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Reversible brain atrophy and reversible developmental retardation in a malnourished infant.

An 11-month-old infant suffering from microcephalus, developmental delay, severe failure to thrive and marked cortical atrophy on brain CT is presented. The cause of this condition was total calorie malnutrition induced by the emotional dysfunction of the mother. Improvement of the maternal-infant relationship, combined with appropriate nutrition, transformed the infant within 2 months into a normally developing baby with body weight and head circumference within the normal percentile range. A corresponding improvement was found in the brain CT.

Cerebral Cortex↗

Reversal effects of nomegestrol acetate on multidrug resistance in adriamycin-resistant MCF7 breast cancer cell line.

BACKGROUND: Chemotherapy is important in the systematic treatment of breast cancer. To enhance the response of tumours to chemotherapy, attention has been focused on agents to reverse multidrug resistance (MDR) and on the sensitivity of tumour cells to chemical drugs. Hundreds of reversal drugs have been found in vitro, but their clinical application has been limited because of their toxicity. The reversal activity of progestogen compounds has been demonstrated. However, classical agents such as progesterone and megestrol (MG) also have high toxicity. Nomegestrol (NOM) belongs to a new derivation of progestogens and shows very low toxicity. We studied the reversal activity of NOM and compared it with that of verapamil (VRP), droloxifene (DRO), tamoxifen (TAM) and MG, and investigated the reversal mechanism, i.e. effects on the expression of the MDR1, glutathione S-transferase Pi (GSTpi), MDR-related protein (MRP) and topoisomerase IIalpha (TopoIIalpha) genes, as well as the intracellular drug concentration and the cell cycle. The aim of the study was to examine the reversal effects of NOM on MDR in MCF7/ADR, an MCF7 breast cancer cell line resistant to adriamycin (ADR), and its mechanism of action. METHODS: MCF7/ADR cells and MCF7/WT, an MCF7 breast cancer cell line sensitive to ADR, were treated with NOM as the acetate ester. With an assay based on a tetrazolium dye [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; MTT], the effects of various concentrations of NOM on MDR in MCF7/ADR cells were studied. Before and after the treatment with 5 microM NOM, the expression of the MDR-related genes MDR1, GSTpi, TopoIIalpha and MRP were assayed with a reverse transcriptase polymerase chain reaction (RT-PCR) immunocytochemistry assay. By using flow cytometry (FCM), we observed the intracellular ADR concentration and the effects of combined treatment with NOM and ADR on the cell cycle. Results collected were analysed with Student's t test. RESULTS: NOM significantly reversed MDR in MCF7/ADR cells. After treatment NOM at 20, 10 and 5 microM, chemosensitivity to ADR increased 21-fold, 12-fold and 8-fold, respectively. The reversal activity of NOM was stronger than that of the precursor compound MG, and comparable to that of VRP. After treatment with 5 microM NOM, the expression of both the MDR1 and the GSTpi mRNA genes began to decline on the second day (P <0.05 and P <0.01, respectively), and reached the lowest level on the third day (both P <0.01); however, on the fifth day the expression levels began to increase again (both P <0.05). The expression of MRP and TopoIIalpha had no significant changes. Changes in the expression of P-glycoprotein (P-gp) and GSTpi were similar to those of their mRNA expressions, showing early declines and late increases. Two hours after treatment with 20, 10 and 5 microM NOM, the intracellular ADR concentration increased 2.7-fold, 2.3-fold and 1.5-fold respectively. However, NOM did not increase ADR accumulation in MCF7/WT cells. FCM data showed that after 48 h of combined administration of NOM (20 microM) and ADR (from low to high concentration), MCF7/ADR cells showed a gradual arrest at the G2M phase with increasing ADR dose. The arrest effect with combined drug treatment was stronger than that with the single ADR treatment. CONCLUSION: MDR is the major mechanism of drug resistance in malignant tumour cells. To overcome MDR and to increase chemosensitivity, many reversal agents have been found. Most progestogen compounds have been demonstrated to have reversal effects, but we found no data on NOM, a new progestogen compound. Our results show that NOM has strong reversal activity. The reversal effects were stronger than those of the precursor compound, MG, and were comparable to that of VRP. Because NOM has low toxicity, it might have good prospects in clinical application. Using RT-PCR and immunocytochemistry assays, we studied the effects of NOM on MDR-related genes. The results were that NOM could markedly downregulate the mRNA and protein expression levels of MDR1 and GSTpi. TopoIIalpha and MRP gene expression showed no significant changes. It is known that P-gp induces MDR in tumour cells mainly by decreasing the intracellular drug concentration. After treatment with NOM, the intracellular drug concentration in MCF7/ADR cells increased significantly. Combined treatment with NOM and ADR induced arrest at the G2M phase. It is worth noting that NOM caused an early decrease and a late increase in the expression of some MDR-related genes in a time-dependent manner. The phenomena raise a question for the continued administration of reversal agents in clinics that merits further study. We demonstrate that NOM has strong reversal effects on MDR in MCF7/ADR cells. The reversal is via different routes, namely downregulating the mRNA and protein expression levels of MDR1 and GSTpi, increasing intracellular drug concentration and arresting cells at the G2M phase (NOM in combination with ADR). The reversal mechanism needs further study.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Reversal of the action of amino acid antagonists by barbiturates and other hypnotic drugs.

