Biomedical subjects

A Ramaswamy

Publications and source records attributed to A Ramaswamy.

At least 19 recordsLinked to original sources

PubMed2006

Short-term preoperative radiotherapy in rectal cancer patients leads to a reduction of the detectable number of lymph nodes in resection specimens.

BACKGROUND AND AIMS: The Union Internationale Contre le Cancer and American Joint Committee on Cancer classification propose that pN(0)-classified colorectal lymphadenectomy specimens will ordinarily include 12 or more tumor-negative lymph nodes. We performed a clinical trial to investigate whether a short-term preoperative radiotherapy (5x5 Gy) leads to a reduction of the number of lymph nodes in rectal cancer specimens after total and partial mesorectal excision (TME and PME, respectively). MATERIALS AND METHODS: Within a 5-year period, 28 (15%) of 148 rectal cancer patients underwent hypofractionated preoperative radiotherapy in this monocenter study, whereas 120 patients (85%) underwent TME/PME surgery alone. The main criterion was the number of lymph nodes in TME/PME specimens. We used a stratified one-sided Wilcoxon-Mann-Whitney test to test for a significant difference in the number of lymph nodes, stratifying for tumor location and postoperative tumor stage. Patients who were suspected of having any alterations in the number of pelvic lymph nodes were excluded from the study. RESULTS: Fewer lymph nodes were detected in the TME/PME specimens of patients who received hypofractionated preoperative radiotherapy compared to patients who underwent TME/PME surgery alone (12 detectable lymph nodes vs 15; p=0.0005). Tumor location (p=0.095) and tumor stage (p=0.093) did not significantly influence the number of lymph nodes in this study. CONCLUSIONS: We conclude that a 5x5 Gy short-term preoperative radiotherapy leads to a reduction in the number of lymph nodes in TME/PME specimens. Because neoadjuvant therapy in rectal cancer for T(2) and T(3) tumors has advanced a new therapeutic standard procedure, in the future, less lymph nodes will be detected in TME/PME specimens. This might influence the required number of lymph nodes in current staging systems for rectal cancer in the future.

Combined Modality Therapy↗

PubMed2006

[Adenoid cystic carcinoma secondary to heterotopic salivary gland tissue of the cervical lymph nodes].

BACKGROUND: The presence of heterotopic salivary gland tissue in intra-, periparotideal and cervical lymph nodes is not an uncommen finding. In some rare cases the salivary gland inclusions in lymph nodes may undergo neoplastic transformation. PATIENT AND METHODS: An isolated and indolent tumor was detected in level III in the right cervical area in a 60 year-old male patient. The histological assessment of the extirpated node seemed to indicate lymph node metastasis of an adenoid cystic carcinoma. The radiological and endoscopic findings did not reveal a primary tumor. RESULTS: Due to the fact of missing of a primary tumor, the diagnosis of an adenoid cystic carcinoma in heterotopic salivary gland tissue of the cervical lymph node was established after long-term observation. CONCLUSION: After exclusion of an occult carcinoma of the salivary glands, the possibility of malignant transformation of heterotopic intranodal salivary gland inclusions should be considered in patients suffering from salivary gland carcinoma in the area of the cervical lymph nodes.

Carcinoma, Adenoid Cystic↗

PubMed2006

Functional thyrotropin receptor attenuates malignant phenotype of follicular thyroid cancer cells.

