Depressed heart rate variability and arterial baroreflex in conscious transgenic mice with overexpression of cardiac Gsalpha

Using a continuous recognition memory procedure for spatial location information, rats were given sequential presentation of individual arms on a 12-arm maze. Each arm contained a Froot Loop reinforcement the first time it was presented, and latency to traverse the arm was measured. A subset of the arms were repeated, but did not contain reinforcement. Repeated arms were presented with lags ranging from zero to six (from zero to six different arm presentations occurred between the first and repeated presentation). After completion of acquisition training (significantly longer latencies for repeated arms in comparison with the first presentation of an arm), rats received lesions of the medial or lateral entorhinal cortex, pre- and parasubiculum, or served as sham-operated controls. Based on continued postsurgery training and additional tests, the results indicated that rats with pre- and parasubiculum or pre- and parasubiculum plus medial entorhinal cortex produced sustained impairment in performing the task. Medial or lateral entorhinal cortex and control lesions did not display any sustained deficits. The data suggest that working memory for spatial location information is mediated primarily by the pre- and parasubiculum, but not medial entorhinal and lateral entorhinal cortex.     

Mooren's ulcer

BACKGROUND: Mooren's ulcer is a rapidly progressive, painful, ulcerative keratitis which initially affects the peripheral cornea and may spread circumferentially and then centrally. Mooren's ulcer can only be diagnosed in the absence of an infectious or systemic cause and must be differentiated from other corneal abnormalities, such as Terrien's degeneration. Although the etiology remains unknown, recent research has proposed an underlying immune process and a possible association with the hepatitis C virus. The response to medical and surgical intervention is typically poor, and the visual outcome can be devastating. CASE SERIES: Three patients presented to our clinic with inferior peripheral corneal defects characteristic of Mooren's ulceration. The first patient, a 67-year-old white male, presented with an area of progressive peripheral thinning of the left inferior cornea 1 week after a preoperative skin cleanser was inadvertently splashed in both eyes. This occurred during a surgical procedure to remove a basal cell carcinoma. The second patient, a 56-year-old white male, was treated for a recurrent left inferior corneal ulcer with impending risk of perforation. The third patient was a 68-year-old white male referred for a painful left inferior peripheral ulcer, which rapidly progressed into a bilateral corneal melt disorder. All patients were diagnosed with Mooren's ulcerative keratitis after they underwent extensive medical and laboratory testing to rule out an infectious or systemic cause of their corneal melt. The first patient was treated with oral steroids, as well as doxycycline, to control his acne rosacea. The second patient responded to aggressive treatment with topical steroid therapy. This patient also tested positive for hepatitis C. The third patient rapidly developed a perforated left cornea and was treated with a penetrating keratoplasty after a patch graft had failed. DISCUSSION: Mooren's ulcer is an idiopathic, painful, progressive ulceration of the peripheral cornea. These ulcers usually respond poorly to conventional therapy, as there is limited knowledge of the pathophysiology of the disease. Evidence of an autoimmune component advocates the use of steroids and immunosuppressive agents. With further research and understanding of Mooren's ulcer, better treatment options may be available in the future.     

A Phase I dose escalation trial of continuous infusion paclitaxel to augment high dose cyclophosphamide and thiotepa plus stem cell rescue for the treatment of patients with advanced breast carcinoma

BACKGROUND: Paclitaxel, an effective chemotherapeutic agent in the management of breast carcinoma, may have activity in women whose disease has recurred after high dose chemotherapy. With this is mind the authors explored the addition of a 120-hour continuous infusion of paclitaxel to a previously reported regimen comprised of high dose cyclophosphamide and thiotepa. METHODS: Thirty-one women with advanced breast carcinoma (30 patients with Stage IV disease and 1 patient with Stage IIIB disease) underwent harvest and cryopreservation of bone marrow and/or peripheral blood progenitor cells. High dose cyclophosphamide (2.5 g/m2) and thiotepa (225 mg/m2) were administered intravenously on Days -7, -5, and -3. Paclitaxel was administered as a 120-hour continuous infusion starting on Day -7. RESULTS: Three patients were treated at the initial cohort dose of 50 mg/m2 (over 120 hours), 6 patients at 100 mg/m2, 6 patients at 125 mg/m2, 6 patients at 150 mg/m2, 6 patients at 180 mg/m2, and 4 patients at 210 mg/m2. All patients completed the treatment protocol as planned with no associated transplant-related deaths. Mucositis as evidenced by either stomatitis or noninfectious diarrhea was experienced by all patients and was determined to be the dose-limiting toxicity at the 210 mg/m2 dose level. One patient with dose-limiting mucositis required intubation for airway protection and also experienced Grade 3 (according to the Cancer and Leukemia Group B common toxicity grading scale) pulmonary and neurologic toxicity. Only one Grade 3 toxicity was encountered below the maximum tolerated dose in a patient who developed diffuse alveolar hemorrhage at a dose of 125 mg/m2. No allergic reactions or clinical evidence of peripheral neuropathies were encountered. Cardiac, hepatic, and renal toxicities were minimal. Response rates in this previously treated patient population were difficult to assess in light of the high incidence of bone metastases; an overall response rate of 24% was obtained. CONCLUSIONS: Paclitaxel at a dose of 180 mg/m2 as a 120-hour continuous infusion may be added safely to high dose cyclophosphamide and thiotepa with autologous stem cell rescue. Further studies are ongoing to evaluate the efficacy and further define the toxicity of this recommended Phase II dose.     

