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Biomedical subjects

E Sheffield

Publications and source records attributed to E Sheffield.

At least 19 recordsLinked to original sources

Anaplastic thyroid carcinoma implantation after fine needle aspiration cytology.

We report the case of a 59-year-old man with a two-month history of a fast-growing, left-sided neck mass and a 5 mm nodule over a thyroid mass at the site of fine needle aspiration cytology performed four weeks earlier. Histopathological studies confirmed anaplastic carcinoma of the thyroid and cutaneous needle track seeding of the primary tumour. The patient succumbed to extensive disease 10 weeks after initial diagnosis. To our knowledge, this is a rare report of implantation of anaplastic thyroid carcinoma along the track of fine needle aspiration. Some factors involved in needle track seeding are: needle size; number of passes; withdrawing the needle without releasing suction; injecting the tumour at time of biopsy; and inherent characteristics of the lesion (e.g. number of cells dislodged, adhesiveness of cells, amount of stroma present, enzymes released and immunologic characteristics).

Biopsy, Fine-Needle↗

Histopathological changes in the human larynx following expanded polytetrafluroethylene (Gore-Tex(R)) implantation.

BACKGROUND: Expanded polytetrafluroethelyne (e PTFE, Gore-Tex(R)) has been advocated as an implant material for medialization of the vocal fold. Animal studies involving rabbits and a porcine model have demonstrated host tolerance of the implant. There have been no reports describing the histological changes in a human laryngectomy specimen with a Gore-Tex implant. CASE PRESENTATION: The histological findings in a laryngectomy specimen of a patient previously implanted with e PTFE for medialization of a paralyzed vocal fold following excision of a vagal neurofibroma were studied.Histopathology revealed a mild foreign-body giant cell granulomatous reaction with some associated fibrosis. The granulomatous response was limited to the periphery of the Gore-Tex and although it closely followed the profile of the material it did not encroach into or significantly break up the material. There was no significant neutrophilic or lymphocytic inflammation. CONCLUSIONS: Our findings are consistent with the animal models confirming that Gore-Tex implantation does not result in a significant granulomatous reaction in the human larynx over a 13-month period. Moreover, there is no evidence of resorption or infection. Further, the lack of lymphocytes in association with the granulomas indicates that there is no significant immunological hypersensitivity. Histologically, the slight permeation by connective tissue is similar to that seen in Gore-Tex vascular and cardiac implants. The degree of the slight giant cell response appears to be dependent on the profile of the material; a sharp edge incited more of a response than a flat surface.

Journal Article↗

Exposure to Asulox inhibits the growth of mosses.

Asulox is a herbicide used to control bracken. Its effects on mosses were investigated to ascertain whether exposure proved as detrimental as found in parallel studies on pteridophytes. Mature gametophytes of 18 mosses were exposed to a range of concentrations of Asulox under standard conditions and the effects on growth monitored. Plants were cut to a standard length, exposed to Asulox solution for 24 h, grown for 3 weeks and total elongation (main stem and branches) measured. EC50 values were calculated and species ranked according to sensitivity. The effects of exposure on total elongation were compared with those on main stem elongation alone. Under the conditions tested, the total elongation of all species was inhibited after exposure to Asulox. The amount of elongation observed after exposure was different for different species and inhibition of elongation occurred at different exposure concentrations. A single regression equation was not adequate to describe the dose response curves of all species tested. An ability to produce secondary branches may confer increased tolerance to Asulox exposure. It is concluded that mosses suffer detrimental effects after exposure to Asulox at concentrations similar to those that affect fern gametophytes such as bracken.

Bryophyta↗

Evaluation of a Tay-Sachs disease screening program.