Thyrotropin (TSH) is a thyroid-specific growth factor inducing differentiated function and growth of thyrocytes in vitro. In thyroid cancer, loss of TSH-receptor (TSHR) expression is a sign of de-differentiation and is believed to contribute to the malignant phenotype. The present studies aimed to determine the in vitro and in vivo effects of functioning TSHR in the follicular thyroid cancer cell line HTC, a subclone of FTC133 cells, lacking endogenous expression of TSHR, and HTCtshr+ cells transfected with human TSHR-cDNA. HTCtshr+ cells grew faster in vitro (doubling time 1.15 vs 1.56 d, p < 0.05) and TSH caused a dose-dependent growth response. Adhesion to and invasion through reconstituted basement membrane were reduced in HTCtshr+ cells, but when stimulated with TSH increased to levels comparable to naïve HTC cells. In vivo, tumor latency was 11 d for naïve HTC as compared to 21 d for HTCtshr+ xenografts. Smaller tumor volumes were registered for HTCtshr+ cells (250 +/- 217 vs 869 +/- 427 mm3, p < 0.05). Angiogenesis, as determined by vascular surface density (VSD) of experimental tumors, was enhanced in naïve HTC tumors (VSD 0.87 +/- 0.1 microm-1 vs 0.55 +/- 0.2 microm-1 in HTCtshr+, p < 0.05). VEGF secretion was more pronounced in naïve HTC cells stimulated with EGF, than in HTCtshr+ cells stimulated with either TSH or EGF. In conclusion, regained expression of functional TSHR in the follicular thyroid cancer cell line HTC alters in vitro features commonly associated with the malignant phenotype. Smaller tumors and reduced angiogenesis of xenotransplanted HTC cells with functioning TSHR suggest a less aggressive in vivo phenotype. The present data highlight the pivotal role of TSHR to affect transformed thyrocytes in vitro and in vivo. They also suggest a role for EGF as a modulator of angiogenesis in thyrocytes devoid of TSHR.

Adenocarcinoma, Follicular↗

PubMed2006

Analysis by cDNA microarrays of gene expression patterns of human adrenocortical tumors.

OBJECTIVES: Adrenocortical carcinoma (ACC) is a rare malignant neoplasm with extremely poor prognosis. The molecular mechanisms of adrenocortical tumorigenesis are still not well understood. The comparative analysis by cDNA microarrays of gene-expression patterns of benign and malignant adrenocortical tumors allows us to identify new tumor-suppressor genes and proto-oncogenes underlying adrenocortical tumorigenesis. DESIGN AND METHODS: Total RNA from fresh-frozen tissue of 10 ACC and 10 benign adrenocortical adenomas was isolated after histologic confirmation of neoplastic cellularity of at least 85%. The reference consisted of pooled RNA of 10 normal adrenal cortex samples. Amplified RNA of tumor and reference was used to synthesize Cy3- and Cy5-fluorescently labeled cDNA in a flip-color technique. D-chips containing 11 540 DNA spots were hybridized and scanned and the images were analyzed by ImaGene 3.0 software. RESULTS: The comparative analysis of gene expression revealed many genes with more than fourfold expression difference between ACC and normal tissue (42 genes), cortical adenoma and normal tissue (11 genes), and ACC and cortical adenoma (21 genes) respectively. As confirmed by real-time PCR, the IGF2 gene was significantly upregulated in ACCs versus cortical adenomas and normal cortical tissue. Genes that were downregulated in adrenocortical tumors included chromogranin B and early growth response factor 1. CONCLUSIONS: Comprehensive expression profiling of adrenocortical tumors by the cDNA microarray technique is a very powerful tool to elucidate the molecular steps associated with the tumorigenesis of these ill-defined neoplasms. To evaluate the role of identified genes, further detailed analyses, including correlation with clinical data, are required.

Adenoma↗

PubMed2005

Rationale for a diagnostic chain in gestational breast tumor diagnosis.

Due to the physiological tissue alterations of the breast during pregnancy and lactation the diagnosis of a breast tumor by palpation, imaging and fine-needle biopsy is difficult and often unreliable. The purpose of our study was to review the value of imaging (mammography and ultrasonography) and biopsy techniques in order to work out a reliable protocol for evaluating gestational tumors. We performed a retrospective analysis of 25 patients with clinical diagnosis of gestational breast tumors during a 4-year period from 1995 to 1999. Specimens were obtained by core biopsy for histological examination. Invasive breast cancer was diagnosed in five patients, malignant lymphoma of the skin in one patient. The tumors in the remaining 19 patients proved benign. The overall accuracy was 0.91 for conventional mammography, 0.76 for conventional and panoramic ultrasound and 0.48 for color-coded sonography. Mammography as the most reliable imaging method should be used to evaluate all patients in whom ultrasonographic findings are suspicious for tumor. Radiation phobia should not prevent the performance of mammography under these circumstances. Nevertheless, all pre-operative methods of diagnosing gestational breast tumors other than core biopsy are unreliable.

