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Biomedical subjects

S W Ewen

Publications and source records attributed to S W Ewen.

At least 19 recordsLinked to original sources

Ruptured Achilles tendons are significantly more degenerated than tendinopathic tendons.

OBJECTIVE: To ascertain whether there is an association between tendinopathic and ruptured Achilles tendons, hypothesizing that the histopathological aspects of tendinosis in tendinopathic tendons are less advanced than those found in ruptured Achilles tendons. METHODS: This was a comparative cohort study at a university teaching hospital. Histological examination was performed using hematoxylin and eosin and alcian blue/periodic acid-Schiff stained slides. The slides were interpreted using a semiquantitative grading scale assessing fiber structure, fiber arrangement, rounding of the nuclei, regional variations in cellularity, increased vascularity, decreased collagen stainability, hyalinization, and glycosaminoglycan. We calculated a pathology score giving up to three marks for each of the above variables, with 0 being normal and 3 being maximally abnormal. All the histology slides were assessed twice in a blinded manner, the agreement between two readings ranging from 0.170 to 0.750 (kappa statistics). RESULTS: We studied biopsy samples from the Achilles tendon of patients undergoing open repair for a subcutaneous rupture of their Achilles tendon (N = 35; average age (+/- SD), 48.4 +/- 16.9 yr; range, 26-80), biopsy specimens from the Achilles tendon of patients undergoing exploration for Achilles tendinopathy (N = 13; average age, 35.7 +/- 12.9 yr; range, 18-67) and specimens of Achilles tendons from individuals with no known tendon pathology (N = 16; average age, 65 +/- 19.1 yr; range, 46-82). The highest mean score of ruptured tendons was significantly greater than that of tendinopathic tendons (17.4 +/- 4.9 vs 10.5 +/- 6.1, P < 0.001), and highest mean score of tendinopathic tendons was greater that that of control tendons (10.5 +/- 6.1 vs 5.9 +/- 7.3) (P < 0.001). CONCLUSION: Ruptured and tendinopathic tendons are histologically significantly more degenerated than control tendons. The general pattern of degeneration was common to the ruptured and tendinopathic tendons, but there was a statistically significant greater degree of degeneration in the ruptured tendons. It is therefore possible that there is a common, as yet unidentified, pathological mechanism that has acted on both of these tendon populations.

Achilles Tendon↗

Subungual glomus tumor of the hallux. A case report.

The authors report a rare case of subungual glomus tumor in the right hallux, which was excised with complete relief of symptoms. They provide a brief description of histological features and review the literature.

Adult↗

Distal proctocolitis and n-3 polyunsaturated fatty acids (n-3 PUFAs): the mucosal effect in situ.

It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.

Animals↗

Decreased levels of heat shock proteins in gut epithelial cells after exposure to plant lectins.

BACKGROUND: The enterocytes of the intestinal epithelium are regularly exposed to potentially harmful substances of dietary origin, such as lectins. Expression of heat shock proteins (HSPs) by this epithelium may be part of a protective mechanism developed by intestinal epithelial cells to deal with noxious components in the intestinal lumen. AIM: To investigate if the lectins PHA, a lectin from kidney beans (Phaseolus vulgaris) and WGA, a lectin from wheat germ (Triticum aestivum) could modify the heat shock response in gut epithelial cells and to establish the extent of this effect. METHODS: Jejunal tissue sections from PHA and WGA fed rats were screened for expression of HSP70, HSP72, and HSP90 using monoclonal antibodies. Differentiated Caco-2 cells, the in vitro counterpart of villus enterocytes, were exposed to 100 microg/ml of PHA-E(4) or WGA for 48 hours and investigated for changes in DNA and protein synthesis by double labelling with [2-(14)C]thymidine and L-[methyl-(3)H]methionine. The relative concentrations of HSP60, HSP70, HSP72, and HSP90 and binding protein (BiP) in these cells exposed to lectins were analysed by polyacrylamide gel electrophoresis and immunoblotting. To establish if lectin exposed differentiated Caco-2 cells were still capable of producing a heat shock response, these cells received a heat shock (40 degrees C, 41 degrees C, and 42 degrees C) for one hour and were allowed to recover for six hours at 37 degrees C. During heat shock and recovery periods, lectin exposure was continued. RESULTS: Constitutive levels of HSPs were measured in the intestinal cells of lactalbumin fed (control) rats, as may be expected from the function of this tissue. However, in PHA and WGA fed rats a marked decline in the binding of antibodies against several HSPs to the intestinal epithelium was found. These results were confirmed by in vitro experiments using differentiated Caco-2 cells exposed to PHA-E(4) and WGA. However, after exposure to lectins, these cells were still capable of heat induced heat shock protein synthesis, and total protein synthesis was not impaired indicating specific inhibition of HSP synthesis in non-stressed cells. CONCLUSIONS: We conclude that PHA and WGA decrease levels of stress proteins in rat gut and enterocyte-like Caco-2 cells, leaving these cells less well protected against the potentially harmful content of the gut lumen.