1 The effects of pentobarbitone (PB) and other sedative/hypnotic drugs have been examined in relation to gamma-aminobutyric acid (GABA) in vitro on the superfused isolated superior cervical ganglion of the rat and in vivo on single units in the brain stem of the anaesthetized rat.2 PB, and other barbiturates, depolarized the ganglion in a dose-dependent manner (threshold concentration 100-300 muM, cf. GABA depolarization threshold 1 muM). The depolarization was reduced in the presence of the selective GABA antagonist (+)-bicuculline methochloride (Bic). Other non-barbiturate sedatives e.g. chlordiazepoxide, amitriptyline, promethazine at concentrations up to 2mM produced no depolarization.3 PB, tested at concentrations up to 80 muM, produced variable effects on the dose-response curve to GABA. On most occasions a slight potentiation occurred in responses to low concentrations of GABA (below 10 muM) coupled with a depression in the responses to concentrations of GABA greater than 10 muM.4 Superfusion with PB in the presence of Bic reversed the depression in the response to GABA produced by Bic. This reversal phenomenon occurred at concentrations of PB too low to depolarize the ganglion and was dependent not only on the concentration of PB but also on that of Bic.5 The reversal potency within an homologous series of barbiturates increased with the size of the alkyl substituent (R2) at C5 on the barbiturate ring. The most potent occurred when the substituent contained 5 carbon atoms (pentobarbitone and amylobarbitone); above this, activity decreased.6 PB reversed the effects of the other GABA antagonists, tetramethylenedisulphotetramine and isopropyl bicyclophosphate and also the non-selective antagonism produced by strychnine. A concomitant reduction by strychnine of responses to the cholinomimetic, carbachol, was not reversed by PB.7 Non-barbiturate sedative/hypnotics also reversed the GABA antagonism produced by Bic. The benzodiazepines were effective at lower concentrations than PB (chlordiazepoxide threshold concentration 0.5 muM, cf. PB 5 muM), however, they only produced a partial reversal even at concentrations much higher than the maximally effective concentration of PB.8 The Bic reversal effect of chloridazepoxide (and other benzodiazepines) lasted many hours after removal from the superfusion solution. By contrast the effect of PB lasted only 15-30 min after its removal.9 Chlordiazepoxide (30 muM) applied in the absence of Bic did not affect the response to GABA but did reduce the depression produced by the subsequent application of Bic even though the chlordiazepoxide had been removed 40 min earlier.10 In the rat brain stem in vivo PB, applied iontophoretically in amounts which neither decreased the spontaneous neuronal firing rate nor affected the response to GABA or glycine, reversed the GABA antagonism induced by iontophoretic application of Bic (in all 23 neurones tested). PB also reversed the antagonism produced by strychnine of responses to glycine although this was less readily observed (5 out of 14 neurones tested).11 Iontophoretic application of other barbiturates and chlordiazepoxide also reversed the effect of Bic. Chlordiazepoxide only produced a partial reversal, as in the isolated ganglion, and no reversal could be demonstrated with flurazepam.12 Intravenous administration of thiopentone (1.3 mg/kg) pentobarbitone (0.4-5.5 mg/kg) hexobarbitone (0.4-0.8 mg/kg) and clonazepam (0.1-0.2 mg/kg) also reversed the effect of iontophoretically applied Bic. The reversal by clonazepam was of much longer duration than that produced by the barbiturates.13 It is suggested that the reversal exhibited by PB and the other hypnotics may be explained by assuming that the amino acids and their antagonists bind to the membrane at separate sites. If the reversal agent has particular affinity only for the antagonist binding site then it may displace the antagonist without affecting the receptor.

Aminobutyrates↗

The use of non-motion-based cues to pre-programme the timing of predictive velocity reversal in human smooth pursuit.