Adolescent↗

PubMed2005

Global detection of molecular changes reveals concurrent alteration of several biological pathways in nonsmall cell lung cancer cells.

To identify the molecular changes that occur in non-small cell lung carcinoma (NSCLC), we compared the gene expression profile of the NCI-H292 (H292) NSCLC cell line with that of normal human tracheobronchial epithelial (NHTBE) cells. The NHTBE cells were grown in a three-dimensional organotypic culture system that permits maintenance of the normal pseudostratified mucociliary phenotype characteristic of bronchial epithelium in vivo. Microarray analysis using the Affymetrix oligonucleotide chip U95Av2 revealed that 1,683 genes showed a >1.5-fold change in expression in the H292 cell line relative to the NHTBE cells. Specifically, 418 genes were downregulated and 1,265 were upregulated in the H292 cells. The expression data for selected genes were validated in several different NSCLC cell lines using quantitative real-time PCR and Western analysis. Further analysis of the differentially expressed genes indicated that WNT responses, apoptosis, cell cycle regulation and cell proliferation were significantly altered in the H292 cells. Functional analysis using fluorescence-activated cell sorting confirmed concurrent changes in the activity of these pathways in the H292 line. These findings show that (1) NSCLC cells display deregulation of the WNT, apoptosis, proliferation and cell cycle pathways, as has been found in many other types of cancer cells, and (2) that organotypically cultured NHTBE cells can be used as a reference to identify genes and pathways that are differentially expressed in tumor cells derived from bronchogenic epithelium.

Apoptosis↗

PubMed2005

What happens to the rectus abdominus fascia after laparoscopic ventral hernia repair?

BACKGROUND: One criticism of laparoscopic ventral hernia repair (LVH) is that the rectus muscles are not re-approximated to the midline, and the effect of LVH repair on the fascial edges is unclear. Progressive migration of the fascial edges toward the midline has been observed anecdotally, but objective evidence remains limited. The purpose of this study is to observe the effect of LVH repair on the rectus abdominus fascia. METHODS: Patients undergoing LVH repair with defects > 10 cm in horizontal diameter were identified prospectively and enrolled. All were repaired laparoscopically with intraperitoneal placement of mesh (DualMesh, W.L. Gore and Associates) using a standard approach. Radio-opaque clips were placed at the fascial edges intraoperatively to mark the defect, and plain abdominal films were taken postoperatively (Time 1) to establish the initial distance between clips (measured in cm). A subsequent follow-up film was taken (Time 2), and the difference in clip distance per patient was recorded. Results were analyzed using a chi-squared test. RESULTS: Twelve patients qualified for analysis and their results were compared. Mean fascial defect size was 15.1 cm (range 8.3-22.0). With respect to change in clip distance from Times 1 to 2, three events were observed: (1) Diminished (i.e. medialized), (2) Enlarged, or (3) No Change. Ten patients (83%) medialized, one patient enlarged, and one patient showed no change (chi2 (d.f. = 2) 9.17, p < 0.0023). CONCLUSIONS: Medialization of the rectus abdominus fascia occurs in the majority of patients undergoing LVH repair. Causes for this phenomenon are unclear: however eliminating intrabdominal pressure with intraperitoneal mesh placement likely plays a role.

Adult↗

PubMed2005

Successful treatment of solid-pseudopapillary tumor of the pancreas with multiple liver metastases.

The solid-pseudopapillary tumor (SPT) is a very rare pancreatic neoplasm that predominantly affects young females. About 450 cases have been described in the world literature and approximately 20% of the reported patients were children. The occurrence of SPT with distant metastases in children is extremely rare with only two previously reported cases. We now report a 16-year-old Asian girl with a large SPT and synchronous multiple liver metastases who was successfully treated in a 2-step strategy, including initial pylorus-preserving partial duodenopancreatectomy, right hemicolectomy, resection and allografting of the portal vein and secondary resection of 12 liver metastases. The patient is disease free after a follow-up of 18 months after resection of the primary tumor, suggesting that an aggressive surgical treatment might also be justified for metastasized SPT.