Tay-Sachs Disease (TSD) is an autosomal recessive neurodegenerative disorder. TSD is prevalent in the Ashkenazi Jewish population, and carrier screening programs have been implemented worldwide in these communities. A screening program initiated in 1997 involving the Melbourne Jewish community (Australia) incorporated education, counselling and carrier testing of high-school students aged 15 to 18 years. This study aimed to assess the participation rates, level of knowledge obtained and predicted feelings and attitudes of the students involved. Seven hundred and ten students participated, there was a 67% uptake for testing with a carrier rate of 1 in 28 determined. The level of knowledge of the students following education was high and of relative importance in regard to decision making, as were their feelings and attitudes about genetic testing for carrier status. A significant impediment to test uptake was the need for blood sampling, resulting in a recommendation for the introduction of DNA analysis on cheek brush samples. The evaluation of this program has given a wider scope for further development as well as providing valuable information for the implementation of community screening programs.

Adolescent↗

The association of platelet-derived growth factor receptor expression, plaque morphology and histological features with symptoms in carotid atherosclerosis.

Platelet-derived growth factor may influence smooth muscle cell migration and proliferation and, therefore, carotid plaque composition and stenosis. Platelet-derived growth factor receptor expression and histological features were compared in carotid plaques from symptomatic and asymptomatic patients. Immunocytochemistry and histology determined platelet-derived growth factor-alpha and -beta receptor expression, white blood cell infiltration, smooth muscle cell, elastin, cholesterol, collagen and intraplaque haemorrhage in carotid artery plaques removed at surgery or the post-mortem. Plaques with > 70% stenosis from asymptomatic (n = 10) and symptomatic patients (n = 27) had higher expression of platelet-derived growth factor and beta receptors and higher scores for macrophages and intraplaque haemorrhage than plaques with < 70% stenosis from asymptomatic patients (n = 33). Plaques with > 70% stenosis from symptomatic patients had significantly lower alpha receptor expression than plaques with > 70% stenosis from asymptomatic patients. The reduction of alpha receptor expression, which may inhibit smooth muscle cell migration, suggests that differential expression of platelet-derived growth factor receptor subunits in plaques may be related to symptoms.

Aged↗

Fern spore extracts can damage DNA.

The carcinogenicity of the vegetative tissues of bracken fern (Pteridium) has long been established. More recently, the carcinogenic effects of the spores of bracken have also been recognized. Both vegetative tissues and spores of bracken can induce adducts in DNA in animal tissues, but the possible genotoxic or carcinogenic effects of spores from fern species other than bracken are unknown. The single-cell gel electrophoresis ('comet') assay was used to investigate whether fern spores can cause DNA damage in vitro. Extracts of spores from six fern species were administered to cultured human premyeloid leukaemia (K562) cells. Spore extracts of five fern species: Anemia phyllitidis, Dicksonia antarctica, Pteridium aquilinum, Pteris vittata and Sadleria pallida, induced significantly more DNA strand breaks than those in the control groups. Only in one species, Osmunda regalis, was the effect no different from that in the control groups. Using extracts from A. phyllitidis and P. vittata, the extent of DNA damage was increased by increasing the original dose 10 times, whereas an experiment in which exposure times were varied suggested that the highest levels of strand breaks appear after 2 h exposure. Simultaneous incubation with human S9 liver enzyme mix ablated the damaging effect of the extracts. Our data show that fern spore extracts can cause DNA damage in human cells in vitro. Considering the strong correlation between DNA damage and carcinogenic events, the observations made in this report may well have some implications for human health.

Comet Assay↗

Congenital glenoid dysplasia.

Glenoid dysplasia is an anomaly of the scapula characterized by underdevelopment of the bony glenoid and adjacent part of the scapular neck which may be seen as a primary isolated condition, in patients with multiple anomalies or ill-defined syndromes, in well-described syndromes, in mucopolysaccharidoses and related conditions, and in certain skeletal dysplasias. The general subject of glenoid dysplasia is reviewed with reference to descriptions in the literature and personal observations.

Abnormalities, Multiple↗

No correlation between phaeochromocytoma catecholamine secretion and granule ultrastructure.