Human smooth pursuit eye movements are principally driven by visual feedback and cannot normally be initiated at will. However, when tracking periodic motion, smooth eye movements reverse direction prior to target reversal, driven by anticipation, not visual feedback. Here, we investigate cognitive control over such eye reversals. Target stimuli were discrete double ramps-constant speed (30 degrees /s) rightwards followed by similar leftward movement, reversal time ranging from 420 ms to 840 ms. Three experimental conditions were examined. In the precued condition, double ramps of randomised reversal time were presented. Prior to ramp presentation audio precues were given with an interval indicating start and reversal time of the unseen, upcoming double ramp. Subjects were able to use these cues to voluntarily control timing of anticipatory eye reversal, so that when occasional false precues gave underestimates of target reversal time, eye reversal occurred before target reversal. Precued eye reversal times were comparable to those in a second, predictable condition, in which double ramps with identical reversal time were given repeatedly without precues. In contrast, reversal occurred much later in a third, reactive condition, also without precues, when unexpected early target reversals occurred sporadically within a series having identical, predictable reversal times. The findings provide evidence that timing of anticipatory smooth eye movement, both at the start of the double-ramp and at its reversal, can be independently controlled at will using non-motion-based timing cues.

Brain↗

Successive olfactory reversal learning in honeybees.

Honeybees Apis mellifera can associate an originally neutral odor with a reinforcement of sucrose solution. Forward pairings of odor and reinforcement enable the odor to release the proboscis extension reflex in consecutive tests. Bees can also be conditioned differentially: They learn to respond to a reinforced odor and not to a nonreinforced one. They can also learn to reverse their choice. Here we ask whether honeybees can learn successive olfactory differential conditioning tasks involving different overlapping pairs of odors. The conditioning schedules were established in order to train the animals with 3, 2, 1, or 0 reversals previous to a last differential conditioning phase in which two additional reversals were present. We studied whether or not successive reversal learning is possible and whether or not learning olfactory discrimination reversals affects the solving of subsequent discrimination reversals. Therefore we compared the responses of bees that had experienced reversals with those of bees that had not experienced such reversals when both are confronted with a new reversal situation. In experiment 1 we showed that bees that had experienced three previous reversals were better in solving the final reversal task than bees with no previous reversal experience. In experiment 2, we showed that one reversal learning is enough for bees to perform better in the final reversal task. The successive different reversals trained in our experiments resemble the natural foraging situation in which a honeybee forager has to switch successively from an initial floral species to different ones. The fact that experiencing such changes seems to improve a bee's performance in dealing with further new exploited food sources has therefore an adaptive impact for the individual and for the colony as a whole.

Animals↗

Reversal of rapidly transported protein and organelles at an axonal lesion.

The time required for both rapid axonally transported organelles (vesicles and tubulo-vesicular structures) and proteins to undergo anterograde to retrograde reversal at a crush site was examined using sciatic nerve preparations obtained from Xenopus laevis. The transport and reversal of a pulse of newly synthesized 35S-labeled proteins was studied with a position-sensitive detector of ionizing radiation. Organelle transport and reversal were studied using video microscopy. Both protein and organelle reversal were assessed in two bathing media: a physiological saline and a medium that was compatible with the intracellular environment (internal medium). The time required for protein transport to reverse at a ligature was determined as a function of the time interval between the application of the ligature and the arrival of the pulse at the ligature (lesion time). In physiological saline, reversal times were greatest, about 3.5 h, when the lesion time was 1 h or less and decreased to approximately 1.5 h for lesion times of 4-12 h. When corrected for the approximately 2 mm length of degeneration caused by the saline, the results were similar to those obtained in internal medium and indicated a minimal reversal time for proteins of about 2 h. Organelle transport was examined close to narrow lesions in single myelinated axons. That the organelles moving away from the lesion represented organelles that had undergone reversed transport was suggested by observation of the reversal of individual organelles, and by a correlation between the flux of organelles towards and away from the lesion. Analysis of organelle flux within and adjacent to a segment of axon isolated by two lesions indicated that 70-80% of organelles moving away from a lesion represented reversed transport. Observations in internal medium were consistent with a reversal time of < 15 min, and in physiological saline < 30 min. The substantially smaller reversal time for organelle transport as compared to protein transport is consistent either with the existence of two types of organelles with different reversal times and hence different reversal mechanisms, or with the possibility that during reversal proteins are off-loaded from carrier organelles and subsequently up-loaded to different organelles.

Animals↗

Rapid, quantitative reverse transcriptase-polymerase chain reaction: application to intraoperative molecular detection of occult metastases in esophageal cancer.

