. A positive family history of the disease is among the most established risk factors for CMM; it is estimated that 10% of CMM cases result from an inherited predisposition. Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM. Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. The highest two-point parametric LOD score (1.82; recombination fraction [theta] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (theta = 0) and a nonparametric LOD score of 4.19 were found at D1S2779 in nine families selected for early age at onset. Additional typing yielded seven adjacent markers with LOD scores 13 in this subset, with the highest parametric LOD score, 4.95 (theta = 0) ( nonparametric LOD score 5.37), at D1S2776. Analysis of 33 additional multiplex families with CMM from several continents provided further evidence for linkage to the 1p22 region, again strongest in families with the earliest mean age at diagnosis. A nonparametric ordered sequential analysis was used, based on the average age at diagnosis in each family. The highest LOD score, 6.43, was obtained at D1S2779 and occurred when the 15 families with the earliest ages at onset were included. These data provide significant evidence of a novel susceptibility gene for CMM located within chromosome band 1p22.