The use of cardiopulmonary bypass and circulatory arrest in the resection of massive tumors

This report describes our experience in five cases, removing a massive soft tissue tumor by means of placing the patient on cardiopulmonary bypass, with profound hypothermia and circulatory arrest. This technique allowed consideration to be given to the resection of tumors previously adjudged "inoperable."     

A rapid assessment of instructional strategies to teach auditory-visual conditional discriminations to children with autism

The purpose of the present investigation was to evaluate a rapid assessment procedure to identify effective instructional strategies to teach auditory-visual conditional discriminations to children diagnosed with autism. We replicated and extended previous rapid skills assessments (Lerman, Vorndran, Addison, & Kuhn, 2004) by evaluating the effects of reinforcement and prompting on the acquisition of auditory-visual conditional discriminations. The results showed that our assessment procedure identified at least one effective instructional strategy for each participant. In addition, our experimental design allowed us to identify the most efficient instructional strategy for all three participants.     

Evaluation of four commercial transport media for the survival of Neisseria gonorrhoeae

We evaluated four commercial transport systems with a standardized inoculum of clinical isolates of N. gonorrhoeae (NG), and assessed survival after holding for up to 48 hours at both ambient and refrigeration temperatures. Suspensions of clinical isolates of NG were standardized and adsorbed onto four transport swab types: Culturette EZ (Becton Dickinson [BD], Cockeysville, MD, USA); Cultureswab (Difco Laboratories, Detroit, MI, USA); Venturi Transystem (Copan Italia, Bovezzo, Italy); and a recently modified Starswab (Starplex Scientific, Etobicoke, ON). Swabs were plated to chocolate agar at 0, 6, 24, and 48 hours, and colonies counted. Each swab type was tested in quadruplicate with each NG strain for all time and temperature variables. There was a marked reduction in NG CFUs after only 6 hours incubation with each of the swabs tested. Survival was best using Venturi Transystem and Cultureswab transports (colony counts were reduced to 15.3% and 13.0%, respectively, at 6 hours) when compared with the Culturette EZ and Starswab (colony counts were reduced to 2.2% and 4.3%, respectively, at 6 hours). After the 24-hour holding period, 94% of the cultures from the Venturi Transystem were positive, 82% from the Cultureswab, 24% from the Starswab; and 17% from the Culturette EZ. After 48 hours, recovery dropped to 72%, 43%, 14%, and 0.04%, respectively. All of the systems tested had at least an 80% decrease in recovered colonies after only 6 hours. Further studies are required to determine how poor transport conditions influence the number of positive cultures and what the public health implications are. Of the swabs tested, Cultureswab and Venturi Transystem were most acceptable.     

Nutritional implications of cephalic phase thermogenic responses

The sensory stimulation of feeding produces a cephalic thermogenic response which coincides with an increase of plasma insulin, catecholamines and glucagon. These responses also take place with sham feeding but not with tube feeding. Vagal denervation of the pancreas as well as atropine administration, block the initial release of insulin and reduce by 50% the thermogenic response and norepinephrine release. An adrenergic blocker also reduces this response by 50%. However, with the simultaneous administration of both atropine and an adrenergic beta-blocker, this reduction is not observed. Indirect evidence suggests that this paradox is possibly explained by an enhanced secretion of glucagon.     

N-tosyl-L-phenylalanyl-chloromethyl ketone eliminates the increase in caspase-3 and bcl-2 caused by brain injury in the newborn rat

N-Tosyl-L-phenylalanyl-chloromethyl ketone (TPCK) is neuroprotective in rat pups. We measured bcl-2, Bax and caspase-3 to determine the mechanisms. Seven-day-old rats had the right carotid artery ligated and were subjected to 2.5 h of 8% oxygen. Ten mg/kg of PTCK or vehicle was given intraperitoneally 15 min prior to hypoxia. At 24 h after hypoxia the brains were removed. Bcl-2 in the hippocampus increased from 0.149 +/- (SE) 0.023 in the shams to 0.289 +/- 0.037 with injury and vehicle (p < 0.05 vs. shams), which was reduced to 0.177 +/- 0.030 by TPCK ( p < 0.05 vs. vehicle). Bcl-2 in the cortex increased from 0.180 +/- 0.037 in the shams to 0.655 +/- 0.078 with injury and vehicle (p < 0.01 vs. shams), which was reduced to 0.354 +/- 0.035 by TPCK (p < 0.01 vs. vehicle). Bax, measured only in the mitochondrial enriched fraction of the cortex, was unchanged. Caspase-3 activity increased with injury to 245 +/- 38% of baseline in the hippocampus (p < 0.01) and to 261 +/- 69% in the cortex (p < 0.01). Treatment with TPCK reduced this to 132 +/- 16% in the hippocampus (p < 0.01 vs. vehicle) and 140 +/- 14% in the cortex (p < 0.05 vs. vehicle). In this experiment TPCK reduces bcl-2 and caspase-3 concentration in animals who have been shown in our previous studies to be protected by TPCK from hypoxic ischemic brain injury. This is consistent with the hypothesis that TPCK produces neuroprotection by blocking the apoptotic cascade between bcl-2 and caspase-3.     

Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease

We evaluated whether contractile fatigue of the quadriceps occurs after cycling exercise in patients with chronic obstructive pulmonary disease (COPD) and whether it could contribute to exercise limitation. Eighteen COPD patients performed two constant work-rate cycling exercises up to exhaustion. These tests were preceded by nebulization of placebo or 500 microg of ipratropium bromide. Muscle fatigue was defined as a postexercise reduction in quadriceps twitch force of more than 15% of the resting value. There was an increase in endurance time postipratropium compared with placebo nebulization (440 +/- 244 seconds vs. 322 +/- 188 seconds, p = 0.06). Nine patients developed contractile fatigue after placebo exercise. In these patients, ipratropium did not increase the endurance time (394 +/- 220 seconds with placebo vs. 400 +/- 119 seconds with ipratropium) despite an 11% improvement in FEV1. In the nine patients who did not fatigue after placebo exercise, endurance time increased from 249 +/- 124 seconds with placebo to 479 +/- 298 seconds with ipratropium (p < 0.05). There was a significant correlation between the improvement in endurance time with ipratropium and quadriceps twitch force at 10 minutes after placebo exercise (r = 0.59, p = 0.01). The occurrence of contractile fatigue during exercise may explain why bronchodilation fails to improve exercise tolerance in some COPD patients.     

Screening for adolescent depression: comparison of the Kutcher Adolescent Depression Scale with the Beck depression inventory

Self-report instruments commonly used to assess depression in adolescents have limited or unknown reliability and validity in this age group. We describe a new self-report scale, the Kutcher Adolescent Depression Scale (KADS), designed specifically to diagnose and assess the severity of adolescent depression. This report compares the diagnostic validity of the full 16-item instrument, brief versions of it, and the Beck Depression Inventory (BDI) against the criteria for major depressive episode (MDE) from the Mini International Neuropsychiatric Interview (MINI). Some 309 of 1,712 grade 7 to grade 12 students who completed the BDI had scores that exceeded 15. All were invited for further assessment, of whom 161 agreed to assessment by the KADS, the BDI again, and a MINI diagnostic interview for MDE. Receiver operating characteristic (ROC) curve analysis was used to determine which KADS items best identified subjects experiencing an MDE. Further ROC curve analyses established that the overall diagnostic ability of a six-item subscale of the KADS was at least as good as that of the BDI and was better than that of the full-length KADS. Used with a cutoff score of 6, the six-item KADS achieved sensitivity and specificity rates of 92% and 71%, respectively-a combination not achieved by other self-report instruments. The six-item KADS may prove to be an efficient and effective means of ruling out MDE in adolescents.     

Suppression of Rac activity induces apoptosis of human glioma cells but not normal human astrocytes

Tumors of glial origin such as glioblastoma multiforme (GBM) comprise the majority of human brain tumors. Patients with GBM have a very poor survival rate, with an average life expectancy of <1 year. We asked whether we could identify a survival pathway in high-grade glioma and oligodendroglioma cells that when suppressed, would induce apoptosis of these tumor cells but not of normal human adult astrocytes. To identify these pathways, we selectively suppressed the activity of a number of proteins (Ras, Rac1, Akt1, RhoA, c-jun, and MEK1/2) hypothesized to play roles in cell survival. We found that suppression of Rac1, a small GTP-binding protein, inhibited survival and produced apoptosis in three human glioma cell lines (U87, U343, and U373). Serum induced the activity of Rac1 and the activity or phosphorylation state of p21-activated kinase 1 and c-Jun NH(2)-terminal kinase (JNK), two intracellular targets of Rac1. Suppression of Rac1 also induced apoptosis in 19 of 21 short-term cultures of human primary cells from grades II and III oligodendroglioma and grade IV glioblastoma that varied in p53, epidermal growth factor receptor, epidermal growth factor receptor vIII, MDM2, and p16/p19 mutational or amplification status. In contrast, inhibition of Rac1 activity did not induce apoptosis of normal primary human adult astrocytes. In both established glioma cell lines and primary glioma cells, apoptosis induced by the inhibition of Rac was partially rescued by activated mitogen-activated protein kinase kinase 1, an activator of JNK, suggesting that JNK functions downstream of Rac1 in glioma cells. These results indicate that Rac1 regulates a major survival pathway in most glioma cells, and that suppression of Rac1 activity stimulates the death of virtually all glioma cells, regardless of their mutational status. Agents that suppress Rac1 activity may therefore be useful therapeutic treatments for malignant gliomas.     

Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease

Exercise-induced oxidative stress has been reported in patients with chronic obstructive pulmonary disease (COPD) and may play a role in muscle fatigue. It is speculated that oxidative stress during exercise originates from the contracting muscles but this has not been documented. The accumulation of lipofuscin, a marker of cellular oxidative damage, was evaluated in the vastus lateralis muscle in 17 patients with COPD and 10 healthy subjects of similar age. Each subject performed a stepwise exercise test up to maximal capacity during which oxygen uptake (VO(2)) was measured. Resting and peak exercise blood gases were also obtained. Two indices of lipofuscin accumulation were used: lipofuscin inclusions/fiber ratio (LI/F) and lipofuscin inclusions/fiber cross-sectional area ratio (LI/CSA). These ratios were also determined for each specific fiber-type. LI/F (P < 0.01) and LI/CSA (P < 0.01) were greater in COPD compared to healthy subjects. LI/F and LI/CSA for all fiber types were also greater in COPD (P < 0.001). In both groups, LI/F (P < 0.001) and LI/CSA (P < 0.01) were higher in type I than in type II fibers. LI/F and LI/CSA did not correlate significantly with resting PaO(2) and SaO(2), peak VO(2), and DeltaPaO(2) and DeltaSaO(2) during exercise (P > 0.05). Increased lipofuscin accumulation, a marker of oxidative damage, was found in the vastus lateralis muscle in patients with COPD compared to healthy subjects. Oxidative damage of muscle tissue may thus be involved in skeletal muscle dysfunction and wasting in COPD.