Renal medicine in the intensive care unit: a narrative review.

Kidney disease, both acute and chronic, is commonly encountered on the intensive care unit. Due to the role the kidneys play in whole body homeostasis, it follows that their dysfunction has wide-ranging implications and can affect prescribing and therapeutic management. This narrative review discusses the pathophysiology of acute kidney injury and chronic kidney disease, and how this relates to critically unwell patients. We cover several aspects of the management of renal dysfunction on the critical care unit, exploring some of the recurrent themes within the literature, including type and timing of kidney replacement therapy, management of acute kidney injury, as well as discussing how novel biomarkers for acute kidney injury may help to identify patients suffering from acute kidney injury as well as risk stratifying these patients. We discuss how early involvement of specialist nephrology services can improve outcomes in patients with kidney disease as well as offer valuable diagnostic and specialist management advice, particularly for patients with established end stage kidney disease and patients who are already known to nephrology services. We also explore some of the ongoing research questions that need to be answered within this arena.

Evaluation of Simultaneous Transmission of Chikungunya Virus and Dengue Virus Type 2 in Infected Aedes aegypti and Aedes albopictus (Diptera: Culicidae).

The simultaneous transmission of chikungunya virus (CHIKV) and dengue viruses (DENV) has been a major public health concern because of their sympatric distribution and shared mosquito vectors. Groups of Aedes aegypti (L.) and Aedes albopictus (Skuse) were orally infected with 1.5 × 10(5) PFU/ml of CHIKV and 3.2 × 10(6) FFU/ml of DENV-2 simultaneously or separately in inverse orders and evaluated for dissemination and transmission by qRT-PCR. Simultaneous dissemination of both viruses was detected for all groups in Ae. aegypti and Ae. albopictus while cotransmission of CHIKV and DENV-2 only occurred at low rates after sequential but not simultaneous infection.

International travel in the immunocompromised patient: a cross-sectional survey of travel advice in 254 consecutive patients.

AIMS: Our primary aim was to determine the rate of overseas travel in immunocompromised individuals attending appropriate clinics at an Australian tertiary care hospital. We also aimed to characterise health-seeking behaviour prior to travel and investigated sources of pre-travel advice, compared travel patterns and activities between three specific immunosuppressed groups, and examined pre-immunosuppression patient serology. METHODS: We implemented a cross-sectional survey of patients between February and August 2012. This survey was implemented among three outpatient populations at Monash Medical Centre, an Australian tertiary care hospital. RESULTS: We recruited 254 immunosuppressed adults from three patient populations: human immunodeficiency virus-positive individuals, renal transplant patients and rheumatology patients requiring immunosuppressive therapy. No clinical intervention was performed. In the 10 years preceding the survey, 153 (60.2%) participants reported international travel. Of these, 105 (68.6%) were immunosuppressed at the time of travel. These patients were 47.6% male and 60% Australian born. Forty per cent were visiting friends and relatives as part of their travel. Fifty-four per cent of those immunocompromised at the time of travel were going to high-risk destinations. Pathology files indicated that serological screening was frequently not performed prior to immunosuppression in the renal transplant and rheumatology groups. CONCLUSIONS: Immunocompromised patients often travel to high-risk destinations with limited or inadequate pre-travel preparations. Doctors caring for the immunocompromised should be aware of travel risks, suitable vaccination protocols and when to refer to specialist travel clinics.

Pharmacokinetics of single-dose rectal zonisamide administration in normal dogs.

BACKGROUND: Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications. HYPOTHESIS/OBJECTIVES: To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and p.o. to dogs. ANIMALS: Eight healthy research dogs. METHODS: Randomized cross-over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG-R), rectally in water (H2O-R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling. RESULTS: Mean maximum plasma zonisamide concentrations (µg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H2O-R (5.00 ± 1.83) (P = .004). Disappearance half-life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG-R (85 ± 69%) was significantly higher than that of H2O-R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects. CONCLUSIONS AND CLINICAL IMPORTANCE: The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H2O-R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 µg/mL) are to be achieved with a single-dose administration.

Who really knows their patients' penicillin adverse drug reaction status? A cross-sectional survey.

This cross-sectional survey of patients with adverse drug reactions (ADR) to penicillin and their treating doctor, nurse and pharmacist was undertaken to identify the extent of healthcare workers (HCW) awareness of their patients' ADR, and antibiotic use in hospital. There were 23 (38%) doctors, 53 (87%) nurses and 40 (66%) pharmacists who were aware of their patient's penicillin ADR, despite more than half of their patients receiving antibiotics. Interventions encouraging 'double checking' may improve antibiovigilance.

