Transplantation of Schwann cell line clones secreting GDNF or BDNF into the retinas of dystrophic Royal College of Surgeons rats

PURPOSE: To assess the capacity of a retrovirus-engineered Schwann cell line (SCTM41), transfected with either a glial cell line-derived neurotrophic factor (GDNF) construct or a brain-derived neurotrophic factor (BDNF) construct, to sustain visual function in the dystrophic Royal College of Surgeons (RCS) rat. METHODS: Cell suspensions were injected into the subretinal space of the right eye of 3-week-old dystrophic RCS rats through a transscleral approach. The left eye remained as an unoperated control. Sham-surgery animals received injections of carrier medium plus DNase to the right eye. All animals were placed on oral cyclosporine. At 8, 12, 16, and 20 weeks of age, animals were placed in a head-tracking apparatus and screened for their ability to track square-wave gratings at various spatial frequencies (0.125, 0.25, and 0.5 cyc/deg). At the end of the experiment, the animals were perfused and processed for histologic assessment of photoreceptor survival. RESULTS: Animals with SCTM41-GDNF-secreting cells, on average, head tracked longer than animals with SCTM41-BDNF-secreting cells, and both performed better than those injected with the parent SCTM41 line. All tracked longer than sham-surgery or nonsurgical dystrophic eyes. Each cell type demonstrated preservation of photoreceptors up to at least 4 months of age, over and above the sham-surgery control. CONCLUSIONS: Engineered Schwann cells sustain retinal structure and function in the dystrophic RCS rat. Cells overexpressing GDNF or BDNF had a greater effect on photoreceptor survival than the parent line or sham surgery. This study demonstrates that ex vivo gene therapy and subsequent cell transplantation can be effective in preserving photoreceptors from the cell death that normally accompanies retinal degeneration.     

Impulsivity and rapid discounting of delayed hypothetical rewards in cocaine-dependent individuals

In this study, crack/cocaine-dependent (CD) and non-drug-using matched control (MC) participants were presented with hypothetical immediate and delayed rewards, with 16 delay conditions ranging from 5 min to 25 years. All participants were presented with hypothetical monetary rewards; however, the CD group was also presented with hypothetical crack/cocaine rewards. The objective value of the rewards ranged from $1 to $1,000. Hyperbolic discounting functions provided a good fit of the data. The CD group discounted monetary rewards at a higher rate than the MC group did, and the CD group discounted crack/cocaine rewards at a higher rate than it did monetary rewards. Moreover, scores on self-report measures indicated greater impulsivity in the CD group when compared with the MC group.     

Properties of internal pilots with the univariate approach to repeated measures

Uncertainty surrounding the error covariance matrix often presents the biggest barrier to achieving accurate power analysis in the 'univariate' approach to repeated measures analysis of variance (UNIREP). A poor choice gives either an overpowered study which wastes resources, or an underpowered study with little chance of success. Internal pilot designs were introduced to resolve such uncertainty about error variance for t-tests. In earlier papers, we extended the use of internal pilots to any univariate linear model with fixed predictors and independent Gaussian errors. Here we further extend our exact and approximate results to UNIREP analysis. For a fixed treatment effect, the inaccuracy in a power calculation depends only on the ratio of the true variance to the value used for planning. The greater complexity of repeated measures requires generalizing misspecification of error variance to the misspecification of the eigenvalues of the error covariance. We recommend approximating the misspecification in terms of the first and second moments of the eigenvalues, for both fixed sample and internal pilot designs. We also describe an unadjusted approach for internal pilots with repeated measures. Simulations illustrate the fact that both positive and negative properties in the univariate setting extend to repeated measures analysis. In particular, internal pilots allow maintaining power or reducing expected sample size when the covariance matrix used for planning differs from the true value. However, an unadjusted approach can inflate test size, at least with small to moderate sample sizes. Hence new, adjusted methods must be developed for small samples. At this time, we caution against using an internal pilot design with repeated measures without first conducting simulations to document the amount of test size inflation possible for the conditions of interest.     

Massive vaginal hemorrhage after uterine fibroid embolization

A 48-year-old woman underwent uterine fibroid embolization (UFE) for menorrhagia. One-month after the procedure she developed massive vaginal bleeding and required an emergency hysterectomy. Pathologic evaluation of the uterus revealed ulceration of the endometrium overlying the necrotic fibroid. Physicians performing UFE should be aware of this rare but potentially life-threatening complication.     

Anxiety levels in women attending colposcopy clinics for treatment for cervical intraepithelial neoplasia: a randomised trial of written and video information

Objective To assess the effectiveness of video information in reducing the level of anxiety in women attending Colposcopy clinics.
Design An observational study followed by a randomised trial.
Setting Colposcopy Clinic, Royal Free Hospital, London.
Participants Between April and December 1999, all new referrals to the clinic with a cervical smear showing moderate or severe dyskaryosis.
Main outcome measure The level of anxiety measured by the Spielberger State Anxiety Inventory.
Conclusion Women attending colposcopy clinics for either diagnosis or treatment, experience a high level of anxiety. The highest levels occur in women attending a one-stop see and treat clinic. The introduction of visual information in the form of an explanatory video prior to attendance significantly reduced anxiety.     

Analysis of compartmental models of type 4 nuclear renograms with calculation of flow rate parameters and instantaneous drainage rates

OBJECTIVE: To estimate the dynamic rates of arterial delivery and renal drainage in renograms with the Homsy sign, using optimized computed compartmental modelling. METHODS: Eleven F-15 renograms and one F+15 renogram (using 99mTc-mercaptoacetyltriglycine) with the Homsy sign were studied, with 26 controls. Compartmental models were constructed for each renogram using components (blood, renal, bladder) linked by variables (arterial rate, drainage rate). Each model was optimized using the Marquadt least-squares method to numerical data from the time-activity curves (TACs). The model renal component at sample points along the TAC was minimized and the corresponding drainage rates calculated. RESULTS: The models were optimized, with a mean (range) r2 of 0.811 (0.68-0.88). There were continuous low drainage rates for all type 4 renograms, with no quadrupling of the flow rate, as predicted by the standard model. CONCLUSION: The standard model is unlikely to be correct and the Homsy sign is probably an artefact seen in patients with impeded urinary drainage. Computer modelling of individual renograms is feasible and can provide useful insights into the pathophysiology of renal uptake and drainage.     

Effect of tumour and chemoradiotherapy on oesophageal motility

Background The contribution of dysmotility to dysphagia in oesophageal cancer is unclear. Aim To examine oesophageal motility in patients with oesophageal carcinoma and to assess the effect of chemoradiotherapy on motility. Methods Stationary manometry and 24-hour pH-metry were performed in 12 patients with oesophageal carcinoma and one week following completion of chemoradiotherapy using 5-fluorouracil (5-FU), cisplatin and 40Gy radiotherapy. Results All patients had abnormal motility prior to treatment. Peristalsis was impaired in 11 patients with a mean (SD) of 25% (9) of waves normally propagated. Eight patients had 20% or more simultaneous waves. Following chemoradiotherapy, the percentage of waves normally propagated increased from 25% (9) to 52% (10) (p < 0.03) and normal peristalsis was restored in four patients. The percentage of simultaneous waves decreased from 38% (11) to 21.6% (10) (p=0.129) while the percentage of dropped or increased waves decreased from 20% (11) to 8.3% (4) (p=0.264). Conclusions Oesophageal motility is disturbed in oesophageal cancer. Dysphagia in oesophageal cancer may be partly explained by oesophageal dysmotility. This is improved by chemotherapy.