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Reversal of the reaction catalyzed by glyoxalase I. Calculation of the equilibrium constant for the enzymatic reaction.

Glyoxalase I catalyzes the formation of S-D-lactoyl-glutathione via the hemimercaptal adduct of methylglyoxal and glutathione. This enzymatic reaction, which has been considered virtually irreversible, was found to be reversible under such conditions that glutathione liberated from the thiolester was trapped. The reverse reaction could be monitored spectrophotometrically by use of 5,5'-dithiobis-(2-nitrobenzoate). In addition to 5,5'-dithiobis-(2-nitrobenzoate), 2,2'-dithiobispyridine and cystamine were used to promote the reverse reaction. S-D-Lactoylglutathione did not hydrolyze in the presence of glyoxalase I under the conditions investigated, as shown by its stability in the absence of thioltrapping agents. Proof of the reversal of the reaction was obtained by demonstrating the formation of stoichiometric amounts of methylglyoxal and glutathione from S-D-lactoylglutathione. Catalysis of the reverse reaction was dependent upon the presence of a bivalent metal ion in the active site of the enzyme. Apoenzyme, obtained by removal of the essential Zn2+ from the active site, did not catalyze the reverse reaction, but catalytic activity was restored by addition of Zn2+, Mg2+, Mn2+, or Co2+. The reverse reaction was also catalyzed by glyoxalase I from yeast. Linear competitive inhibition (Ki = 0.64 mM) was obtained with 5,5'-dithiobis-(2-nitrobenzoate), which necessitated correction of the apparent kinetic parameters of the reverse reaction. The corrected values for the reverse reaction catalyzed by glyoxalase I from human erythrocytes with S-D-lactoylglutathione as substrate were kcat = 3.6 s-1 and Km = 1.9 mM. Combination of these values with the corresponding parameters for the forward reaction allowed calculation, through the Haldane relation, of the equilibrium constant, Keq = 1.1 X 10(4), for the isomerization between the hemimercaptal of methylglyoxal and glutathione and S-D-lactoylglutathione. The strong reversible competitive inhibitor of the forward reaction, S-p-bromobenzylglutathione, also inhibited the reverse reaction competitively (Ki = 0.38 microM).

Disulfides↗

Successive reversal of concurrent discriminations by macaques (Macaca mulatta): proactive interference effects.

Rhesus monkeys received concurrent within-session training on eight, two-choice object pairs and then underwent successive reversals of these problems. Initially, reversals required about six times more training than acquisition with no improvement over seven successive reversals. Surprisingly, performance on these eight problems was unimpaired if they were embedded in different eight-problem tasks, thereby indicating a release from proactive interference. When the original eight problems again underwent successive reversal, no improvement was seen over seven reversals, although there was significantly less error-per-reversal than in the initial test. Subsequently, monkeys appeared to be developing a learning set for successive reversal because performance on successive reversal of eight novel problems was not different from that seen with the old familiar task. Set acquisition was confirmed when proficient reversal was eventually achieved on both old and new concurrent tasks. Thus, "concurrent reversal set" did develop, but it required arduous training to overcome proactive interference effects on memory. The ubiquitous influence of measurement context on organization of monkey memory was noted.

Animals↗

Requesting information about and obtaining reversal after tubal sterilization: findings from the U.S. Collaborative Review of Sterilization.

OBJECTIVE: To determine the cumulative probabilities over 14 y of requesting information on sterilization reversal and of obtaining a reversal and to identify risk factors observable at sterilization for both measures of regret. DESIGN: The U.S. Collaborative Review of Sterilization, a prospective cohort study. SETTING: Fifteen medical centers in 9 cities. PATIENT(S): 11,232 women. MAIN OUTCOME MEASURE(S): Cumulative probabilities of requesting information on reversal and undergoing reversal. RESULT(S): The 14-y cumulative probability of requesting reversal information was 14.3% (95% confidence interval [CI], 12.4%-16.3%). Among women aged 18 to 24 y at sterilization, the cumulative probability was 40.4% (95% CI, 31.6%-49.2%). Women aged 18 to 24 y were almost 4 times as likely to request reversal information as were women > or = 30 years of age (adjusted rate ratio [RR], 3.5; 95% CI, 2.8-4.4). Number of living children was not associated with requesting reversal information. The overall cumulative probability of obtaining reversal was 1.1% (95% CI, 0.5-1.6). Younger women (18 to 30 y) were more likely to obtain reversal (RR, 7.6; 95% CI, 3.2-18.3). CONCLUSION(S): Women who were sterilized at a young age had a high chance of later requesting information about reversal, regardless of their number of living children.

