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Planned exploration of pediatric liver transplant recipients reduces posttransplant morbidity and lowers length of hospitalization.

BACKGROUND: Pediatric liver transplantation (eg, orthotopic liver transplantation) has been associated with decreased graft survival compared with adult transplantation; this has been attributed to the increased difficulty of the procedure in small children and the increased number of technical variants that have been used to increase the supply of small livers. OBJECTIVES: To adopt a policy of planned exploration (PLANEX) of children on the seventh day after orthotopic liver transplantation, to obtain a liver biopsy specimen, to identify and treat potential technical problems at that time, and to evaluate the effect of this strategy on the length of hospitalization and morbidity rate in 60 children who underwent orthotopic liver transplantation. DESIGN: The PLANEX was adopted progressively during a 3-year period. A retrospective study was conducted that compared outcomes between patients who did and did not undergo PLANEX. Data were collected from chart review with a complete follow-up of patients. SETTING: A university medical center at which 130 liver transplantations are performed annually in adults and children. PATIENTS: Sixty children who received primary transplants between October 1992 and December 1996 were studied. INTERVENTIONS: Standard, partial, and living-donor transplantations were performed. Routine procedures performed at PLANEX included hematoma evacuation, tissue culture, inspection of all anastomoses, intraoperative ultrasonographic verification of vessel patency, open liver biopsy, and definitive abdominal closure. MAIN OUTCOME MEASURES: The duration of the primary hospitalization was the main outcome measure. Surgical complications and graft and patient survival rates were also analyzed. RESULTS: The mean +/- SD length of hospitalization for 24 recipients who underwent PLANEX was 16.5 +/- 5.7 days compared with 19.2 +/- 4.7 days for 6 patients (25%) who had significant findings at exploration (P = .34). In the 36 patients who did not undergo PLANEX, 10 patients (28%) required unplanned explorations (on median posttransplant day 13) that identified the following 13 complications: biliary (n = 4), undiscovered enterotomy (n = 6), hemoperitoneum (n = 2), and partial vascular thrombosis (n = 1). The mean length of hospitalization for recipients who did not require exploration was 19.3 +/- 3.9 days (PLANEX, P = .28); however, in patients who required unplanned exploration, the mean length of hospitalization increased to 41.2 +/- 15.5 days (median, 43 days). The mean length of hospitalization of recipients who underwent unplanned exploration was significantly increased compared with recipients who underwent PLANEX with significant intraoperative findings (P = .02). CONCLUSIONS: In this series, early identification and repair of surgical problems in asymptomatic patients on day 7 significantly decreased the hospital stay and morbid consequences of surgical problems. This aggressive approach may improve overall graft and patient survival.

Adolescent↗

Calibrating space: exploration is important for allothetic and idiothetic navigation.

Allothetic and idiothetic navigation strategies rely on very different cues and computational procedures. Allothetic navigation uses the relationships between external cues (visual, auditory, and olfactory) and mapping or geometrical calculations to locate places. Idiothetic navigation relies on cues generated by self-movement (proprioceptive cues or cues from optic, auditory, and olfactory flow, or efference copy of motor commands) and path integration to locate a present location and/or a starting point. Whereas it is theorized that exploratory behavior is used by animals to create a central representation of allothetic cues, it is unclear whether exploration plays a role in idiothetic navigation. Computational models suggest that either a reference frame, calibrated by exploration, or vector addition, without reference to exploration, could support path integration. The present study evaluated the contribution of exploration in these navigation strategies by comparing its contribution to the solution of both allothetic and idiothetic navigation problems. In two experiments, rats were trained to forage on an open table for large food pellets, which they then carried to a refuge to eat. Once trained, they were given probe trials from novel locations in either normal light, which permits the use of allothetic cues, or in infrared light, which requires the use of idiothetic cues. When faced with a new problem in either lighting condition, the rats first explored the foraging table before navigating directly home with the food. That exploration is equally important for allothetic and idiothetic navigation, suggests that both navigation strategies require a calibrated representation of the environment.