OBJECTIVE: Our earlier data showed that quantitative reverse transcriptase-polymerase chain reaction can discriminate patients with node-negative cancer who are at high risk for recurrence. The objective of this study was to determine whether a new, more rapid quantitative reverse transcriptase-polymerase chain reaction assay could provide this information in a time frame suitable for intraoperative decision making. METHODS: We studied formalin-fixed, archived lymph nodes from 30 patients with histologically determined node-negative esophageal cancer with rapid quantitative reverse transcriptase-polymerase chain reaction to measure expression of carcinoembryonic antigen messenger RNA. We also performed rapid quantitative reverse transcriptase-polymerase chain reaction on 37 snap-frozen lymph nodes from 23 patients. Eleven of the 23 patients had benign esophageal disorders (negative control group). The other 12 had esophageal cancer, 6 with histologically determined positive lymph nodes and 6 with histologically determined negative lymph nodes. RESULTS: In the retrospective analysis of archival tissue from 30 patients with esophageal cancer with histologically determined negative lymph nodes, rapid quantitative reverse transcriptase-polymerase chain reaction predicted disease recurrence with a sensitivity and a specificity of 90% and 80%, respectively, and was comparable to conventional quantitative reverse transcriptase-polymerase chain reaction. In the frozen-tissue analysis rapid quantitative reverse transcriptase-polymerase chain reaction detected significantly higher levels of carcinoembryonic antigen expression in all 12 of the histologically determined positive lymph nodes than in the benign nodes. For 2 of these 12 nodes the intraoperative frozen-section analysis had negative histologic results, and N1 status was determined only on final pathologic examination. Rapid (intraoperative) quantitative reverse transcriptase-polymerase chain reaction discriminated both nodes as positive. Among the 14 histologically determined negative nodes, 1 of 3 nodes from 1 patient showed increased carcinoembryonic antigen according to rapid quantitative reverse transcriptase-polymerase chain reaction, and this patient had a clinical recurrence. CONCLUSIONS: In our study we were able to rapidly discriminate patients with node negative-esophageal cancer who had a high risk of recurrence. In frozen tissues rapid quantitative reverse transcriptase-polymerase chain reaction correlated with final pathologic report for 11 of 12 patients. In the 1 discordant case, the quantitative reverse transcriptase-polymerase chain reaction result was positive and may have detected microscopically occult metastasis, because this patient did have disease recurrence. Rapid quantitative reverse transcriptase-polymerase chain reaction was more sensitive than intraoperative frozen sections for detecting metastatic disease. These data suggest that rapid quantitative reverse transcriptase-polymerase chain reaction may have a prognostic role and could guide intraoperative decisions.

Aged↗

Serial reversal learning of position discrimination in developing rats.

The current study established a procedure to evaluate the capability of rats on postnatal days (PND) 21, 26, and 30 to perform a spatial serial reversal task using a T-maze. Training consisted of an acquisition session followed by a series of six reversal sessions. To examine the role of proactive interference in the serial reversal effect, the point of reversal was manipulated so that it occurred at the start of each session (between-sessions) or the midpoint of each session (within-sessions). Performance was initially impaired during the first reversal but improved dramatically across the series. Reversal between-sessions enhanced this serial reversal effect in comparison to reversal within-sessions. Experiment 1 showed that rats of all ages learned the between-sessions serial reversal task at a comparable rate. However, on the within-sessions task, PND21 rats were impaired relative to the PND26 and 30 rats, which did not differ. Experiment 2 revealed that the addition of a tactile cue that is correlated with each phase of reversal eliminated age and task differences in serial reversal performance. These findings suggest that higher-order cognitive processes underlying serial reversal are present during the weanling period, but there is some improvement with age under conditions involving high memory interference and/or difficulty in detecting the transition between reversal phases.

Age Factors↗

Reversal of Hartmann's procedure: effect of timing and technique on ease and safety.