Adult↗

Pregnancy rates following fimbriectomy reversal via neosalpingostomy: a 10-year retrospective analysis.

OBJECTIVE: To establish parameters associated with successful fimbriectomy reversal and to estimate monthly fecundability and cumulative pregnancy rates through life-table analysis. DESIGN: Series report. SETTING: University-based infertility clinic. PATIENT(S): Forty-one women undergoing surgery for tubal sterilization reversal. INTERVENTION(S): Surgical fimbriectomy reversal. MAIN OUTCOME MEASURE(S): Time from sterilization to reversal, laparoscopy vs. laparotomy, uni- vs. bilateral fimbriectomy reversal, Bruhat vs. suture, tubal lengths, postsurgical hysterosalpingogram, ovulation induction, incidence of pregnancy and outcome, and life-table analysis to determine pregnancy rate. RESULT(S): The mean time from sterilization to reversal was 11.5 years. Of the 41 women who underwent fimbriectomy reversal, 6 (14.6%) conceived. Sixteen reversals were performed by laparotomy resulting in 4 (25%) pregnancies, whereas 25 were performed laparoscopically resulting in 2 (8%) pregnancies. Eight had unilateral salpingostomies and 33 bilateral, of which 1 of 8 (12.5%) and 5 of 33 (15.2%) conceived, respectively. Using the Bruhat technique, 1 of 11 (9%) conceived vs. 5 of 30 (16.7%) that underwent reversal using sutures. The mean postoperative tubal length for the 6 women who conceived was 8 cm vs. 6.7 cm in the 35 women who did not conceive. Postoperatively, 26 women received ovulation induction and 1 (3.8%) conceived whereas 5 (33.3%) conceptions occurred in 15 women who did not require ovulation induction. Using life-table analysis with 619 postsurgical cycles, the monthly fecundability was.0097. The cumulative conception rate after 5 years was 31.2%. CONCLUSION(S): Neosalpingostomy for the reversal of fimbriectomy sterilization represents a viable option for fertility restoration. The best candidates for this procedure are spontaneously ovulatory and have a tubal length of more than 7 cm.

Adult↗

In vitro enzymatic activity of human immunodeficiency virus type 1 reverse transcriptase mutants in the highly conserved YMDD amino acid motif correlates with the infectious potential of the proviral genome.

Reverse transcriptases contain a highly conserved YXDD amino acid motif believed to be important in enzyme function. The second amino acid is not strictly conserved, with a methionine, valine or alanine occupying the second position in reverse transcriptases from various retroviruses and retroelements. Recently, a 3.5-A (0.35-nm) resolution electron density map of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase positioned the YMDD motif within an antiparallel beta-hairpin structure which forms a portion of its catalytic site. To further explore the role of methionine of the conserved YMDD motif in HIV-1 reverse transcriptase function, we have substituted methionine with a valine, alanine, serine, glycine, or proline, reflecting in some cases sequence motifs of other related reverse transcriptases. Wild-type and mutant enzymes were expressed in Escherichia coli, partially purified by phosphocellulose chromatography, and assayed for the capacity to polymerize TTP by using a homopolymeric template [poly(rA)] with either a DNA [oligo(dT)] or an RNA [oligo(U)] primer. With a poly(rA).oligo(dT) template-primer, reverse transcriptases with the methionine replaced by valine (YVDD), serine (YSDD), or alanine (YADD) were 70 to 100% as active as the wild type, while those with the glycine substitution (YGDD) were approximately 5 to 10% as active. A proline substitution (YPDD) completely inactivated the enzyme. With a poly(rA).oligo(U) template-primer, only the activity of mutants with YVDD was similar to that of the wild type, while mutants with YADD and YSDD were approximately 5 to 10% as active as the wild-type enzyme. The reverse transcriptases with the YGDD and YPDD mutations demonstrated no activity above background. Proviruses containing the reverse transcriptase with the valine mutation (YVDD) produced viruses with infectivities similar to that of the wild type, as determined by measurement of p24 antigen in culture supernatants and visual inspection of syncytium formation. In contrast, proviruses with reverse transcriptases containing the YADD and YSDD mutations were less infectious than wild-type virus. These results point to the critical role of methionine of the YMDD motif in the activity of HIV-1 reverse transcriptase and subsequent replication potential of the virus.

