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Biomedical subjects

N Leonard

Publications and source records attributed to N Leonard.

At least 37 records · Page 2Linked to original sources
PubMed2000

A retrospective study of outcome of Mohs' micrographic surgery for cutaneous squamous cell carcinoma using formalin fixed sections.

The surgical management of recurrent or large squamous cell carcinoma (SCC) can be challenging as tumours often extend beyond visible margins. Micrographic surgery is a potentially effective method of ensuring complete clearance of tumour. A retrospective study of all cases of SCC treated by micrographic surgery in this department between 1986 and 1996 has been done. Sixty-one patients were treated using a formalin-fixed paraffin-embedded tissue technique with a median follow-up of 4 years. In two cases there was local recurrence and in three others metastasis to local lymph nodes. The overall cure rate was 92% (56 of 61), which compares favourably with published series using chemosurgery and frozen tissue techniques. The results show that this technique of micrographic surgery is a satisfactory and cost-effective alternative to conventional frozen section techniques in the treatment of SCC. The formalin-fixed tissue method has the advantage of providing high-quality permanent histological sections using existing conventional pathology services.

Adult↗
PubMed2000

Herpes simplex virus type 1 as a cause of widespread intracorneal blistering of the lower limbs.

Herpes simplex virus (HSV) infections often manifest as acute self-limiting eruptions of grouped vesicles, which have a tendency to recur. Common manifestations include that of gingivostomatitis, vulvovaginitis, recurrent erythema multiforme, herpetic whitlow, and eczema herpeticum. We report a case of HSV-1 presenting as a symmetrical intracorneal blistering eruption involving the lower limbs in a patient with no previous history of herpes simplex infection.

Blister↗
PubMed2000

A technique for the evaluation of failed fallopian tube ligation with metal clips.

The evaluation of fallopian tubes after failed tubal ligation can be difficult because conventional histopathological techniques are unable to section the metal clips when in situ. Once the clips have been removed, any evidence of tube patency is lost. This report describes a technique of embedding and sectioning that enables sections to be made while the metal clips are still in situ. This is a modification of a method first described to embed mineralised bone and involves the use of plastic embedding and a diamond saw. Using this technique, a permanent record is made of the tube location and patency.

Adult↗
PubMed1998

Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.

Sickle red cells bind significant amounts of soluble laminin, whereas normal red cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin, whereas another putative laminin binding protein, CD44, does not. Ligand blots also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU appears to be the major laminin-binding protein of sickle red cells. Previously reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this protein may also serve as a laminin receptor in malignant tumors.

Anemia, Sickle Cell↗
PubMed1998

Fatal pleomorphic xanthoastrocytoma with meningeal gliomatosis.

AIMS: To report the previously undescribed phenomenon of extensive meningeal gliomatosis in a pleomorphic xanthoastrocytoma (PXA) and to examine possible prognostic features. CASE DETAILS: An 11-year-old girl underwent excision of a left temporoparietal pleomorphic xanthoastrocytoma and 8 months later underwent re-excision of a local tumour recurrence. Although mitoses were not present in any of the resection specimens, the development of necrosis and increased immunoreactivity for proliferating cell nuclear antigen (PCNA) indicated anaplastic transformation in the recurrent tumour. Three months later extensive meningeal gliomatosis with minimal local recurrence resulted in death. CONCLUSIONS: Subarachnoid dissemination of a locally recurrent PXA in the absence of mitotic activity is an extremely unusual occurrence. PCNA expression in the initial excision specimens did not predict subsequent anaplastic transformation.

Astrocytoma↗
PubMed1998

Expression of nitric oxide synthase in inflammatory bowel disease is not affected by corticosteroid treatment.

