Fine-scale movements and habitat use of juvenile southern flounder Paralichthys lethostigma in an estuarine seascape.

Habitat use of juvenile southern flounder Paralichthys lethostigma was examined within a shallow estuarine seascape during June and July 2011 using acoustic telemetry. Fine-scale movement and habitat use of P. lethostigma was investigated with an acoustic positioning system placed in a seascape that varied in habitat type, physicochemical conditions and bathymetry. The use of different habitat types was examined with Euclidean distance-based analyses, and generalized additive models were used to determine the relative importance of habitat type relative to physicochemical conditions and bathymetry. Tracks of P. lethostigma ranged in distance between 1477 and 8582 m and speed was 4·2 ± 1·1 m min⁻¹ (mean ± s.e.) for all P. lethostigma combined. Depth, slope and habitat type had the most influence on P. lethostigma occurrence and deep sandy areas with shallow slopes were used most frequently. In addition, depth use by P. lethostigma was influenced by tidal cycles, indicating habitat use varies temporally and is dynamic. Finally, temperatures <30·5° C were used more than warmer waters within the study area. The results successfully identify movements by juvenile P. lethostigma, and indicate that definitions of essential habitats need to account for dynamics in habitat use.

How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity.

[Lysophospholipids and cancer: current status and perspectives]. / Lysophospholipides et cancer: état des lieux et perspectives.

Circulating phospholipids carrying a single esterified fatty acid, the so-called lysophospholipids, are now considered as mediators of the intercellular communication. Their major members are the lysophosphatidic acid and the sphingosine 1-phosphate, two molecules displaying biological activities similar to those of growth factors or cytokines, through a recently identified subfamily of G protein-coupled receptors. They are involved in various biological processes, e.g., brain development and angiogenesis, but the following evidences suggest that these lipids are also significant actors of tumour development: (i) they stimulate the growth, survival and migration of tumour cells from various origins (ovary, prostate, glioblastoma...); (ii) they are abundant in malignant effusions; (iii) the lysophospholipid-producing enzymes are tumourigenic. Even if it remains necessary to define the role of these "oncolipids" in relationship with oncogenes and tumor suppressors, they may well be the mediators of an efficient autostimulatory system of the proliferating and migratory capacities of cancer cells, suggesting that lysophospholipids could represent novel valuable targets for anticancer pharmacology.

Preclinical evaluation of the reinforcing and discriminative stimulus effects of agomelatine (S-20098), a melatonin agonist.

Agomelatine (S-20098), an analog of melatonin, has shown promise as a chronobiotic in animal models of sleep phase disorders and is being developed for clinical use. Previous research has shown that the pharmacological profile of melatonin-like drugs overlaps that of gamma-amino butyric acid (GABA) agonists. Given the potential of drugs within the latter class for recreational abuse in humans, evaluation of this potential for melatonin analogs that target similar therapeutic indications is important. In the present study, agomelatine was tested in animal models of the subjective and reinforcing effects of CNS depressant drugs; i.e., diazepam discrimination in rats and IV methohexital self-administration in rhesus monkeys, respectively. Neither agomelatine nor melatonin substituted for diazepam in rats trained to discriminate 2.5 mg/kg diazepam from vehicle. Further, agomelatine was not self-administered by rhesus monkeys. These results suggest that agomelatine would not produce diazepam-like intoxication in humans, nor would it likely be subject to abuse.

Poor discriminatory performance of the Pediatric Risk of Mortality (PRISM) score in a South African intensive care unit.

OBJECTIVE: The use of the Pediatric Risk of Mortality (PRISM) score or other scoring systems in the intensive care unit (ICU) is of great importance for evaluating the efficacy and efficiency of a particular ICU. However, the PRISM score was developed and validated in the United States and subsequently validated in Europe, but has not been evaluated in a less affluent society. In general, scoring systems should be used only in populations similar to the reference population in which the prediction model was developed. We set out to determine the applicability of the PRISM score at Baragwanath Hospital, South Africa. DESIGN: Prospective, descriptive study. SETTING: Twenty-four-bed multidisciplinary ICU. PATIENTS: We analyzed 1,528 consecutive pediatric admissions from January 1989 to June 1994. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PRISM scores, Therapeutic Intervention Scoring System scores, demographic, and clinical data collected prospectively were entered and stored by means of a commercial software package at the time of admission of each patient. The prediction of actual mortality by PRISM scoring was evaluated by the Hosmer and Lemeshow goodness-of-fit test (chi2[8 degrees of freedom]). Receiver operating characteristic curves were constructed and compared with those curves from pediatric ICU populations in the United States and Europe. Individual receiver operating characteristic curves were constructed for surgical and nonsurgical patients, age categories, and diagnostic categories. Compared with European and American ICU populations, our patients were younger, were mostly nonsurgical emergency admissions, stayed longer in the ICU, and were more severely ill with a higher admission PRISM score and overall mortality rate. Respiratory and septic diagnoses predominated, with very few surgical cases admitted. The Hosmer and Lemeshow goodness-of-fit test showed a significant failure of the PRISM scoring system to accurately predict mortality over a wide range of expected mortality rates (chi2[8 degrees of freedom] = 465, p = 0). Similarly, receiver operating characteristic analysis indicated a poor predictive power (Az = 0.73 +/- 0.01 [SEM]), with an area under the curve significantly less than that for the PRISM reference population (p = 0). PRISM showed equally poor discriminatory function at all age groups and diagnostic categories. CONCLUSIONS: The PRISM score needs to be recalibrated or recalculated for our patient population in view of the high discrepancy and poor discriminatory function shown. Part of the inaccuracy may derive from different demographic characteristics of our ICU population and a different pattern of diseases. It appears that PRISM is not population independent.

