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The benefit of video-assisted thoracoscopic surgery before planned abdominal exploration in patients with suspected advanced ovarian cancer and moderate to large pleural effusions.

OBJECTIVE: To analyze the findings and impact on the management of video-assisted thoracoscopic surgery (VATS) before planned abdominal exploration in patients with suspected advanced ovarian cancer and moderate to large pleural effusions. METHODS: We reviewed the charts of all patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS from 10/01 to 7/03. VATS was performed under double lumen endotracheal anesthesia. A 2-cm chest wall incision was made in the fifth intercostal space on the side of the effusion. The thoracoscope was introduced and biopsies of suspicious lesions were performed through the single incision. After VATS, all patients had a chest tube placed through the incision, and those with malignant effusions underwent talc pleurodesis either intraoperatively or postoperatively. RESULTS: Twelve patients underwent VATS during the study period. Median operative time for VATS was 31 min (range: 20-49 min) with no complications attributable to the procedure. The median amount of pleural fluid drained was 1000 ml (range: 500-2000 ml). Solid, pleural-based tumor was found in six cases (50%), with nodules >1 cm noted in four patients (33%) and nodules <1 cm noted in two patients (17%). Of the six cases with no grossly visible pleural tumor, the pleural fluid was positive for malignant cells in two patients (17%) and negative in four patients (33%). Further initial patient management included the following: laparotomy with optimal cytoreduction, 6 (50%); diagnostic laparoscopy, 3 (25%); and no abdominal exploration, 3 (25%). Final diagnosis of primary disease site was as follows: ovary, 9 (75%); fallopian tube, 1 (8%); endometrium, 1 (8%); and lymphoma, 1 (8%). Based on the findings during VATS, laparotomy and attempted cytoreduction were avoided in four patients (33%), and the cytoreductive procedure was modified in one patient (8%). CONCLUSION: Fifty percent of patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS had solid pleural-based tumor identified, and in 33% of cases the tumor nodules were >1 cm in diameter. VATS should be considered in these cases to delineate the extent of disease, treat the effusion, and to potentially select patients for either intrathoracic cytoreduction or a neoadjuvant chemotherapy approach.

Abdomen↗

Rapid mixing methods for exploring the kinetics of protein folding.

Information on the time-dependence of molecular species is critical for elucidating reaction mechanisms in chemistry and biology. Rapid flow experiments involving turbulent mixing of two or more solutions continue to be the main source of kinetic information on protein folding and other biochemical processes, such as ligand binding and enzymatic reactions. Recent advances in mixer design and detection methods have opened a new window for exploring conformational changes in proteins on the microsecond time scale. These developments have been especially important for exploring early stages of protein folding.

Animals↗

Exploring the frontiers of therapeutic exon skipping for Duchenne muscular dystrophy by double targeting within one or multiple exons.

Through antisense-induced single-, double-, and multiexon skipping, we have previously demonstrated restoration of dystrophin expression in Duchenne muscular dystrophy (DMD) patient-derived muscle cells in vitro. In this study we further explored the frontiers of this strategy by using specific combinations of 2'-O-methyl phosphorothioate antisense oligonucleotides (AONs) targeting either one or multiple exons. We show that skipping efficiencies may indeed be improved by targeting two putative splicing regulatory sequences within one exon. In particular, such double targeting was effective for the thus far "unskippable" exons 47 and 57. We previously reported the feasibility of multiexon skipping spanning exon 45 to exon 51, using a combination of AONs targeting both outer exons (45 and 51). This would be applicable to 13% of all DMD patients. We here explored the frontiers of multiexon skipping both to increase the number of patients that can be treated with the same set of AONs and to mimic large deletions found in relatively mildly affected BMD patients. We aimed at inducing larger multiexon-skipping stretches, such as exons 17-51, exons 42-55, and exons 45-59. However, this appeared complicated and may be dependent on cotranscriptional splicing and the size of the flanking introns.

Cells, Cultured↗

Laparoscopic common bile duct exploration: the past, the present, and the future.

BACKGROUND: The advent of laparoscopic cholecystectomy (LC) has created a dilemma for treating patients with known or suspected choledocholithiasis. With rapid technologic growth and experience in laparoscopic skills, many surgeons are now routinely performing laparoscopic common bile duct exploration (LCBDE) and questioning the wisdom of preoperative endoscopic retrograde cholangiography (ERC) with or without endoscopic sphincterotomy. The purpose of this article is to review the current literature on the subject of LCBDE and critically evaluate the clinical results of this emerging technology. METHODS: Medline and Science Citation Index databases were used to search English language articles published on LCBDE since 1989. RESULTS: Transcystic common bile duct exploration has a better clearance rate, and carries less morbidity and mortality compared with laparoscopic choledochotomy. Compared with two-stage ERCP and LC, one-stage LC and LCBDE seems to be associated with a shorter hospital stay, a quicker recovery, less expense, and less morbidity and mortality. CONCLUSIONS: LCBDE is a feasible, safe and effective procedure that carries a low morbidity and mortality and will decrease the need for unnecessary ERC in the future for suspected or proved choledocholithiasis.