AIM: To examine the effect of corticosteroid treatment on the expression of inducible nitric oxide synthase (iNOS) in the colon of patients with inflammatory bowel disease. METHODS: Four groups of patients were studied: (1) ulcerative colitis treated with high dose corticosteroids (six patients, 10 blocks); (2) ulcerative colitis patients who had never received corticosteroids (10 patients, 16 blocks); (3) Crohn's disease treated with high dose corticosteroids (12 patients, 24 blocks); (4) Non-inflammatory, non-neoplastic controls (four patients, six blocks). Full thickness paraffin sections of colons removed at surgery were immunostained with an antibody raised against the C terminal end of iNOS. Sections were assessed semiquantitatively for the presence and degree of inflammation and immunoreactivity for nitric oxide synthase. RESULTS: Cases of ulcerative colitis and Crohn's disease with active inflammation showed strong staining for nitric oxide synthase. The staining was diffuse in ulcerative colitis and patchy in Crohn's disease, in accordance with the distribution of active inflammation. Staining was seen in epithelial cells and was most intense near areas of inflammation such as crypt abscesses. Non-inflamed epithelium showed no immunoreactivity. Treatment with corticosteroids made no difference to the amount of nitric oxide synthase. CONCLUSIONS: Expression of nitric oxide synthase is increased in both ulcerative colitis and Crohn's disease and appears to be unaffected by treatment with corticosteroids. Disease severity necessitated surgery in all the cases included in this study, regardless of whether or not the patients had received long term corticosteroid treatment. It seems therefore that a high level of iNOS expression and, presumably, production of nitric oxide characterise cases which are refractory to clinical treatment; this suggests that specific inhibition of the enzyme may be a useful therapeutic adjunct.

Anti-Inflammatory Agents↗
PubMed1997

An unusual case of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an inherited disorder characterized by recurrent self-limiting attacks of joint, chest and abdominal pain associated with fever. The most serious complication in FMF is the development of amyloidosis, which usually leads to death from renal failure within a year. The use of colchicine has dramatically reduced this complication. We describe a 56-yr-old female patient with FMF in whom the arthropathy became the dominant clinical feature, resulting in the development of an erosive large and small joint arthritis during the course of the disease. The patient was treated with colchicine, but despite this, later developed amyloidosis confirmed on rectal biopsy, and chlorambucil was added to her treatment. For 10 yr, she also suffered intermittent abdominal pain and had terminal ileal changes suggestive of Crohn's disease. However, she was found to have ischaemic colitis at post mortem secondary to amyloidosis. Ischaemic bowel disease is an extremely unusual event in FMF. Other factors which may have contributed to the terminal ischaemia in this patient include anaemia secondary to blood loss and a drug-induced myelodysplasia, as well as hypotension during the final septicaemic illness. Clinicians should consider an ischaemic colitis as a possible differential diagnosis of abdominal pain in patients with FMF even in the absence of other clinical evidence of systemic amyloidosis.

Abdominal Pain↗
PubMed1997

Autopsy findings in the tongues of 20 patients with AIDS.

An extensive examination of the tongue was performed at autopsy in 20 consecutive patients who had died with AIDS. Abnormalities in the tongue were detected in 18 (90%) of the cases; the commonest lesions were ulceration (11), candidosis (8) and small foci of hyperkeratosis (10). The most extensive lesions were caused by Aspergillus infection (1), non-Hodgkin's lymphoma juxtaposed with Kaposi's sarcoma (1), herpetic infection (1) and candidosis (5). The disease causing death was identified in the tongue in two cases. There was a surprisingly low prevalence of oral hairy leukoplakia, which may be related to anti-viral or retroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Peptic duodenitis--does it exist in the second part of the duodenum?

AIM: To re-evaluate all patients diagnosed histologically as having peptic duodenitis who had known endomysial antibody (EMA) test results to find out whether they would still be classified as peptic duodenitis on histological analysis and to review their subsequent clinical course. METHODS: All mucosal biopsy specimens of the second part of the duodenum which were reported as showing features of peptic duodenitis and on which a serum EMA test had been done between January 1990 and January 1995 were reviewed. The number of intraepithelial lymphocytes (IELs) per 500 epithelial cells was also counted. The cases were re-assigned to one of three clinical categories: normal, coeliac disease or peptic duodenitis. Clinical details were reviewed for any cases where the re-assigned diagnosis and the EMA test result did not correlate. RESULTS: Of the 24 cases, 21 showed a correlation between morphology and immunology-that is, if the biopsy specimen was characteristic of coeliac disease, the EMA was positive and if the biopsy specimen was normal or characteristic of peptic duodenitis, the EMA was negative. Three cases had a negative correlation: two had a positive EMA test but a biopsy diagnosis of peptic duodenitis and one had a normal duodenal biopsy specimen with a positive EMA test. On review of their clinical details, two of the three patients were diagnosed with coeliac disease and the other with silent coeliac disease. EMA test results and IEL counts correlated with the final diagnosis in all cases. CONCLUSIONS: The diagnosis of peptic duodenitis on biopsy specimens of the second part of the duodenum was not substantiated in 92% of cases. On review of 24 cases, a histological diagnosis of peptic duodenitis was reached in four. In difficult cases, the histological appearances should be correlated with the EMA test result and the IEL count. Correlation of this kind should leave no cases of coeliac disease undiagnosed.

