Distortion and size calibration of the scanning laser ophthalmoscope (SLO) laser-beam raster.

PURPOSE: The Rodenstock scanning laser ophthalmoscope (SLO) is useful for mapping retinal function and for developing and evaluating visual rehabilitation methods. It is essential to know the visual angle subtended by stimuli in the SLO laser-beam raster and to accurately measure angular distances between objects in the final SLO image. To accomplish this, the angular extent of the SLO laser-beam raster must be calibrated. METHODS: We developed a simple method and apparatus for calibrating the raster and used it for repeated calibrations during a 3-month period. RESULTS: The laser-beam raster is quite stable in shape and size, but it is trapezoidally distorted in the vertical direction. Consequently, SLO images are distorted. CONCLUSIONS: Trapezoidal distortion of the SLO laser-beam raster can cause stimulus size to change as much as 10% from the top to the bottom of the raster. Measurements of fixed horizontal retinal landmark distances in SLO images can also vary as much as 10%. We developed a straightforward mathematical method for correcting distortion in SLO image measurements.     

Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake

Previous work has reported that the 5-hydroxytryptamine (5-HT)_1A agonist, 8-hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6–250 µg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non-fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used.     

Impact of automatic orders to discontinue vancomycin therapy on vancomycin use in an antimicrobial stewardship program.

We examined the possible unintended consequences of a 72-hour automatic order to discontinue vancomycin therapy in an antimicrobial stewardship program (ASP). Of 120 patients, 11 had vancomycin therapy discontinued at 72 hours without a call to the ASP, and 7 experienced a treatment interruption of 6-36 hours. All discontinuation of therapy was considered appropriate, and the 7 treatment interruptions did not have clear clinical consequences. Only one-third of patients had ASP stickers that warned of impending discontinuation of vancomycin therapy placed appropriately in the medical record.     

Classroom seating for children with attention deficit hyperactivity disorder: therapy balls versus chairs.

OBJECTIVE: The purpose of this study was to investigate the effects of therapy balls as seating on in-seat behavior and legible word productivity of students with attention deficit hyperactivity disorder (ADHD). Additionally, social validity was assessed to evaluate teacher and student opinions regarding the intervention. METHOD: A single subject, A-B-A-B interrupted time series design was employed across 3 students (2 males, 1 female) with ADHD. The study was conducted in a 4th grade inclusive classroom during daily language arts. During phases 1 and 3, the 3 participants and all other class members sat on chairs (in-seat on chair); during phases 2 and 4, everyone sat on therapy balls (in-seat on ball). Dependent variables were in-seat behavior and legible word productivity. Data were graphed and visually analyzed for differences between phases. RESULTS: Results demonstrated increases in in-seat behavior and legible word productivity for the students with ADHD when seated on therapy balls. Social validity findings indicated that generally the teacher and students preferred therapy balls. CONCLUSION: This study provides evidence that use of therapy balls for students with ADHD may facilitate in-seat behavior and legible word productivity.     

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin.     

Perturbation of copper (Cu) homeostasis and expression of Cu-binding proteins in cadmium-resistant lung fibroblasts.

To probe mechanisms of cadmium (Cd) damage to the lung extracellular matrix (ECM), we developed Cd-resistant (CdR) rat lung fibroblasts (RFL6) by incubation with graded concentrations of Cd. CdR cells downregulated lysyl oxidase (LO), a copper (Cu)-dependent enzyme essential for crosslinking of collagen and elastin in the ECM, in conjunction with upregulation of other Cu-binding proteins including Cu,Zn-superoxide dismutase (SOD1), copper chaperone for SOD1 (CCS1), metallothionein (MT), and Menkes P-type ATPase (ATP7A), a Cu transporter in the membrane of the Golgi apparatus, as well as gamma-glutamylcysteine synthetase (gamma-GCS), an enzyme for glutathione biosynthesis. Reduction and loss of cytoplasmic distribution of LO in CdR cells were accompanied by its dislocation with the Menkes P-type ATPase and the endoplasmic reticulum marker. CdR cells displayed a defect in LO catalytic activity but an enhancement in Cu,Zn-SOD catalytic activity consistent with the protein expression levels of these enzymes. Although long-term Cd exposure of cells enhanced the Menkes P-type ATPase protein expression, actually, it reduced Cu-dependent catalytic activity of this enzyme in parallel with the deficiency of LO. The low level of 64Cu bound to the LO fraction and the high level of 64Cu bound to the MT fraction provide direct evidence for limitation of Cu bioavailability for LO existing in the CdR cells. These results suggest that downregulation of LO is linked with upregulation of other Cu-binding proteins and with alteration in Cu homeostasis in the CdR phenotype.     

Nursing as science: a critical question.

Nursing is a profound human activity generally influenced by two dynamics--the relationship between patient and nurse and the scientific paradigm. Often overlooked, however, are the incongruities that arise between these two dynamics. The patient-nurse relationship encompasses sameness, closeness, and connection, whereas science requires distance, detachment, and differentiation to fulfil the demands of objectivity. The patient-nurse relationship is both profound and intangible, whereas science attends only to that which can be observed and measured. The authors explore these dynamics and the incongruities between them. They consider the demands made by science on the patient-nurse relationship and, conversely, the place of the patient-nurse relationship in the development of nursing as science. These issues are critical to the advancement and practice of nursing.     

General practitioners: child accident prevention and 'The Health of the Nation'

It has recently been suggested in the ‘Health of the Nation’that specific accident prevention activities should be undertakenby general practitioners. This study reports the findings froma survey of general practitioners in Nottinghamshire assessingknowledge, attitudes and current practices in accident prevention.The findings suggest that more than two-thirds of respondinggeneral practitioners are aware of the extent of childhood mortalityfrom accidental injuries and of the risk factors for accidentalinjury. Knowledge scores were higher for women, those aged 44years and under, those on the child health surveillance list,those with experience of hospital or community paediatrics,and those with postgraduate qualifications in paediatrics. Morethan 50% of general practitioners hold positive views towardsthe activities suggested in the ‘Health of the Nation’and more than 40% are already carrying out such activities.Positive attitudes are more commonly held in women and thoseon the child health surveillance list. There was a significantcorrelation between knowledge score and attitude score. Forall accident prevention activities covered in the questionnaire,fewer practitioners undertook an activity than held a positiveattitude towards that activity. Accident prevention work iscurrently more likely to be undertaken by general practitionerson an opportunistic basis than on a systematic population basis.If general practitioner intervention is demonstrated to be effective,a shift towards a population approach may be more successfulin reducing injury rates.