Animals↗

Scan-directed unilateral cervical exploration for parathyroid adenoma: a legitimate approach?

Thallium-Technetium isotope subtraction scanning was used routinely as a preoperative localization investigation in 90 patients with primary hyperparathyroidism who were submitted to "first-time" cervical exploration from 1985 to 1988. When the scintigram demonstrated a single focus of activity suggesting the site of a solitary parathyroid adenoma, a scan-directed exploration was carried out. If the tumor was found at the location suggested by the scan, it was then removed and the ipsilateral normal parathyroid was biopsied. The contralateral side of the neck was not explored in these patients. A total of 48 patients underwent unilateral cervical exploration while the remaining 42 individuals had a standard bilateral neck operation performed. The difference in operating times for patients who had a solitary adenoma and who underwent unilateral and bilateral neck exploration, respectively, was statistically highly significant (71 minutes versus 97 minutes, p less than 0.001). At mean follow-up of 16.8 months, no patient who had a unilateral neck exploration performed for solitary parathyroid adenoma demonstrated persistent or recurrent hypercalcemia.

Adenoma↗

Unilateral neck exploration for primary hyperparathyroidism: analysis of a controversy using a mathematical model.

Most endocrine surgeons explore both sides of the neck and identify all parathyroid glands when operating on patients with primary hyperparathyroidism. Others, however, advocate the unilateral approach, i.e., if an adenoma and a normal gland are identified, the contralateral side is not explored. We analyzed the strategy of the unilateral approach using a mathematical model to determine the variables that influence the probability of missing a tumor on the unexplored side of the neck. Assuming the frequency of single adenoma is 80%, hyperplasia 14%, double adenomas 4%, triple adenomas 1%, and carcinoma 1%, and the probability of missing a tumor on the explored side is 5%, we found that: 1. Only 41% of the patients treated by the unilateral approach undergo unilateral exploration. This is increased to 62% when a localization study with a sensitivity of 80% is used pre-operatively. 2. The probability of missing a tumor on the unexplored side of the neck parallels the prevalence of multiple adenomas. Half of the patients with triple adenomas and two-thirds of the patients with double adenomas will have a missed tumor when treated by the unilateral approach. 3. Patients who undergo unilateral exploration have an additional 7% to 8% probability of missing a tumor that would have been found if bilateral exploration is performed. This risk is lowered to 2% by a pre-operative localization study that is 80% sensitive. 4. A prospective study will require 684 patients, randomized to the unilateral or bilateral approach, to have an 80% statistical power (alpha = 0.05, beta = 0.20) of detecting a difference between a 5% and a 10% risk of missing a tumor.

Adenoma↗

Focused cervical exploration for primary hyperparathyroidism without intraoperative parathyroid hormone monitoring or use of the gamma probe.

Selected patients with primary hyperparathyroidism (pHPT) who have a positive preoperative sestamibi scan can be managed safely and successfully with a focused cervical exploration without either adjuvant intraoperative parathyroid hormone (PTH) monitoring or use of a gamma probe. This article reports a retrospective analysis of a consecutive series of patients surgically treated at a tertiary referral center. From August 1998 to August 2002, 100 patients (68 women, 32 men; mean age 63 years [range: 29-89 years]) underwent a focused cervical approach without intraoperative PTH monitoring or use of the gamma probe after perioperative sestamibi injection. The study group comprised 9% of all patients (n = 1063) undergoing cervical exploration for pHPT during the study period. Ninety patients underwent an initial exploration, and 10 others underwent repeat cervical exploration following prior parathyroid (n = 7) or thyroid (n = 3) operation. Sestamibi scanning correlated with one enlarged parathyroid gland in all patients. Other enlarged glands were, however, not demonstrated in three patients (true positive = 97%; false negative = 3%). The single enlarged glands excised in all patients had a mean weight of 795 mg (range: 90-3640) and were histologically compatible with an adenoma. Postoperatively, 97% of patients were eucalcemic. Three patients remained hypercalcemic (3%). Of the three patients with persistent hypercalcemia, one underwent successful re-exploration with excision of a 500 mg second adenoma, whereas the other two patients (with confirmed familial HPT) remained hypercalcemic. Mean hospitalization was 0.5 days (range: 0-3 days). There was no operative mortality. No patients had permanent hypocalcemia. Postoperative morbidity occurred in three patients: two self-limiting cervical hematomas and one permanent vocal cord paralysis. Selected patients with pHPT due to single-gland disease and an unequivocally positive preoperative sestamibi scan can safely and successfully be managed with a focused unilateral cervical exploration without either intraoperative PTH monitoring or use of the gamma probe. Further experience with this surgical approach seems warranted to determine the overall cure rate, operative morbidity, and the sensitivity and specificity of preoperative localization studies.