Adult↗
PubMed1997

To operate or not to operate? The value of fine needle aspiration cytology in the assessment of thyroid swellings.

AIMS: To evaluate all thyroid fine needle aspirations (FNA) done over a six year period to assess the accuracy and value of the technique. METHODS: There were 335 FNAs of which 184 had subsequent histology and 49 others had clinical follow up, providing 233 patients for analysis. All cytology and histology was reviewed with no significant alterations in diagnosis. The FNAs were classified into three groups: benign, suspicious (recommend excision), and malignant. The histology and medical records were reviewed to determine whether the cytology was accurate. RESULTS: There were 130 benign FNAs, 126 had non-malignant histology or normal clinical follow up, and four had malignancies on histology (two lymphomas, one follicular carcinoma, and one carcinoma not otherwise specified). There were 45 suspicious FNAs. Of these five had either follicular or papillary carcinoma, 14 had follicular adenomas, and 26 had colloid nodular goitres or normal clinical follow up. Of the 21 malignant FNAs, 11 had carcinoma and 10 had either a non-malignant histology or normal follow up. There were 126 true negatives, 30 true positives, 4 false negatives, and 36 false positives. This gives a sensitivity of 88%, a specificity of 78%, a positive predictive value of 46%, a negative predictive value of 97%, and an accuracy of 80%. CONCLUSIONS: FNA cytology of the thyroid has a high negative predictive value, which is useful to reassure the majority of patients presenting with thyroid enlargement. However, a negative FNA should never exclude malignancy if there is a strong clinical suspicion. If this rule is adhered to a large number of patients will be spared unnecessary surgery and no malignant nodule will go untreated.

Adenoma↗
PubMed1997

Parvovirus B19 infection in AIDS patients.

Bone marrow of 61 HIV-1-infected patients and 23 control patients was examined to determine the incidence of B19 infection and its clinical impact in HIV-1-infected persons. Of the 61 HIV-infected patients studied, ages ranged from 22-47 years with a mean of 33.2 years. There was a man:woman ratio of 3.8:1. With regard to staging of HIV disease at the time of bone marrow sampling, 52 patients were CDC group 4, 5 patients were CDC group 3, and 4 patients were CDC group 2. Control patients, were not known to be HIV-1-infected, and had one of the following conditions: lymphoma, leukaemia, thrombocytopenia, thrombocytosis, anaemia, multiple myeloma, raised serum IgM. Thirteen of 61 HIV-infected patients and 0 of 23 control patients were positive for B19 DNA in bone marrow (two-tailed P value = 0.016). Within the HIV-infected group, the average haemoglobin among persons testing B19 DNA positive (n = 13) was 11.1 g/dl, compared with 11.5 g/dl among persons testing B19 DNA negative (n = 48). In conclusion, B19 persistence may be common and frequently subclinical in AIDS patients.

Adult↗
PubMed1996

Gut barrier failure in experimental obstructive jaundice.

Bacterial translocation from the gastrointestinal tract is central to current concepts of endogenous sepsis. Studies were designed to evaluate the potential relevance of translocation to the high incidence of infection in obstructive jaundice. Sprague-Dawley rats underwent laparotomy and division of the bile duct or sham ligation. In Study 1, rats were sacrificed after 24 hr, 1 week, and 3 weeks and the mesenteric lymph node complex, cecum, and blood were cultured and plasma endotoxin was measured. In Studies 2 and 3, sham-and bile duct-ligated rats were challenged after 1 week with operative trauma and intravenous endotoxin, respectively. Animals were sacrificed after a further 24 hr. No translocation was observed in sham-operated rats. Although colonization of the mesenteric lymph nodes was not seen in bile duct-ligated rats after 24 hr, this was evident in 75% of rats after 1 and 3 weeks. Surgical trauma and endotoxin produced bacterial translocation in 33 and 40%, respectively, of sham-operated animals; this was enhanced in bile duct-ligated rats to 75% (P < 0.01 vs shams) and 93% (P < 0.001 vs shams), respectively. Endotoxin resulted in positive blood cultures in 71% of jaundiced rats compared with none of the sham group injected with endotoxin (P < 0.001). Biliary obstruction produces bacterial translocation and this process is enhanced by surgical trauma and endotoxin. The data support the thesis of gut barrier failure in jaundice and suggest that therapies targeted toward decreasing bacterial translocation may merit evaluation in the prophylaxis and treatment of infection in the jaundiced patient.

Animals↗
PubMed1996

Impaired gut barrier function in malnourished patients.

