Ossification of the posterior longitudinal ligament.
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Biomedical subjects
Publications and source records attributed to J H Wong.
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Thioredoxins are 12-kDa proteins functional in the regulation of cellular processes throughout the animal, plant, and microbial kingdoms. Growing evidence with seeds suggests that an h-type of thioredoxin, reduced by NADPH via NADP-thioredoxin reductase, reduces disulfide bonds of target proteins and thereby acts as a wakeup call in germination. A better understanding of the role of thioredoxin in seeds as well as other systems could be achieved if more were known about the target proteins. To this end, we have devised a strategy for the comprehensive identification of proteins targeted by thioredoxin. Tissue extracts incubated with reduced thioredoxin are treated with a fluorescent probe (monobromobimane) to label sulfhydryl groups. The newly labeled proteins are isolated by conventional two-dimensional electrophoresis: (i) nonreducing/reducing or (ii) isoelectric focusing/reducing SDS/PAGE. The isolated proteins are identified by amino acid sequencing. Each electrophoresis system offers an advantage: the first method reveals the specificity of thioredoxin in the reduction of intramolecular vs. intermolecular disulfide bonds, whereas the second method improves the separation of the labeled proteins. By application of both methods to peanut seed extracts, we isolated at least 20 thioredoxin targets and identified 5-three allergens (Ara h2, Ara h3, and Ara h6) and two proteins not known to occur in peanut (desiccation-related and seed maturation protein). These findings open the door to the identification of proteins targeted by thioredoxin in a wide range of systems, thereby enhancing our understanding of its function and extending its technological and medical applications.
Merkel cell or cutaneous neuroendocrine carcinoma is a malignant tumor with a propensity toward local and systemic recurrence. A new surgical technique, intraoperative lymphatic mapping and selective sentinel lymph node dissection (SSLND), has been demonstrated to have a high predictive value for the detection of metastatic disease in the regional lymphatic basin in cutaneous melanoma. The use of this technology may be particularly useful to accurately stage patients with Merkel cell carcinoma (MCC) because this tumor has a frequent propensity toward regional nodal metastases. Intraoperative lymphatic mapping and SSLND were performed on 6 patients with biopsy-proven MCC. Three patients with MCC had positive disease in the sentinel lymph node(s). SSLND is a feasible technique with minimal procedural morbidity to detect clinically occult disease in patients with MCC.
The mobilization of storage proteins (glutelins) in germinating rice seeds was accompanied by an ordered sequential combination of proteolysis and reduction of disulfide groups. Mobilization was followed by application of non-reducing/reducing two dimensional-PAGE after monobromobimane labeling of the sulfhydryl groups of the proteins in intact seeds.
OBJECTIVE: Increasing evidence supports that the sentinel node (SN) is at greatest risk for harboring metastatic disease. This study describes a novel technique to identify the SN in colorectal carcinoma. METHODS: Within 30 minutes of resection, colorectal specimens were injected submucosally with isosulfan blue in four quadrants. Blue lymphatic channels were identified in the mesentery and followed to the blue-stained SN(s), which were then harvested. The specimen was fixed in formalin and subsequently analyzed in the usual fashion. Blue-stained nodes that were negative by hematoxylin and eosin staining were further analyzed by immunohistochemical staining. RESULTS: During a 6-month period, 26 patients with adenocarcinoma of the colon and rectum undergoing routine resection were studied. There were 18 men and 8 women ranging in age from 29 to 86 years (median 66). Blue-stained SNs were identified in 24 of 26 specimens. The mean number of SNs identified per patient was 2.8 +/- 1.6. Seventy-three SNs were identified from a total of 479 lymph nodes harvested. The mean number of nodes identified per patient was 18.4 +/-7. A total of 67 lymph nodes in 12 patients were identified by hematoxylin and eosin staining to have evidence of metastatic disease. Fourteen (20%) of these nodes in six patients were stained blue. However, with immunohistochemical staining, only one blue node did not have evidence of metastatic tumor in a lymphatic basin with tumor present. Four patients (29%) whose lymphatic basins were negative by hematoxylin and eosin staining were upstaged by immunohistochemical staining of the SN. CONCLUSIONS: Ex vivo mapping of the colon and rectum is technically feasible and may provide a useful approach to the ultrastaging of colorectal carcinoma.