Amino Acid Sequence↗

KATP channel openers reverse immune complex-induced airways hyperreactivity independently of smooth muscle relaxation.

Many openers of ATP-dependent potassium channels (KATP channel openers) cause bronchorelaxation, whereas only a few of them have been claimed to reverse airways hyperreactivity. We investigated whether the antihyperreactive effect is a general feature of KATP channel openers and whether this property is linked to their ability to relax airways smooth muscle. For this purpose, the potency of the four KATP channel openers, bimakalim, rilmakalim, levcromakalim and SDZ PCO 400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent -1 -enyloxy)-2H-1-benzopyran-6-carbonitrile), to inhibit bombesin- or histamine-induced bronchoconstriction and to reverse immune complex-induced airways hyperreactivity to histamine in guinea pigs, was compared to salbutamol, following intratracheal administration to minimize pharmacokinetic differences. Total lung resistance (RL) was determined in anaesthetized, ventilated guinea pigs. Bronchoconstriction, measured as increase in RL, was elicited in normoreactive animals by i.v. infusion of bombesin (100 ng/kg/min) or by i.v. injection of histamine (1.8-10 micrograms/kg). Airways hyper-reactivity was induced by acute i.v. administration of preformed immune complexes. I.v. bolus injections of histamine were used to define the sensitivity of the airways prior to and after the exposure to immune complex. Levcromakalim (ED50 = 150 micrograms/kg), bimakalim (ED50 = 4 micrograms/kg), rilmakalim (ED50 = 40 micrograms/kg) and SDZ PCO 400 (ED50 = 280 micrograms/kg) reverse bombesin-induced bronchoconstriction with lower potency than salbutamol (ED50 = 1 microgram/kg). The four KATP channel openers and salbutamol also reversed immune complex-induced airways hyperreactivity to histamine with ED50 values which were markedly lower than those for reversal of bombesin-induced bronchoconstriction; the rank order of potency was rilmakalim (ED50 = 0.2 microgram/kg) > bimakalim (ED50 = 0.5 microgram/kg) > SDZ PCO 400 (ED50 = 3.2 micrograms/kg) > levcromakalim (ED50 = 22 micrograms/kg). Salbutamol (ED50 = 0.008 microgram/kg) was the most potent compound in this test. Bimakalim, levcromakalim and SDZ PCO 400 did not inhibit histamine-induced bronchoconstriction in normoreactive guinea pigs at doses which completely reversed immune complex-induced airways hyperreactivity to histamine. For rilmakalim and salbutamol, 60-130 times higher doses were needed for protection against histamine-induced bronchoconstriction in normoreactive guinea pigs than for reversal of airways hyperreactivity. There was a poor correlation between the ED50 values for inhibition of histamine- or bombesin-induced bronchoconstriction in normoreactive guinea pigs and the reversal of immune complex-induced airways hyperreactivity. It is thus concluded that the ability of KATP channel openers to reverse immune complex-induced airways hyperreactivity is independent of their ability to reverse or prevent bronchoconstriction and thus from their ability relax airway smooth muscle.

Albuterol↗

Influence of simultaneous pattern-reversal electroretinogram recording on visual evoked potentials.