The gastrointestinal tract is essential to host defence, acting as a barrier to absorption and translocation of gut antigens, including bacteria. In experimental models, protein malnutrition is permissive to gut barrier failure and endogenous infection. A clinical correlate has not been described. Intestinal morphology and barrier function to food protein antigens was studied in malnourished patients. Thirty-five individuals were evaluated, 20 malnourished patients and 15 well nourished hospital controls. Morphology was assessed from endoscopic biopsies of the second part of the duodenum, and serum immunoglobulin (Ig) G antibodies to gliadin and beta-lactoglobulin were measured. No antibody to food proteins was evident in the control group. In contrast, serum IgG antibodies to at least one antigen were present in 15 malnourished patients and to both antigens in ten (P < 0.0001 versus controls). Severely malnourished patients were more likely to have both antibodies present than those with mild or moderate malnutrition (P < 0.05). Antibody-positive malnourished patients had significantly better nutritional status than antibody-negative patients with malnutrition (P < 0.05). In no group of patients was there morphological evidence of abnormal mucosa or an immunological infiltrate. Gut barrier function is compromised in malnourished patients which suggests a mechanism that may facilitate gut-derived infection and sepsis.

Adult↗
PubMed1995

Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.

Bacterial translocation from the gastrointestinal tract and macrophage activation are central to current theories of sepsis. The relevance of both in obstructive jaundice is unclear. The effect of bile duct ligation for 7 days on bacterial translocation to mesenteric lymph nodes and on macrophage activation in a rat model was examined. Compared with an incidence of zero in sham-ligated controls, bile-duct ligated rats had a 67 per cent incidence of Gram-negative colonization of mesenteric lymph nodes. This was associated with a significant (P < 0.001) decrease in macrophage tumour necrosis factor, superoxide anion and nitric oxide production compared with that in sham controls. Spontaneous bacterial translocation occurs in experimental obstructive jaundice and is associated with marked suppression of macrophage activation. This suggests a mechanism whereby jaundiced patients may be more susceptible to persistent infection but relatively protected against uncontrolled sepsis.

Animals↗
PubMed1995

High-dose interleukin 2 promotes bacterial translocation from the gut.

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) (n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli occurred in all rats treated with 10(5) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics and occasional mucosal disruption was seen only in the group receiving 10(5) IU. These data show that rIL-2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.

Animals↗
PubMed1995

Detection of Epstein-Barr virus DNA in tongue tissues from AIDS autopsies without clinical evidence of oral hairy leukoplakia.

Epstein-Barr virus (EBV) DNA was detected by in situ hybridization at 3 sites of 30 samples taken from clinically normal lateral border of tongue mucosa from 15 AIDS autopsies and in none of 20 samples from 10 controls. The first positive case showed a thin layer of parakeratosis correlated with positive signals for EBV in one area and an adjacent area without obvious parakeratosis was also positive for EBV. These findings were present on both sides of the tongue. The second case was unilaterally positive for EBV and parakeratosis was absent. The hybridization signals were localised to koilocyte-like cells in the stratum spinosum, as in oral hairy leukoplakia (OHL). These observations suggest that the in situ hybridization technique can detect very early or subclinical OHL, and supports the role of EBV in the pathogenesis of this lesion.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Neuroproliferation in the mucosa is a feature of coeliac disease and Crohn's disease.

The pathogenesis of villous damage in coeliac disease is unknown. Change to the delicate neuromuscular core may be significant and this study stained various categories of coeliac disease and controls with neuron-specific enolase (NSE) to examine neurofilaments in the mucosa. The amount of NSE staining was evaluated using computer image analysis. The first part of the study compared coeliac disease with Crohn's disease, carcinoma, and biopsy specimens from normal subjects. There was increased NSE staining in both the coeliac disease and Crohn's disease cases but not in carcinomas or normal controls. This difference was statistically significant. The average value for the coeliac disease patients was 50% higher than that of Crohn's disease patients. The second part of the study compared treated coeliac disease with untreated coeliac disease. Treated coeliac disease cases had normal amounts of NSE staining, which were the same as normal controls. These findings suggest that neuroproliferation is a feature of coeliac disease and Crohn's disease. Both share a common feature--namely chronic inflammation--which has been occasionally associated with neuroproliferation. The fact that neuroproliferation resolves with treatment is further evidence for its association with chronic inflammation. The extra neuroproliferation seen in coeliac disease compared with Crohn's disease may contribute to the architectural abnormalities seen in coeliac disease.

Celiac Disease↗