Algorithms↗

Duplex scanning replaces arteriography and operative exploration in the diagnosis of potential cervical vascular injury.

BACKGROUND: The pursuit of a diagnosis is more aggressive in suspected cervical vascular injury than in extremity vascular proximity injury, since the complications of missing the neck injury may result in irreversible neurologic damage. Most institutions use arteriography and operative exploration, but these modalities identify only 10% of cervical vascular traumas. While duplex scanning is the screening test of choice for carotid occlusive disease, few published reports have described experience with this modality in cervical vascular trauma. PATIENTS AND METHODS: To determine if duplex scanning can replace arteriography or operative exploration as the initial screening modality in the assessment of potential cervical vascular trauma, we performed a prospective evaluation in two parts. First, we used duplex scanning and cervical arteriography, concomitantly, to rule out injury in 15 patients. We then used duplex scanning alone in 85 patients, reserving arteriography for cases in which the scan revealed an arterial injury. RESULTS: Duplex scans and arteriography and operation diagnosed cervical vascular trauma equally well. Eight injuries were identified in all areas of the cervical arterial tree. No duplex scans have been falsely negative or falsely positive. Use of duplex scans instead of arteriography saved $1,252 per case. CONCLUSIONS: Duplex scanning detects cervical vascular injuries as effectively as arteriography or operation, and is faster and less expensive. This approach expands the utility of diagnostic ultrasound in the evaluation of trauma patients. It has become the procedure of choice for diagnosing cervical vascular trauma at our institution.

Angiography↗

99m-Technetium sestamibi localized solitary parathyroid adenoma as an indication for limited unilateral surgical exploration.

BACKGROUND: Because of its successful localization of solitary adenomas, 99m-Technetium sestamibi (MIBI) may challenge the standard operation for primary hyperparathyroidism. METHODS: Thirty-five consecutive patients underwent preoperative MIBI localization to optimize a surgical approach. Single-site localization in 21 patients directed a limited unilateral neck exploration (UNE) with adenomectomy and ipsilateral gland biopsy. Fourteen patients who did not localize underwent bilateral neck exploration (BNE). Conversion to a bilateral operation was required in 1 UNE patient because no adenoma was found on that side. RESULTS: There were no significant differences in preoperative and postoperative serological markers between the two groups. However, the total operative time for UNE (49 +/- 21 minutes) was significantly less than for BNE (103 +/- 45 minutes; P <0.001). CONCLUSIONS: Preoperative MIBI scan-directed limited unilateral neck operation may be used reliably for primary hyperparathyroidism due to a single adenoma, and thereby reduce operative time, extent of surgical dissection, and risk.

Adenoma↗

Subxiphoid anterior mediastinal exploration.

A new surgical technique for anterior mediastinal exploration is described. The technique involves application of a Carlens mediastinoscope by means of a subxiphoid incision. The procedure provides complete exploration of the anterior mediastinal compartment and allows the surgeon to obtain a positive biopsy of the tumor or its lymph node metastases without sternotomy.

Anesthesia, General↗

Space exploration with and without the aid of vision in hemisphere-damaged patients.

Space exploration carried out under visual control and in its absence (blindfolded condition) was investigated in 20 RBD patients, 10 LBD patients and 20 normal controls with a modified version of Chedru's test (pressing the keys of a keyboard). Conventional tests for visual hemi-inattention permitted to classify RBD patients in a group with visual neglect (RBD VN+) and a group without visual neglect (RBD VN-). On the visual version of the test both RBD groups showed a preference for pressing the keys ipsilateral to the lesion side, but this tendency was more marked in the RBD VN+ group than in any other brain-damaged group. On the tactile version of the test only RBD VN+ patients showed a gradient favouring the pressing of the ipsilateral half of the keyboard. This ipsilateral preference was, however, significantly less marked than that found when the performance was assisted by vision. No relation between neglect in the blindfolded condition and tactile extinction was found. The nature of space exploration in the absence of vision is discussed and the existence of tactile neglect is questioned.