Scaling of hemolysis in needles and catheters

Relying on concepts found in prospect theory (D. Kahneman & A. Tversky, 1979), the value function of voice-based participation (i.e., the relationship between the amount of voice received and the value attached to that quantity) was examined. In keeping with tenets of prospect theory, the value function of voice exhibited a nonlinear pattern. Points were identified in which voice displayed significant improvements and diminishing marginal returns on response measures of process fairness, decision control, and outcome satisfaction. Task meaningfulness, a moderator of voice-based participation, did not change the general shape of the value function but did influence the intensity of participant reactions at low and high levels of voice. Voice influence, a second moderator of voice-based participation, had minimal impact on participant responses.     

Retinitis pigmentosa inversa

BACKGROUND: Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases, with a prevalence of about 1 in 3500 to 4500. Retinitis pigmentosa inversa is a rare variant of this disorder characterized by areas of choroidal degeneration with pigment migration and bony spicule formation in the macular area. In contrast to more typical forms of RP, this anomaly destroys central vision, leaving peripheral vision intact. CASE REPORT: A 47-year-old white male was followed for about 7 years with evidence of progressive retinal pigment epithelial atrophy and hyperpigmentation affecting both maculae. Since 1970, he had noted difficulty seeing at night as well as an acquired hearing deficit that appeared to be getting worse, ultimately impairing his ability to safely drive a truck. Medical history was positive for either chloroquine or hydroxychloroquine use for 2 to 3 years as malaria prophylaxis while he served in Vietnam. In addition, his father in Louisiana had visual loss of unknown cause. During the 7-year period, the condition progressed rapidly. The patient became virtually blind secondary to visual acuity loss with dense central and paracentral scotomas. The peripheral visual fields remained intact. After several years of extensive examinations, including laboratory, electroretinography, and genetic testing, a definitive diagnosis of RP inversa was made. DISCUSSION: RP inversa is a rare form of tapetoretinal degeneration that is characterized by decreased central vision with normal peripheral vision. A recessive form of inheritance has been postulated but never substantiated. Although there is currently no treatment, recent studies have indicated that 15,000 IU of vitamin A palmitate daily may slow the progression of retinitis pigmentosa; however, it is unknown whether this treatment would be effective for the inverse form of RP. Differential diagnoses include Leber's congenital amaurosis, central gyrate atrophy, central areolar choroidal sclerosis, progressive cone-rod dystrophy, syphilitic retinopathy, retinal toxicity from phenothiazine use, and chloroquine/hydroxychloroquine retinopathy.     

Mannhein index in the prognosis and treatment of acute peritonitis

Coronary Artery Disease (CAD) remains the major cause of mortality and morbidity in the Western World. The oxidation of low-density lipoproteins (LDLs) by free radicals is associated with initiation of atherosclerosis and therefore, development of CAD. LDLs are protected from oxidation by antioxidants and in times of antioxidant deficiency are more likely to be oxidized. Hypercholesterolaemic patients are at a higher cardiovascular risk and may, therefore, require more antioxidant protection. Increased consumption of red wine containing antioxidants is thought to account for the lower incidence of CAD in Mediterranean countries. Red wine, although rich in antioxidants, is not suitable as routine therapy for prevention of CAD. OBJECTIVE: To evaluate the effects of a capsule formulation of an antioxidant polyphenolic extract of grapes on serum total antioxidant activity and vitamin C and E levels. METHOD: A single-blinded randomised, placebo-controlled cross-over study was undertaken in 20 young volunteers. Subjects were given two capsules containing 300 mg of grape procyanidin extracts (Leucoselect-phytosome) or placebo daily for 5 days. Blood samples were taken at the start of the study and end of the study and assayed for antioxidant activity and vitamins C and E levels. After a washout period of at least 2 weeks, the study was repeated with the second treatment. RESULTS: The extract had no effect on serum vitamins C and E levels but increased serum total antioxidant activity (TAC). On day 5, TAC increased from 408.1+/-22.9 to 453.3+/-453.3 micromol/l trolox equivalents 1 hour postdose. CONCLUSION: The capsules increased serum antioxidant activity but the longer-term clinical implications need to be assessed in further randomised clinical trials.     