PURPOSE: The optimal time for reversal of Hartmann's procedure is controversial. Significant operative difficulty and morbidity have been reported for Hartmann's reversal. The purpose of this study was to examine 11 years' experience with Hartmann's reversal, with particular attention to rate of reversibility, operative difficulty, and timing of reversal. METHODS: Case records of all patients undergoing either Hartmann's procedure or Hartmann's reversal at St. Vincent's Hospital between 1981 and 1991 were examined. Patients having Hartmann's reversal were divided into an early group (before 15 weeks) and a late group (after 15 weeks). These groups were compared in terms of morbidity and mortality, bed stay, and operative difficulty. RESULTS: Hartmann's procedure was performed on 111 patients, mostly for advanced cancer and complicated diverticular disease. Of 96 patients who survived, 50 (52 percent) underwent reversal. Of those with diverticular disease, 40 of 48 (83 percent) underwent reversal. Mortality for Hartmann reversal was 2 percent; anastomotic leak rate 4 percent; and overall complication rate 26 percent. Early reversal was performed in 13 patients and late reversal in 37 patients. There was no difference between these groups in mortality, morbidity, or anastomotic leakage. However, bed stay was longer in the early group and graded operative difficulty greater. In particular, cases in which adhesion density was most severe and in which accidental enterotomy occurred were more common in the early group (P = 0.02, Miettinen's modification of Fisher's exact test). CONCLUSIONS: Hartmann's reversal can be performed with an acceptable morbidity and mortality in most survivors of complicated diverticular disease. Operative difficulty appears to be less after a delay of 15 weeks.

Anastomosis, Surgical↗

Reversible ischemia in severe stress technetium 99m-labeled sestamibi perfusion defects assessed from gated single-photon emission computed tomographic polar map Fourier analysis.

BACKGROUND: Detection of reversible ischemia and regional viability by inference from the presence of preserved resting myocardial thickening on dynamic electrocardiographic-gated tomographic (GSPECT) images obtained after stress injection could potentially obviate the need for a separate resting injection. This would decrease the cost, effort, duration, and radiation exposure of diagnostic myocardial perfusion imaging. The aim of this study was to determine whether functional images derived from GSPECT stress myocardial perfusion images, which represent indices of regional wall thickening, could predict the pattern of reversibility of perfusion defects in myocardial segments with severe perfusion defects on stress 99mTc-labeled sestamibi (99mTc-sestamibi) images. METHODS AND RESULTS: Reversible ischemia in myocardial segments with severe hypoperfusion (< or = 50% of normal activity) on stress 99mTc-sestamibi images was assessed with GSPECT indexes of myocardial thickening, as reflected by an increase in regional count density during systole. GSPECT bullseye plots were generated for each of eight frames acquired after stress 99mTc-sestamibi injection in 44 patients with coronary artery disease and at least one severe perfusion defect on summed (ungated) SPECT images. With first harmonic Fourier amplitude (AMP) and AMP/perfusion ratio (APR) images, regional myocardial systolic thickening was assessed according to a nine-segment model as absent, markedly reduced, mildly reduced, or normal thickening. These data were compared on a regional basis with defect reversibility determined with resting sestamibi images. Of 124 severe stress defects, 32 showed absent, 53 minimal, 35 partial, and four complete reversibility on resting images. AMP and APR scores had 75% and 82% agreement on the presence or absence of reversibility on resting images, respectively (both p < or = 0.00005), and both had significant agreement (p = 0.0072 and p < or = 0.00005, respectively) with resting reversibility grades by kappa analysis. AMP correctly identified 83% of the defects that were reversible on resting images, whereas the APR identified 96% (p = 0.0014 for sensitivity of APR vs AMP). On analysis of the triad of segment scores, the AMP slightly underestimated the degree of resting reversibility (p = 0.0002), whereas APR images indicated more reversibility than did resting images (p < or = 0.00005). AMP and APR indicated a greater degree of reversibility than did resting images in at least one myocardial segment in 13 (30%) and 27 (61%) of the 44 patients, respectively. CONCLUSIONS: The presence and degree of reversible ischemia in severe stress sestamibi perfusion defects seen on resting images can be detected reliably by the pattern of regional myocardial thickening demonstrated by Fourier analysis of GSPECT polar maps. When indexed for degree of perfusion, the APR images predict a greater degree of reversibility than do resting images.

Adult↗

Pseudocholinesterase-mediated hydrolysis is superior to neostigmine for reversal of mivacurium-induced paralysis in vitro.