Adenoma↗

Incidence of residual intracranial AVMs after surgical resection and efficacy of immediate surgical re-exploration.

BACKGROUND: The true incidence of residual lesions after surgical resection of AVMs is not well documented in the literature. Partial surgical resection is thought to not confer any improvement over the natural history risk of hemorrhage of AVMs, and in certain cases may actually increase the risk of hemorrhage. Over the past 11 years, we have adopted a policy of immediate postoperative angiography with immediate surgical re-exploration if a residual lesion is seen. The purpose of the present study was to review our experience to determine the incidence of residual lesions and subsequent outcome. METHODS: From June 1991 to June 2002, 324 patients underwent craniotomy and surgical AVM resection. As per protocol, all patients underwent immediate postoperative angiography. We have a protocol for immediate surgical re-exploration if a residual lesion is seen on postoperative angiographic exam. FINDINGS: There were total six patients (1.8% of patients operated with intracranial AVMs) with residual lesions on postoperative angiography. All six patients underwent immediate surgical re-exploration with complete 100% obliteration; two patients required two re-exploration procedures. There was one operative complication: posterior cerebral artery and superior cerebellar artery infarcts after re-exploration of residual lesion after surgical resection of a large occipito-temperal-parietal AVM. There were no other morbidities and no mortalities. CONCLUSIONS: The incidence of residual lesions seen on postoperative angiography after AVM surgery at an experienced center is 1.8%. Because of the potential imminent danger of hemorrhage from a residual lesion, we recommend a policy of immediate postoperative angiography (or intraoperative angiography if image quality is satisfactory) for all AVM surgery and early surgical re-exploration if a residual lesion is seen.

Adult↗

MSM in HIV-prevention trials are sexual partners with each other: An ancillary study to the EXPLORE intervention.

The EXPLORE study evaluated a behavioral intervention to prevent HIV seroconversion among men who have sex with men (MSM). The present ancillary study enrolled 345 EXPLORE participants at one study site (Boston) and assessed high-risk sexual behavior with other EXPLORE participants. It also assessed sexual intentions across other EXPLORE participants, HIV-negative individuals, and unknown HIV serostatus partners. Thirty-one percent reported having sex with another EXPLORE participant: 27% unprotected receptive oral sex with ejaculation (UO), 30% unprotected insertive anal sex (UIA), and 34% reported unprotected receptive anal sex (URA). Significant relationships between intentions to engage in UO, UIA, and URA, and type of partner emerged with intentions to engage in UO, UIA, and URA higher in HIV-negative partners, other EXPLORE participants, and unknown-HIV serostatus partners. Future HIV-prevention studies recruiting MSM at increased sexual risk of HIV infection should address participants potentially becoming sexual partners with each other.

Adolescent↗

Partial reversal of ethanol-induced reductions in exploration by two benzodiazepine antagonists (flumazenil and ZK 93426).

