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Biomedical subjects

J W Grant

Publications and source records attributed to J W Grant.

At least 19 recordsLinked to original sources

Primary central nervous system lymphoma: a single-centre experience of 55 unselected cases.

AIMS: Current treatment for primary central nervous system lymphoma (PCNSL) involves high-dose methotrexate (HDMTX) with or without radiotherapy. Many published studies describing this approach include a highly selected group of patients. We report a single-centre experience of unselected cases of PCNSL. MATERIALS AND METHODS: We retrospectively reviewed the case notes of 55 consecutive patients diagnosed with biopsy-proven PCNSL between 1995 and 2003 at Addenbrooke's Hospital Cambridge, UK. We describe the treatment and outcome, including survival, treatment-related toxicity and long-term functional disability. RESULTS: At diagnosis, 45% of patients were considered unfit to receive treatment with HDMTX, owing to poor performance status or comorbidity. These patients had a median survival of 46 days and may not have been included in other published studies. The remaining patients were treated with a chemotherapy regimen, which included HDMTX. Patients who received at least one cycle of a chemotherapy containing HDMTX had a median survival of 31 months. Forty per cent did not complete planned chemotherapy owing to toxicity, disease progression or death. The median survival of patients treated with HDMTX aged 60 years compared with patients aged under 60 years was 26 months vs 41 months (P = 0.07), respectively. Younger patients treated with HDMTX, who achieved complete remission with chemotherapy, had a median survival of 56 months. We identified a high incidence of functional disability among survivors, resulting from a combination of the tumour itself, the neurosurgical procedure required for diagnosis and the late neurotoxicity of combined chemoradiotherapy. CONCLUSION: The treatment of PCNSL is associated with significant early and late toxicity. Further attempts to improve treatment should address mechanisms to reduce this toxicity. In particular, the benefit of radiotherapy in patients who achieve complete remission with HDMTX will remain uncertain until it is addressed in a multicentre, randomised trial.

Adult↗

Cutaneous metastases from a hypopharyngeal malignancy.

We present an unusual case of carcinoma of the piriform fossa, presenting with cutaneous metastases. These metastases are very rare, present in the late stages of disease, and are usually associated with distant metastases and poor prognosis. They often suggest aggressive disease. We believe that cutaneous metastases from a malignancy in the piriform fossa are more unusual than those from other sites of the head and neck.

Carcinoma, Squamous Cell↗

Effect of fluid forcing on vestibular hair bundles.

A dynamic 3-D hair bundle model including inertia and viscous fluid drag effects based on the finite element method is presented. Six structural components are used to construct the hair bundle--kinocilium, stereocilia, upper lateral links, shaft links, tip links, and kinocilial links. Fluid drag is distributed on the surface of cilia columns. Bundle mechanics are analyzed under two distinct loading conditions: (1) drag caused by the shear flow of the surrounding endolymph fluid (fluid-forced), (2) a single force applied to the tip of the kinocilium (point-forced). A striolar and a medial extrastriolar vestibular hair cell from the utricle of a turtle are simulated. The striolar cell bundle shows a clear difference in tip link tension profile between fluid-forced and point-forced cases. When the striolar cell is fluid forced, it shows more evenly distributed tip link tensions and is far more sensitive, responding like an on/off switch. The extrastriolar cell does not show noticeable differences between the forcing types. For both forcing conditions, the extrastriolar cell responds serially--the nearest tip links to the kinocilium get tensed first, then the tension propagates to the farther tip links.

Algorithms↗

Malignant eccrine poroma in breast cancer-related lymphoedema.

We describe the first case of malignant eccrine poroma arising in a lymphoedematous site. The patient had long-standing lymphoedema of the upper limb following breast cancer treatment. Lymphoedema is a recognised complication of breast cancer treatment and a risk factor for the subsequent development of malignancy. Possible mechanisms for this are discussed.

Aged↗

Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions.