Attention↗

Value of endoscopic ultrasonography in the diagnosis of common bile duct stones: comparison with surgical exploration and ERCP.

An accurate and safe preoperative method of imaging the common bile duct is essential for the proper diagnosis of calculous biliary tract disease, especially in the current era of laparoscopic cholecystectomy. The value of endoscopic ultrasonography in detecting common duct stones has been reported, albeit in small series. The aim of this retrospective study was to assess the accuracy of EUS in a large series of patients. We compared EUS to direct cholangiography in the evaluation of 422 patients for common duct stones. Ductal stones were imaged by EUS in 168 patients (43.4%). No complications were encountered. EUS failed in 2.3% of cases, ERCP failed in 8.3%, and surgical exploration failed in 0.5%. Comparison of EUS with surgical exploration in 185 patients showed a sensitivity of 94.9%, a specificity of 97.8%, and an accuracy of 95.9%. EUS was compared to ERCP in 219 patients. All common duct stones found by ERCP were evident by EUS. Concordance was obtained in 91.3% of cases. Review of videotapes disclosed 3 false-positives and 16 unequivocal true-positives. We conclude that EUS is a safe and highly accurate means of detecting common duct stones and should be proposed before laparoscopic cholecystectomy in patients at risk of choledocholithiasis.

Adolescent↗

Gastric outlet obstruction with benign endoscopic biopsy should be further explored for malignancy.

BACKGROUND: Gastric outlet obstruction is commonly considered a complication of peptic ulcer disease. Malignancy accounts for up to 39% of gastric outlet obstruction. The object of this study was to evaluate the reliability of endoscopic biopsies in excluding malignancy as the cause of gastric outlet obstruction. METHODS: A retrospective study of 40 consecutive patients admitted with gastric outlet obstruction was conducted. Patient demographics, their use of H2-receptor antagonists or nonsteroidal anti-inflammatory drugs, and history of peptic ulcer disease were recorded. Histopathologic results of the endoscopic biopsy and surgical specimen were reviewed. The diagnosis based on the surgical specimen was considered the gold standard. RESULTS: Sixteen patients (40%) had malignant gastric outlet obstruction. Seven patients had gastric adenocarcinoma and nine had extragastric tumors. The patients with malignant obstruction were significantly older (> 55 years) (p = 0.03; odds ratio: 95% CI: 5.21 [1.05-23.49]). Gastric cancer patients had less frequently a history of peptic ulcer disease when compared with patients with benign gastric outlet obstruction (p = 0.04; odds ratio: 95% CI: 5 [1.04-38.13]). Endoscopic biopsy to detect malignant obstruction had poor sensitivity (i.e., 37%) when compared with biopsies of the surgical specimen. In three of seven patients with gastric cancer (40%), repeated jumbo biopsies were negative for malignancy. CONCLUSION: Patients with gastric outlet obstruction who had endoscopic biopsies negative for cancer should be explored surgically before embarking on medical therapy. The surgical exploration is especially important in gastric outlet obstruction patients who are considered at high risk for malignancy, that is, those who are older and have no history of peptic ulcer disease.

Adolescent↗

Factors related to fatigue; priority of interventions to reduce or eliminate fatigue and the exploration of a multidisciplinary research model for further study of fatigue.

A growing interest in the health problem presented by fatigue, both in clinical practice and research, coupled with a decreasing number of reported studies on fatigue in the last decade, make an updated and systematic review of factors related to fatigue necessary. A search of the literature, comprising 53 studies, was therefore undertaken to explore the following research questions: Which significantly social-demographic, cure-related, and care-related factors are significantly correlated with fatigue? And which nursing interventions need priority in experimental research to reduce or eliminate fatigue? Reported factors related to fatigue in analysed studies show that the correlations between the specific cure- and care-related factors and fatigue are similar among the various investigated (patient) populations. This result supports the concept of the non-specific character of fatigue. The intervention of primary effectiveness most suggested in this study is 'energy management'. Interventions of secondary importance which emerge are those of 'emotional support', 'activity therapy' and 'coping enhancement'. This study makes clear that the exploration of a research model for fatigue, with social-demographic, cure- and care-related factors is useful and that care-related factors have their own effects on fatigue not necessarily dependent upon the presence of medical diseases or cure-related factors. In general, multi-related factors could be assessed. Implications and relevant questions for further research on fatigue are also given.

Clinical Nursing Research↗

The unilateral pediatric inguinal hernia: Should the contralateral side by explored?