A series of experiments was performed to examine the effects of two benzodiazepine antagonists, flumazenil and ZK 93426, on the behavioral changes caused by ethanol (2 g/kg) in a holeboard test. The interaction between ethanol and low doses of diazepam (0.2 and 0.5 mg/kg) was also investigated. Both flumazenil and ZK 93426 reversed the reduction in exploration caused by ethanol, but tended to increase exploration when administered alone. In contrast, diazepam, which also increased exploration alone, tended to enhance the reduction in exploration caused by ethanol. Diazepam reduced the motor stimulant action of ethanol. The partial reversal by the two antagonists of the reduction in exploration caused by ethanol was not due to alterations in blood ethanol concentrations but may have resulted from their intrinsic exploration-increasing effects or an antagonism of an endogenous ligand for central benzodiazepine receptors.

Animals↗

Robots and humans: synergy in planetary exploration.

How will humans and robots cooperate in future planetary exploration? Are humans and robots fundamentally separate modes of exploration, or can humans and robots work together to synergistically explore the solar system? It is proposed that humans and robots can work together in exploring the planets by use of telerobotic operation to expand the function and usefulness of human explorers, and to extend the range of human exploration to hostile environments.

Extraterrestrial Environment↗

Unpacking commitment and exploration: preliminary validation of an integrative model of late adolescent identity formation.

A model of identity formation comprising four structural dimensions (Commitment Making, Identification with Commitment, Exploration in Depth, and Exploration in Breadth) was developed through confirmatory factor analysis. In a sample of 565 emerging adults, this model provided a better fit than did alternative two- and three-dimensional models, thereby validating the unpacking of both exploration and commitment. Regression analyses indicated that Commitment Making was significantly related to family context in accordance with hypotheses. Identification with Commitment and both exploration dimensions were significantly related to adjustment and family context, again in accordance with hypotheses. Identification with Commitment was positively related to positive adjustment indicators and negatively to depressive symptoms, whereas Exploration in Breadth was positively related to depressive symptoms and substance use. Exploration in Depth, on the other hand, was positively related to academic adjustment and negatively to substance use. Implications and suggestions for future research are discussed.

Achievement↗

Further evidences that risk assessment and object exploration behaviours are useful to evaluate emotional reactivity in rodents.

In this study, we tested the ability of risk assessment and exploration behaviours to emphasise PH effects. Indeed, postnatal handling (PH) decreases emotional reactivity in rats but inconsistent behavioural results can be observed and may be due to false negative (i.e. existing effects are not detected). Risk assessment behaviours were measured in the elevated plus maze, in the free exploration paradigm and in the open field. In addition, we measured object exploration behaviours towards familiar/new objects in the open field. PH increased general activity in the elevated plus maze and in the free exploration paradigm and risk assessment behaviours allowed demonstrating that these effects were specific to emotional reactivity. In the open field, PH increased object exploration as early as first exposition while general activity was unaffected. PH also decreased behavioural inhibition in response to the introduction of a novel object. On the whole, our results show that risk assessment and object exploration behaviours are valuable tools to measure more precisely emotional reactivity in rodents. This reinforces the idea that these behaviours should be used more frequently in order to avoid false negative when emotional reactivity changes are expected in unconditioned conflict tests.

Analysis of Variance↗

Inhibition within the nucleus tractus solitarius (NTS) ameliorates environmental exploration deficits due to cerebellum lesions in an animal model for autism.