Shooting at the DARC: potential issues with species-specific antimalarials.

Scientific drug design enables the production of novel agents that may be specific for individual malaria species, particularly by targeting their methods of cellular entry. Though there are practical and theoretical barriers to introducing novel agents into clinical practice, there may also be theoretical benefits to encourage further investigation of such agents, including a reduction in the rate of development of falciparum resistance. This paper discusses the potential risks and benefits such agents using the example of CCR5 blockers, drugs which are already in use for HIV treatment, but may be able to block DARC, the site of Plasmodium vivax into the human red blood cell.

One or more bound planets per Milky Way star from microlensing observations.

Most known extrasolar planets (exoplanets) have been discovered using the radial velocity or transit methods. Both are biased towards planets that are relatively close to their parent stars, and studies find that around 17-30% (refs 4, 5) of solar-like stars host a planet. Gravitational microlensing, on the other hand, probes planets that are further away from their stars. Recently, a population of planets that are unbound or very far from their stars was discovered by microlensing. These planets are at least as numerous as the stars in the Milky Way. Here we report a statistical analysis of microlensing data (gathered in 2002-07) that reveals the fraction of bound planets 0.5-10 AU (Sun-Earth distance) from their stars. We find that 17(+6)(-9)% of stars host Jupiter-mass planets (0.3-10 M(J), where M(J) = 318 M(⊕) and M(⊕) is Earth's mass). Cool Neptunes (10-30 M(⊕)) and super-Earths (5-10 M(⊕)) are even more common: their respective abundances per star are 52(+22)(-29)% and 62(+35)(-37)%. We conclude that stars are orbited by planets as a rule, rather than the exception.

An orbital period of 0.94 days for the hot-Jupiter planet WASP-18b.

The 'hot Jupiters' that abound in lists of known extrasolar planets are thought to have formed far from their host stars, but migrate inwards through interactions with the proto-planetary disk from which they were born, or by an alternative mechanism such as planet-planet scattering. The hot Jupiters closest to their parent stars, at orbital distances of only approximately 0.02 astronomical units, have strong tidal interactions, and systems such as OGLE-TR-56 have been suggested as tests of tidal dissipation theory. Here we report the discovery of planet WASP-18b with an orbital period of 0.94 days and a mass of ten Jupiter masses (10 M(Jup)), resulting in a tidal interaction an order of magnitude stronger than that of planet OGLE-TR-56b. Under the assumption that the tidal-dissipation parameter Q of the host star is of the order of 10(6), as measured for Solar System bodies and binary stars and as often applied to extrasolar planets, WASP-18b will be spiralling inwards on a timescale less than a thousandth that of the lifetime of its host star. Therefore either WASP-18 is in a rare, exceptionally short-lived state, or the tidal dissipation in this system (and possibly other hot-Jupiter systems) must be much weaker than in the Solar System.

Prospective comparison of the clinical impacts of heterogeneous vancomycin-intermediate methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-susceptible MRSA.

Although methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (RVS-MRSA; including vancomycin-intermediate S. aureus [VISA] and heterogeneous VISA [hVISA]) have been linked with vancomycin treatment failure, it is unclear whether they are more pathogenic than vancomycin-susceptible MRSA (VS-MRSA). We prospectively assessed patients with clinical MRSA isolates during a 10-month period to determine clinical status (infection versus colonization) and therapeutic outcome before correlating these findings with the results of detailed in vitro assessment of vancomycin susceptibility, including population analysis profile (PAP) testing. hVISA and VISA were defined by standard PAP criteria (area-under-the-curve ratio compared to that of the reference hVISA strain Mu3 [>or=0.9]) and routine CLSI criteria (vancomycin MIC, 4 to 8 microg/ml), respectively. Among the 117 patients assessed, 58 had RVS-MRSA isolates (56 hVISA and 2 VISA) and 59 had VS-MRSA isolates; the patient demographics and comorbidities were similar. RVS-MRSA was associated with a lower rate of infection than VS-MRSA (29/58 versus 46/59; P = 0.003), including a lower rate of bacteremia (3/58 versus 20/59, respectively; P < 0.001). The cure rates in RVS-MRSA and VS-MRSA groups were not statistically different (16/26 versus 31/42; P = 0.43), but the post hoc assessment of treatment regimes and study size made detailed conclusions difficult. The results of the macro method Etest correlated well with the PAP results (sensitivity, 98.3%, and specificity, 91.5%), but broth microdilution and our preliminary RVS-MRSA detection method correlated poorly. All isolates were susceptible to linezolid and daptomycin. These data suggest that detailed prospective laboratory identification of RVS-MRSA isolates may be of limited value and that, instead, such in vitro investigation should be reserved for isolates from patients who are failing appropriate anti-MRSA therapy.

Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.

In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.

All in the family: a belated response to Knudson-Martin's feminist revision of Bowen theory.

The first formal attempt at revising Bowen theory within the marriage and family therapy literature is represented in the work of Knudson-Martin (1994). Claiming that several of the theory's concepts are defined at odds with female development, Knudson-Martin (1994) reconceptualizes and expands Bowen theory to rectify these perceived shortcomings. In turn, we address several fundamental concerns with Knudson-Martin's critique and revision of Bowen theory. An alternative representation of Bowen Theory, as well as its relationship to feminist thought, is put forth. Suggestions for the field's future relationship to Bowen theory are also discussed.

Trans-species hair growth induction by human hair follicle dermal papillae.

A series of experimental bioassays has shown that the dermal papilla of the adult rodent vibrissa hair follicle retains unique inductive properties. In view of the many phenotypic and functional differences between specific hair follicle types, and the growing interest in hair follicle biology and disease, it remains important to establish that the human hair follicle dermal papilla has equivalent capabilities. In this study we tested the ability of human hair follicle papillae to induce hair growth when implanted into transected, athymic mouse vibrissa follicles. The implanted papillae that interacted with mouse follicle epithelium created new fibre-producing follicle end bulbs. The origin of the papillae in the recombinant structures was confirmed using laser capture microdissection and human specific gender determination by PCR. The demonstration that intact adult human dermal papillae can induce hair growth has implications for molecular analysis of basic hair growth mechanisms, particularly since the study involved common epithelial-mesenchymal signalling and recognition properties across species. It also improves the prospects for a cell-based clinical approach to hair follicle disorders.

A randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of a Chinese herbal product (P07P) for the treatment of canine atopic dermatitis.

A randomized, double-blind, placebo-controlled trial of P07P, a product derived from a traditional Chinese herbal remedy, was undertaken in 50 dogs with atopic dermatitis. Owners recorded a daily itch score for 4-14 days before treatment and during treatment. Packets of powder containing P07P or placebo were added to the food once daily for 8 weeks. Dogs were assessed for erythema, surface damage, overall coat condition and seborrhoea by the same investigator, as well as for pruritus and general demeanour, at 0 (visit 2), 28 (visit 3) and 56 (visit 4) days of treatment or at withdrawal. Investigator and owner assessments of response were recorded after 28 and 56 days of treatment or at withdrawal. The predefined primary outcome measure was the owners' assessment of response at the end of treatment. Nine of the 24 dogs (37.5%) in the P07P group but only 3 of the 23 dogs (13%) in the placebo group were considered to have improved, but this difference was not statistically significant (P = 0.09). There was a significantly higher withdrawal rate due to worsening of condition in the placebo group (P = 0.04). Mean daily itch score in the second 28-day period of the study was significantly higher than baseline in the placebo group (P = 0.01) but not in the P07P group (P = 0.30). Pruritus scores showed a significant deterioration from baseline at the final visit in the placebo group (P = 0.01) but not in the P07P group (P = 1.00). There was a significant difference between the groups in change from baseline in erythema score at visit 3 (P = 0.05). There were no significant differences (P > 0.05) in surface damage, seborrhoea, overall coat condition and general demeanour scores within or between the groups throughout the study. The product was well tolerated with no severe or serious adverse events recorded. P07P may be beneficial as a novel nonsteroidal therapy for the management of dogs with atopic dermatitis.

Dissecting embryonic and seedling morphogenesis in Arabidopsis by promoter trap insertional mutagenesis.

