Neuronal subpopulations of developing rat hippocampus containing different calcium-binding proteins behave distinctively in trimethyltin-induced neurodegeneration

The present study investigates, by immunocytochemistry, the behavior of different neuronal subpopulations of the developing rat hippocampus, selectively labeled by the calcium-binding proteins calbindin D28-k (CB), parvalbumin (PV), and calretinin (CR), in neurodegenerative processes induced by the neurotoxicant trimethyltin (TMT). Previous studies on adult rats indicated that CB-immunoreactive (IR) neurons were affected by TMT, while PV- and CR-IR neurons were selectively spared. The present findings show that only CR-IR neurons are spared in developing rats, and in addition the number of CR-IR neurons are significantly higher in the DG of treated animals. On the contrary, PV-IR neurons, spared in adult rats, were affected by TMT during development. CB-IR neurons were affected also in developing rats, as in adults. The different postnatal time-courses of calcium-binding protein expression in relationship to the time of TMT administration (presence of CR but absence of PV) could have a role in the different behavior of CR- and PV-IR cells in developing rats.     

Effects of methyltestosterone on insulin secretion and sensitivity in women

The frequent coexistence of hyperandrogenism and insulin resistance is well established; however, whether a cause and effect relationship exists remains to be established. In this study we tested the hypothesis that short-term androgen administered to women would induce insulin resistance. To test this hypothesis, regularly menstruating, nonobese women were studied before and during methyltestosterone administration (5 mg tid for 10-12 days) by the hyperglycemic (n=8) and euglycemic, hyperinsulinemic (n=7) clamp techniques. Short-term methyltestosterone administration had no significant effects on the fasting levels of glucose, insulin, c-peptide, glucagon, or glucose turnover. During the hyperglycemic clamp studies, the mean glucose level during the final hour was 203+/-2 and 201+/-1 mg/dL in the methyltestosterone and control studies, respectively. The insulin response to this hyperglycemic challenge was slightly but not significantly greater during methyltestosterone treatment (first phase 59+/-8 vs. 50+/-8 microU/mL in controls; second phase 74+/-9 vs. 67+/-9 microU/mL in controls; total insulin response 133+/-16 vs. 117+/-15 microU/mL in controls). In spite of this, glucose uptake was reduced from the control study value of 10.96+/-1.11 to 7.3+/-0.70 mg/kg/min by methyltestosterone (P < 0.05). The ratio of glucose uptake per unit of insulin was also significantly reduced from a control study value of 14.3+/-1.4 to 9.4+/-1.3 mg/kg/min per microU/mL x 100 during methyltestosterone administration. In the euglycemic hyperinsulinemic clamp studies, insulin was infused at rates of 0.25 and 1.0 mU/kg/min to achieve insulin levels of approximately 25 and 68 microU/mL, respectively. During low-dose insulin infusion, rates of endogenous hepatic glucose production were equivalently suppressed from basal values of 2.37+/-0.29 and 2.40+/-0.27 mg/kg/min to 0.88+/-0.25 and 0.77+/-0.26 mg/kg/min in the methyltestesterone and control studies respectively. Whole body glucose uptake during low-dose insulin infusion was minimally affected. During the high-dose insulin infusion, endogenous hepatic glucose production was nearly totally suppressed in both groups. However, whole body glucose uptake was reduced from the control value of 6.11+/-0.49 mg/kg/min to 4.93+/-0.44 mg/kg/min during methyltestosterone administration (P < 0.05). Our data demonstrate that androgen excess leads to the development of insulin resistance during both hyperglycemic and euglycemic hyperinsulinemia. These findings provide direct evidence for a relationship between hyperandrogenemia and insulin resistance, and its associated risk factors for cardiovascular disease.     