Development of herniography as a diagnostic tool has reopened the question of whether the asymptomatic groin should be explored at the time of unilateral herniorrhaphy in infants. In an attempt to provide data toward the formulation of an answer, the authors review 32 yr of experience with 160 infant hernias. They represent a sequential, unselected series of pediatric patients whose hernias were repaired only if confirmed by examination, and whose postoperative fate has been assessed over extended periods of time. Ninety-six percent of the group were able to be evaulated over an average follow-up interval of 20 yr. It was discovered that of the total group of children with hernias, 29% developed a hernia on the opposite side at some time in their lives. The chance of contralateral occurrence was found not to vary with the child's age at time of first repair, but was found to depend on which side the original repair involved; if the first repair was on the left, the child's chance of contralateral involvement was 41%; if on the right, the risk was only 14%. Morbidity was insignificant with the notable exception of testicular atrophy, which occurred in 2% of the group. The authors conclude that despite the 29% overall risk of future contralateral development, bilateral exploration is not justified for two reasons: First, that a number of unnecessary procedures would be performed, two operations to prevent each subsequent right-sided hernia, and six operations to preclude each later left-sided occurrence; Second, that the risk of bilateral testicular trauma, though slight, is too great.

Atrophy↗

Human disease mortality kinetics are explored through a chain model embodying principles of extreme value theory and competing risks.

The distributions for human disease-specific mortality exhibit two striking characteristics: survivorship curves that intersect near the longevity limit; and, the clustering of best-fitting Weibull shape parameter values into groups centered on integers. Correspondingly, we have hypothesized that the distribution intersections result from either competitive processes or population partitioning and the integral clustering in the shape parameter results from the occurrence of a small number of rare, rate-limiting events in disease progression. In this report we initiate a theoretical examination of these questions by exploring serial chain model dynamics and parameteric competing risks theory. The links in our chain models are composed of more than one bond, where the number of bonds in a link are denoted the link size and are the number of events necessary to break the link and, hence, the chain. We explored chains with all links of the same size or with segments of the chain composed of different size links (competition). Simulations showed that chain breakage dynamics depended on the weakest-link principle and followed kinetics of extreme-values which were very similar to human mortality kinetics. In particular, failure distributions for simple chains were Weibull-type extreme-value distributions with shape parameter values that were identifiable with the integral link size in the limit of infinite chain length. Furthermore, for chains composed of several segments of differing link size, the survival distributions for the various segments converged at a point in the S(t) tails indistinguishable from human data. This was also predicted by parameteric competing risks theory using Weibull underlying distributions. In both the competitive chain simulations and the parametric competing risks theory, however, the shape values for the intersecting distributions deviated from the integer values typical of human data. We conclude that rare events can be the source of integral shapes in human mortality, that convergence is a salient feature of multiple endpoints, but that pure competition may not be the best explanation for the exact type of convergence observable in human mortality. Finally, while the chain models were not motivated by any specific biological structures, interesting biological correlates to them may be useful in gerontological research.

Computer Simulation↗

Ultrasound guided needle localization and microsurgical exploration for incidental nonpalpable testicular tumors.

PURPOSE: We describe a technique by which incidental, nonpalpable intratesticular tumors are excised using intraoperative ultrasonography and the operating microscope. MATERIALS AND METHODS: Men with impalpable intratesticular tumors incidentally detected by ultrasonography underwent intraoperative ultrasound guided needle localization and microsurgical exploration of the mass. The testis was delivered through an inguinal incision and placed on ice to minimize warm ischemia. Two rubber shod vascular clamps were placed across the spermatic cord. The tumor was identified by ultrasound and localized with a 30 gauge needle, which was placed adjacent to the tumor. An operating microscope providing 6x to 25x magnification was used to excise the lesion with a 2 to 5 mm. margin. Tissue diagnosis was obtained by frozen section. Multiple random biopsies of the remaining parenchyma were done to confirm absent malignancy. RESULTS: Ultrasound showed incidental, nonpalpable testis tumors in 4 of the 65 men who underwent infertility evaluation and were entered into the microsurgical testis biopsy database between January 1995 and December 2001. All lesions were hypoechoic. Frozen section analysis of the lesions revealed 2 Leydig cell tumors, 1 mass with an inconclusive pathological diagnosis and 1 inflammatory mass. On permanent section the latter 2 lesions were seminoma. The seminomas were 1.6 and 0.9 cm. in the greatest diameter, and the Leydig cell tumors were 0.35 and 0.2 cm., respectively. Random biopsies were positive for seminoma and intratubular germ cell neoplasia in both testes with seminoma. These 2 patients subsequently opted to undergo radical orchiectomy. No residual tumor was detected in either radical orchiectomy specimen. CONCLUSIONS: Intraoperative ultrasound guided needle localization with microsurgical exploration is a safe and effective approach to even small impalpable testicular masses. This technique provides the opportunity to identify and remove benign and malignant lesions, and preserve the testis when the lesion is benign. In cases of a solitary testis or bilateral synchronous lesions the technique allows a potentially testis sparing operation for small malignancies.