BACKGROUND: The metabolic hydrolysis of mivacurium (and succinylcholine) is markedly impaired in the presence of hereditary or acquired defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium paralysis. In the current study, the role of exogenous cholinesterases and/or of anticholinesterase, neostigmine, in the reversal of deep mivacurium-induced paralysis, was studied. The rat phrenic-diaphragm preparation, in a fixed volume of Krebs solution, was chosen to eliminate the confounding effects on the dissipation of neuromuscular effects caused by hydrolysis, elimination, and redistribution of the drug. METHODS: In the phrenic-diaphragm preparation, mivacurium was administered to obtain >90% single twitch inhibition. Single twitch responses (0.1 Hz) were monitored for 60 min, after which the response to train-of-four stimulation was tested. The reversal of mivacurium by 0.5, 1.0, or 2.0 units/ml of (true) acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase and by neostigmine, 0.1, 1.0, or 10.0 micrograms/ml tested. The efficacy of human plasma cholinesterase, 1 unit/ml in combination with each of the above neostigmine concentrations, also was examined. The reversal of succinylcholine-induced paralysis by the acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase (1 unit/ml) alone and in the presence of neostigmine (10.0 micrograms/ml) was additionally tested as a positive control. A train-of-four ratio > 0.75 was considered adequate reversal. RESULTS: Acetylcholinesterase was a poor hydrolyzer of mivacurium, as bioassayed by reversal of paralysis. Bovine pseudocholinesterase in concentrations of 0.5 and 1.0 units/ml did not effectively reverse single twitch and train-of-four responses by 60 min, but bovine pseudocholinesterase (2 units/ml) and all concentrations of human plasma cholinesterase did. Neostigmine alone, tested at all concentrations, was an incomplete reversal drug. Clinical or therapeutic concentrations (0.1 and 1.0 micrograms/ml) of neostigmine did not, but pharmacologic concentrations (10 micrograms/ml) interfere with the efficacy of human plasma cholinesterase (1 unit/ml). Bovine pseudocholinesterase and human plasma cholinesterase equally reversed the effects of succinylcholine but acetylcholinesterase did not, whereas the addition of 10 micrograms/ml neostigmine to the enzymes inhibited the reversal of succinylcholine. CONCLUSIONS: Human plasma cholinesterase will reverse mivacurium more effectively than bovine pseudocholinesterase, but both will effectively reverse succinylcholine. Acetylcholinesterase has no effects on either relaxant. The anticholinesterase neostigmine was an incomplete reversal drug. Pharmacologic concentrations of anticholinesterases do, while clinical or therapeutic concentrations do not, completely inhibit the metabolic activity of pseudocholinesterases.

Animals↗

Effect of reversal of catheter ports on recirculation: comparison of the PermCath with Tesio Twin Catheter.

To study the effect of the reversal of the blood ports on blood flow rate (QB), percentage recirculation, and blood urea nitrogen (BUN) clearance, we compared 12 well functioning chronic hemodialysis catheters (7 PermCaths and 5 Tesio Twin Catheters) in both standard and reversed blood flow setups. The reversal of PermCath ports caused no change in the QB (307+/-20 ml/min vs. 314+/-9 ml/min, standard vs. reversed hook-up, respectively), but a significant increase in percentage recirculation (2.5+/-1.8% vs. 12+/-4.6%, standard vs. reversed hook-up, respectively, p = 0.02). Reversal of the Tesio Twin Catheter ports caused a significant decline in QB (296+/-13 ml/min vs. 250+/-16 ml/min, standard vs. reversed hook-up, respectively, p = 0.02), but no significant change in percentage recirculation (2.8+/-1.4% vs. 3.8+/-2.5%, standard vs. reversed hook-up, respectively, p = not significant). Reversal of the ports caused no significant change in BUN clearance with the PermCath (264+/-18 ml/min vs. 257+/-17, standard vs. reversed hook-up, respectively, p = 0.8), but a significant decline in BUN clearance with the Tesio Twin Catheter (247+/-11 ml/min vs. 216+/-13.5 ml/min, standard vs. reversed hook-up, respectively, p = 0.015). In conclusion, our results suggest that reversed hook-up of a well functioning Tesio Twin Catheter is associated with a significant decline in QB and BUN clearance, but no change in percentage recirculation; however, inadvertent reversed hook-up of a well functioning PermCath can lead to a considerable increase in percentage recirculation but no change in QB or BUN clearance.

Adult↗

Premature beats elicit a phase reversal of mechanoelectrical alternans in cat ventricular myocytes. A possible mechanism for reentrant arrhythmias.