Development can be considered to comprise the co-ordinated regulation of patterning at different levels: patterning of cells to form tissues, patterning of tissues to form organs, and patterning of organs to generate the characteristic architecture of the organism. These processes are expected, in turn, to be mediated by the precise spatial and temporal regulation of patterns of gene expression during development, which depend on appropriate signalling mechanisms. In order to investigate molecular events of morphogenesis in plants, we have utilized a system of promoter trap insertional mutagenesis in Arabidopsis, to generate both phenotypic mutants and gene fusions that represent markers useful in studying the regulation of patterning. A screen of transgenic seedlings containing a T-DNA promoter trap has led to the identification of mutants defective in seedling shape and embryonic development, and of GUS fusion genes that are expressed in spatially restricted patterns. Mutants have been crossed with marker lines expressing cell type-specific GUS activities, to investigate their cellular organization. For example, the POLARIS marker gene is expressed in the embryonic and seedling root tip. When crossed with hydra, which lacks an embryonic root, and with emb30, which lacks both embryonic and seedling roots, it is nevertheless expressed in the correct relative position, and we hypothesize that it represents a novel marker of root positional information, independent of root morphogenesis.

The role of ultrasonography and inferior vena cava filter placement in high-risk trauma patients.

Undetected lower-extremity deep-vein thrombosis (LEDVT) in the trauma patient can lead to significant morbidity and mortality. The purpose of this study was to: 1) evaluate the role of ultrasonography in the early detection of LEDVT in high-risk trauma patients; 2) identify prognostic indicators that predict LEDVT; and 3) evaluate the efficacy of selected inferior vena cava (IVC) filter placement in the prevention of pulmonary emboli. From October 1993 through December 1994, all adult multiple-trauma patients admitted to the Trauma Service who required prolonged bed rest (>3 days) or sustained a lower-extremity, pelvic, or spinal fracture with paralysis were prospectively studied with serial physical examinations and lower-extremity venous ultrasounds within 72 hours of admission and then weekly until discharge. Two hundred twenty-eight patients were entered into the study. Thirty-nine patients (17%) developed ultrasound evidence of LEDVT; of these, only seven (18%) were evident on physical examination. This allowed 32 patients (82%) with unsuspected LEDVT to receive earlier definitive therapy. Multivariate logistic regression analysis of LEDVT with various predictors found age, hospital length of stay, and lower-extremity trauma to be significant predictors of LEDVT (P < 0.05). Twenty-nine patients (74%) had immediate IVC filter placement upon ultrasound identification of proximal LEDVT. None of these patients developed pulmonary emboli. Ten patients (26%) with a LEDVT were treated with systemic anticoagulation alone. One of these patients sustained a fatal pulmonary embolus. In a historic control group of 234 high-risk trauma patients admitted in the 14 months prior to implementing screening ultrasounds, six patients sustained pulmonary emboli (P < 0.05). Screening ultrasounds combined with selective placement of IVC filters play an important role in reducing the morbidity and mortality associated with LEDVT in high-risk trauma patients.

Human hair follicle regeneration following amputation and grafting into the nude mouse.

In this study we investigated the capacity of the human hair follicle to regenerate a fiber-forming bulb after its amputation. We removed the bases from terminal follicles from a variety of sites and transplanted the follicles onto athymic mice, either still attached to a skin graft or as subcutaneous implants of individual follicles. External hair growth was observed on the skin grafts, and histology of the follicles revealed restoration of dermal papillae and follicle bulb structures. This result suggests that the capacity of hair follicles to regenerate their lower structures after removal, which was first demonstrated on whisker follicles, may be a general phenomenon. It emphasizes the importance of specific cellular subpopulations within the follicle and the role of dermal-epidermal interactions in adult follicle activities.

Restoration of hair growth by surgical implantation of follicular dermal sheath.

The capacity of lower follicle dermal sheath to restore hair growth was tested by removing the lower halves of follicles, and then immediately implanting material containing dermal sheath cells from these bases, into the remaining upper epidermal follicle cavity. Over 60% of recipient follicles produced stout emergent vibrissa fibres and some operations resulted in multiple hair production from a single follicle. Histological examination revealed new dermal papillae within large bulb structures which were sited below the level of amputation--a feature that indicated that the new dermal papilla was derived from implanted material. For many follicles, the failure to produce emergent fibres could be accounted for after histological examination. These results provide clear evidence that lower follicle dermal sheath cells are capable of replacing those of the dermal papilla and it shows that they can do so in the context of the upper follicle. However, because elements of lower follicle epidermis were present in the implant material, the interactive sequence of events cannot be established. Dermal sheath cells have immense potential for papilla cell replacement: questions remain as to whether the distinction between sheath and papilla cells is one of context, or whether the transition requires specific external influences.