Little is known about the influence of the presence of a gold-foil electrode on pattern-reversal visual evoked potential recording, although simultaneous pattern-reversal electroretinography has been applied in several clinical investigations. We compared the results of pattern-reversal visual evoked potentials simultaneously recorded with pattern-reversal electroretinograms with those obtained during separate pattern-reversal visual evoked potential recording in 10 normal subjects. Transient response (reversal rate, 1 Hz; check size, 30') and steady-state response (reversal rate, 5 Hz; check size, 120', 60', 30', 15' and 7.5') were analyzed under the stimulus contrast condition of 90%. Neither P100 latency in transient responses nor amplitudes in steady-state responses exhibited significant change at any check size when they were recorded separately or simultaneously with pattern-reversal electroretinograms. The results suggest that the gold-foil electrode exerts no significant influence on pattern-reversal visual evoked potentials. Simultaneous pattern-reversal electroretinogram and visual evoked potential recording is therefore confirmed to be a clinically useful method. This procedure makes the synchronous recording of both responses possible under the identical stimulus conditions.

Adult↗

Completely reversed acute rejection is not a significant risk factor for the development of chronic rejection in renal allograft recipients.

Although acute rejection (AR) has been shown to correlate with decreased long-term renal allograft survival, we have noted AR in recipients who subsequently had stable function for more than 5 years. We reviewed 109 renal graft recipients with a minimum of 1 year graft survival and follow-up of 5-8 years. Post-transplant sodium iothalamate clearances (IoCI) measured at 3 months and yearly thereafter were used to separate recipients into 2 groups. In 61 patients (stable group), there was no significant decrease ( > 20 % reduction in IoCl over 2 consecutive years) in IoCl. Forty-eight patients had significant declines in IoCl (decline group). Groups were compared for incidence, severity, timing, and completeness of reversal of AR. Rejection was considered completely reversed if the post-AR serum creatinine (Scr) returned to or below the pre-AR nadir Scr after anti-rejection therapy. The incidence of AR was not significantly different between groups (47% vs 52%). A trend toward a lower mean number of AR episodes per patient was noted in the stable group (0.69 vs 1.04, P = 0.096), but the timing of AR was not different. Steroid-resistant AR occurred in approximately 25 % of both groups. A striking difference was seen in complete reversal of AR, with the stable group having 100% (42/42 episodes of AR in 29 patients) complete reversal whereas only 32 % (8/25) of the patients in the decline group had complete reversal (P < < 0.001). Of 8 declining patients with complete reversal, graft loss was due to chronic rejection (CR) in only 3. Seventeen declining patients had incomplete reversal of AR, and 82 % (14/17) lost their grafts to CR. Overall, only 8% (3/37) of the recipients with complete reversal of AR developed CR. No patients with incompletely reversed AR had stable long-term function as measured by IoCl. AR is not invariably deleterious to long-term renal graft function if each episode of AR can be completely reversed.

Acute Disease↗

Hartmann's colectomy and reversal in diverticulitis: a population-level assessment.

PURPOSE: This study was designed to assess the costs and outcomes of colostomy and colostomy reversal in patients with diverticulitis and examine the impact of such procedures on the health care system. METHODS: We employed a retrospective design and used a Washington State administrative database to identify patients undergoing operations with colostomy (1987-2002) who were followed over time. Descriptive and comparative analysis was performed, focusing on patients with diverticulitis. RESULTS: There were 16,556 patients who underwent colostomy and 5,420 (32.7 percent) were for diverticulitis and its related complications (mean age, 64.8 +/- 15.1 years; 53.2 percent female). In patients with diverticulitis, the rate of colostomy reversal was 56.3 percent (80 percent in patients less than 50 years, and 30 percent in patients over 77 years). The in-hospital mortality rate after colostomy reversal was 0.36 percent, and was 2.6 percent in those over 77 years of age. After colostomy reversal a second stoma was used in 3.4 percent, reoperation was required for bleeding complications in 0.6 percent, and infectious complications were noted in 2 percent. The length of time from colostomy to its reversal was approximately five months (138.1 +/- 164 days; interquartile range, 72-156). The relationship between the length of time from colostomy to reversal was evaluated and the adjusted odds of a second stoma being used at the time of colostomy reversal were 45 percent higher (odds ratio, 1.45; 95 percent confidence interval, 1.22, 1.73) for each increase in time interval (<3, 6-9, 9-12, >12 months). CONCLUSIONS: One-third of all colostomies were related to diverticulitis and only 56 percent were reversed. We identified a higher than expected mortality rate among older patients undergoing colostomy reversal. The impact of colostomy and reversal operations on both patients and the health care system is significant.

