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Biomedical subjects

A G Robertson

Publications and source records attributed to A G Robertson.

At least 19 recordsLinked to original sources
PubMed2004

Histological changes in radial forearm skin flaps in the oral cavity.

We reported previously that skin flaps transplanted to the oral cavity in reconstructive surgery for oral cancer frequently acquired the gross appearance of buccal mucosa. The changes were shown to be reactive in nature. The "changed" flaps generally had a heavier infiltration of leukocytes in the dermis and appeared to have thicker epithelium. The present study quantifies these parameters, as well as the numbers of intraepithelial leukocytes. The flaps that had acquired the gross appearance of oral mucosa had significantly thicker epithelium, larger numbers of dermal leukocytes, and more intraepidermal inflammatory cells per unit length than flaps that retained the gross appearance of thin skin. No correlation was found between these changes and radiotherapy.

Adult↗
PubMed2004

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).

Carcinoma, Squamous Cell↗
PubMed2002

Practical methods for compensating for missed treatment days in radiotherapy, with particular reference to head and neck schedules.

Unscheduled interruption of a radiotherapy treatment can lead to significant loss in local tumour control, particularly in tumours that repopulate rapidly. General guidelines for dealing with such treatment gaps have been issued by the Royal College of Radiologists and more specific advice on the use of compensation methods has been published previously [Hendry et al., Clin Oncol 1996;8:297-307; Slevin et al., Radiother Oncol 1992;24:215-220]. This article further elaborates on the practical application of these methods. It sets out the main considerations arising in the especially critical case of head and neck treatments and simple calculations are used to illustrate the approaches which may be adapted for particular situations. Radiobiological parameter values are suggested for use in the calculations, but these may require modification in the light of further research in this important area.

Appointments and Schedules↗
PubMed2002

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.

Carcinoma, Squamous Cell↗
PubMed2002

Vaccine development: the biological weapon imperative.

The biological warfare capabilities of state and non-state actors continue to grow worldwide, both in sophistication and breadth. More than a dozen nations, including Iraq, Iran, Libya, Syria and North Korea, are either actively pursuing or possess biological weapons for use against their enemies. There is also a heightened awareness of the use of such agents by terrorist groups, a possibly deleterious side-effect of an increased awareness by the general public. This paper looks at the growing threat of the use of biological agents by both national programmes and non-state actors, the possible agents which might be considered for use, and the potential role that vaccine development may have in protecting both military and civilian populations against biological weapons attacks in the future.

Biological Warfare↗
PubMed2001

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.

Adult↗
PubMed2001

Identification and structure of the nerve growth factor binding site on TrkA.

Nerve growth factor (NGF) is involved in the development and maintenance of the nervous system and has been implicated as a possible therapeutic target molecule in a number of neurodegenerative diseases, especially Alzheimer's disease. NGF binds with high affinity to the extracellular region of a tyrosine kinase receptor, TrkA, which comprises three leucine-rich motifs (LRMs), flanked by two cysteine-rich clusters, followed by two immunoglobulin-like (Ig-like) domains. We have expressed the second Ig-like domain as a recombinant protein in E. coli and demonstrate that NGF binds to this domain with similar affinity to the native receptor. This domain (TrkAIg(2)) has the ability to sequester NGF in vitro, preventing NGF-induced neurite outgrowth, and in vivo, inhibiting NGF-induced plasma extravasation. We also present the three-dimensional structure of the TrkAIg(2) domain in a new crystal form, refined to 2.0 A resolution.

Animals↗
PubMed2001

Recombinant human nerve growth factor for clinical trials: protein expression, purification, stability and characterisation of binding to infusion pumps.

Nerve growth factor (NGF) has been suggested to be of therapeutic benefit to patients with Alzheimer's disease. One of the early changes in this disease is a loss of cholinergic function within the brain, and NGF is able to rescue cholinergic neurons both in vitro and in vivo. We describe the production of recombinant human beta-NGF (rhNGF), using baculovirus infection of insect cells; its purification, formulation and subsequent stability for use in clinical trials. Tests were also carried out to monitor release of protein from infusion pumps and catheters for intracerebroventricular administration (icv). Initial problems with non-specific binding were overcome using a blocking formula.

