Topical cyclosporine inhibits conjunctival epithelial apoptosis in experimental murine keratoconjunctivitis sicca

PURPOSE: Increased apoptosis in the conjunctival epithelium has been observed in experimental murine keratoconjunctivitis sicca (KCS). Topical cyclosporine (CsA) has been noted to reduce conjunctival epithelial apoptosis in chronic canine and human KCS. The purpose of this study is to determine if topical CsA treatment inhibits conjunctival epithelial apoptosis in a murine model of KCS. METHODS: Dry eye was induced in 3 groups of C57BL6 mice by subcutaneous injection of scopolamine TID and exposure to an air draft and low-humidity environment for 16 hours per day for 12 days. The dry eye control group received no topical treatment; a second group received 1 microL of 0.05% CsA topically TID (dry eye + CsA); and the third group received 1 microL of the castor oil vehicle of CsA topically TID (dry eye + vehicle). Normal mice were used as untreated controls. After 12 days, the mice were killed, and the right eyes and eyelids were excised, frozen, and cryosectioned. Transmission electron microscopy (TEM) was performed on conjunctival and corneal samples taken from the left eyes. Apoptosis was detected in frozen sections with the ApopTag (ISOL) In Situ Oligo Ligation Kit, which specifically detects DNA fragmentation. Immunohistochemical staining was performed to detect activated caspase-3. Conjunctival goblet cell number was counted in tissue sections stained with period acid Schiff (PAS) reagent. These assays were performed on 2 separate sets of mice. RESULTS: Compared with untreated controls and dry eye mice receiving CsA, the number of ISOL-positive epithelial cells in the bulbar and tarsal conjunctiva was significantly greater in the dry eye control and dry eye mice + vehicle groups (P < 0.01 for both groups). There was no significant difference in the number of ISOL-positive conjunctival epithelial cells between the dry eye control and dry eye + vehicle mice. There was no significant difference in ISOL-positive cells in the corneal epithelium between the untreated controls and the 3 treatment groups. Dry eye + CsA mice showed less activated caspase-3 staining than the dry eye control and the dry eye + vehicle groups. TEM showed loss of superficial differentiated cells and extensive nuclear fragmentation characteristic of apoptosis in the dry eye control and dry eye + vehicle groups but not in the dry eye + CsA group. There was significant loss of goblet cells in the bulbar and tarsal conjunctivae of the dry eye control and the dry eye + vehicle groups compared with untreated controls and the dry eye + CsA group. CONCLUSIONS: Topical CsA significantly reduced conjunctival epithelial apoptosis and protected against goblet cell loss in experimental murine KCS. Inhibition of apoptosis appears to be a key mechanism for the therapeutic effect of CsA for KCS.     

RSEP1 is a novel gene with functional involvement in neuropathic pain behaviour

Neuropathic pain from nerve injury by trauma, disease or surgery often causes prolonged suffering. To explore the molecular mechanisms that underlie neuropathic pain, we used mRNA from the L4--5 segments of the lumbar spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain, and differentially screened a cDNA library from the rat brain. A novel gene, termed RSEP1 (Rat Spinal cord Expression Protein 1), was identified. Northern blots revealed that RSEP1 was expressed mainly in the central nervous system including the cerebral cortex, hippocampus, brainstem and spinal cord, as well as in the kidney and ovary. In situ hybridization showed a high level of RSEP1 expression in the CA1, CA3 and dentate gyrus regions of the hippocampus and the small sensory neurons in the dorsal horn, as well as the large neurons in the ventral horn of the spinal cord. Intrathecal injection of RSEP1 antisense oligonucleotide into the spinal cord lumbar enlargement attenuated neuropathic pain behaviours in CCI rats, suggesting a functional involvement of RSEP1 in neuropathic pain.     

Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial

Increased attention has been given to the alternatives to stimulants in the treatment of attention deficit hyperactivity disorder (ADHD) in both adults and children. This short-term, double-blind trial was designed to evaluate the extended-release form of bupropion in adult subjects meeting DSM-IV and the Utah Diagnostic Criteria for ADHD. Outcome measures were the Clinical Global Impressions-Improvement (CGI-I) and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), which assesses adult ADHD symptoms. Outcome (defined by the CGI-I, average WRAADDS scores, or a 50% improvement on the WRAADDS) favored bupropion SR over placebo, but achieved statistical significance on only one, post hoc measure. Other measures showed trends for improvement with bupropion. Given the small size of this study, these findings deserve further exploration.     