BACKGROUND: It is uncertain whether biochemical markers of catecholamine secretion in patients with phaeochromocytoma correlate with tumour ultrastructure granule morphology. METHODS: Fifteen patients with an adrenal phaeochromocytoma (n=13) or paraganglioma (n=2) (three men, 12 women; age 17-79 years) were studied. Catecholamine secretion was estimated by measuring urinary levels of free noradrenaline, adrenaline and dopamine. The number and type of secretory granules were evaluated by two independent observers on electron micrographs (area analysed approximately 70 microm2). Large round or elongated medium-density granules were adrenaline-type granules, whereas electron-dense granules lying in a vacuole were of noradrenaline type. RESULTS: No correlation was found between noradrenaline output and the number or percentage of noradrenaline-type granules, although tumours with normal noradrenaline output had only a minority of this type of granule (less than 25 per cent). Adrenaline-type granules were predominant (77 per cent of 163 granules) in a tumour secreting only adrenaline, but the proportion of adrenaline-type granules in six tumours with normal adrenaline output varied significantly (range 7-89 per cent). It was not possible to evaluate the granule type associated with dopamine secretion because one tumour secreting 14900 nmol dopamine and 1570 nmol adrenaline daily had a predominance of noradrenaline-type granules (63 per cent of 132 granules) and two dopamine-secreting tumours (5500 and 4250 nmol per day respectively) had 93 and 13 per cent noradrenaline-type granules. CONCLUSION: The lack of correlation between hormone output and granularity suggests that other factors determine secretory patterns in these tumours.

Adolescent↗

Early diagnosis of subependymal giant cell astrocytoma in patients with tuberous sclerosis.

We present 19 patients with tuberous sclerosis complex and subependymal giant cell astrocytoma. The mean age at the time of tumor diagnosis was 9.4 years (range, 1.5 to 21 years). Computed cranial tomography (CT) or cranial magnetic resonance imaging (MRI) identified the lesion which was resected in all cases. Seven patients had hydrocephalus and there was an interval increase in the tumor size or a large tumor without hydrocephalus in 12 patients. Surgical criteria included: (1) presence of hydrocephalus; (2) interval increase in tumor size; (3) new focal neurologic deficit attributable to the tumor; and/or (4) symptoms of increased intracranial pressure. Eight patients were identified through a surveillance program involving annual computed cranial tomography. All of these eight patients had their tumor removed prior to the development of symptoms, none had neurologic deficits which persisted after surgery, and none has so far developed recurrent subependymal giant cell astrocytoma. In contrast, of the 11 patients from the non-surveillance group 7 were symptomatic at tumor diagnosis, 1 had a complicated postoperative course, 2 developed recurrent giant cell astrocytoma, and 1 had an extensive lesion that could not be completely excised. Periodic cranial imaging may help to identify subependymal giant cell astrocytomas in tuberous sclerosis patients before they become symptomatic. Earlier diagnosis and treatment could reduce surgical morbidity and the risk of tumor recurrence.

Adolescent↗

Renal lesion growth in children with tuberous sclerosis complex.