BACKGROUND: Alternans of the ST segment of the ECG is an important risk factor for sudden cardiac death. Premature beats during alternans and the development of discordant alternans are associated with the onset of ventricular tachycardia and ventricular fibrillation. Moreover, premature beats can switch the pattern of alternans from discordant to concordant alternans. The mechanisms of how a premature beat can elicit a pattern shift in alternans and develop malignant ventricular arrhythmias are not clear. The purpose of this cellular study was to determine the electrical and mechanical restitution properties during cycle length-induced alternans and to determine how premature and delayed beats affect the resultant phase of alternans. METHODS AND RESULTS: A perforated patch recording method and video-based edge detector were used to record action potentials and contractions, respectively, from single ventricular myocytes enzymatically isolated from the cat heart. Electrical and mechanical restitution curves were determined by programmed test beats delivered at different cycle lengths during mechanoelectrical alternans. At 35 degrees C, 97.8% of cells exhibited concordant cellular alternans (action potentials with the larger action potential duration [APD] were associated with the larger contraction, and action potentials with the smaller APD exhibited the smaller contraction). The sequence or phase of concordant cellular alternans could be systematically reversed by (1) early premature beats that followed only action potentials with the shorter APD and smaller contraction (type 1 phase reversal; n = 34) or (2) late delayed beats that followed only action potentials with the longer duration and the larger contraction (type 2 phase reversal; n = 14). A phase reversal point was defined as a threshold time interval that resulted in switching the sequence of the alternating beats. A test stimulus at the phase reversal point caused temporary suppression of mechanoelectrical alternans. Lower temperatures (32 degrees C) or decreases in the basic cycle length induced larger beat-to-beat changes in the magnitude of alternans (APD or contraction) and significantly shifted the phase reversal point to earlier premature intervals for type 1 phase reversal. The interval of the phase reversal point was a function of the contractile ratio (the magnitude of the larger contraction/smaller contraction for two consecutive beats, r = .93) and not the APD ratio (longer APD/shorter APD; r = .501). In cells stimulated at cycle lengths longer than the threshold of alternans, a single premature beat could elicit a damped form of concordant mechanoelectrical alternans. A critically timed second premature beat reversed the phase of the damped alternans. CONCLUSIONS: Properly timed premature or delayed beats during cycle length-induced alternans consistently reversed the phase of cellular mechanoelectrical alternans. Reversal of the phase of alternans was dependent on recovery of mechanical activity, not electrical activity. The premature stimulus interval at the phase reversal point can be predicted by the magnitude of mechanical alternans. Thus, during cycle length-induced alternans, mechanical alternans governs the phase of electrical alternans. From the present results, a multi-cellular model is proposed that may explain how critically timed premature beats cause a regional change in the phase of mechanical alternans and thereby result in discordant electrical alternans or dispersion of refractoriness. Premature beats that induce phase reversal in mechanoelectrical alternans may contribute to the development of reentrant arrhythmias.

Action Potentials↗

Effects of teacher attention on digit-reversal behavior in an elementary school child.

Teacher attention was systematically manipulated to modify digit-reversal behavior in an elementary school child. Almost invariably, the child reversed the order of digits (e.g., writing 21 as the sum of 5 + 7) when adding numbers yielding a two-digit sum. The child, along with classmates, was given 20 addition problems a day for the duration of the study, and the number of reversals was recorded. During an initial baseline period, the teacher responded to digit reversals by marking them as incorrect and then giving the child "extra help" until all sums were correctly ordered. The child's present and previous teacher had both responded to reversals in this manner for approximately one year before the present study began. An experimental period followed during which the rate of reversals decreased sharply. During this period, all sums were marked as correct (whether reversed or not); "extra help" with reversals was discontinued; and correct, i.e., non-reversed, response forms were responded to with a smile, a pat on the back, and a brief comment. A reversal period followed, during which the teacher responded to reversals as she had in the first baseline period. An increase in the rate of reversals to baseline level occurred within three days. A final period, replicating the first experimental period followed, and was characterized by a sharp decrease in the rate of reversals.

Journal Article↗

Patient characteristics associated with vasectomy reversal.

PURPOSE: More than 30 million couples throughout the world are using vasectomy as a method of birth control. It is estimated that up to 6% of men who undergo voluntary sterilization will eventually request reversal, despite the high cost and relatively low success rate of the procedure. We identified characteristics that predict which vasectomy patients may request reversal. We also examined the cost and effectiveness of pre-vasectomy sperm cryopreservation followed by intrauterine insemination as an alternative method of achieving pregnancy. MATERIALS AND METHODS: We reviewed medical charts of 365 patients who underwent vasectomy and 290 who underwent vasectomy reversal between 1990 and 1997. Data were collected on patient age at the time of vasectomy, religion, occupation, wife employment status, number of marriages, number of children, reason for reversal, and number of years between vasectomy and reversal. Based on previously reported values, pregnancy rates and cost per successful pregnancy were estimated for vasectomy reversal surgery, and compared with a calculated cost per pregnancy for sperm cryopreservation and intrauterine insemination. RESULTS: Patient factors significantly associated with increased vasectomy reversal included younger age at time of vasectomy (p < 0.001) and a wife who worked outside the home (p < 0.001). Vasectomy reversal occurred 12.5 times more often (95% confidence interval [CI] 7.6 to 20.7) in men who underwent vasectomy in their 20s than in men who were older. Men whose wives were not employed requested reversal 0.48 times as often (95% CI 0.33 to 0.71) as those whose wives worked. Men who were younger at vasectomy tended to wait longer before reversal (median 10 years) than other patients (p < 0.001). At 10 years our calculated pregnancy rates and cost per pregnancy were 44% and $12,727 for vasectomy reversal, and 41% and $9,512 for intrauterine insemination with banked sperm (3 attempts). CONCLUSIONS: Patients who requested vasectomy reversal most often chose voluntary sterilization at a younger age. We believe that younger men should be given better pre-vasectomy counseling. However, the success rate and cost-effectiveness of sperm cryopreservation before vasectomy, with subsequent intrauterine insemination, may make this nonsurgical alternative desirable for younger couples who choose vasectomy even when properly informed about reversal rates.

