Peristaltic motion of Jeffrey fluid with nonlinear mixed convection.

Since previous few decays the consideration of non-Newtonian liquids motion due to its immense usages in medicine, biology, industrial procedures, chemistry of catalysts and in environment. Various studies examine the significance of bio-materials flow in physiological procedures to explore the cure of diagnosed symptoms of disease appearing during movement in a human physiological system. To illustrate the characteristics of physiological liquids various non-Newtonian models have been proposed, but yet no such single liquid model is exploited which describes all the properties of nonlinear behaving liquids. Among these several non-Newtonian models, Jeffery liquid model should be reduced to its base fluid case (i.e. viscous liquid) by choosing λ1 = λ2 = 0. Various physiological materials which represents both linear and nonlinear characteristics respectively blood is one of these. Jeffery fluid and peristaltic motion have some common properties such as radii, relaxation time and retardation time. Moreover heat and mass transfer is also an important phenomenon which is suitable for various physiological processes such as hemodialysis and oxygenation etc. Thus due to such motivating facts this research is conducted to investigate the peristaltic motion of electrically conducting Jeffery liquid. The peristaltic propagating channel walls are asymmetric and inclined. Joule heating and magnetic field effects are considered by applying magnetic field in transverse direction to the flow. Further conservation laws modelled the flow situation via considering quadric mix convection, thermos diffusion and diffusion-thermos, heat generation and absorption, chemical reaction with activation energy features. Moreover, creeping flow and long wavelength assumptions are used to simplify the mathematical modelling. The reduced system of equation is solved numerically through built-in technique in Mathematica software. This built-in technique is working through ND Solve command and shooting and RK-Felburg numerical schemes are behind this technique. These numerical results are used to discuss the flow quantities i.e., velocity, temperature and concentration against the sundry dimensionless quantities. Examining the results it comes to know that both thermal and concentration nonlinear mix convection have oppositely affecting the axial velocity. Both heat and mass transfer are escalating function of thermo-diffusion/diffusion-thermo aspects.

Discovery of dual-target natural antimalarial agents against DHODH and PMT of Plasmodium falciparum: pharmacophore modelling, molecular docking, quantum mechanics, and molecular dynamics simulations.

Malaria is a lethal disease that claims thousands of lives worldwide annually. The objective of this study was to identify new natural compounds that can target two P. falciparum enzymes; P. falciparum Dihydroorotate dehydrogenase (PfDHODH) and P. falciparum phosphoethanolamine methyltransferase (PfPMT). To accomplish this, e-pharmacophore modelling and molecular docking were employed against PfDHODH. Following this, 1201 natural compounds with docking scores of ≤ -7 kcal/mol were docked into the active site of the second enzyme PMT. The top nine compounds were subjected to further investigation using MM-GBSA free binding energy calculations and ADME analysis. The results revealed favourable free binding energy values better than the references, as well as acceptable pharmacokinetic properties. Compounds ZINC000013377887, ZINC000015113777, and ZINC000085595753 were scrutinized to assess their interaction stability with the PfDHODH enzyme, and chemical stability reactivity using molecular dynamics (MD) simulation and density functional theory (DFT) calculations. These findings indicate that the three natural compounds are potential candidates for dual PfDHODH and PfPMT inhibitors for malaria treatment.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma.

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

The ability of lymphoscintigraphy to direct sentinel node biopsy in the clinically N0 neck for patients with head and neck squamous cell carcinoma.

This study aimed to evaluate the ability of lymphoscintigraphy (LSG) to direct sentinel node biopsy (SNB) in the identification of occult metastases in the clinically N0 neck for patients with head and neck squamous cell carcinoma (HNSCC). 57 clinically N0 neck sides in 48 patients were assessed using the triple diagnostic approach of pre-operative LSG, intra-operative use of a gamma probe and blue dye. SNB was performed after radiocolloid and blue dye injection. Pre-operative LSG and the intra-operative use of a gamma probe identified radioactive sentinel nodes, and visualization of blue stained lymphatics identified blue sentinel nodes. 104 sentinel nodes were harvested from 43 patients. The identification rate was 90% (43 of 48). Of the 104 nodes harvested, 17 of 62 (27%) nodes identified as both radioactive and blue were positive for occult metastases compared with 5 of 42 (12%) nodes identified as hot or blue only (p<0.05). Sentinel nodes were identified in 39 of 48 (81%) patients using LSG. Of 39 patients in whom sentinel nodes were identified using LSG, 37 of 39 (95%) had radioactive sentinel nodes harvested intra-operatively. In patients who had no sentinel nodes identified on LSG, 4 of 9 (44%) had radioactive sentinel nodes harvested intra-operatively. This difference was statistically significant using the t-test (p<0.05). LSG directs SNB and is essential in the identification of occult metastases within the clinically N0 neck for patients with HNSCC.