Adolescent↗

Reversal operations after brain damage.

The ability to perform reversals--that is, the appreciation of the relationship between original and transformed states of knowledge--is critical to human thought processes. In order to assess whether a number of "special-purpose processors" are responsible for reversal operations, depending on the particular context in which the reversal is couched, or whether a single "core processing mechanism" subserves a critical aspect of reversal operations regardless of the specific context, patients with localized brain damage were asked to solve eight reversal problems. Visual and auditory reversals mediated by linguistic and non-linguistic symbol systems were presented. The findings demonstrate that patients with insult to the anterior portion of the right hemisphere encounter more difficulty performing reversals than patients with right posterior insult, Broca's aphasics, and fluent aphasics. This is regardless of the symbol system mediating the reversal, regardless of the modality of presentation, and regardless of the amount of available processing time. Subjects with insult to the posterior region of the left hemisphere or the right hemisphere also exhibit some difficulty solving reversal problems, although their difficulties appear modality specific. These data lend support to the claim that a core processing mechanism may play a critical role in the performance of reversal operations.

Aphasia, Broca↗

Nicotine reverses consolidated long-term potentiation in the hippocampal CA1 region.

Long-term potentiation (LTP) has a memory-like consolidation period during which it becomes progressively stabilized. However, it is unknown how the consolidation is achieved. The present study demonstrates that nicotine reverses stabilized LTP in the hippocampal CA1 region, providing the first evidence that consolidated LTP can be reversed. The nicotine-induced reversal appeared to work by reversing cellular processes involved in stabilizing LTP, as LTP was readily induced again after reversal. The effect of nicotine was mediated, in large part, via desensitization of alpha7 nicotinic acetylcholine receptors (nAChRs), as an alpha7 nAChR-selective antagonist mimicked the nicotine effect. A non-selective N-methyl-d-aspartate receptor (NMDAR) antagonist completely abolished the nicotine-induced reversal, whereas an NR2B-containing NMDAR-selective antagonist had no effect. Furthermore, both the protein phosphatase 1/protein phosphatase 2A inhibitor okadaic acid and the protein phosphatase 2B (calcineurin) inhibitor cyclosporin A blocked the nicotine-induced reversal. Taken together, our results suggest that the reversal of stabilized LTP depends on the activation of NR2A-containing NMDARs and dephosphorylation. Thus, the consolidation of LTP appears to be the interruption of signaling leading to NR2A-containing NMDAR-dependent activation of protein phosphatases, which can be circumvented by nicotine-induced signaling. LTP induced in chronic nicotine-treated hippocampi contained a component that is immune to reversal, and thus acute nicotine was no longer effective to reverse consolidated LTP. These results demonstrate the differential effects of acute and chronic nicotine exposure on the cellular processes that are potentially involved in learning and memory.

Aconitine↗

Preclinical evaluation for noninvasive reversal following long-term vas occlusion with styrene maleic anhydride in langur monkeys.

A preclinical evaluation for reversal through a noninvasive approach following long-term vas occlusion with styrene maleic anhydride (SMA) has been attempted in langur monkeys at the level of semen parameters, sperm functional tests, semen biochemistry, histology and ultrastructure of reproductive organs, hematology and serum clinical biochemistry including antisperm antibodies (ASA), prostate-specific antigen (PSA) and testosterone. Noninvasive reversal through palpation, percutaneous squeezing and electrical stimulation, forced vibratory movements and suprapubic percussion in the inguinal segments and per-rectal digital massage was attempted in seven langur monkeys after 540 days following vas occlusion. The results revealed instant azoospermia reversal on the same day of reversal with impaired sperm quality, which showed gradual improvement and normospermia with normal motility and viability after 60-90 days of reversal. Sperm functional tests, including ultrastructure of spermatozoa, indicative of sterility in the initial ejaculations, reached normalcy after 90-120 days of reversal. The seminal plasma biochemistry indicative of obstructive azoospermia regained a normal pattern after 90-120 days of reversal. The morphology of testes that showed focal degeneration during 540 days of vas occlusion and that of vasa deferentia that showed exfoliation of epithelial cells resumed to normal morphology comparable with control animals after 150 days of reversal. The morphology of the epididymis, seminal vesicle and prostate did not show appreciable changes following vas occlusion and after noninvasive reversal compared with those of control animals. Hematology, serum clinical chemistry, ASA, PSA and testosterone fluctuated within control limits, indicating safety of the procedure at the level of accessory reproductive organs. The results suggest that noninvasive reversal is feasible even after long-term vas occlusion with SMA and is safe without adverse side effects.