A 28-year-old woman with an infiltrating ductal carcinoma in the upper outer quadrant of the left breast diagnosed by excisional biopsy underwent lumpectomy, intraoperative lymphatic mapping, and sentinel node dissection. This was followed by an immediate completion axillary node dissection using a hand-held gamma probe and isosulfan blue to map the lymphatics. Preoperative breast lymphoscintigraphy showed drainage into the axilla and an apparent area of radiocolloid accumulation in the inferior hemisphere of the left breast. Because our protocol called only for removal of axillary sentinel nodes, the inferior hemisphere radiocolloid accumulation was not removed. The patient did not complete local regional therapy with breast irradiation and developed a mass in the inferior hemisphere of the left breast, which on biopsy was shown to be metastatic breast cancer in an intramammary lymph node. This case illustrates the potential value of breast lymphoscintograms to identify unusual sites of lymphatic drainage that may prove to be clinically relevant.
Genetic studies are interesting not only in the diagnosis and screening of new cases within a family harboring a particular disease, but also in understanding the underlying genetic and molecular factors related to that disease. Such studies revealed 3 categories of cerebral arteriovenous malformations in relationship to possible genetic factors. The first one concerns cerebral arteriovenous malformations in relationship to inherited diseases where a genetic support is clearly identified. Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) represents the most classical picture. The second category corresponds to familial cases of cerebral arteriovenous malformations were several members and relatives of the same family harboring the pathology without clear demonstration of any genetic basis. The third category includes cerebral arteriovenous malformations described in association with neurocutaneous disorders issued from maldevelopment events. Sturge-Weber disease and Wyburn-Mason syndrome best illustrate this category. A review of these categories will help in a better understanding of some genetic issues related to cerebral arteriovenous malformations.
OBJECTIVE: The aim of this study was to evaluate the findings when pathologic ultrastaging techniques are applied in conjunction with sentinel node dissection in patients with vulvar cancer. METHODS: Patients with squamous cell cancer of the vulva underwent intraoperative lymphoscintigraphy following intradermal injection of 99mTc-labeled sulfur colloid at the site of the primary tumor. Isosulfan blue dye was also injected at the tumor site to facilitate identification of the sentinel node in the groin. Following removal, the sentinel node was then bisected and examined in the standard manner using hematoxylin and eosin staining. Negative nodes were subjected to additional ultrastaging evaluation with serial sectioning and immunohistochemical staining. RESULTS: Nine patients with 10 primary tumors underwent radical local excision of the primary tumor and sentinel node dissection of the groin. Sentinel nodes were identified and removed in all patients. One node was positive by conventional staining; the remainder were all negative. Of these negative nodes, 2 were found to be positive for micrometastases on serial sectioning and immunohistochemical staining. Therefore 2 of 3 positive nodes were not detected using conventional histologic techniques. CONCLUSION: Sentinel node dissection appears to be technically feasible in patients with vulvar cancer. Pathologic ultrastaging combined with sentinel node dissection appears to be highly sensitive for detecting subclinical micrometastases in the regional lymphatics. This technique potentially provides a more accurate assessment with less surgical morbidity than conventional inguinalfemoral lymphadenectomy.
Although the role of axillary lymph node dissection is controversial with respect to survival benefits, its role as a staging procedure has been well established since nodal involvement is the most reliable prognostic indicator for patients with breast cancer. Selective sentinel lymph node (SLN) dissection is gaining acceptance as a useful staging procedure because it is minimally invasive and spares approximately 70-80% of the patients a more extensive axillary lymph node dissection. The evolving techniques for selective SLN dissection using blue dye and radiotracer methods are reviewed in this article. Based on the classic definition of the breast lymphatic drainage and recently published articles addressing the issue of peritumoral and intradermal injections, a possible new and simplified approach using intradermal injection may identify the axillary SLN more quickly and reliably. This article emphasizes the importance of a multidisciplinary approach in the identification of SLNs by preoperative lymphoscintigraphy performed by expert nuclear medicine physicians, the intraoperative mapping and harvesting of SLNs by well trained surgeons and the meticulous examination of SLNs by experienced pathologists. Therefore, to achieve the highest rate of accuracy regarding SLN status, it is imperative that a multidisciplinary team with close communication and cooperation be formed. The clinical significance of SLNs will be determined by results from follow-up and clinical trials.