Animals↗
PubMed2001

Specificity in Trk receptor:neurotrophin interactions: the crystal structure of TrkB-d5 in complex with neurotrophin-4/5.

BACKGROUND: The binding of neurotrophin ligands to their respective Trk cellular receptors initiates intracellular signals essential for the growth and survival of neurons. The site of neurotrophin binding has been located to the fifth extracellular domain of the Trk receptor, with this region regulating both the affinity and specificity of Trk receptor:neurotrophin interaction. Neurotrophin function has been implicated in a number of neurological disorders, including Alzheimer's disease and Parkinson's disease. RESULTS: We have determined the 2.7 A crystal structure of neurotrophin-4/5 bound to the neurotrophin binding domain of its high-affinity receptor TrkB (TrkB-d5). As previously seen in the interaction of nerve growth factor with TrkA, neurotrophin-4/5 forms a crosslink between two spatially distant receptor molecules. The contacts formed in the TrkB-d5:neurotrophin-4/5 complex can be divided into a conserved area similar to a region observed in the TrkA-d5:NGF complex and a second site-unique in each ligand-receptor pair-formed primarily by the ordering of the neurotrophin N terminus. CONCLUSIONS: Together, the structures of the TrkB-d5:NT-4/5 and TrkA-d5:NGF complexes confirm a consistent pattern of recognition in Trk receptor:neurotrophin complex formation. In both cases, the N terminus of the neurotrophin becomes ordered only on complex formation. This ordering appears to be directed largely by the receptor surface, with the resulting complementary surfaces providing the main determinant of receptor specificity. These features provide an explanation both for the limited crossreactivity observed between the range of neurotrophins and Trk receptors and for the high-affinity binding associated with respective ligand-receptor pairs.

Amino Acid Motifs↗
PubMed2001

Treatment of oral cancer: the need for defined protocols and specialist centres. variations in the treatment of oral cancer.

The authors of this study aimed to identify treatment philosophies for oral cancer within the west of Scotland and to investigate any survival differences associated with the various treatment options by means of a retrospective review of case notes and cancer registry data. All patients with squamous cancer of the tongue or floor of the mouth were identified from the West of Scotland Cancer Registry for the period 1984-1990. A total of 206 patients were available for study. Five different treatment protocols were identified: 5% of patients underwent biopsy only, 16% biopsy plus radiotherapy, 11% excisional biopsy, 25% radical surgery, and 42% radical surgery plus radiotherapy. Tumour staging by the TNM classification was an important factor that determined outcome. When adjusting for T stage and nodal involvement, there was a significant effect of treatment protocol on both the disease-free period (P < 0.001) and on survival (P < 0.001). The treatment options were used differently by individual clinicians and were related to stage of the disease. One hundred and forty-four (70%) of the patients were treated by a single combined head and neck unit based within the plastic surgery unit at Canniesburn Hospital. The remaining 62 were treated in 13 different units throughout the west of Scotland. For those not treated in the combined head and neck unit, the increased hazard for recurrence was 1.43 (95% confidence interval (CI) 1.01-2.02), and the increased hazard ratio for death was 1.48 (95% CI 1.06-2.06) when adjusting for tumour stage, and nodal involvement. Treatment philosophies for oral cancer have a significant effect on outcome. There is a need to develop clearly defined protocols based on staging and site of disease. We believe that treatment should be carried out within a multidisciplinary setting in a combined head and neck cancer unit.

Adult↗
PubMed2001

Increasing dietary supervision can reduce weight loss in oral cancer patients.