Diabetes mellitus in dogs: a study of the critical difference for canine serum fructosamine

The purpose of this study was to calculate the critical difference between two analytical measurements of serum fructosamine concentration in dogs. The critical difference can be used to judge whether the difference between two consecutive analytical results from the same animal is due to natural variation. Blood samples from 15 apparently clinically healthy beagle dogs were collected once a week for six consecutive weeks. The serum fructosamine concentration was measured by the reduction test with nitroblue tetrazolium and the critical difference was calculated from the component of variance for weeks within dogs (sigma2s) and the residual variance (sigma2e). The critical difference between two consecutive analytical results was 33.5 micromol/litre.     

Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer

PURPOSE: Squamous cancer of the upper aerodigestive tract is a disheartening disease. Despite our best efforts, the long-term survival rate remains only 15% to 40%, and surgical cures often decrease the quality of life owing to the loss of swallowing and speech organs. A better understanding of tumor dynamics and the discovery that thiosulfate can neutralize cisplatin led us to develop a treatment plan that combines a rapid superselective high-dose intraarterial delivery of cisplatin (CDDP), simultaneous intravenous infusion of its antagonist, thiosulfate, and radiation therapy. METHODS: Patients with advanced head and neck squamous cancer were entered into the protocol after a multidisciplinary evaluation that included CT or MR imaging. Forty-two patients constituted the first cohort. After baseline angiography, an arterial acceptance test determined the maximum infusion rate that the tumor's nutrient artery would accept. CDDP was then infused at that rate, usually within 3 to 5 minutes, while the antagonist thiosulfate was given intravenously. In the second cohort of 85 patients with stage 3 or 4 previously untreated and unresectable disease, local radiation was added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was delivered regionally on the basis of the known radiosensitizing effect of CDDP. RESULTS: Cohort 1 allowed us to develop the infusion technique and to establish a dose quantity and delivery frequency. When 150 mg/m2 was administered weekly for 4 weeks, no severe toxicity was found. In cohort 2, 72 (92%) of the remaining 78 patients had complete disappearance of their tumor. Seventeen severe toxic events were associated with 323 femoral catheterizations. One patient died of pulmonary embolus, precluding follow-up evaluation. Six patients had neurologic sequelae, three with transient and three with permanent strokes. CONCLUSION: Rapid superselective chemotherapy with CDDP combined with a circulatory systemic antagonist allowed delivery of an antitumoral drug directly into the lesion while protecting the kidneys and bone marrow from the agent's systemic effects. Use of a dose regimen of 150 mg CDDP/m2 per week for 4 weeks resulted in the disappearance of a large percentage of advanced squamous cancers.     

Canine neosporosis: clinical signs, diagnosis, treatment and isolation of Neospora caninum in mice and cell culture

Clinical signs, diagnosis, treatment and isolation of Neospora caninum from two littermate dogs are described. Three of six pups from a Labrador bitch developed paralysis. Neosporosis was diagnosed ante mortem by serological examination in two of the affected pups. At necropsy, tissue cysts were seen in unstained smears and in histologic sections of their brains. Tissue cysts were often thin-walled (approximately 1 micron) but antigenically and ultrastructurally identified as N. caninum. Furthermore, N. caninum (isolates NC-4, NC-5) was isolated in mice and in cell cultures inoculated with neural tissues of these two dogs. Serological diagnosis of neosporosis using a variety of tests is discussed.     

7Li nuclear magnetic resonance study for the determination of Li+ properties in neuroblastoma SH-SY5Y cells

Lithium has been used clinically in the treatment of manic depression. However, its pharmacologic mode of action remains unclear. Characteristics of Li+ interactions in red blood cells (RBCs) have been identified. We investigated Li+ interactions on human neuroblastoma SH-SY5Y cells by developing a novel 7Li NMR method that provided a clear estimation of the intra- and extracellular amounts of Li+ in the presence of the shift reagent thulium-1,4,7,10-tetrazacyclododecane-N,N',N',N'-tetramethylene phosphonate (HTmDOTP4-). The first-order rate constants of Li+ influx and efflux for perfused, agarose-embedded SH-SY5Y cells in the presence of 3 mM HTmDOTP4- were 0.055 +/- 0.006 (n = 4) and -0.025 +/- 0.006 min(-1) (n = 3), respectively. Significant increases in the rate constants of Li+ influx and efflux in the presence of 0.05 mM veratridine indicated the presence of Na+ channel-mediated Li+ transport in SH-SY5Y cells. 7Li NMR relaxation measurements showed that Li+ is immobilized more in human neuroblastoma SH-SY5Y cells than in human RBCs.     