Swelling-induced arachidonic acid release via the 85-kDa cPLA2 in human neuroblastoma cells

Arachidonic acid or its metabolites have been implicated in the regulatory volume decrease (RVD) response after hypotonic cell swelling in some mammalian cells. The present study investigated the role of arachidonic acid (AA) during RVD in the human neuroblastoma cell line CHP-100. During the first nine minutes of hypo-osmotic exposure the rate of 3H-arachidonic acid (3H-AA) release increased to 250 +/- 19% (mean +/- SE, n = 22) as compared with cells under iso-osmotic conditions. This release was significantly inhibited after preincubation with AACOCF3, an inhibitor of the 85-kDa cytosolic phospholipase A2 (cPLA2). This indicates that a PLA2, most likely the 85-kDa cPLA2 is activated during cell swelling. In contrast, preincubation with U73122, an inhibitor of phospholipase C, did not affect the swelling-induced release of 3H-AA. Swelling-activated efflux of 36Cl and 3H-taurine were inhibited after preincubation with AACOCF3. Thus the swelling-induced activation of cPLA2 may be essential for stimulation of both 36Cl and 3H-taurine efflux during RVD. As the above observation could result from a direct effect of AA or its metabolite leukotriene D4 (LTD4), the effects of these agents were investigated on swelling-induced 36Cl and 3H-taurine effluxes. In the presence of high concentrations of extracellular AA, the swelling-induced efflux of 36Cl and 3H-taurine were inhibited significantly. In contrast, addition of exogenous LTD4 had no significant effect on the swelling-activated 36Cl efflux. Furthermore, exogenous AA increased cytosolic calcium levels as measured in single cells loaded with the calcium sensitive dye Fura-2. On the basis of these results we propose that cell swelling activates phospholipase A2 and that this activation via an increased production of AA or some AA metabolite(s) other than LTD4 is essential for RVD.     

Photorefractive keratectomy versus laser in situ keratomileusis for moderate to high myopia. A randomized prospective study

OBJECTIVE: This report presents the results of a randomized clinical trial of photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK). DESIGN: A randomized, prospective multicenter clinical trial. PARTICIPANTS: A total of 220 eyes of 220 patients entered the study cohort: 105 randomized to PRK and 115 to LASIK. The mean preoperative manifest refraction spherical equivalent was -9.23 diopters (D) in the PRK group and -9.30 D in the LASIK group. INTERVENTION: All patients received a one-pass, multizone excimer laser ablation as part of either a PRK or LASIK procedure using the Summit Apex excimer laser. Attempted corrections ranged from 6.00 to 15.00 D. MAIN OUTCOME MEASURES: Data on uncorrected and spectacle-corrected visual acuity, predictability,and stability of refraction, corneal haze, and flap complications were analyzed. Patients were observed for up to 6 months. RESULTS: One day after surgery, 0 (0.0%) and 3 (4.5%) eyes in the PRK group saw 20/20 and 20/40 or better uncorrected, respectively, while 7 (10%) and 48 (68.6%) eyes in the LASIK group saw 20/20 and 20/40 or better, respectively. At 6 months after PRK, 13 (19.1%) and 45 (66.2%) eyes saw 20/20 and 20/40 or better, respectively, while after LASIK, 16 (26.2%) and 34 (55.7%) eyes saw 20/20 and 20/40 or better, respectively (odds ratio = 0.56 for likelihood of uncorrected visual acuity < 20/40 for PRK vs. LASIK, 95% confidence interval [CI] = 0.31-1.19). After PRK, 39 eyes (57.4%) were within 1.0 D of attempted correction compared with 24 eyes (40.7%) in the LASIK group (odds ratio = 0.50 for likelihood fo undercorrection 1.0 D for PRK vs. LASIK, 95% CI = 0.24-1.04); however, the standard deviation of the predictability was similar between groups: 1.01 D for PRK and 1.22 D for LASIK. From months 1 to 6, there was an average regression of 0.89 D in the PRK group and 0.55 D in the LASIK group. After PRK, eight eyes (11.8%) had a decrease in spectacle-corrected visual acuity of two Snellen lines or more; after LASIK, two eyes (3.2%) had a decrease of two lines or more (odds ratio = 3.89 for risk of loss of spectacle-corrected visual acuity for PRK vs. LASIK, 95% CI = 0.71-21.30). Only two eyes had postoperative spectacle-corrected visual acuity less than 20/32, however. CONCLUSIONS: Although improvement in uncorrected visual acuity is more rapid in LASIK than in PRK, efficacy outcomes in the longer term generally are similar between the two procedures. There is a greater tendency toward undercorrection in LASIK eyes using the specific laser and nomogram in this study, but the scatter in achieved versus attempted correction is similar, suggesting little difference in the accuracy of the two procedures. A suggestion of decreased propensity for loss of spectacle-corrected visual acuity in LASIK eyes requires further investigation.