Biopsy↗

Immediate exploration of the unilateral acute scrotum in young male subjects.

Physical exertion, sexual activity or trauma can precipitate cremasteric contraction and result in torsion of a testicle with an underlying congenital anomaly. A high index of suspicion is required by the primary care doctor if acute torsion is to be diagnosed early for immediate reduction. The duration of torsion and the degree of twisting determine the long-term salvage rate of testicular tissue. An aggressive policy of immediate exploration of the unilateral acute scrotum in young men resulted in exploration of twice as many cases of acute epididymitis as torsion of the testis or its appendages but also resulted in an immediate orchiopexy (salvage) rate of 90 per cent and a long-term salvage rate of 73 per cent of patients with acute torsion of the testis.

Acute Disease↗

Exploration and motor activity in juvenile and adult rats exposed to hypergravity at 1.8 G during development: a preliminary report.

Pups from gestating rats exposed to hypergravity (1.8 G) or to normal gravity at the perinatal period were evaluated for motor activity, exploration and social interactions during juvenile and adult stages. By comparison to controls, the hypergravity group had shorter latencies before choosing a maze arm in a T-maze and a lower number of exploratory pokes in a hole board. During dyadic encounters, the hypergravity group had a lower number of self-grooming episodes and shorter latencies before crossing under the opposing rat. In contrast, no intergroup differences were observed during exploration of an elevated plus-maze and a light-dark box. These results indicate that exposure to 1.8 G during development appears to decrease exploratory tendencies in the hole board and fear-related responses in T-maze and social interaction tests.

Aging↗

Exploring trafficking GTPase function by mRNA expression profiling: use of the SymAtlas web-application and the Membrome datasets.

Despite complete sequencing of the human and mouse genomes, functional annotation of novel gene function still remains a major challenge in mammalian biology. Emerging strategies to help elucidate unknown gene function include the analysis of tissue-specific patterns of mRNA expression. A recent study investigated the steady-state mRNA expression profiling of the vast majority of protein-encoding human and mouse genes across a panel of 79 human and 61 mouse nonredundant tissues. The microarray data from this study constitutes the Genomics Institute of Novartis Foundation (GNF) Human and Mouse Gene Atlases and is publicly available for exploration through the SymAtlas web-application (http://symatlas.gnf.org/). We have recently reported the use of these data and hierarchical clustering algorithms to generate a global overview of the distribution of Rabs, SNAREs, and coat machinery components, as well as their respective adaptors, effectors, and regulators. This systems biology approach led us to propose Rab-centric protein activity hubs as a framework for an integrated coding system, the membrome network, which orchestrates the dynamics of specialized membrane architecture of differentiated cells. Here, we describe the use of the SymAtlas web-application and the Membrome datasets to help explore trafficking GTPase function. The human and mouse membrome datasets are available through the Membrome homepage (http://www.membrome.org/) and correspond to subsets of the SymAtlas content restricted to known membrane trafficking components. Considering the fragmentary nature of the current reductionist approaches in elucidating trafficking component functions, the membrome datasets provide a more focused systems biology perspective that not only complements our current understanding of transport in complex tissues but also provides an integrated perspective of Rab activity in controlling membrane architecture.

Animals↗

Comparison of N2O- and chlordiazepoxide-induced behaviors in the light/dark exploration test.

Earlier research has demonstrated similarities in the behavioral effects of nitrous oxide (N2O) and benzodiazepine (BZ) drugs such as chlordiazepoxide (CP). The present research was conducted to compare the behavioral effects of N2O and CP in mice in the light/dark exploration test. When challenged with either N2O or CP, mice exhibited significant dose-dependent increases in the time spent in the light compartment and also in the number of transitions between the light and dark compartments. Pretreatment with BZ receptor antagonist flumazenil (FLU), the GABA(A) receptor antagonist SR-95531 or the selective neuronal nitric oxide (NO) synthase (nNOS) inhibitor 7-nitroindazole (7-NI) all antagonized anxiolytic effects of N20 and CP. Based on these findings, it was concluded that N20 and CP evoke similar behavioral effects in the light/dark exploration test that are similar in their interaction with BZ and GABA(A) receptor antagonists. There also appears to be a specific role for nNOS in generating the NO involved in mediation of these effects.

Analgesics, Non-Narcotic↗