Confirmation of the safety of central venous catheterisation in critically ill infants and children--the Baragwanath experience.

OBJECTIVE: To evaluate, in critically ill children, the safety and effectiveness of routine central venous catheterisations (CVCs) performed by residents from all disciplines. DESIGN: Prospective audit of all CVCs over a 24-month period. SETTING: Multidisciplinary intensive care unit at Baragwanath Hospital, Soweto. PATIENTS: All critically ill patients 12 years of age or younger requiring CVC. All percutaneous sites (subclavian, internal jugular and femoral) were used; these were selected by the attending doctor and not influenced by the audit. RESULTS: There were 272 catheterisation attempts, of which 241 (88.6%) were successful. Patient age and size but not disease severity influenced incidences of both catheterisation failure and minor bleeding. The latter was the commonest early complication, occurring in 63 (23.2%) successful catheterisations. There were 7 major complications-3 pneumothoraces, 2 tachyarrhythmias and 2 major bleeds, all with subclavian vein catheterisation. Catheter-related infections (CRIs) occurred in 85 (51.2%) of 166 lines and catheter-related septicaemia (CRS) in 10 (5.7%) of 175 lines where there were sufficient data for evaluation. No patient or line factor, including duration of insertion, influenced CRI or CRS. In CRI, Staphylococcus epidermidis was the commonest organism. Other common CRI isolates were Enterococcus faecalis, Klebsiella spp. and Candida albicans. Six different organisms were implicated in CRS. CONCLUSIONS: CVC is a safe procedure with a high success rate. The femoral vein is the recommended percutaneous site of choice as it carries no great risk of sepsis and does not expose the patient to the hazard of intrathoracic complications.

Changes in vancomycin pharmacokinetics in critically ill infants.

We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t1/2el) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P = 0.007) larger than that on day 8 (0.44 l/kg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 micrograms/ml) (P = 0.02) and mean t1/2el (5.3 vs 3.4h) (P = 0.01) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t1/2el. Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

Clinical characteristics of black asthmatic children.

A prospective study of 455 black asthmatic children (277 boys) attending the Baragwanath Hospital asthma clinic was undertaken. A history was obtained by means of a standardised questionnaire and skin tests were performed. Cough was the commonest presenting symptom and upper respiratory tract infections, exercise and cold weather the commonest symptom precipitants. The relative incidences of the other precipitants reflected the environment of the study population. Associated atopic conditions were present in 75.5% of patients and a family background in 22.2%. Other respiratory diagnoses were commonly made, particularly tuberculosis, which was diagnosed in 7.4%. Fewer than one-third had no positive skin reaction. The commonest allergens were grasses, pollen and house-dust mites. The high proportion of house-dust mite sensitivity (44.2%) contradicts beliefs that they are rare at higher altitudes.

Comparison of central venous pressure measurements in the intrathoracic and the intra-abdominal vena cava in critically ill children.

A prospective study was conducted to compare simultaneous intrathoracic and intra-abdominal central venous pressures in 10 critically ill, ventilated paediatric intensive care patients. Central venous pressures were measured using the water column technique over a 6 h study period. There was excellent correlation between intrathoracic and intra-abdominal vena caval pressure measurements (r = 0.974, p < 0.001). The difference between paired measurements did not exceed the limits of agreement (+/- 2SD, -2.36 to 4.42 cm H2O). The mean (SD) difference between readings was small (1.03 +/- 1.69 cmH2O) and was within clinically tolerable limits. These data suggest a clinically useful, close relationship between intra-abdominal and conventional intrathoracic central venous pressure measurement in this group of patients.

An outbreak of shigellosis aboard a cruise ship caused by a multiple-antibiotic-resistant strain of Shigella flexneri.

From October 23 to October 27, 1989, an outbreak of gastroenteritis occurred aboard a cruise ship in the Caribbean. The 818 passengers and 518 crew members were surveyed for gastrointestinal symptoms; 72 (14%) of 512 passengers and 12 (3%) of 388 crew members who answered the survey reported having a diarrheal illness. Multiple-antibiotic-resistant Shigella flexneri 4a was isolated from 19 ill passengers and two ill crew members. Thirteen people were hospitalized, and prolonged duration of illness was associated with taking an antibiotic to which the isolated strain of Shigella was resistant. A case-control study of food items implicated German potato salad as the vehicle of transmission. It was prepared and probably infected by a food handler from a country where multiple-antibiotic-resistant Shigella is common. Spread may have been facilitated by the limited availability of toilet facilities for the galley crew. This outbreak demonstrates how antibiotic-resistant strains can be introduced into the United States, where they can pose treatment problems. The continuing problem of foodborne gastrointestinal disease in settings such as cruise ships underscores the need for basic hygienic control for food handlers and food preparation areas. In addition, the availability of adequate working conditions for crew members, including appropriately furnished toilet facilities, may be important issues that must be addressed in order to decrease the frequency of diarrhea outbreaks aboard cruise ships.

Fatal injuries caused by underarm use of shoulder belts.

Safety belt use has dramatically increased in the past decade in North America because of safety belt use laws. Underarm use of shoulder belts is a means of relieving neck irritation and other complaints from shoulder belts but may result in serious or fatal injuries. Loads far in excess of the injury tolerance of the lower chest and upper abdomen are imposed by the shoulder belt in the underarm position. Six recent cases are presented in which fatal injury was caused by underarm use of shoulder belts. Lacerations of the liver, spleen, intestines, mesentery, diaphragm, and aorta, and spine injury have occurred in accidents, most of which should have been survivable. The motoring public must be warned that underarm use of shoulder belts is hazardous and may cause fatal injuries in otherwise survivable accidents.