Modulatory influence of stimulus parameters on optokinetic head-tracking response

Optokinetic testing is a non-invasive technique, widely used for visual functional evaluation in rodents. The modulatory influence of optokinetic stimulus parameters such as contrast level and grating speed on head-tracking response in normal and retinal degenerate (RD) mice (rd10) and rats (S334ter-line-3) was evaluated using a computer-based testing apparatus. In normal (non-RD) mice and rats, specific stripe width and grating speed was found to evoke maximum optokinetic head-tracking response. In line-3 RD rats, the contrast sensitivity loss was slow and remained close to the baseline (normal control) level until very late in the disease, whereas, in rd10 mice the progression of the contrast sensitivity loss was more rapid. Observed differences between rd10 mice and line-3 RD rats in the progression of contrast sensitivity loss may not be directly related to the degree of photoreceptor loss. In young RD mice, the modulatory influence of stimulus parameters on optokinetic head-tracking response was similar to normal control animals. During later stages, slower grating speed was required to evoke the maximum optokinetic response. Grating speed had lesser apparent influence on the response properties of line-3 RD rats. Discrepancies between the two RD models in the modulatory influence of optokinetic stimulus parameters can be the manifestation of fundamental species differences and/or differences in the degeneration pattern. This study highlights the importance of careful selection of appropriate stimulus parameters for testing optokinetic head-tracking response in RD animals.     

Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: a single center experience

Arsenic trioxide (As(2)O(3)) has been found effective in the treatment in the treatment of acute promyelocytic leukemia (APML). Most studies with As(2)O(3) involve patients with APML who have relapsed following standard therapy. Between January 1998 and July 2000, 14 patients were recruited for an ongoing trial of As(2)O(3) in the treatment of newly diagnosed APML. Arsenic trioxide was administered at a dose of 10 mg/day until complete remission (CR) was achieved. Afterward, a consolidation course and a maintenance schedule consisting of As(2)O(3) as a single agent were administered over 6 months. There were 3 early deaths related to intra-cerebral hemorrhage: two on day 3 and one on day 4. Of the 11 evaluable patients, one died on day 21 secondary to uncontrolled sepsis, while the remaining 10 (91%) have attained CR. The average time to CR was 52.3 days (range: 34-70 days). One patient developed an isolated central nervous system (CNS) relapse and subsequently went into a second CR following therapy with triple intrathecal chemotherapy, cranial irradiation, and an additional 4-week course of systemic As(2)O(3). This patient, as well as the remaining nine, has continued to remain in CR at a median follow up of 15 months (range: 2-33 months). Eight out of 10 patients achieved molecular remission at variable periods during their consolidation and maintenance schedules. One patient developed an ATRA syndrome and was administered daunorubicin (40 mg/day) for 2 days. The side effects with this therapy were minimal and did not require cessation of therapy in any patient. There was no significant hepatic toxicity. In our experience, arsenic trioxide is effective in inducing and maintaining remission in patients with APML with minimal side effects. The optimal regimen and total dose required need to be defined.     

Tea tree oil concentration in follicular casts after topical delivery: determination by high-performance thin layer chromatography using a perfused bovine udder model

Tea tree oil, a popular antimicrobial agent is recommended for the treatment of acne vulgaris, a disease of the pilosebaceous unit. Tea tree oil formulations (colloidal bed, microemulsion, multiple emulsion, and liposomal dispersion containing 5% w/w tea tree oil) were applied to bovine udder skin. The follicular uptake of tea tree oil upon application was determined by a cyanoacrylate method. Tea tree oil was determined by quantifying terpinen-4-ol content using high-performance thin layer chromatography. The accumulation of tea tree oil in the follicular casts was 0.43 +/- 0.01, 0.41 +/- 0.009, 0.21 +/- 0.006, and 0.16 +/- 0.005 percentage by weight (milligram oil/gram of sebum plug) for microemulsion, liposomal dispersion, multiple emulsion, and colloidal bed, respectively. This is the first study of its kind to quantify tea tree oil concentration in the follicles.     