Histological classification of laryngeal epithelial lesions is highly subjective, and methods of cytological detection are not well developed. Improved determination of aberrant cell cycle entry may allow increased objectivity in histological assessment and enable the development of less invasive diagnostic cytology tests. Sections of normal larynx (n=10), laryngeal dysplasia (n=20) and laryngeal squamous cell carcinoma (SCC) (n=10) were classified according to the Ljubljana classification and stained for markers of cell cycle entry, minichromosome maintenance protein-2 (Mcm-2) and Ki67. Expression patterns were compared using double labelling confocal microscopy. There was a correlation between Mcm-2 and Ki67 labelling indices (rho=0.93; 95% CI [0.84, 0.97]) and both markers showed increased expression from normal epithelium to SCC (Mcm-2, P=0.001; Ki67, P=0.0002). Importantly, there was minimal expression of Mcm-2 or Ki67 in the most superficial layers of normal larynx and abnormal or atypical hyperplasia, in contrast to carcinoma in situ and SCC. Clusters of Mcm-2/5-positive cells were present in cytological preparations from SCC, but not from those showing atypical hyperplasia or inflammation in non-neoplastic tissue. Minichromosome maintenance protein-2 staining may increase the objectivity and reliability of histological grading of laryngeal epithelial lesions. Laryngeal brushings, combined with immuno-enhanced liquid-based cytology, could be useful, as a less invasive approach, to the detection of laryngeal malignant and premalignant lesions.

Antigens, Neoplasm↗

Spread of a recurrent lentigo maligna into a graft: a case for conservative treatment.

Lentigo maligna is an in situ malignant melanoma for which the treatment of choice is surgical excision. The recurrence rate in lentigo maligna is high and hence other treatments, such as cryotherapy, laser therapy, radiotherapy and Mohs' chemosurgery, have been described. Despite the high recurrence rate, spread of a lentigo maligna into a skin graft is rare. We describe a case of a recurrent lentigo maligna spreading into a skin graft, which, along with the cases described in the literature, highlights the presence of a group of low-grade malignant lentiginous lesions that may be managed by careful follow-up and observation.

Aged↗

Influence of an interdental full pin on stability of an acrylic external fixator for rostral mandibular fractures in dogs.

OBJECTIVE: To determine total stiffness and gap stiffness of an external fixation system in a canine mandibular fracture gap model incorporating a full interdental pin as the only point of rostral fixation in a bilateral type-I external fixator. SAMPLE POPULATION: 10 canine mandibles. PROCEDURE: Bilateral mandibular ostectomies were performed between premolars 3 and 4. A type-I external fixator incorporating a full interdental pin was placed to stabilize a 0.5-cm fracture gap. Four pin configurations (intact mandibular bodies with fixator; ostectomized mandibular bodies and complete fixator; ostectomized mandibular bodies with caudal pins of rostral fragment cut; ostectomized mandibular bodies with all pins of rostral fragment cut) were tested in dorsoventral bending 5 times on each mandible. The full interdental pin remained intact in all configurations. Total stiffness and gap stiffness were determined for each configuration on a materials testing machine. RESULTS: Total stiffness of intact mandibles was significantly greater than that of ostectomized mandibles, regardless of external fixator configuration. However, total stiffness and gap stiffness were not significantly different among different external fixator configurations applied to ostectomized mandibles. CONCLUSION AND CLINICAL RELEVANCE: External fixator configurations with only the full interdental pin engaging the rostral fragment were as stiff as configurations that had 2 or 4 additional pins in the rostral fragment for the applied loads. External fixators for rostral mandibular fractures may be rigidly secured with rostral fragment implants applied extracortically, avoiding iatrogenic trauma to teeth and tooth roots.

Animals↗

The use of ultrasound-guided cutting-needle biopsy in paediatric neck masses.