Weight loss after treatment for intraoral malignancy is common and can impair patient recovery and wound healing. We report a reduction in weight loss in patients undergoing combined-modality treatment (surgery + radiotherapy) after an increase in dietary supervision and changes to the patient dietary protocol. Two groups of patients were compared: Group I received treatment before the protocol changes, and Group II received treatment after the changes took effect. After surgery the average weight loss for Group I was 3.67% compared with 2.42% for Group II (P < 0.05), after radiotherapy the average weight loss for Group I was 6.56% compared with 4.83% for Group II (P < 0.05), and after combined-modality treatment the average weight loss for Group I was 9.83% compared with 6.6% for Group II (P < 0.05). The successful protocol changes included increased supervision of patients by the dedicated head-and-neck team dietitian when patients were undergoing radiotherapy, including the period between completion of surgery and commencement of radiotherapy. The period of time spent without specialist dietary supervision was therefore reduced. Specific guidelines were devised to allow for increased dietary input when required, specifically, if patients lost weight for > or = 2 wk or if they were being fed enterally. These changes were made after an audit that demonstrated that severe weight loss in this group of patients was common. We have demonstrated that regular appraisal of weight loss in this group of patients is valuable and that this weight loss can be reduced if appropriate action is taken.

Adult↗
PubMed2000

Identification of syntaxin 1A as a novel binding protein for presenilin-1.

Mutations in the presenilin 1 gene have been shown to result in Alzheimer's disease. Presenilin 1 is a multi-transmembrane protein with a large hydrophilic loop near the C-terminus. This region is required for known functions of presenilin 1. We have constrained this loop within the active site of the bacterial protein, thioredoxin, to mimic its native conformational state. This hybrid protein was used as bait in a yeast two hybrid screen in an attempt to identify presenilin binding proteins. By this method syntaxin 1A, a synaptic plasma membrane protein, was identified as a novel binding protein for presenilin 1. In vitro experiments confirm the two-hybrid results suggesting that PS1 binds syntaxin under physiological conditions.

Alzheimer Disease↗
PubMed2000

Natural history and patterns of recurrence of tongue tumours.

This retrospective study comprises 226 patients with squamous cell carcinoma of the tongue treated at Canniesburn Hospital, Glasgow between 1980 and 1996. The male:female ratio was 1.2:1 and the average age was 64 years. The ratio of anterior 2/3 to posterior 1/3 tongue lesions was 1.8:1. A total of 23% of patients were clinically staged as T1, 50% were T2 and 27% were T3/T4. At presentation 156 patients (69%) had a clinically negative neck, while 110 patients (49%) had a neck dissection at the time of treatment of the primary. A comparison between the clinical and pathological T and N stages highlighted the difficulties of clinical TNM staging with upstaging of the primary T stage in 21% of patients and downstaging in 6% and upstaging of neck disease in 36% and downstaging in 7.7%. The incidence of clinically occult disease in the neck was 41% including six patients (4.5%) with occult disease in the contralateral neck.

Adult↗
PubMed2000

A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer.

An E1B 55 kDa gene-deleted adenovirus, Onyx-015, which reportedly selectively replicates in and lyses p53-deficient cells, was administered by a single intratumoral injection to a total of 22 patients with recurrent head and neck cancer. The objectives of this Phase I study were to determine the safety, feasibility, and efficacy of this therapy and determine any correlation to p53 status. Six cohorts were investigated with a dose escalation from 10(7)-10(11) plaque-forming units. Toxicity was assessed using NCIC criteria. Tumor response was assessed by clinical and radiological measurement. Blood samples were taken to detect adenovirus DNA and neutralizing antibody to adenovirus. Tumor biopsies were taken to detect adenovirus by in situ hybridization. Treatment was well tolerated, with the main toxicity being grade 1/2 flu-like symptoms. Dose-limiting toxicity was not reached at the highest dose of 10(11) plaque-forming units. Twenty-one of the 22 patients treated showed an increase in neutralizing antibody to adenovirus. In situ hybridization showed viral replication in 4 of 22 patients treated, all of whom had mutant p53 tumors. Using conventional response criteria, no objective responses were observed. However, magnetic resonance imaging scans were suggestive of tumor necrosis at the site of viral injection in five patients, three of whom were classified using nonconventional criteria as partial responders, and two of whom were classified using nonconventional criteria as minor responders. Of these five cases, four had mutant p53 tumors. The response duration for the three partial responders was 4, 8, and 12 weeks. An additional eight patients had stable disease in the injected tumors lasting from 4-8 weeks. These preliminary results show that intratumoral administration of Onyx-015 is feasible, well tolerated, and associated with biological activity. Further investigation of Onyx-015, particularly with a more frequent injection protocol and in combination with systemic chemotherapy, is warranted.