Pleomorphic adenomas: post-operative radiotherapy is unnecessary following primary incomplete excision: a retrospective review.

BACKGROUND: Current standard treatment of Pleomorphic Salivary Adenoma (PSA) of the Parotid Gland is by surgical excision. The management of incomplete excision remains undecided with post-operative radiotherapy advocated by some and observation by others. METHODS: 190 patients who underwent resection of PSA of the parotid gland within the West of Scotland region from 1981 to 2008 were identified and data collected. RESULTS: 78/190 patients had a primary incomplete excision. 25/78 received post-operative radiotherapy and 53 were observed. Recurrences occurred in 11/53 in those observed and in 1/25 of those who received radiotherapy. 21/25 complained of significant side effects from the radiotherapy. 38 surgeons performed 190 procedures, with a range of experience from 1 to28 procedures. CONCLUSIONS: Radiotherapy does appear to reduce recurrence with incomplete excision, however it is associated with significant side effects. We therefore feel radiotherapy should not be routinely recommended. Subspecialisation should be adopted to increase the operating surgeon's experience.

Micrometastases and isolated tumour cells in sentinel lymph nodes in oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: The occurrence of micrometastases (MMs) and isolated tumour cells (ITCs) in oral sentinel lymph node (SLN) biopsy is poorly known, and the definitions and clinical significance of MMs and ITCs in SLN biopsy are controversial. We compared the UICC/TNM definitions of MMs and ITCs with our previously published sentinel node protocol to assess how the adoption of the UICC/TNM criteria would affect the staging of nodal micrometastatic disease. METHODS: Of 107 patients who had a SLN biopsy and pathology at 150 microm intervals, 35 with metastatic tumour were included. Eighty-six SLNs were reassessed using the UICC/TNM definitions for MMs and ITCs. Findings were linked to the final pathology in the subsequent neck dissection. RESULTS: Initial H&E sections showed metastases in 24 patients (in 34 out of 61 SLN), 8 of whom (9 SLNs) had MMs. Additional step serial sections revealed metastatic deposits in a further 11 patients (15 out of 25 SLNs were positive) which were reassessed as MMs (6 patients) or ITCs (5 patients). Subsequent neck dissection revealed additional metastases in 46% of patients with MM, whilst one of the ITC patients had subsequent neck metastases (20%). CONCLUSION: Despite some limitations, the UICC/TNM classification provides an objective, uniform method of detecting MMs and ITC's. Unlike in cases with ITC, metastases in other non-SLNs were common when a micrometastasis was detected in a SLN, indicating need for further treatment of the neck.

The unexpected sites of melanoma regional recurrences.

UNLABELLED: Sentinel node biopsy is a means of identifying nodal involvement in melanoma and lymphoscintigraphy identifies unpredictable sites of melanoma sentinel nodes in up to 25% of cases. Whilst there is a dearth of recent publications in this area, it nevertheless remains an interesting observation that unpredictable sites of sentinel nodes are so common as to be accepted as normal. This study was performed to determine if this high rate of unpredictable lymphatic drainage was reflected in clinical practice, where therapeutic lymph node dissections were performed for pathologically confirmed regional disease. METHODS: Patients undergoing regional lymph node dissections for histologically proven malignant melanoma were identified from a computer database. Patient details were analysed from case records. RESULTS: Two hundred and forty-three case records were examined and 237 were suitable for analysis. The site of the primary was the head and neck in 50 (21%), trunk in 73 (31%), upper limb in 27 (11%) and lower limb in 87 (37%). In 15 cases (6%), the first site of regional disease was unpredictable. In these 15 cases, the site of the primary was the head and neck in two, trunk in 11, upper limb in one and lower limb in one. In 37 cases (16%), a subsequent site of nodal recurrence was unpredictable. Clinicians should be aware that patients with melanomas, particularly of the trunk, especially those in whom a therapeutic nodal dissection has been performed, may have nodal disease at unpredictable sites. However, unexpected sites of regional disease are not as common as sentinel node biopsy would suggest. Guidelines for lymph node examination in cutaneous melanoma are suggested based on these findings.

The nodal neck level of sentinel lymph nodes in mucosal head and neck cancer.