Carcinogenicity of radon/radon decay product inhalation in rats--effect of dose, dose rate and unattached fraction

PURPOSE: The effects of inhalation of radon/radon decay products at different total doses, dose rates and 'unattached' fractions were investigated in a life span study in rats. MATERIALS AND METHODS: 1574 rats inhaled radon/radon decay products in a purpose-built recirculating exposure system that provided stable/reproducible exposure conditions. 501 were maintained as controls. RESULTS: Lung tumour incidences were significantly elevated in most exposed groups. The study power was insufficient to resolve the shape of the dose and dose rate response curves, but combination of this data with that from other studies demonstrated that for high cumulative exposures, the lifetime excess absolute risk increases with increasing exposure durations and for low cumulative exposures the opposite trend occurs. Exposure did not increase leukaemia incidences. A small number of non-lung tumour types including mammary fibroadenoma showed elevated incidences in some exposed groups, however not consistently across all exposure groups and showed no dose or dose rate relationship. CONCLUSIONS: Radon/radon decay product exposure caused excess lung tumours in rats along with limited non-lung effects. The results are consistent with the findings that at low cumulative exposures decreasing exposure concentrations or protracting the time over which the dose is delivered, reduces lung tumour risk. At higher levels, decreasing exposure concentrations or protracting exposure time increases lung tumour risk.     

Does off-pump coronary artery bypass reduce the incidence of clinically evident renal dysfunction after multivessel myocardial revascularization?

In this prospective, observational trial, we determined whether off-pump coronary artery bypass (OPCAB) was associated with less postoperative renal dysfunction (RD) compared with coronary bypass surgery with cardiopulmonary bypass (CABG). All patients undergoing primary, isolated coronary surgery at our institution in the year 2000 participated. Data collected on each patient included demographics, preoperative risk factors for RD, perioperative events, and serum creatinine concentrations from date of admission until discharge or death. The criteria for RD was both a >or=50% increase from preoperative creatinine and an absolute postoperative creatinine >or=2.0 mg/dL (177 microM). Student's t-test or the Fisher's exact test was used to compare groups. Stepwise multiple logistic regression identified determinants of RD; P < 0.05 significant. The CABG group (n = 119) differed from the OPCAB group (n = 220) with respect to age (64 +/- 13 versus 67 +/- 10 yr, P = 0.0074) and number of distal grafts (median 4 versus 3, P = 0.0003). Type of operation did not associate with the presence of postoperative RD: 18 (8.2%) of 220 OPCAB patients versus 12 (10%) of 119 CABG patients (P = 0.55). Our data suggest that choice of operative technique (OPCAB versus CABG) is not associated with reduced renal morbidity.     

Aneurysm of aortocoronary saphenous vein graft: case report and literature review

True aneurysms of aortocoronary saphenous vein bypass grafts are a relatively rare complication of bypass surgery, but because the complications of thrombosis, embolization, or rupture are potentially fatal, this condition requires immediate surgical intervention. We describe a 78-year-old man who had undergone coronary bypass 15 years previously and who presented with a saphenous vein graft that was severely degenerated and aneurysmally enlarged throughout its course, measuring as much as 5 to 6 cm in certain locations. Redo coronary artery bypass grafting using the right and left internal thoracic arteries and resection of the aneurysm were performed. We also present a review of the literature regarding diagnosis, management, and treatment of this condition.     

Using the Rasch model to develop a revised Gambling Attitudes and Beliefs Scale (GABS) for use with male college student gamblers

Research suggests that an overwhelming majority of college students gamble, with between 2-9% of U.S. students meeting DSM-IV criteria for pathological gambling. Despite the prevalence of gambling among college students, accurate and easily implemented methods for the assessment of gambling involvement among college students are lacking. Thus, the purpose of the current study was to establish the psychometric properties of a measure of gambling attitudes and beliefs (GABS) and demonstrate this measure's association with gambling frequency and an established gambling screen among 374 U.S. male college students during 1995-1997. Using techniques based in modern test theory (e.g., Rasch model), we identified a set of 10 items that reliably rank-ordered students in relation to their positive attitudes and beliefs about gambling. Further, the resulting 10 items accounted for variance in gambling behavior beyond that provided by a more standard consequences-based assessment measure. Use of this measure for the improvement of gambling assessment in college students is recommended.