Philosophy of science in doctoral nursing education revisited

Because every scientific theory and all research methods are tied to some philosophical framework, it is important that scientists within a given discipline be aware of the philosophical orientations that serve as the basis for developing theory and advancing knowledge. Nurse scientists have been challenged recently to examine the discipline's philosophical underpinnings in order to understand the evolutionary process of nursing science. The inclusion of the study of philosophy of science in doctoral nursing curriculum has remained a topic of periodic discourse. Whereas some assert that it promotes the essential process of philosophical reflection necessary for scientific exploration of relevant phenomenon, others contend that nurse scientists' preoccupation with this issue has diverted their attention from the real business of nursing science--that of knowledge development that will lead to legitimization of nursing as a discipline. Philosophy of science provides a useful frame of reference in which to appreciate the unfolding of nursing as a discipline. It should not be viewed as a distraction but rather a critical step in the transformation of the doctoral student into a productive nurse scientist. Doctoral programs remain the most logical place in which to educate future scholars regarding nursing's unique philosophical foundations and their implications for scientific inquiry and continued knowledge development. Creating and maintaining liaisons between nursing and philosophy departments--as well as requiring courses that emphasize the interrelationships among philosophy of science, nursing theory, and nursing research--are just a few of the strategies whereby doctoral programs can actively promote advancement of the discipline.     

Klebsiella pneumoniae panophthalmitis: a possible complication of endoscopic variceal injection sclerotherapy

Complication of endoscopic variceal injection sclerotherapy for esophageal variceal hemorrhage is not unusual. However, sclerotherapy complicated panophthalmitis was never reported before. We report such an unusual complication and discuss its possible mechanism and treatment.     

Early inpatient rehabilitation after elective hip and knee arthroplasty

CONTEXT: Inpatient rehabilitation after elective hip and knee arthroplasty is often necessary for patients who cannot function at home soon after surgery, but how soon after surgery inpatient rehabilitation can be initiated has not been studied. OBJECTIVE: To test the hypothesis that high-risk patients undergoing elective hip and knee arthroplasty would incur less total cost and experience more rapid functional improvement if inpatient rehabilitation began on postoperative day 3 rather than day 7, without adverse consequences to the patients. DESIGN: Randomized controlled trial conducted from 1994 to 1996. SETTING: Tertiary care center. PARTICIPANTS: A total of 86 patients undergoing elective hip or knee arthroplasty and who met the following criteria for being high risk: 70 years of age or older and living alone, 70 years of age or older with 2 or more comorbid conditions, or any age with 3 or more comorbid conditions. Of the 86 patients, 71 completed the study. INTERVENTIONS: Random assignment to begin inpatient rehabilitation on postoperative day 3 vs postoperative day 7. MAIN OUTCOME MEASURES: Total length of stay and cost from orthopedic and rehabilitation hospital admissions, functional performance in hospitals using a subset of the functional independence measure, and 4-month follow-up assessment using the RAND 36-item health survey I and the functional status index. RESULTS: Patients who completed the study and began inpatient rehabilitation on postoperative day 3 exhibited shorter mean (+/-SD) total length of stay (11.7+/-2.3 days vs 14.5+/-1.9, P<.001), lower mean (+/-SD) total cost ($25891+/-$3648 vs $27762+/-$3626, P<.03), more rapid attainment of short-term functional milestones between days 6 and 10 (36.2+/-14.4 m ambulated vs 21.4+/-13.3 m, P<.001; 4.8+/-0.8 mean transfer functional independence measure score vs 4.3+/-0.7, P<.01), and equivalent functional outcome at 4-month follow-up. CONCLUSION: These data showed that high-risk individuals were able to tolerate early intensive rehabilitation, and this intervention yielded faster attainment of short-term functional milestones in fewer days using less total cost.