Clinical observations suggest that abnormalities within the cerebellum and/or the cerebellum--cholinergic forebrain connections may be key to explain the severe behavioral deficits and increases in seizures seen in autism. In order to explore functional relationships between brain areas implicated in many of the core behavioral features of autism, experiments utilizing animal models for specific autism-like behaviors have increased in recent years. In the current study, we used a rodent model for the autism-like behavior of environment exploration deficits to examine the role of the cerebellum and its connectivity to the forebrain. In addition, due to the possible common neural pathways between seizures and autism-like behaviors, we explored the possibility for limiting autism-like behaviors via antiseizure brainstem and cerebellar circuitry. In two experiments, adult male rats showed a significant decrease in exploration behavior following developmental cerebellar suction lesions (experiment 1) or i.c.v. saporin injections specifically targeting Purkinje cells, but not after the addition of saporin-induced cholinergic forebrain lesions (experiment 2). In both experiments, the anticonvulsant treatment of inhibition of the medullary nucleus tractus solitarius (NTS) restored exploration behavior to control levels. These findings suggest that specific neuronal populations within the cerebellum are responsible for mediating exploration behavior, and these neuronal populations are similar to the circuitry involved in limbic motor seizures in that they are sensitive to brainstem inhibition. Furthermore, these results suggest this connection could be utilized in order to control behavioral deficits seen in autism with treatments, such as vagal nerve stimulation, which are effective against pharmaco-resistant seizures.

Animals↗

Progress and problems in the exploration of therapeutic targets.

Drugs exert their therapeutic effect by binding and regulating the activity of a particular protein or nucleic acid target. A large number of targets have been explored for drug discovery. Continuous effort has been directed at the search for new targets and more-extensive exploration of existing targets. Knowledge of these targets facilitates the understanding of molecular mechanisms of drugs and the effort required for drug discovery and target searches. Areas of progress, current focuses of research and development and the difficulties in target exploration are reviewed. The characteristics of the currently explored targets and their correlation to the level of difficulty for target exploration are analyzed. From these characteristics, simple rules can be derived for estimating the difficulty level of target exploration. The feasibility of predicting druggable proteins by using simple rules and sequence-derived physicochemical properties is also discussed.

Animals↗

Exploring the visual world: the neural substrate of spatial orienting.

Inspecting the visual environment, humans typically direct their attention across space by means of voluntary saccadic eye movements. Neuroimaging studies in healthy subjects have identified the superior parietal cortex and intraparietal sulcus as important structures involved in visual search. However, in apparent contrast, spatial disturbance of free exploration typically is observed after damage of brain structures located far more ventrally. Lesion studies in such patients disclosed the inferior parietal lobule (IPL) and temporo-parietal junction (TPJ), the superior temporal gyrus (STG) and insula, as well as the inferior frontal gyrus (IFG) of the right hemisphere. Here we used functional magnetic resonance imaging to investigate the involvement of these areas in active visual exploration in the intact brain. We conducted a region of interest analysis comparing free visual exploration of a dense stimulus array with the execution of stepwise horizontal and vertical saccades. The comparison of BOLD responses revealed significant signal increases during exploration in TPJ, STG, and IFG. This result calls for a reappraisal of the previous thinking on the function of these areas in visual search processes. In agreement with lesion studies, the data suggest that these areas are part of the network involved in human spatial orienting and exploration. The IPL dorsally of TPJ seem to be of minor importance for free visual exploration as these areas appear to be equally involved in the execution of spatially predetermined saccades.

Adult↗

Long-term results of unilateral neck exploration for preoperatively localized nonfamilial parathyroid adenomas.

BACKGROUND: Unilateral neck exploration for sporadic parathyroid adenomas remains a contentious policy. The morbidity is lower than for bilateral surgery, but the long-term outcome may be inferior. METHODS: The results of a policy of unilateral neck exploration for primary hyperparathyroidism based on preoperative localization are reviewed. RESULTS: Over a 10-year period, 89 patients were operated on, 57 undergoing unilateral neck exploration. Unilateral neck exploration significantly reduced operative time (P < 0.0001) and postoperative hypocalcaemia (P = 0.021). Over a mean biochemical follow-up of 38 months, recurrent hypercalcaemia occurred in 6% of patients, including 3.5% of those undergoing unilateral neck exploration, an additional 10% of patients were normocalcaemic with an inappropriately elevated parathormone level. CONCLUSIONS: A policy of unilateral neck exploration can achieve comparable long-term results to more extensive bilateral surgery.