Adolescent↗

PubMed2005

Novel rearrangement of chromosome band 22q11.2 causing 22q11 microdeletion syndrome-like phenotype and rhabdoid tumor of the kidney.

The 22q11.2 microdeletion syndrome is the most frequent microdeletion syndrome in humans, yet its genetic basis is complex and is still not fully understood. Most patients harbor a 3-Mb deletion (typically deleted region [TDR]), but occasionally patients with atypical deletions, some of which do not overlap with each other and/or the TDR, have been described. Microduplication of the TDR leads to a phenotype similar, albeit not identical, to the deletion of this region. Here we present a child initially suspected of having 22q11 microdeletion syndrome, who in addition developed a fatal malignant rhabdoid tumor of the kidney. Detailed cytogenetic and molecular analyses revealed a complex de novo rearrangement of band q11 of the paternally derived chromosome 22. This aberration exhibited two novel features. First, a microduplication of the 22q11 TDR was associated with an atypical 22q11 microdeletion immediately telomeric of the duplicated region. Second, this deletion was considerably larger than previously reported atypical 22q11 deletions, spanning 2.8 Mb and extending beyond the SMARCB1/SNF5/INI1 tumor suppressor gene, whose second allele harbored a somatic frameshift-causing sequence alteration in the patient's tumor. Two nonallelic homologous recombination events between low-copy repeats (LCRs) could explain the emergence of this novel and complex mutation associated with the phenotype of 22q11 microdeletion syndrome.

Chromosome Deletion↗

PubMed2005

An authentic malignant epithelioid hemangioendothelioma of the thyroid: a case report and review of the literature.

Hemangioendotheliomas of the thyroid are neoplasms that are rarely encountered in the Alpine region in Europe. The endemic goiter in this iodine-deficient region can be considered as a predisposing factor. We report the second case of an epithelioid hemangioendothelioma (EHE) of the thyroid gland and the first clinical case with malignant behavior. A 73-year-old woman with a long history of multinodular goiter presented with a rapidly growing thyroid mass, free of distant metastases. A total thyroidectomy was performed. Histologically the lesion had characteristic epithelioid and spindle cell proliferation in a background of chondromyxoid stroma. Cytoplasmic vacuolization in the epithelioid and spindle cells were present. Tumor cells were positive for factor VIII-related antigen, MNF116, PAN-ceratin, CD 34, and CD 31 and negative for cytokeratin allowing the diagnosis of EHE. Nine months after the primary resection the tumor locally recurred. A palliative resection was performed in a second operation followed by interferon-alpha therapy. The patient rapidly developed a second local relapse and died 13 months after the diagnosis of an EHE had been made. An improvement of the very poor prognosis of this rare tumor may depend on early tumor diagnosis and surgery combined with a multimodal treatment.

Aged↗

PubMed2004

Evaluation of the development of lung hypoplasia in the premature lamb.

BACKGROUND: The death rate from human diaphragmatic hernia (CDH) ranges from 50 to 80%, mainly due to the associated lung hypoplasia. To prevent these irreversible pathological and physical defects, the question of intrauterine surgical intervention arises. The histological changes of the lung tissue after inducement of a diaphragmatic hernia were examined. Of special interest was the time elapsing until the development of lung hypoplasia. METHODS: A model of intrauterine inducement of diaphragmatic hernia was established using five fetal lambs to study consecutive pulmonary hypoplasia. Inducement of a diaphragmatic hernia was undertaken between 105 and 108 days' gestation. Lung tissue was examined histologically on postoperative days 8, 17, 21, 22, and 25 after inducement of the defect. RESULTS: On postoperative days 8, 17, and 21, no signs of pulmonary hypoplasia were found on histological examination. A pulmonary hypoplasia was found in two fetuses (on the 22nd and 25th postoperative day). The pathological and anatomical examination of a unilateral pulmonary hypoplasia after a short period of time shows that the artificially created diaphragmatic defect is a good model for producing a congenital diaphragmatic hernia. DISCUSSION: The severity of the pulmonary hypoplasia is related to the duration of lung compression by the herniated organs. The time elapsing until the development of lung hypoplasia is shorter than expected. Tracheal occlusion seems to be an effective strategy for treatment of the defect CDH, but the best technique for achieving occlusion, and particularly the ideal point in time to carry out "Fetendo," are unknown. Further research into this congenital illness is required in order to treat it.

