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Biomedical subjects

M D Graham

Publications and source records attributed to M D Graham.

At least 19 recordsLinked to original sources

Isolation of a lactoferrin cDNA clone and its expression in human breast cancer.

A cDNA library constructed from mRNA from a human breast carcinoma metastasis was screened with a polyclonal antibody to deglycosylated human milk fat globule membrane, resulting in the isolation of eight clones from a total of 10(5) plaques. One of these (J16) was identified as lactoferrin. It was highly expressed (as a 2.5 Kb mRNA) in lactating breast and in both normal resting tissue taken from adjacent to carcinoma or from reduction mammoplasties. Immunoreactive lactoferrin was localised to ductal cells and their secretions in both normal and mildly hyperplastic ducts. In a normal tissue screen J16 was highly expressed in stomach, poorly in skin and lymphocytes and absent from other organs examined. It was variably expressed in 33/59 invasive primary breast tumours; lactoferrin protein in these was heterogeneously distributed in epithelial tumour foci. Presence of J16 was inversely related to expression of oestrogen receptor protein (P = 0.0001). There was no significant relationship to other clinical parameters. We also found immunoreactivity in 20/41 (49%) cases of ductal carcinoma in situ. Expression was not observed in any breast or gastric cell line examined. Thus lactoferrin appears to be down regulated in some forms of cancer. The presence of lactoferrin could be a contraindication for effective endocrine therapy.

Biomarkers, Tumor

Patterns of vestibular function following vestibular nerve section.

Bithermal caloric irrigations, low-frequency rotational chair stimulation, and posturography were performed on 20 patients before and after vestibular nerve section. Twelve patients demonstrated acute postoperative spontaneous nystagmus and rotational vestibulo-ocular reflex (VOR) asymmetry. Eight patients demonstrated minimal acute postoperative spontaneous nystagmus and VOR asymmetry. Four patients had suppression of all vestibular function characterized by an absent contralateral caloric response, low VOR gain, and falls on posturography when required to rely solely on vestibular input to maintain posture. Four patients had a severe preoperative vestibular loss and no acute change in vestibular function following surgery. Over time, 5 patients continued to manifest elevated spontaneous nystagmus, 2 patients manifested a persistent rotational VOR asymmetry, and 5 patients exhibited a return of caloric function in the operated ear. It is suggested that multiple clinical factors contributed to the variable vestibular responses demonstrated in this study.

Adult

Operative management of acoustic neuromas: the priority of neurologic function over complete resection.

The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post-operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity.

Adult

Comparison of computerized tomography and magnetic resonance imaging for the postoperative assessment of residual acoustic tumor.

Ten patients with surgically confirmed residual cerebellopontine angle neuromas, imaged by both computerized tomography (CT) with iodine contrast and magnetic resonance (MR) with and without gadolinium enhancement, are reviewed to identify the strengths and limitations of MR as compared with CT imaging. MR imaging offers superior anatomic resolution in multiple imaging planes without ionizing radiation, but it is expensive and has adverse effects on some patients. CT imaging offers good anatomic resolution, but in only one or two planes. CT is both less expensive and generally well tolerated, but allergy to the iodine contrast is not uncommon. The cases presented demonstrate the adequacy of CT imaging of residual tumor. However, in some cases MR imaging provided important additional detail. MR imaging also demonstrated postoperative changes within the brain stem and cerebellum. In our experience, CT imaging remains a satisfactory, unambiguous approach to the assessment of known postoperative residual cerebellopontine angle neuromas. MR imaging provides superior resolution, however, and should be used when better definition of tumor detail is needed for management decisions or when multiple follow-up scans are anticipated, so that the exposure to ionizing radiation is limited. MR is also useful to investigate postoperative neurologic dysfunction. Postoperative changes and residual tumors are more difficult to interpret on MR than on CT. Guidelines are proposed to help distinguish residual tumor from postoperative changes and scarring.

Adult

Clinical assessment of postural stability following vestibular nerve section.

Little is known about the recovery of postural control in patients following acute vestibular loss. This paper reports on the results of moving-platform posturography to assess the recovery of postural stability in 24 patients following vestibular nerve section. Posturography was abnormal prior to surgery in 17% of the patients. Seven days following surgery, 44% of the patients demonstrated vestibular deficit patterns, while 56% of the patients had normal posturography. Posturography was normal in all patients 1 month following surgery. Abnormal posturography was subsequently noted in 21% of the patients between 3 and 20 months following surgery. Each of the patients with abnormal preoperative posturography subsequently demonstrated abnormal late postoperative posturography. These results suggest that perioperative posturography may be useful in the evaluation and counseling of patients considering ablative vestibular surgery.

Adult

Breast conserving surgery in the management of in situ breast carcinoma.