OBJECTIVE: Neck masses are common in children. Although there is a low incidence of therapeutically significant pathology, biopsy is occasionally required for evaluation. Open biopsy or fine needle aspiration may be used to obtain tissue. Open biopsy provides material suitable for histological analysis but requires general anaesthesia. Cytological material obtained by fine needle aspiration is often inconclusive. A core of histological material may also be obtained by percutaneous cutting-needle biopsy, a recognised procedure at other anatomical sites, usually performed under local anaesthesia. MATERIALS AND METHODS: There are few accounts using cutting needles in adult neck masses and no previous paediatric series. We present our experience of ultrasound-guided core biopsies of neck masses in 15 children ranging in age from three months to 16 years. RESULTS: Thirteen biopsies were easily performed without sedation as an outpatient procedure under topical and injected local anaesthetic. In all fifteen cases the procedure was well tolerated and a tissue successfully obtained. CONCLUSION: Ultrasound guided cutting needle biopsies of head and neck masses of children can be performed under local anaesthesia in the majority of cases.

Adolescent↗

A finite element method for mechanical response of hair cell ciliary bundles.

This paper describes the development of a methodology for performing a mechanical analysis of hair cell ciliary bundles. The cilia were modeled as shear deformable beams, and interconnections were modeled as two-force members. These models were incorporated into software, which performs a finite element analysis of a user-defined bundle. The algorithm incorporates aspects of the bundle such as geometric realignment and buckling of compressed side links. A sample bundle is introduced and results of modeling it are presented.

Actins↗

Management of neck lumps--a triage model.

We report our experience in the out-patient triage of 100 patients presenting with a lump in the neck. The out-patient visit consisted of a general history and examination, assessment of the upper air and food passages and, where indicated, ultrasound and core needle biopsy of the lump. Other investigations were performed as appropriate. One hundred neck lump patients were seen in a 9 month period. Ninety-six of these lumps were diagnosed on an out-patient basis, only four requiring admission for formal excision biopsy. Among the diagnoses were eleven lymphomas, nine parotid neoplasms, nine lymph node metastases, five thyroglossal cysts, and four branchial cysts. Almost half the patients seen had either a reactive lymphadenopathy, or no abnormality. The establishment of a tissue diagnosis on an out-patient basis allowed appropriate referrals to be made and management plans to be formulated. The theoretical risk of seeding of malignant cells in the needle tract is acknowledged and discussed.

Adolescent↗

Extrinsic Fabry-Perot interferometer for measuring the stiffness of ciliary bundles on hair cells.

We have developed an extrinsic Fabry-Perot interferometer (EFPI) to measure displacements of microscopic, living organelles in the inner ear. The EFPI is an optical phase-shifted instrument that can be used to measure nanometer displacements. The instrument transmits a coherent light signal to the end of a single glass optical fiber where the measurement is made. As the coherent light reaches the end of the fiber, part of this incident signal is reflected off the internal face of the fiber end (reference reflection) and part is transmitted through the end of the fiber. This transmitted light travels a short distance and is reflected off the surface whose displacement is to be measured (the target). This sensing reflection then reenters the fiber where it interferes with the reference reflection. The resulting interference signal then travels up the same optical fiber to a detector, where it is converted into a voltage that can be read from an oscilloscope. When the target moves, the phase relation between reference and sensing reflections changes, and the detector receives a modulated signal proportional to the target movement. Reflections of as little as 1% at both the sensor tip and target surfaces produce good results with this system. We use the EFPI in conjunction with fine glass whiskers to measure the stiffness (force per unit deflection) of stereociliary bundles on hair cells of the inner ear. The forces generated are in the tenths of picoNewton range and the displacements are tens of nanometers. Here we describe the EFPI and its development as a method for measuring displacements of microscopic organelles in a fluid medium. We also report experiments to validate the accuracy of the EFPI output and preliminary measurements of ciliary bundle stiffness in the posterior semicircular canal.

Animals↗

The histopathology of de Quervain's disease.

The histopathological appearances of the tendon sheath and synovium from 23 patients treated surgically for de Quervain's disease are described and compared with 24 controls. The condition was not characterized by inflammation, but by thickening of the tendon sheath and most notably by the accumulation of mucopolysaccharide, an indicator of myxoid degeneration. These changes are pathognomonic of the condition and are not seen in control tendon sheaths. The term 'stenosing tenovaginitis' is a misnomer and we believe that de Quervain's disease is a result of intrinsic, degenerative mechanisms rather than extrinsic, inflammatory ones.

Adult↗