Sentinel node biopsy is emerging as a successful means of identifying subclinical lymph node disease in mucosal head and neck cancer. Sentinel node studies in melanoma and breast cancer have identified sentinel nodes at unusual sites and the technique is redefining our understanding of dynamic lymphatic flow. In this study, the sentinel nodes in mucosal head and neck malignancies were mapped according to their site within the neck and this was correlated with tumour site within the oral cavity. Fifty-two necks were explored for sentinel nodes from tumours located in the tongue (23 cases), floor of mouth (12 cases), palate (six cases), retromolar trigone (five cases), alveolus (three cases), buccal mucosa (two cases), tonsil (two cases) and lip (one case). In total, 124 sentinel nodes were found in levels I-V. Two hot spots were found in the tonsils and were not excised, two nodes were located in level IIB, four nodes were found in level IV, three in the contralateral neck and one in level V. The sentinel nodes located at unusual sites would not have been excised in a supraomohyoid neck dissection and the study has improved our understanding of dynamic lymph flow from tumours.

Improved staging of cervical metastases in clinically node-negative patients with head and neck squamous cell carcinoma.

BACKGROUND: The management of the N0 neck in oral and oropharyngeal cancer is often determined by the risk of metastases related to features of the primary tumor. Where the risk of metastases is >20%, elective neck dissection (END) has been advocated. This study reviewed clinical staging, surgical staging, pathologic staging, and histopathologic parameters to determine the prediction of nodal metastases and micrometastases in patients with head and neck squamous cell carcinoma. METHODS: A prospective series of 61 clinically neck node-negative patients undergoing surgical resection of a T1/2 intraoral or oropharyngeal invasive squamous cell carcinoma and surgical staging of the neck, with sentinel node biopsy (SNB) alone or SNB-assisted END, between June 1998 and March 2002 were included in this study. RESULTS: Pathologic upstaging of the clinically N0 neck occurred in 27 (44%) of 61 patients. Routine pathology with hematoxylin and eosin upstaged disease in 22 of 27 patients (sensitivity of 81%). Five patients with micrometastasis were staged pN1mi after stepped serial sectioning and immunohistochemistry. Tumor thickness, a noncohesive invasive front, and perineural and bone invasion were all histological predictors for cervical metastases. Five patients with micrometastases were staged pN1mi. CONCLUSIONS: Both clinical staging and routine pathologic staging underestimate the presence of nodal metastases. Staging with either SNB alone or SNB-assisted END shows promise in the management of the N0 neck by identifying patients with micrometastases (pN1mi).

The impact of immunohistochemistry on sentinel node biopsy for primary cutaneous malignant melanoma.

Sentinel node biopsy (SNB) has emerged as an accurate means of identifying nodal disease in patients with malignant melanoma. Superselection of pathological nodes has allowed improved pathological staging of disease. The aim of this study was to look at the impact of immunohistochemistry on pathological staging of sentinel nodes. The first 100 patients undergoing SNB for primary cutaneous malignant melanoma were included in this study. Sentinel node harvesting was performed with the aid of preoperative lymphoscintigraphy and the intraoperative use of both a gamma probe and blue dye. If the sentinel nodes contained tumour on either routine pathology or immunohistochemistry, patients were offered a therapeutic lymph node dissection (TLND). Patients underwent no other treatment to the primary lymph node basin if the sentinel node was free of metastases. In all, 95 patients had at least one node identified, and 25 were staged SNB positive and offered subsequent TLND. We found that 76% (19/25) of SNB positive patients were staged positive on routine pathology, and 24% (6/25) were staged with immunohistochemistry. Immunohistochemistry upstaged disease in 8% of patients (6/76). In all, 21 of the patients staged positive with SNB underwent TLND; 50% (8/16) of the patients staged sentinel node positive with routine pathology showed no further disease in the TLND, compared with 100% (5/5) of the patients staged sentinel node positive with immunohistochemistry only (P<0.05). Three patients have developed recurrence within the nodal basin following a negative SNB. The sensitivity of the procedure is currently 89% (25/28), with a mean follow-up of 24 months. Immunohistochemistry is an essential part of identifying micrometastasis in sentinel nodes, upstaging 8% of patients in our series. Patients with micrometastatic disease may well have a different prognosis from those with occult disease, and careful delineation of these patients is required to determine the prognostic influence of micrometastasis.

The learning curve for sentinel node biopsy in malignant melanoma.