PURPOSE: Renal lesions, including angiomyolipoma, renal cysts (simple and polycystic kidney disease) and renal cell carcinoma, develop in patients with tuberous sclerosis complex. While there is limited information that these lesions may grow in adults with tuberous sclerosis complex, the incidence, characterization and growth rate in children have not been reported. Also, the age at which these lesions first appear, thus providing insight into their natural history, is unknown. We present our data from a longitudinal renal surveillance study of children with tuberous sclerosis complex. MATERIALS AND METHODS: Since 1985 children with tuberous sclerosis complex at our hospital have undergone periodic renal imaging by ultrasonography or computerized tomography to monitor renal lesions. A total of 35 girls and 25 boys 1 to 18 years old have undergone at least 2 or more annual renal ultrasounds. RESULTS: On initial evaluation 33 of 60 children (55%) (mean age 6.9 years) had an identifiable renal lesion, which increased to 48 of 60 (80%) at followup (mean age 10.5 years). Angiomyolipoma was the most frequent lesion (75%) followed by simple renal cysts (17%). Angiomyolipomas increased in size and/or number in 10 of 18 boys (56%) and 18 of 27 girls (66%). The largest growth rate in 1 year was from 0 to 4 cm. and from 5 to 9 cm. in diameter. The youngest patient demonstrated lesions at age 2 years. The average age at which a normal ultrasound became abnormal was 7.2 years. While a total of 27 patients had a normal ultrasound on entering the study, lesions had developed in 15 at followup (11 with angiomyolipomas, 4 with cysts). Five patients had cysts that had disappeared at followup. A 7-year-old boy had a 9 cm. renal cell carcinoma removed. One patient has renal lesions characteristic of autosomal dominant polycystic kidney disease. CONCLUSIONS: Renal involvement in patients with tuberous sclerosis complex begins in infancy, and angiomyolipoma is the most common lesion (75%). Angiomyolipomas are more likely to grow than remain stable, although the rate of growth varies. Simple renal cysts may appear or disappear with time but angiomyolipomas do not disappear. An initially normal renal ultrasound does not rule out future development of lesions. Periodic surveillance is indicated in children with tuberous sclerosis complex.

Adolescent↗

Vein quality influences neointimal hyperplasia in an organ culture model of human saphenous vein.

OBJECTIVES: The severity of pre-existing pathological changes in human saphenous vein (HSV) correlates with the development of vein graft stenosis and graft patency. The aim of this study was to investigate the influence of pre-existing intimal hyperplasia on development of the neointima in vitro, using an organ culture model. MATERIALS AND METHODS: Segments of HSV were harvested during coronary artery bypass surgery. Histology was performed on part of the vein; the remainder was maintained in culture. Pre-existing intimal thickness (PIT) in HSV from day 0 and neointimal thickness (NIT) in cultured HSV were measured using computerised image analysis on histological sections. Day 0 and 14 veins were compared with respect to intimal hyperplasia. RESULTS: Twelve pairs of veins were examined. A mean tissue ATP of 297 nmoles/g wet weight for cultured. HSV confirmed cell viability. Mean PIT was 180 microns (CI: 86-274) and mean NIT was 60 microns (CI: 48-72), with a significant correlation between them using the Spearman Rank test (Rs = 0.72; p = 0.008). CONCLUSIONS: Pre-existing vein quality as measured by PIT correlates with the development of neointimal hyperplasia in culture, adding further support to clinical evidence that poor vein quality predisposes to vein graft stenosis due to an inherent susceptibility to intimal hyperplasia.

Graft Occlusion, Vascular↗

Angioscopy for quality control of saphenous vein during bypass grafting.

OBJECTIVES: Although autogenous vein is the conduit of choice for infrainguinal bypass grafting, some 20-30% of vein grafts fail during the first year postoperatively. Many of these failed veins are now known to have pre-existing pathological changes. Angioscopy enables intraoperative endoluminal visualisation of veins and can reveal anomalies, some previously unsuspected, despite preoperative Duplex ultrasound mapping and normal external appearances. The aim of this study was to compare angioscopic findings with contemporary histological appearances and with subsequent graft outcome and ultimately, to identify those endoluminal features which might be predictive for failure. METHODS: Angioscopic vein inspection was carried out using Olympus 1.4 and 2.2mm angioscopes in patients undergoing femoropopliteal/distal bypass. Severe disease in the veins of five patients led to preferential use of polytetrafluoroethylene (PTFE) for above-knee bypasses. The remaining 38 videotaped sequences were reviewed by two surgeons and scored using a scale of 0 to 3, based on frequency and distribution of angioscopically detected lesions. These included haemorrhagic mural plaques, flimsy intraluminal strands, webs/bands and mobile/adherent thrombus. Vein harvested at operation was assessed by a pathologist according to the level of pre-existing abnormality. RESULTS: There were significant associations between angioscopy/histology scores and graft survival (chi 2 = 22.00; df:3; p < 0.001; chi 2 = 22.43; df:3; p < 0.001 respectively). There was a significant correlation between angioscopy and histology scores (R8 = 0.725; p < 0.001). CONCLUSIONS: Angioscopy allows immediate identification of the at risk, poor quality vein graft at the time of surgery, without the delays inherent with histological preparation and assessment. Recognition of abnormalities at angioscopy may ultimately improve graft outcome by prospectively eliminating use of poor vein.