Superior colliculus responses to light - preserved by transplantation in a slow degeneration rat model

PURPOSE: To determine whether retinal transplantation can preserve visual responses in the superior colliculus (SC) of the S334ter-line-5 rat, a transgenic model for slow photoreceptor degeneration, which is more similar to human retinitis pigmentosa than the fast degeneration line 3 S334ter rat. METHODS: Visual responses to a light flash were recorded in the SC. Rats that had received embryonic day (E) 19-20 fetal retinal sheet transplants at the age of 26-30 days were tested at the ages of 200-254 days. Controls were age-matched rats without surgery and with sham surgery. As a baseline, in no-surgery line-5 rats, the temporal pattern of visual sensitivity loss was evaluated electrophysiologically in the SC from 60 days up to one year of age. RESULTS: In untreated S334ter-line-5 rats, decline in visual sensitivity in the SC was parallel to the photoreceptor loss. At 109 day of age, a relative scotoma developed in the area of the SC corresponding to the nasal retinal region. At 200-254 days of age, the majority of the SC was devoid of any light-driven responses. In contrast, at this time point, transplanted rats with 'good' retinal grafts with normal lamination had visual responses in the caudal region of the SC, the area corresponding topographically to the transplant location in the retina. In these rats, the various parameters of SC responses such as the latency of the onset of the visual response, the response peak amplitude and the consistency of the visual response were significantly different from the control groups (no-surgery, sham surgery, 'poor' transplants) and were more comparable to normal albino rats, however, with a slightly longer latency (70-90 vs. 30-50 msec). CONCLUSIONS: Fetal retinal sheet transplantation showed a long-term rescue effect on visual function in this animal model of slow photoreceptor degeneration.     

Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo

Erythropoiesis is critically dependent on erythropoietin (EPO), a glycoprotein hormone that is regulated by hypoxia-inducible factor (HIF). Hepatocytes are the primary source of extrarenal EPO in the adult and express HIF-1 and HIF-2, whose roles in the hypoxic induction of EPO remain controversial. In order to define the role of HIF-1 and HIF-2 in the regulation of hepatic EPO expression, we have generated mice with conditional inactivation of Hif-1alpha and/or Hif-2alpha (Epas1) in hepatocytes. We have previously shown that inactivation of the von Hippel-Lindau tumor suppressor pVHL, which targets both HIFs for proteasomal degradation, results in increased hepatic Epo production and polycythemia independent of Hif-1alpha. Here we show that conditional inactivation of Hif-2alpha in pVHL-deficient mice suppressed hepatic Epo and the development of polycythemia. Furthermore, we found that physiological Epo expression in infant livers required Hif-2alpha but not Hif-1alpha and that the hypoxic induction of liver Epo in anemic adults was Hif-2alpha dependent. Since other Hif target genes such phosphoglycerate kinase 1 (Pgk) were Hif-1alpha dependent, we provide genetic evidence that HIF-1 and HIF-2 have distinct roles in the regulation of hypoxia-inducible genes and that EPO is preferentially regulated by HIF-2 in the liver.     

Psychosocial outcomes following electroconvulsive therapy in a community setting: retrospective chart review with 2-year follow-up.

OBJECTIVE: Electroconvulsive therapy (ECT) continues to be one of the most effective biological therapies for patients with mood disorders. Numerous studies address clinical response; however, few have examined psychosocial or occupational outcomes following ECT, especially in community settings. This study aimed to examine these outcomes in short- and long-term naturalistic follow-up of ECT conducted in a community hospital. METHODS: A retrospective chart review was conducted of all patients who received ECT at Ridge Meadows Hospital in Maple Ridge, British Columbia, between January 1997 and December 2003. Charts were evaluated with the Clinical Global Impression (CGI), Global Assessment of Functioning, and Social and Occupational Functioning Assessment Scales prior to ECT and at 6 months, 1 year, and 2 years post-ECT. RESULTS: A total of 90 patients with mood disorders underwent ECT; 86.5% were rated on the CGI as "markedly ill" to "among the most extremely ill" at baseline. All clinical ratings improved at every follow-up point, and by the end of 24 months, 56.6% of patients were rated as "much improved" or "very much improved" on the CGI. Similarly, the measures of psychosocial functioning also showed significant improvement throughout the follow-up period. CONCLUSIONS: These findings show that substantial and meaningful improvement occurred in clinical and psychosocial outcomes after ECT conducted in a community hospital. These changes were robust and stable over the 2-year follow-up period. Limitations of the study include the retrospective ratings, the open-label use of ECT, and the naturalistic treatment in follow-up.     

Widespread cognitive impairment in psychogenic anterograde amnesia

A 34-year-old man without a past history of any psychiatric or neurological disorder developed severe anterograde amnesia following a psychological trauma. Initial assessment of neuropsychological functions 3 months after the psychological trauma indicated severe memory deficits for acquiring new information in both verbal and visual modalities with widespread cognitive deficits in attention, executive functions, and intellectual ability. Importantly, working and remote memory were intact. The case illustrates that psychogenic anterograde amnesia might be associated with a wider range of cognitive deficits. Possible neurobiological explanations are discussed to explain large cognitive impairments associated with anterograde psychogenic amnesia.