Animals↗

Sex-role reversal in vertebrates: behavioural and endocrinological accounts.

Sex-role reversal occurs when females compete more intensely than males for access to mates. In this paper, we survey the occurrence of sex-role reversal in vertebrates: we focus on behavioural aspects of sex-role reversal and we examine possible endocrinological correlates of this phenomenon. The best documented cases among vertebrates of sex-role reversal occur in fish and birds. In nearly all sex-role reversed species or populations, females have higher potential reproductive rates than males. Some species in which females were previously thought to be the predominant competitors for mates (for instance seahorses and a dendrobatid frog), appear not to be sex-role reversed according to recent studies. The endocrinology of sex-role reversal has been studied in only a few species and therefore remains poorly understood. In birds, which probably have been studied the most in this respect, steroid hormones appear to follow the typical ancestral conditions (for instance no reversal of testosterone levels) in sex-role reversed species, whereas prolactin, a principal regulator of the onset and maintenance of incubation, departs from the usual avian pattern in that it is higher in males than in females. The study of sex-role reversed behaviour offers unique opportunities not only to test sexual selection theory, but also to enhance our understanding of the neuroendocrine mechanisms mediating behavioural sex differences.

Journal Article↗

Combined analysis of resting regional wall thickening and stress perfusion with electrocardiographic-gated technetium 99m-labeled sestamibi single-photon emission computed tomography: prediction of stress defect reversibility.

BACKGROUND: The high photon flux and stable distribution of the myocardial perfusion agent 99mTc-labeled sestamibi allow the perfusion data to be acquired in an electrocardiographic (ECG)-gated mode, such that information on resting regional wall thickening may be obtained simultaneously with stress perfusion data. The objective of this study was to assess whether visual analysis of resting regional wall thickening provided by ECG-gated acquisition of 99mTc-labeled sestamibi stress perfusion images correlates with and predicts the reversibility of stress-induced perfusion defects, potentially obviating the need for rest imaging. METHODS AND RESULTS: Fifty-nine patients referred for myocardial perfusion imaging were studied with rest and stress single-photon emission computed tomographic (SPECT) sestamibi imaging, and the stress perfusion data were acquired in an ECG-gated mode. Visual analysis of the presence and reversibility of stress perfusion defects on standard imaging was correlated with the wall thickening data from the poststress gated SPECT images. Quantitative circumferential profile analysis of the short-axis images was performed to assess the influence of relative stress perfusion defect severity on the correlation between wall thickening and defect reversibility. Among the 72 segments with stress-induced perfusion defects and visually apparent wall thickening on ECG-gated SPECT images, 69 were reversible on rest imaging (positive predictive value of 96% for wall thickening to predict stress defect reversibility). Of the 35 segments with stress-induced defects and no apparent wall thickening on ECG-gated SPECT images, however, 14 (40%) demonstrated significant stress defect reversibility on rest imaging. This result represents a negative predictive value of only 60% for the lack of apparent wall thickening to predict correctly an irreversible stress defect. Among the segments with reversible stress perfusion defects and visually apparent wall thickening, relative stress sestamibi activity was higher (51% +/- 10% [percentage of peak]) than in segments with reversible stress defects and no visually apparent wall thickening (39% +/- 4% of peak activity [p < 0.0001]). CONCLUSIONS: Visual evidence of wall thickening by poststress ECG-gated SPECT sestamibi imaging in the territory of a stress-induced perfusion defect correlates highly with stress defect reversibility on rest imaging and may obviate the need to perform rest imaging, thereby potentially reducing the time and cost involved in myocardial perfusion imaging. The absence of visually apparent wall thickening, however, underestimates the prevalence of stress defect reversibility on rest imaging; in such instances, rest imaging must be performed to differentiate ischemia from infarction in the territory of a stress perfusion defect.