Adult↗

Reverse redistribution on exercise thallium scintigraphy: relationship to coronary patency and ventricular function after myocardial infarction.

OBJECTIVE: To define prevalence, pathophysiology and relation to thrombolytic therapy of reverse redistribution (appearance of a new, or worsening of an existing, scintigraphic defect on 4 h delayed images compared with the stress thallium image). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral centre. PATIENTS: Sixty-three patients with acute myocardial infarction. INTERVENTIONS: Tomographic exercise thallium scintigraphy, radionuclide angiography, and quantitative coronary angiography. MAIN RESULTS: Tomographic exercise thallium scintigraphy performed at day 10 revealed fixed defects in 15 patients, reversible defects in 22 patients and reverse redistribution in 26 patients; no difference in treatment assignment (tissue plasminogen activator versus placebo) was found among the three groups. Left ventricular function was similar in patients with fixed or reversible defects and reverse redistribution; global ejection fraction was 48 +/- 14, 51 +/- 10 and 48 +/- 5%, respectively, and regional infarct ejection fraction was 36 +/- 15, 40 +/- 13 and 37 +/- 18%, respectively. However, nitroglycerin administration resulted in a significantly greater improvement in regional ejection fraction in reverse redistribution patients (5 +/- 4%) than that in patients with fixed defect (2 +/- 5%, P < 0.05) or reversible defects (3 +/- 5%, P < 0.05). The infarct-related artery had a greater cross-sectional area in reverse redistribution patients (1.5 +/- 1.42 mm2) compared with those with reversible defects (0.50 +/- 0.26 mm2, P < 0.05), but was similar to fixed defect patients (1.04 +/- 0.88). CONCLUSIONS: Reverse redistribution on tomographic thallium scintigraphy is a frequent phenomenon (occurring in 40% of patients following acute myocardial infarction) and is independent of thrombolytic therapy. Patients with reverse redistribution have a more widely patent infarct-related artery and similar ventricular function, but significantly greater functional improvement following nitroglycerin administration compared with those with reversible or fixed defects. These data suggest myocardial salvage within the infarct zone in some patients with reverse redistribution.

Animals↗

Relationship between reverse redistribution on planar thallium scintigraphy and regional myocardial viability: a correlative PET study.

UNLABELLED: The purpose of this study was to assess myocardial metabolic activity in the area of reverse redistribution and determine the prognostic value of reverse redistribution and PET imaging. Reverse redistribution is thought to be a manifestation of reperfusion therapy and associated with a favorable clinical outcome. Preliminary observations from the Thrombolysis and Myocardial Infarction (TIMI) trial suggest that reverse redistribution is associated with higher incidence of future cardiac events. METHODS: Thirty-two patients with chronic coronary artery disease and reverse redistribution on planar thallium scintigraphy had PET 13NH3/18FDG imaging. Radionuclide angiocardiography was performed in 23 patients. RESULTS: Fifty segments showed reverse redistribution on planar thallium images; 19 segments had normal 13NH3 and 18FDG uptake and 17 were ischemic by PET criteria. Thus, a total of 72% (36 of 50) of reverse redistribution segments were PET viable. Sixty-one percent of segments with abnormal regional wall motion and reverse redistribution were PET scar. On follow-up, 31% (10/32) had a cardiac event (nine unstable angina and one myocardial infarction). Fifty percent of patients (5/10) with cardiac events had severe reverse redistribution and PET viability versus 9% (2/22) without cardiac events (p = 0.01). CONCLUSIONS: The majority of thallium reverse redistribution segments was PET viable as judged by 18FDG uptake. Viability in areas of reverse redistribution is not inferred by regional wall motion analysis. Regional PET viability identifies patients with reverse redistribution with a higher likelihood of future cardiovascular events. PET viability assessment may be helpful with the impact of reverse redistribution on planar thallium scintigraphy.

Aged↗