BACKGROUND: The feasibility of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) in settings other than high-volume specialized clinics has been questioned. We sought to determine the feasibility of SLND in a university-affiliated private teaching hospital. METHODS: A multidisciplinary sentinel node program was established to include surgeons, nuclear medicine physicians, and pathologists. Within this program, 79 patients with cutaneous melanoma underwent attempted SLND after cutaneous lymphoscintigraphy (CL), between January 1994 and December 1998. All sentinel nodes were examined by hematoxylin-eosin staining and determined whether negative for evidence metastatic disease by both S-100 and HMB 45 immunohistochemical staining. RESULTS: CL was successful in 77 (97%) of 79 patients. A total of 88 lymphatic basins were found to be at risk for metastatic disease by CL. SLND was not successful in the two patients who did not have a successful CL. Sentinel nodes were identified in all but three patients with the remaining 88 lymphatic basins (technical success, 97%). There was one false negative in this group of patients (approximately 1%). CONCLUSIONS: SLND is a highly accurate way of staging the regional node basin. Our technical success rates and false-negative rates indicate the feasibility of this approach in settings other than high-volume specialty clinics.
Intraoperative lymphatic mapping (ILM) and selective lymphadenectomy are revolutionary concepts that, in a short period, have shown the potential to alter dramatically the management of many patients with solid neoplasms. The rapid adaptation of this approach to the staging of solid neoplasms by the surgical oncology community has resulted in an explosion of data. Initially described as a surgical technique in which each surgeon had to climb a learning curve, ILM and selective lymph node dissection (SLND) are now recognized as a multidisciplinary surgical approach to the management of the patient with cutaneous melanoma and breast cancer. The potential values of ILM and SLND are being examined vigorously now in numerous other solid neoplasms.
The role of sentinel lymphadenectomy in the management of malignancies other than melanoma and breast cancer is being increasingly explored. Improved staging of solid tumors holds great promise for refining treatment recommendations and gaining insight into the biologic behavior of these malignancies. This article summarizes the growing experiences with sentinel lymphadenectomy in solid tumors other than cutaneous melanoma and breast cancer.
Sentinel lymph node (SLN) mapping has been found to be highly effective in correctly predicting the nodal status for melanoma and for breast cancer. This study shows that SLN mapping also is highly successful in colorectal cancer, posing minimal cost and no complications. The procedure accurately determines the presence or absence of nodal micrometastasis in more than 96% of cases. This article reviews the in vivo and ex vivo techniques for SLN mapping in colorectal cancer, along with its limitations and pitfalls.
There is considerable controversy regarding the introduction and granting of credentials for sentinel lymphadenectomy in breast cancer. Given the workload of the average general surgeon and current procedural guidelines, two to three years would be required to demonstrate competence before a surgeon might perform sentinel lymphadenectomy without an immediate completion axillary node dissection. This article reviews issues related to the introduction of sentinel lymphadenectomy in the general surgeon's armamentarium.
Selective sentinel lymphadenectomy is a standard staging procedure for patients with melanoma and is rapidly evolving into a standard procedure for breast cancer. A well-trained, multidisciplinary team is essential for the success of such a procedure. Clinical trials are under way to determine the clinical significance of sentinel lymph nodes in melanoma and breast cancer. The techniques of harvesting are being developed in other solid cancers, such as gynecologic and gastrointestinal cancer. Cellular and molecular techniques are being used to study the mechanism of micrometastasis.