Adult↗

Prediction of functional recovery in acute myocardial infarction: comparison between sestamibi reverse redistribution and sestamibi/BMIPP mismatch.

BACKGROUND: It has been known that Tc 99m sestamibi/iodine 123 betamethyliodophenylpentadecanoic (123I-BMIPP) (sestamibi/BMIPP) mismatch is an indicator of viable myocardium in acute myocardial infarction (AMI). We have reported that reverse redistribution of sestamibi in AMI indicates the patency of infarct-related artery and a preserved left ventricular function in the chronic stage. In this study we investigated the relationship between reverse redistribution of sestamibi and sestamibi/BMIPP mismatch in patients with AMI. METHODS: Twenty-three patients with AMI who received direct percutaneous transluminal coronary angioplasty underwent both BMIPP and sestamibi SPECT within 2 weeks after onset. Sestamibi images were obtained 1 hour (early) and 3 hours (delayed) after injection of sestamibi. BMIPP imaging was carried out 30 minutes after injection. The left ventricle was divided into 17 segments, and regional myocardial uptakes of the tracers in each segment were scored from 0 (normal) to 3 (no activity). A reverse redistribution pattern was defined as an increase of > or =1 in the regional score at the delayed images. More reduced BMIPP uptake than sestamibi uptake in each segment was determined as sestamibi/BMIPP mismatch. Contrast left ventriculography was performed soon after revascularization and repeated 1 month later. RESULTS: Of 15 patients with sestamibi reverse redistribution, sestamibi/BMIPP mismatch was observed in 14 patients (93%), whereas mismatch was seen in only one of seven patients (14%) without reverse redistribution (p < 0.01). In patients with sestamibi reverse redistribution, regional scores of BMIPP agreed with those of early and delayed images of sestamibi in 51 segments (46%) and in 92 segments (83%), respectively. In the chronic stage, both regional wall motion and left ventricular ejection fraction improved in patients with sestamibi reverse redistribution (wall motion score: 6.7 +/- 2.4 vs 2.7 +/- 2.1, p < 0.01; ejection fraction: 56% +/- 7% vs 64% +/- 8%, p < 0.01), but not in those without reverse redistribution. CONCLUSION: Both reverse redistribution of sestamibi and sestamibi/BMIPP mismatch reflect the recovery of left ventricular function and thus imply myocardial viability in AMI. Because the presence of reverse redistribution of sestamibi agreed with that of sestamibi/BMIPP mismatch, additional BMIPP images can be replaced by the delayed images after a single injection of sestamibi.

Aged↗

Intergenerational transmission of role reversal between parent and child: dyadic and family systems internal working models.

The current study examined the intergenerational transmission of role reversal within a developmental psychopathology framework. Role reversal is a relationship disturbance in which a parent looks to a child to meet the parent's need for comfort, parenting, intimacy, or play, and the child attempts to meet these needs. In a normative sample, n=138, fathers and mothers reported on childhood role reversal with their mothers as part of the Adult Attachment Interview, AAI (George, Kaplan, & Main, 1984). Mother-child role reversal was then assessed in an observational paradigm when children were 2 years of age. Based on theories of dyadic and family systems internal working models we hypothesized gender specific replications of role reversal in the next generation. Indeed, mothers who reported role reversal with their mothers during the AAI tended to engage in higher levels of role reversal with their toddler-aged daughters. Furthermore, when fathers reported role reversal with their mothers during the AAI, mothers tended to engage in higher levels of role reversal with their toddler-aged sons. The importance of the inclusion of fathers in family research, the relationship between role reversal and attachment, and implications for preventive interventions are discussed.

Adult↗

Jejunoileal bypass reversal: effect on renal function, metabolic parameters and stone formation.