Animals↗

The growth of an established murine non-Hodgkin lymphoma tumour is limited by switching to a phytohaemagglutinin-containing diet.

The growth of a non-Hodgkin lymphoma, developing subcutaneously as a solid tumour in NMRI mice, is markedly diminished by including phytohaemagglutinin (PHA), a lectin present in raw kidney bean (Phaseolus vulgaris), in the diet. In the experiment described in this communication the effect of first allowing tumours to develop for 5 days before switching the mice to a diet containing PHA at different concentrations was tested to establish whether or not feeding the lectin at late times also resulted in reducing tumour growth. This switch of diet indeed proved to be effective in slowing down growth of the lymphoma tumour. The reduced rate of growth occurs in a dose-dependent manner. We have suggested that a competition between the gut epithelium undergoing PHA-stimulated hyperplasia and the developing tumour may occur for polyamines and other nutrients from a common body pool and this could be an important contributory factor with regard to the observed low level of tumour growth following the feeding of PHA-containing diet. Recent data which showed that the level of hyperplasia of the small bowel in response to feeding the PHA diets was higher in non-injected mice compared to those which had been injected with tumour cells substantiated the concept of competition between gut and tumour for nutrients and other requirements for growth.

Animals↗

Effect of diets containing genetically modified potatoes expressing Galanthus nivalis lectin on rat small intestine.

Diets containing genetically modified (GM) potatoes expressing the lectin Galanthus nivalis agglutinin (GNA) had variable effects on different parts of the rat gastrointestinal tract. Some effects, such as the proliferation of the gastric mucosa, were mainly due to the expression of the GNA transgene. However, other parts of the construct or the genetic transformation (or both) could also have contributed to the overall biological effects of the GNA-GM potatoes, particularly on the small intestine and caecum.

Animals↗

A combination of dietary protein depletion and PHA-induced gut growth reduce the mass of a murine non-Hodgkin lymphoma.

The results presented in this study show that a switch from a non-protein diet (NPD) to one of a normal protein content (LA) on the day of subcutaneous injection of non-Hodgkin lymphoma tumour cells greatly favoured the development and growth of the tumour. Interestingly, however, inclusion of the plant lectin phytohaemagglutinin (PHA) in the LA diet appeared to compete with the effect of switch to the protein-rich diet, resulting in decreased tumour size and an increased incidence of necrosis. PHA was shown to induce hyperplasia of the gut even in the presence of the growing tumour. This observation together with the fact that gut hyperplasia also occurred in animals which were fed NPD supplemented with PHA, indicated the strength of PHA as a growth signal. It would seem likely that this 'normal' growth is able to compete with the tumour for important growth factors and nutrients, including polyamines, effectively starving the tumour for these molecules and resulting in its decreased rate of proliferation.

Animals↗

The inflammatory and cytotoxic effects of a nitric oxide releasing cream on normal skin.