Animals↗

PubMed2003

Bioengineered human bone tissue using autogenous osteoblasts cultured on different biomatrices.

Surgical treatment of critical-size posttraumatic bone defects is still a challenging problem, even in modern bone and joint surgery. Progress in cellular and molecular biology during the last decade now permits novel approaches in bone engineering. Recent conceptual and technical advances have enabled the use of mitotically expanded, bone-derived cells as a therapeutic approach for tissue repair. Using three different tissue carrier systems, we successfully cultivated human osteoblasts in a newly developed perfusion chamber. We studied cell proliferation and the expression of osteocalcin, osteopontin, bone morphogenetic protein-2A, alkaline phosphatase, and vascular endothelial growth factor as parameters for osteoblast function and viability. Adherence of highly enriched human osteoblasts had already started after 1 h and resulted in completely overgrown human bone pieces after 10 days. Expression analysis of bone-specific alkaline phosphatase indicated differentiating osteoblasts, whereas the high mRNA expression of osteocalcin and osteopontin revealed terminally differentiated osteoblasts and the process of mineralization. Additionally, gene expression was significantly higher when demineralized bone was used as biomatrix, compared to autoclaved bone and hydroxyapatite ceramics. We conclude that with our newly developed perfusion culture system, vital autogenous bone implants of clinically applicable size can be generated within 17 days in order to manage critical-size bone defects.

Animals↗

PubMed2003

[Hyperaldosteronism persisting after subtotal adrenalectomy].

BACKGROUND: Primary aldosteronism is known to be caused by aldosterone-producing adenoma (APA). Total adrenalectomy is the standard procedure. In contrast to bilateral adrenal diseases (e.g., MEN II pheochromocytomas), there is no consensus about the effect of subtotal adrenalectomy. CASE REPORT: A 44-year-old patient with primary aldosteronism caused by APA underwent subtotal adrenalectomy including removal of one adenoma. Because hypertension and hypokalemia did not disappear and hyperaldosteronism persisted, the patient had to undergo reoperation in which the adrenalectomy was completed. DISCUSSION: Subtotal adrenalectomy in patients with Conn's syndrome is an interesting therapeutic option,whereas its effect is much higher in hereditary diseases of the adrenal gland. The benefit of preserved adrenal tissue has to be weighed against a possible persistence of hyperaldosteronism, especially in cases with normal opposite adrenal glands.

Adrenal Cortex Neoplasms↗

PubMed2003

Lymph node topography of the head and neck in New Zealand White rabbits.

Investigations of the lymphogenic metastatic spread of VX2 carcinomas in New Zealand White rabbits require an exact knowledge of the topography of cervical and facial lymph nodes. The topography of neck lymph nodes was evaluated from 16 rabbits macroscopically, histologically and by lymphographic investigations, and the possibility of their surgical removal (neck dissection) was examined. The upper aerodigestive tract and the ear of New Zealand White rabbits drain via four consistent groups of 12-18 lymph nodes. Except for the paratracheal lymph node, they are all easily accessible to surgery. The data presented in this study encourage the use of induced VX2 carcinomas in New Zealand White rabbits as an animal model to study the lymphogenic metastatic spread of squamous cell carcinomas of the head and neck. Such investigations could lead to an improvement of surgical and pharmaceutical treatment of this tumour entity.

Animals↗

PubMed2002

Sentinel node detection in N0 cancer of the pharynx and larynx.