Adenoma↗

Management of impalpable testes: indications for abdominal exploration.

Various approaches to the management of the impalpable testis in cases of cryptorchidism have been advocated. The authors' experience over the past 13 years was reviewed to try to determine an optimal approach. Of 1,305 patients with undescended testicles seen between February 1982 and December 1995, 157 boys (12.03%) had impalpable testes with 17 having bilateral impalpable testes for a total of 174 impalpable testes. A hernia sac was present in 155 impalpable testes with a testicle present in all cases. No hernia sac was found in 19 impalpable testes, five of which had no testicle present. This was confirmed by either open exploration or laparoscopy. One hundred forty-eight boys underwent groin exploration as initial treatment, 13 of these had bilateral impalpable testes. In addition to the five absent testicles with no hernia sac, one patient with a hernia sac and no testicle evident benefited from subsequent laparoscopy to identify an intraabdominal testicle. All other patients underwent routine orchidopexy or orchidectomy (one case with grossly malformed testicle). Nine boys underwent laparoscopy as initial treatment, four of these had bilateral impalpable testes. Two abnormal testicles were found and removed. Groin exploration and subsequent orchidopexy was definitive treatment in all other cases. The association of a hernia sac with an impalpable undescended testicle is very significant (P < .00001 Fisher's Exact test). The absence of a sac therefore may reflect an alternate diagnosis. When no sac is found with a testicle in the groin, this may represent an ectopic testicle. When no sac is found with no testicle, this may represent a vanishing testicle. From this experience the authors conclude that groin exploration should be the initial approach to impalpable testes. The presence of a hernia sac with an absent testicle demands further exploration; the absence of a hernia sac with an absent testicle suggests a vanishing testicle and may need no further exploration.

Adolescent↗

Role of laparoscopy in patients with previous negative exploration for impalpable testis.

OBJECTIVES: To evaluate the impact of laparoscopy in the treatment of patients with previous negative inguinal exploration for impalpable undescended testes. METHODS: A retrospective review was performed of patients who underwent laparoscopy after prior incomplete or "questionable" negative inguinal explorations for nonpalpable undescended testes. RESULTS: Twenty-seven males aged 1 to 22 years old, with 30 impalpable testes, underwent laparoscopy after prior negative open exploration. The operative notes were available for all patients. In 9 patients (33%), blind-ending spermatic vessels, vas deferens, and a closed ring were found. However, in the remaining 18 patients (67%), viable intra-abdominal or inguinal gonads (9 patients) and intra-abdominal remnants (9 patients) were identified. In 1 patient, seminoma of an intra-abdominal testis was present. CONCLUSIONS: When a patient is referred with an inconclusive previous open exploration for an impalpable gonad, laparoscopy has an important role in establishing or refuting the diagnosis of an absent testis. Moreover, therapeutic laparoscopy provides definitive options to standard open techniques when a viable testis or remnant is encountered. In this study, laparoscopy proved more accurate than open exploration with operative notes available defining the nature of the exploration.

Adolescent↗

Exploring environments by hand or foot: time-based heuristics for encoding distance in movement space.

In Experiment 1, blindfolded observers judged (a) the distance of pathways felt by hand and (b) the straight-line distance between pathway endpoints inferred from such exploration. In Experiment 2, blindfolded observers made corresponding estimates after traversing similar pathways on foot. Pathways were explored under three different speeds. Under both manipulatory and ambulatory exploration, there was substantial length distortion of inferred distance: The straight-line distance was increasingly overestimated with increases in the length of the explored pathway. With manipulatory exploration, slower movements increased length distortion, but duration effects proved secondary to effects of spatial extent. For ambulatory exploration, no duration effects were obtained. Observers used time-independent heuristics, that is, a footstep metric for estimating the pathway actually travelled and a spatial imaging strategy for estimating the inferred line between pathway endpoints. The studies establish length distortion as a general phenomenon in movement space and identify its major causes as spatial rather than temporal.

Adult↗