We describe the pro-inflammatory and cytotoxic effects of nitric oxide in vivo in human skin. Nitrite and ascorbic acid were mixed on the skin of 12 normal volunteers, three times daily, to release nitric oxide. Exposure to nitric oxide was varied by randomizing the concentration of nitrite and duration of application. Nitric oxide treated skin showed significant increases in cells expressing CD3, CD4, CD8, CD68, neutrophil elastase, ICAM-1, VCAM-1, nitrosotyrosine, p53, and apoptotic cells compared with skin treated with ascorbic acid alone. There was no significant increase in mast cells. Following application of nitric oxide there were significantly fewer CD1a positive Langerhans cells in the epidermis. These appeared to lose dendritic morphology and migrate from the epidermis. There was no significant difference in staining for Ki-67, a marker related to proliferating cell nuclear antigen, between active and control skin but staining was greater after exposure to higher dose nitric oxide than the low dose. Apoptosis, cytotoxicity, and p53 staining were relatively greater after 48 h exposure than after 24 h. These results suggest that nitric oxide is pro-inflammatory and is toxic to DNA, leading to the accumulation of p53 and subsequent apoptosis. High-dose nitric oxide paradoxically led to a smaller increase in macrophages and T cells than low dose suggesting an immunosuppressive effect of higher levels.

Apoptosis↗

Lipid accumulation in obese Zucker rats is reduced by inclusion of raw kidney bean (Phaseolus vulgaris) in the diet.

The effects of inclusion of different levels of raw kidney bean (Phaseolus vulgaris) of high lectin content (27 g/kg meal) in a high-quality (lactalbumin) control diet were tested in nutritional trials on the growth and metabolism of obese Zucker (fafa) rats and their lean littermates in comparison with pair-fed controls. All diets contained 100 g total protein/kg and either 50 g lipids/kg (low fat) or 150 g lipids/kg (moderate fat). The growth of both obese and lean rats on bean diets was retarded by the daily bean intake in a dose-dependent manner. However, most of this was because bean-fed rats contained less body fat than the controls after 10 d. Thus, after feeding low-fat diets containing up to 130 g kidney bean/kg (lectin intake < or = 0.2 g/kg body weight (BW) per d) in both 10 d and 70 d trials, the bodies of obese rats contained less fat but not protein than their pair-fed controls. Moreover, by increasing the lipid content of the diet to 150 g/kg, the level of bean inclusion could be increased to 280 g/kg (lectin intake > or = 0.4 g/kg BW per d) without loss of body protein and skeletal muscle. Although these rats contained more body fat than those which were fed on low-fat diets, their weight reduction could be accounted for exclusively by reduced lipid content. In contrast, significant body protein loss occurred when the same diet of high lectin content was fed to lean littermates. Plasma insulin levels were significantly depressed in the obese Zucker rats on bean diets but the pancreas was not significantly enlarged nor its insulin content changed in 10 d trials. However, significant pancreatic growth occurred on long-term (70 d) bean feeding compared with pair-fed controls. The results suggest that, in addition to animal nutrition, it may also be possible to use the bean lectin as a dietary adjunct or therapeutic agent to stimulate gut function and ameliorate obesity if a safe and effective dose-range can be established for human subjects.

Animals↗

The induction of gut hyperplasia by phytohaemagglutinin in the diet and limitation of tumour growth.

The growth of a transplantable murine non-Hodgkin lymphoma tumour, developing either intraperitoneally as an ascites tumour or subcutaneously as a solid tumour, has been shown to be markedly diminished by including phytohaemagglutinin (PHA), a lectin present in raw kidney bean (Phaseolus vulgaris) in the diet. In NMRI mice fed PHA within the range 0.45-7.0 mg/g diet, tumours which developed during a 10 day period after subcutaneous injection of cells were about 35% of the dry weight of those in lactalbumin-fed (control) animals. The reduced rate of growth occurred in a dose-dependent manner within the range 0.45-3.5 mg/g diet. Based on these observations it has been suggested that a competition between the gut epithelium undergoing hyperplasia and the developing tumour may occur for nutrients from a common body pool, and this may be an important factor with regard to the observed initial low level of tumour growth following the feeding of a PHA-containing diet. Observations which showed that the level of hyperplasia of the small bowel in response to feeding the PHA diets was higher in non-injected mice compared to those which had been injected with tumour cells substantiated the concept of competition between gut and tumour for nutrients etc. required for growth. Experiments with a second murine tumour cell line (a plasmacytoma) in Balb/c mice gave similar results indicating that the effect of PHA was not restricted to a single tumour system.