Neck lymph node status is the most important factor for prognosis in head and neck squamous cell carcinoma. Sentinel node detection reliably predicts the lymph node status in melanoma and breast cancer patients. This study evaluates the predictive value of sentinel node detection in 50 patients suffering from pharyngeal and laryngeal carcinomas with a N0 neck as assessed by ultrasound imaging. Following 99m-Technetium nanocolloid injection in the perimeter of the tumour intraoperative sentinel node detection was performed during lymph node dissection. Postoperatively the histological results of the sentinel nodes were compared with the excised neck dissection specimen. Identification of sentinel nodes was successful in all 50 patients with a sensitivity of 89%. In eight cases the sentinel node showed nodal disease (pN1). In 41 patients the sentinel node was tumour negative reflecting the correct neck lymph node status (pN0). We observed one false-negative result. In this case the sentinel node was free of tumour, whereas a neighbouring lymph node contained a lymph node metastasis (pN1). Although we have shown, that skipping of nodal basins can occur, this technique still reliably identifies the sentinel nodes of patients with squamous cell carcinoma of the pharynx and larynx. Future studies must show, if sentinel node detection is suitable to limit the extent of lymph node dissection in clinically N0 necks of patients suffering from pharyngeal and laryngeal squamous cell carcinoma.

Adult↗

PubMed2002

Number and location of radiolabeled, intraoperatively identified sentinel nodes in 48 head and neck cancer patients with clinically staged N0 and N1 neck.

The value of sentinel node (SN) biopsy for squamous cell carcinoma of the head and neck (HNSCC) has not been determined yet. A critical evaluation of this concept seems to be mandatory with regard to the increasing acceptance of SN biopsy in other tumor entities. Against the background of the results of 48 previously untreated patients, a reproducible technique for SN biopsy in the head and neck level, which has been adjusted to the special topographic conditions of this anatomic region, is presented. Methods included intraoperative SN biopsy, which was performed in 48 previously untreated patients suffering from squamous cell carcinoma (2x lower lip, 8x oral cavity, 20x oropharynx, 15x larynx, 3x hypopharynx). Using ultrasound imaging, 43 patients were staged as N0 necks, and 5 patients were staged as N1 necks. Fine-needle aspiration cytology (FNAC) was performed in cases of doubt. Surgery on the neck was carried out according to the suspected stage of lymphogenic spread once the SN1 as well as one or two further hot nodes (SN2, SN3) had been identified. Numbers and distribution of the intraoperatively excised nodes SN1-3 were documented according to their relation to the tumor location. Post-operatively, the histologic results of the intraoperatively excised nodes SN1-3 were compared to the histologies of the neck dissection specimen. Results showed that in all 48 patients, a SN1 could be identified intraoperatively. In 20 cases an additional SN2 and in 6 cases a SN3 was diagnosed. In carcinomas of the lower lip and oral cavity, the SN1 was found in 4 cases in level I (2x lower lip, 2x floor of the mouth) and in 6 cases in level II (6x lateral tongue). In carcinomas of the oropharynx, the respective nodes were found in 17 of 20 cases in level II (carcinomas of the tonsil) and in 3 cases in level III (carcinomas of the base of the tongue). In supraglottic carcinomas the SN1 was identified in 8 of 10 cases in level II and in 2/5 patients with glottic carcinomas, while in 3/5 glottic carcinomas as well as in all hypopharyngeal carcinomas, the SN1 was found in level III. In relation to the predictiveness of the detected SN, it has to be remarked that in 38 patients a SN1 free of tumor was representative for the regional lymph node status (pN0). An isolated metastasis (pN1) was diagnosed in the SN (9x SN1, 1x SN2) in 10 patients. In conclusion, the results of a SN biopsy modified to a strictly intraoperative method of detection are encouraging. Critical indications showed that a thorough and standardized technical performance of the injection as well as a mandatory, so far unchanged, neck dissection form the basis for the development of a SN concept for SCCs of the upper aerodigestive tract. The value of the SN concept, however, currently remains unclear for patients suffering from HNSCC.

Adult↗

PubMed2002

[The sentinel node concept in head and neck squamous cell carcinoma--a critical analysis in 100 patients].