Quality assurance data were collected prospectively for children who were sedated (n = 922) or given general anaesthesia (n = 140) for magnetic resonance imaging (MRI) or computerized tomography (CT). The data included patient characteristics, concurrent medication, adequacy of sedation, adverse events and requirement for escalated care. The quality of scans was evaluated. Reasons for preselection of general anaesthesia included previously failed sedation (28%), potential for failed sedation (32%) and perceived medical risk (14%). Hypoxaemia occurred in 2.9% of sedated children, and was more common in children classified as ASA III or IV. Sedation was inadequate for 16% of children and failed in 7%. Failed sedation was associated with greater age (P = 0.009), higher ASA status (P = 0.04) and use of benzodiazepines as sole sedatives (P < 0.03). More of the children who underwent general anaesthesia were ASA III or IV than sedated children, yet the procedure was successful in all the children who underwent general anaesthesia, with one incident of laryngospasm. Excessive motion was noted in 12% of scans of sedated children and 0.7% of those completed with general anaesthesia. We conclude that sedation of children for MRI and CT is associated with risks of hypoxaemia and of inadequate or failed sedation. These adverse events were more likely to occur in older children, those with a higher ASA status and those in whom benzodiazepines had been used as sole sedatives. For a preselected high-risk group of children, general anaesthesia may make MRI and CT scans more successful with minimal adverse events.
OBJECTIVE: Although cerebrovascular malformations have been characterized histologically, a systematic examination of such lesions by transmission electron microscopy has not been previously published. In this preliminary study, we describe the ultrastructural pathological features of cerebral arteriovenous malformations (AVMs) and cavernous malformations (CMs). METHODS: Using transmission electron microscopy, we examined three CMs and three AVMs microsurgically harvested from patients, for conventional indications. Normal control cerebral tissue was obtained from two patients undergoing surgery for epilepsy. Specific attention was directed at components of the vascular wall, endothelial cell (EC) morphology, intercellular tight junctions, and the subendothelial layer. RESULTS: In embolized AVM vessels, ECs were disrupted, with preservation of the underlying subendothelial vessel wall. Nidal vessel walls of AVMs showed disorganized collagen bundles. In CM specimens, ECs lined attenuated cavern walls that were composed of an amorphous material lacking organized collagen. Peripheral to the CMs, capillaries were often surrounded by rings of hemosiderin. Tight junctions between ECs were present in AVMs and control specimens, but substantial inter-EC gaps were found in CMs. Subendothelial smooth muscle cells were present in AVM and control specimens, but they were sparse or poorly characterized in CMs. CONCLUSION: Surgically resected vascular malformations demonstrate abnormal ultrastructural pathological features. The preoperative embolization of AVMs results in EC denudation, with preservation of vessel wall structural integrity. The thin walls of CMs, lacking significant subendothelial support, along with the rarity of intact tight junctions between ECs, may contribute to the known propensity of CMs for recurrent microhemorrhage.
BACKGROUND AND PURPOSE: We review preliminary experience with patients harboring intracerebral hematoma (ICH) treated by stereotactic computed tomographic (CT) guided thrombolysis and aspiration and assess procedure feasibility and safety. METHODS: Twelve patients with supratentorial ICH >/=25 mL without suspected underlying structural etiology or coagulopathy and an initial Glasgow Coma Scale (GCS) score of >/=5 were treated. A catheter was directed stereotactically or manually into the ICH through a burr hole under CT guidance. Hematoma aspiration was followed by instillation of urokinase (5 000 to 10 000 IU). This was repeated every 6 to 8 hours at bedside, with interval CT imaging, until the ICH volume diminished to <25 mL, less than half of its initial volume, or after a maximum of 10 aspirations/instillations. RESULTS: Mean age was 69 years (range 55 to 82 years). Median initial GCS was 12 (range 5 to 14). There were 7 ganglionic and 5 lobar ICH, and baseline hematoma size ranged 29 to 70 mL (mean 46 mL). Final ICH volume ranged from 14 to 51 mL (mean 21 mL), with ICH volume reduction by an average of 57% (range 38% to 70%). One patient (8. 3%) suffered hematoma expansion during the procedure. At 6 months after the procedure, 3 patients (25%) had achieved a good recovery (Glasgow Outcome Scale [GOS] score of 5), 5 patients (42%) were dependent (GOS 3), and 1 (8.3%) remained vegetative (GOS 2). Three patients (25%) died in hospital (1 from cardiac arrhythmia and 2 from respiratory failure). CONCLUSIONS: CT-guided thrombolysis and aspiration appears safe and effective in the reduction of ICH volume. Further studies are needed to assess optimal thrombolytic dosage and must include controlled comparisons of mortality, disability outcome, time until convalescence, and cost of care in treated and untreated patients.