Animals↗

Salmonella enterica var Typhimurium and Salmonella enterica var Enteritidis express type 1 fimbriae in the rat in vivo.

In a series of experiments rats were dosed with purified type 1 fimbriae from Salmonella enterica var Enteritidis or with fimbriated cultures of either S. enterica var Typhimurium or S. enterica var Enteritidis. Paraffin-wax embedded histological sections of jejunal and ileal tissue were taken and stained by the streptavidin biotin complex (sABC) staining technique for the detection of salmonella and type 1 fimbriae. On oral infection with Enteritidis and Typhimurium both bacteria were shown to be closely associated with the rat ileal epithelium and expressed type 1 fimbriae, thus clearly demonstrating that type 1 fimbriae are expressed by salmonellae in vivo. Moreover, association with the ileum was also shown to occur when purified type 1 fimbriae were orally administered to rats. Our results suggest that type 1 fimbriae alone or in combination with other fimbriae may play an important role in the early stages of infection with these pathogenic bacteria.

Animals↗

Both free and complexed trypsin inhibitors stimulate pancreatic secretion and change duodenal enzyme levels.

Secretion of pancreatic digestive enzymes was measured in pancreatic cannulated rats after duodenal stimulation with Kunitz or Bowman-Birk protease inhibitors or their complexes with trypsin and/or chymotrypsin. Free and complexed inhibitors were bound by the duodenal epithelium, stimulated the discharge of cholecystokinin, and significantly increased secretion rates of alpha-amylase, trypsinogen, and chymotrypsinogen. Inasmuch as secretion rates returned to basal levels with cholecystokinin-A receptor antagonists, the stimulation was likely to be mediated by cholecystokinin. Soya factors also influenced the duodenal concentration of pancreatic enzymes under simulated feeding conditions. Thus the level of alpha-amylase increased while the trypsin concentration decreased in rats gavaged with free or complexed inhibitors. The same was true for chymotrypsin when the Bowman-Birk inhibitor was used, but the Kunitz inhibitor and its trypsin complex actually raised the luminal concentration of chymotrypsin. Accordingly, because soya inhibitors remained effective in stimulating pancreatic secretion after elimination of their inhibitory activity by complex formation, it is questionable whether the signal for cholecystokinin secretion was solely due to lowering of duodenal protease levels.

Animals↗

Risk of contamination from laparoscopic carbon dioxide insufflators.

Ten high flow laparoscopic carbon dioxides insufflators were examined to determine whether there was significant particulate or bacterial contamination of the gas delivered to patients. The gas delivery tubing and connections in the insufflators were also examined for the presence of bacterial colonization and for evidence of retrograde passage of body fluids to the insufflator. Metallic particulate debris was recovered from gas from all 10 insufflators. Staphylococci were recovered from the insufflated gas from one insufflator and from the internal tubing of three insufflators. Swabs from the internal tubing of two insufflators showed evidence of contamination by blood. The metallic particulate contamination of the insufflated gas may not be of clinical significance but the presence of bacteria and blood is a concern. Simple measures to minimize the risk of retrograde flow of gas and fluid to the insufflator should be followed and the provision of a filter between the patient and the insufflator is recommended.

Carbon Dioxide↗

Magnetic resonance imaging of thyroid swellings.

The preoperative diagnosis of some thyroid neoplasms remains difficult even with the routine use of fine-needle aspiration cytology. The potential of nuclear magnetic resonance imaging (MRI) to discriminate between different thyroid pathologies was explored prospectively and compared with the final pathology in a series of 37 patients. MRI yielded high-quality images of the thyroid swelling but did not provide additional information to differentiate benign from neoplastic lesions. MRI does not contribute to the routine management of thyroid swellings.

Carcinoma, Papillary↗

Histoplasmosis--a ten year follow-up.

A patient with chronic disseminated histoplasmosis was followed after successful treatment with amphotericin B for 10 years until his death from chronic obstructive airways disease. Necropsy showed that Histoplasma organisms could still be identified in the adrenal and pancreatic abscesses, though none appeared viable on electron microscopy. Excision of such abscesses should be considered in view of their potential as a reservoir of organisms.

Aged↗