Adult↗

The aetiology of vein graft stenoses.

The aetiology of vein graft stenosis is poorly understood. In a cohort of 88 patients, the mean internal diameter of the vein grafts that developed a stenosis was 3.7 (3.1-4.2) mm compared to 4.7 (4.4-5.0) mm in those that did not (p = 0.006). The mean lowest compliance value in the 11 patients who developed a stenosis was 0.1 (0.07-0.13) % per mmHg compared to 0.21 (0.19-0.23) % per mmHg in the rest (p < 0.001). The presence of vein incompetence, site of tributaries or valves and the degree of endothelial cell loss were not related to the development of vein graft stenoses. The presence of a macrophage infiltrate (p < 0.001), lymphocyte infiltrate (p < 0.025) and subendothelial smooth muscle cells (p < 0.05) were all significantly more common in those grafts that developed a stenosis. Vein quality is an important factor in the development of graft stenoses.

Aged↗

Pre-bypass morphological changes in vein grafts.

Random vein samples taken prior to bypass surgery have shown certain pathological features. Long saphenous vein was taken from the groin (proximal) and knee to mid-calf (distal) of 85 patients undergoing femoro-distal bypass over a 2-year period. During this period only four patients had cephalic arm vein used; this was also studied. Histological examination was performed using haematoxylin and eosin and van Geison stains. Intimal hyperplasia was seen in 62 (73%) proximal and 74 (87%) distal samples. There were significantly more distal veins with moderate to severe focal hyperplasia and circular muscle hypertrophy (p < 0.05 and p < 0.001). Changes of diffuse intimal hyperplasia were seen in three of the cephalic veins. Muscle hypertrophy occurred in 58 (68%) of proximal segments compared to 75 (88%) of distal segments (p < 0.005). This study shows that significant pathological changes are seen in long saphenous and cephalic veins thought to be "normal". These changes are more evident in the distal long saphenous vein. These changes may have a significant effect on the outcome of vein bypass.

Aged↗

Vein compliance: a preoperative indicator of vein morphology and of veins at risk of vascular graft stenosis.

Compliance measurements of 53 long saphenous veins before femorodistal bypass have been performed using a duplex scanner with venous occlusion for distension. These have been compared with the histological features of the veins. There was significantly more moderate or severe focal hyperplasia and circular muscle hypertrophy in distal long saphenous vein than in its proximal counterpart (P < 0.01 and P < 0.05 respectively). The mean (95 per cent confidence interval) compliance of distal vein with moderate or severe hyperplasia was 0.16 (0.13-0.19) compared with 0.29 (0.22-0.36) for that with no, minimal or mild hyperplasia (P = 0.001). The mean compliance of distal vein with moderate or severe muscle hypertrophy was 0.19 (0.17-0.21) and of vein with no, minimal or mild hypertrophy 0.25 (0.21-0.29) (P = 0.14). The mean lowest compliance in seven patients who developed stenosis was 0.10 (0.07-0.13) compared with 0.21 (0.16-0.26) in the rest (P < 0.001). Preoperative measurement of vein compliance can be used to identify vein with marked pre-existing intimal hyperplasia and as a predictor of future graft stenosis.

Compliance↗