BACKGROUND: The value of Sentinel Node (SN) concept is a current issue in clinical oncology. Few investigations deal with SN biopsy in head and neck squamous cell carcinomas (HNSCC). For this reason the SN concept was investigated based on the results of the so far largest group of 100 patients. METHOD: Three groups of patients were investigated. Group 1: In 30 patients (6 x oral cavity, 24 x oropharynx) a dynamic lymphoscintigraphy was performed. Group 2: 60 previously untreated patients (12 x oral cavity, 23 x oropharynx, 16 x larynx, 9 x hypopharynx); neck lymph node status on ultrasound imaging: 39 x N0, 5 x N1, 16 x N2, intraoperative identification of the SN during neck dissection (ND) accomplished according to the extent of assumed lymphogenic metastatic spread; postoperative comparison of the histological result of the SN with the neck dissection specimen. Group 3: 10 previously treated patients (1 x oral cavity, 5 x oropharynx, 1 x larynx, 3 x hypopharynx) in whom an intraoperative SN biopsy was performed. RESULTS: Group 1: In 20/30 patients a cervical lymph drainage could be visualized on dynamic lymphscintigraphy and an activity enrichment above the mean metastatic region could be identified transcutaneously. Group 2: In 34 patients the tumorfree SN1 reflected the regional lymph node status. In 9 patients an isolated tumor metastasis (pN1) was found in the intraoperatively identified SN1 and in a further patient in the SN2 (pN1). CONCLUSION: The results of SN biopsy are encouraging in cases of clinical N0-necks. Nevertheless the data demonstrates that extensive investigations followed by a critical analysis of the results are required. The presented results suggest that the value of the SN concept seems to be of minor importance in cases of advanced lymphogenic metastatic spread.

Adult↗

PubMed2001

Singlet oxygen (1O(2)) disrupts platelet aggregates.

INTRODUCTION: Important mediators of activated polymorphonuclear leukocytes (PMN) are the oxidants HOCl and chloramine, which generate the nonradical photon-emitting oxidant singlet oxygen (1O(2)). Since 1O(2) inhibits platelet aggregation, we became interested in a possible oxidant mediated reversibility of platelet aggregation. METHODS: Chloramine T (CT) is a stable 1O(2) generator that mimics the natural chloramine N-chloro-taurine. Platelet-rich plasma (PRP) was incubated with CT 0-8 min after addition of the aggregation agonist (10 microM adenosine-5'-diphosphate, ADP, or 5 microg/ml collagen) and the aggregation was monitored. Platelet function was also analyzed by the platelet function analyzer, PFA-100. Fifty microliters of 200 micromol/l ADP was added to 400 microl PRP. After 1 min at 37 degrees C, 50 microl of 0 or 30 mmol/l CT was added, and after an incubation for 3 min at 37 degrees C, 50 microl of 25% glutaraldehyde was added. The samples were analyzed in a transmission microscope at x3000 and x7000 magnification. RESULTS: Chloramines inhibit platelet function in PRP: about 1 mM CT suppresses 50% of the aggregatory capacity of thrombocytes in normal PRP (effective dose 50%, ED(50)=1 mM chloramine), which is identical to the ED(50) for CT in whole blood. The ADP- or collagen-induced platelet aggregation can be reversed by addition of CT: up to 2 min after the addition of ADP as the aggregation inducer, the aggregation is reversible to more than 70% by addition of a 1O(2) release-inducer (3 mM CT). In contrast, addition of CT 8 min after the addition of ADP results only in about 50% reversal of platelet aggregation. The electron microscopic images of platelets before ADP, after incubation for 4 min at 20 micromol/l ADP, after incubation for 1 min at 20 micromol/l ADP, and a further incubation for 3 min at 3 mmol/l CT demonstrate an ADP-dependent formation of platelet aggregates, which are disrupted by 1O(2) into the single platelets; a phenomenon comparable to the decomposition of a puzzle or the continental drift of the major earth plates. The morphology of oxidized and unoxidized platelets is similar. CONCLUSION: This study demonstrates that 1O(2) inhibits and reverses platelet aggregation. The physiologic signal action and the direct anticoagulant action of 1O(2) might be a new principle for pharmacologic intervention in atherothrombosis.

Blood Platelets↗