Sentinel node biopsy (SNB) has emerged as an accurate means of identifying nodal micrometastasis in cutaneous melanoma. In order to assess our learning curve, we compared our first 30 cases with our subsequent 30 cases. A total of 60 patients underwent SNB for cutaneous melanoma, using preoperative lymphoscintigraphy together with the intraoperative use of a Neoprobe and Patent Blue V dye. At least one sentinel node was identified in 93% of patients (90% in our first 30 cases; 97% in our subsequent 30 cases). Sentinel nodes contained tumour in 21% of cases. Of the sentinel nodes that contained tumour in the first 30 cases, 87% were identified by Neoprobe examination and 60% using blue dye. In the second 30 cases, the tumour-containing sentinel nodes were identified in all cases by both the Neoprobe and the blue dye. The sentinel node appeared to be the only involved node in 71% of patients. In the first 30 patients, one patient with a negative sentinel node developed nodal recurrence. These data confirm the feasibility of the sentinel-node technique in cutaneous melanoma. However, there is a learning curve, and the technique should be performed only by limited numbers of people with suitable training.

The First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer and adoption of a multicenter trial protocol.

BACKGROUND: Sentinel node biopsy (SNB) is a new technique in staging the clinically N0 neck. On June 25 and 26, 2001, the First International Conference on Sentinel Node Biopsy in Mucosal Head and Neck Cancer took place in Glasgow, United Kingdom. METHODS: Twenty-two centers contributed results on the use of SNB as a staging tool in head and neck squamous cell carcinoma. The pathology of the sentinel node was compared with that of the pathologic neck specimen. RESULTS: Three hundred sixteen clinically N0 necks were included. Sentinel nodes were identified in 301 necks (95%). Of these 301 necks, 76 necks were staged positive with SNB, and 225 were staged negative. The overall sensitivity of the procedure was 90%. Centers who had performed < or = 10 cases had a lower sensitivity (57%), discovering only 4 of 7 metastatic nodes, in comparison with 72 of 77 metastatic nodes discovered for centers that had performed >10 cases (sensitivity, 94%). CONCLUSIONS: The cumulative results of all those who contributed to the first international conference confirm that there is a role for SNB for staging the clinically N0 neck, and it has a similar sensitivity to that of a staging neck dissection.

A suggested method for sentinel node biopsy in squamous cell carcinoma of the head and neck.

BACKGROUND: Debate continues over the management of the N0 neck in head and neck malignancy. Therefore, the possibility of performing sentinel node biopsy in these patients was investigated to formulate a method for the procedure. METHODS: Patients undergoing prophylactic or therapeutic neck dissections were injected with either Patent Blue V dye alone or with blue dye and 99m-Tc labeled Albures. The latter group underwent preoperative lymphoscintigraphy. During surgery, blue stained lymphatics were followed to blue nodes, and a neoprobe was used to identify radioactive nodes. RESULTS: In 5 of 13 patients receiving blue dye, a blue node was identified, but none contained tumor. Metastases were identified in other neck nodes in 3 of 5. Sentinel nodes were identified in 15 of 16 patients receiving dye, and Albures. Sentinel node biopsy was accurate in 7 of 7 necks containing impalpable metastases when all nodes had been evaluated after dissection. DISCUSSION: Sentinel node biopsy using blue dye and radiocolloid may prove to be a reliable technique in the N0 neck and warrants further investigation.

The accuracy of head and neck carcinoma sentinel lymph node biopsy in the clinically N0 neck.

BACKGROUND: Sentinel lymph node (SLN) biopsy originally was described as a means of identifying lymph node metastases in malignant melanoma and breast carcinoma. The use of SLN biopsy in patients with oral and oropharyngeal squamous cell carcinoma and clinically N0 necks was investigated to determine whether the pathology of the SLN reflected that of the neck. METHODS: Patients undergoing elective neck dissections for head and neck squamous cell carcinoma accessible to injection were enrolled into our study. Sentinel lymph node biopsy was performed after blue dye and radiocolloid injection. Preoperative lymphoscintigraphy and the perioperative use of a gamma probe identified radioactive SLNs; visualization of blue stained lymphatics identified blue SLNs. A neck dissection completed the surgical procedure, and the pathology of the SLN was compared with that of the remaining neck dissection. RESULTS: Sentinel lymph node biopsy was performed on 40 cases with clinically N0 necks. Twenty were pathologically clear of tumor and 20 contained subclinical metastases. SLNs were found in 17 necks with pathologic disease and contained metastases in 16. The sentinel lymph node was the only lymph node containing tumor in 12 of 16. CONCLUSIONS: The SLN, in head and neck carcinomas accessible to injection without anesthesia, is an accurate reflector of the status of the regional lymph nodes, when found in patients with early tumors. Sentinel lymph nodes may be found in clinically unpredictable sites, and SLN biopsy may aid in identifying the clinically N0 patient with early lymph node disease. If SLNs cannot be located in the neck, an elective lymph node dissection should be considered.