Adenovirus E1B Proteins↗
PubMed1999

Improved survival for patients with clinically T1/T2, N0 tongue tumors undergoing a prophylactic neck dissection.

BACKGROUND: Prophylactic surgical treatment of the neck in "early tongue tumors" is a controversial issue. METHODS: From a database of 226 patients with squamous cell carcinoma of the tongue treated at Canniesburn Hospital, Glasgow, U.K., between 1980 and 1996, a total of 137 patients with a minimum follow up of 24 months or until death were clinically identified as being T1/T2, N0 (UICC) when first seen. These patients were divided into three groups according to the management of the neck; 53 patients did not have a neck dissection at any time (NKD0), 47 patients underwent a synchronous neck dissection at the time of treatment of the primary (NKDS), and 37 patients subsequently required a metachronous neck dissection when lymph node metastasis became clinically apparent (NKDM). These three groups were compared with respect to age, sex, site, duration of symptoms, previous treatment (if any), initial treatment protocol, resection margin, type of neck dissection (if any), loco-regional recurrence, systemic escape, number of positive lymph nodes, and presence of extracapsular spread. Disease-related survival was calculated using Kaplan-Meier survival curves with logrank test and chi-square statistical analysis. RESULTS: The pT stage was upgraded to T3/4 in 3/53 patients (6%) of the NKD0 group, 11/47 patients (23%) of the NKDS group, and 2/37 patients (5%) of the NKDM group (p < 0.001). The 5-year determinate survival rates for the three groups were: NKD0 59.7%, NKDS 80.5%, NKDM 44.8%, and (NKD0 + NKDM) 53.6% with a statistically significant improvement in survival for NKDS vs NKDM (logrank 10.58, p = 0.001) and for NKDS vs (NKD0 + NKDM) (logrank 6.06, p = 0.014). The incidences of positive nodes in the NKDS and NKDM groups were 18/47 patients (38%) and 32/37 patients (86%) respectively. Neck positive patients in the NKDM group had a significantly greater number of positive nodes in comparison with N positive patients in the NKDS group (chi trend, p = 0.001), a higher incidence of extracapsular spread, 30/32 vs 9/18 (chi test, p < 0. 0001), and decreased survival. The incidence of occult cervical metastasis for the whole group was 41%. CONCLUSION: Patients with clinical T1/2, N0 tongue tumors who underwent a synchronous neck dissection had an improved survival outcome even though as a group they had a higher incidence of occult metastasis, relatively more T2 lesions, a worse pT stage, and had more posterior third lesions requiring more difficult initial surgery. Tongue tumors have a high incidence of subclinical nodal disease, which is less curable when it presents clinically. The information gleaned from the nodal status allows a more informed plan of adjuvant therapy.

Adult↗
PubMed1999

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.

Biopsy↗
PubMed1999

Interstitial iridium-192 implantation for recurrent and/or locally advanced head and neck cancer.

We report our experience with the use of interstitial iridium-192 implantation in the management of patients with recurrent and locally advanced squamous cell carcinoma of the head and neck. Between June 1992 and July 1998 this technique was employed in the management of two groups of patients: (1) a primary group, comprising 42 patients who had presented for the first time with advanced head and neck disease, and had therefore not undergone any previous treatment; and (2) a salvage group of 16 patients with recurrent disease previously treated with external beam radiotherapy (four received therapy to the neck, one to the cheek, eight to the tongue and three to the floor of the mouth). The follow-up in each group was short, ranging from 3 to 56 months. The overall response in the primary group was 38/42 (90%). A complete response was achieved in 35/42 (83%). In the salvage group, the overall response was 13/16 (81%); 4/16 (25%) showed a complete response and 9/16 (56%) a partial response. The estimated percentage surviving at 1 year for patients with primary disease is 70% (95% confidence interval (CI) 54-86). For those receiving salvage therapy the estimated percentage surviving at 1 year is 45% (95% CI 19-71).

Adult↗