PURPOSE: While the effect of jejunoileal bypass (JIB) reversal has been well studied regarding hepatic function, there is little information regarding the effect of reversal on renal function and even less data regarding the metabolic urinary stone environment. We evaluated the results of JIB reversal on renal function, the urinary stone milieu and the clinical development of recurrent calculi in affected patients. MATERIALS AND METHODS: From 1995 to 2003, 4 female patients with a mean age of 48.2 years underwent JIB reversal primarily for refractory stone disease. The clinical and metabolic courses prior to and following bypass reversal were reviewed specifically to evaluate renal function, serum and urinary metabolic stone profiles, and clinical stone formation. RESULTS: At initial presentation following JIB all 4 patients had significantly increased 24-hour urinary oxalate (range 80 to 160 mg, mean 112.5, normal less than 50) and significantly low 24-hour urinary citrate (range 5 to 62 mg, mean 21.5, normal greater than 320). Following reversal 24-hour urinary oxalate normalized to between 31 and 36 mg (mean 33.75). However, 24-hour urinary citrate continued to be low (range 215 to 248 mg, mean 226.5). After JIB reversal all 4 patients continued to have new stones until the commencement of urinary alkalization, following which only 1 had 1 calculus, which occurred 47 months after reversal. After JIB mean serum creatinine was 1.48 mg/dl (range 0.8 to 1.9) and mean urinary creatinine excretion was 0.91 mg per hour (range 0.69 to 1.15). After JIB reversal mean serum creatinine was 1.28 mg/dl (range 0.6 to 2.0) and mean urinary creatinine excretion was 1.0 mg per hour (range 0.85 to 1.10). CONCLUSIONS: JIB reversal normalizes 24-hour urinary oxalate. While urinary citrate improves, it continues to be low and such patients are at high risk for recurrent stone formation. However, in this setting appropriate replacement therapy has a significant and positive impact on that propensity.

Adolescent↗

Abnormal Doppler velocimetry and blood flow volume in the middle cerebral artery in very severe intrauterine growth restriction: is the occurence of reversal of compensatory flow too late?

OBJECTIVES: To determine the time course of quantified volumetric flow and pulsatility index changes in the middle cerebral arteries of severe intrauterine growth restricted fetuses with absent or reversed end diastolic flow velocities (AREDFV) on umbilical artery Doppler with a view to defining the threshold for early intervention before the onset of reversal of adaptation. SETTING: Fetal growth clinic of a large UK teaching hospital. SAMPLE: Seventeen severe intrauterine growth restricted (AC < third centile for gestation and gender) fetuses with abnormal umbilical artery Doppler velocimetry and oligohydramnios (amniotic fluid index <third centile for gestation). METHODS: One to three daily Doppler velocimetry and quantified volume flow of the middle cerebral artery Doppler velocimetry of the umbilical arteries and daily cardiotocography. RESULTS: Reversal of adaptation occurred in eight fetuses, four of which ended as stillbirths and four as neonatal deaths. In two of these fetuses, this had already occurred before the diagnosis of intrauterine growth restriction. In the others, the onset was rapid and difficult to predict. Volume flow in the middle cerebral arteries decreased in those fetuses exhibiting reversal of adaptation but rose in the nine in which compensatory Doppler indices persisted. The decrease in volume flow occurred before the onset of reversal of adaptation in the pulsatility index. In the fetuses exhibiting reversal of adaptation, the rise in the pulsatility index was consistent over 48 hours compared with the physiological fluctuations in pulsatility index in some fetuses where the rise was only for 24 hours followed by a fall. Quantified volume flow fell in the fetuses before reversal of adaptation set-in. The umbilical artery Doppler indices fluctuated between absent and reversed end diastolic velocities within the same fetus irrespective of the changes in the middle cerebral artery Doppler indices. CONCLUSION: Reversal of adaptation is of sudden onset and is associated with poor prognosis. Predicting its occurrence on Doppler indices is difficult as the changes may be very rapid. However, volume flow changes appear to be slower and of earlier onset than the pulsatility index changes. This may therefore be a more useful tool in predicting imminent reversal of adaptation and therefore early delivery.

Adult↗