In a retrospective review of 73 patients with in situ breast carcinoma seen in the Combined Breast Clinic at the Royal Marsden and St. George's Hospitals between 1969 and 1988, 20 (27%) were found to have in situ lobular and 53 (73%) in situ intraduct carcinoma. Of 19 patients with in situ lobular carcinoma treated by breast conserving surgery alone there were three (16%) recurrences of in situ lobular carcinoma and one (5%) of infiltrating carcinoma after a mean follow-up period of 65.8 months. Of 53 patients with in situ intraduct carcinoma, 37 were treated by breast conserving surgery alone and in this group there were 14 (38%) recurrences, of which seven (19%) were in situ intraduct and seven (19%) were infiltrating carcinoma, after a mean follow-up of 96.5 months. Following successful salvage there were no breast cancer related deaths in either group.

Adult

Extracanalicular osteomas of the temporal bone.

Extracanalicular osteomas of the temporal bone are rare neoplasms. Eight new cases are reported and a review of the literature is presented. These tumors are benign, slow growing, and composed predominantly of mature bone. Although they may occur anywhere in the temporal bone, they are prevalent in the mastoid and squama. Except for cortical lesions that are seen initially as cosmetic deformities, these tumors are usually unsuspected roentgenographic findings. Treatment is indicated for symptomatic osteomas. Mastoid lesions are readily excised. Tumors involving the middle and inner ear are most frequently small and tend to remain stable in size; consequently they are usually managed expectantly.

Adult

Panel discussion: glomus jugulare tumors of the temporal bone. Radiological appearance of glomus tumors.

Depending upon the stage of pathogenesis, some glomus tumors demonstrate characteristic radiographic findings which permit a presumptive diagnosis of this type of tumor. Three factors are helpful in interpreting multidirectional tomography of the temporal bone when a glomus tumor is suspected. The tumor shows a predilection for bony erosion of the carotid crest and hypotympanum. It tends to destroy bone in its path by small lobulated invasions producing a fairly well demarcated border of crescentic shaped translucencies. In contradistinction to other tumors and infections, glomus tumors tend to spare the lateral wall of the attic and the ossicular chain even when the tumor if fairly well advanced in size.

Glomus Jugulare Tumor

The ultrastructure of cholesterol granuloma of the middle ear: an electron microscope study.

The ultrastructure of giant cells in cholesterol granuloma is described, with particular reference to their role in the absorption of cholesterol needles. Cholesterol is a highly resistant substance in its crystalline form and it is confirmed that the giant cells are endowed with endoplasmic structures and organelles and are partly crowded with lysosomes, as evidence of the active role of the giant cells in the absorption and removal of cholesterol formed in the granuloma from blood, mucus or necrotic material.

Adult

Human otoconia in surgical specimens.

The utricular otoconia of four patients, which were removed during surgical procedures (one for an eighth nerve section operation and three for removal of acoustic neuromas) with the use of the translabyrinthine approach, were observed with the scanning electron microscope. The otoconia of these patients showed some abnormal features. In three of the four patients, a number of otoconia were found to have cracked lines. One of these patients was a 14-year-old boy; the other patients were more than 40 years old. In the remaining case, the otoconial facet surfaces were rough, and a few otoconia were unusually shaped.

Adolescent

Human incus long process depressions in the surface of the normal ossicle.

Depressions in the bone surface of the normal human incus long process are found with great frequency. This paper reviews the frequency and distribution of these depressions, discusses their histologic appearance, and speculates upon their significance. While their clinical significance is unclear, they may be related to several conditions encountered in otologic practice.

Ear Ossicles

Acromegaly and the temporal bone.

Acromegaly is a chronic disease of middle life resulting from excessive secretion of growth hormones by the acidophil cells of the anterior pituitary. The typical clinical features include enlargement of the skull, thorax, hands and feet. Recently, three patients with acromegaly have been operated upon for active otologic disease. In spite of massive mastoid cortex bone, the structures of the otic capsule were found to be of normal dimensions and in the usual relationships.

Acromegaly

Toward organism identification through analysis of bacterial colonies.

The clinical problem of bacterial identification has been approached by applying pattern-recognition techniques to multi-wavelength surface-scattering and reflectance data derived from real-time scans of isolated colonies. Preliminary results, obtained from blood-agar plates inoculated with a mixture of staphylococci, streptococci and escherichieae, indicate that these organisms can be differentiated with better than 90% certainty, provided the colonies are physically separated and their growth conditions closely controlled. Data collection and classification characteristics of the experimental system are briefly described; it is felt that the technique, possibly expanded to include boundary characteristics of the colonies, may offer a viable means of identifying clinically important bacteria.

Autoanalysis

The jugular bulb: its anatomic and clinical considerations in contemporary otology.

Advances in neurotologic diagnosis and surgery has pointed to the need for a complete reassessment of the relationship and significance of the jugular bulb and sigmoid sinus is discussed and selected temporal bone sections presented to illustrate the varying locations of the jugualr bulb. Considerations in differential diagnosis are presented and examples of surgical procedures are discussed wherein the jugular bulb was encountered and the methods of management are detailed in these instances.

Adult