A case of unusual histiocytic colitis in a chronic alcoholic obese patient with ankylosing spondylitis.

A 64 year-old Caucasian man was first investigated 21 years ago for persistent diarrhoea. A colonoscopy revealed an erosive pancolitis with unusual vacuolated macrophages. Characteristics of ulcerative colitis or Crohn's disease were absent. Similar findings were observed consistently over the following years. A treatment with Sulfasalazine, Methotrexate or Budesonide was efficient. Histiocytic colitis is rare, and the various causes and different diagnoses are reviewed. The cause for the chronic pancolitis in this obese chronic alcoholic remains unknown at the time of writing. Links to the dyslipidaemia and chronic ankylosing spondylitis presented by the patient are possible hypotheses worth investigating further.

The good student is more than a listener - The 12+1 roles of the medical student.

BACKGROUND: The process of medical education, particularly in the fast evolving new era of medical metaschools, is a broad and complex issue. Harden & Crosby claimed that a good teacher is more than a lecturer, and identified 12 roles that certify a good and capable teacher. However, this is only half the truth: the good student is more than a listener. Teaching-and-learning is not simply a one-way process, and, as medical students are not children, the relationship between teacher and students involves andragogy rather than pedagogy. We therefore propose the 12+1 roles of the student. SUMMARY OF WORK: The Harden & Crosby paper was distributed in a class of 90 third year Ioannina University medical students, who were asked to think about the student's roles. A small discussion group brainstormed ideas, which were then refined further by the authors. SUMMARY OF RESULTS: 12+1 roles of the good medical student were produced and grouped into six areas: information receiver, in lectures and clinical context; role model in learning, in class, with the added subarea of comparative choice of role models; teaching facilitator and teacher's mentor; teacher's assessor and curriculum evaluator; active participator and keeping-up with curriculum; resource consumer/co-creator and medical literature researcher. The ideal student should fulfil the majority if not all of these complementary roles. TAKE-HOME MESSAGE: These 12+1 student's roles are complementary to the 12 roles of the teacher and help reshaping our understanding of today's medical education process.

External or internal lateral osteotomy: why I choose the external percutaneous approach.

The authors present their surgical experience with the management of patients with dorsum deformities using a precise technique: the external percutaneous approach. The indications for this technique have still not been set out very clearly in the rhinological textbooks or manuals, and so novices (and not only novices) have difficulty in understanding and applying it. We therefore try to systematise and clarify these indications in brief, together with the technical details, providing a comparison with another technique that is in very widespread use at present: the internal lateral osteotomy. Although the external percutaneous approach is not used very often--in our experience in 30% of cases only--we find the results very satisfactory and we recommend it when it is required by the anatomic conditions.

Is there an increased incidence of surgically removed thyroid carcinoma in Belgium ten years after Chernobyl? A study of hospital discharge data.

In order to provide some answers to the much debated subject of the consequences of the Chernobyl accident, this study attempts to measure the incidence of surgically removed thyroid cancers in Belgium ten years following the explosion. The analysis was made from the hospital discharge data between 1993 and 1998. It offers the advantage of national coverage in spite of certain validity limits. The results show an increase in surgically removed thyroid cancers, which is not, however, evident in the more susceptible younger generation who were involved at the time of the accident. Furthermore, the geographic distribution of the incidence is more marked in the south of the country, unaffected by the radioactive iodine contamination of 1986, which was more prevalent in the east of the country. The study of the type of surgery involved shows a rise in the proportion of total thyroidectomies. These findings are in favour of the hypothesis of a causal effect linking the increased incidence of thyroid cancers to medical practice and surgery in particular and not to the consequence of the possible contamination.

Subchronic inhalation of mixtures of cigarette smoke constituents in Xpa-/-p53+/- knock-out mice: a comparison of intermittent with semi-continuous exposure to acetaldehyde, formaldehyde, and acrolein.

We investigated whether inhaling peak concentrations of aldehydes several times daily is more damaging than semi-continuously inhaling low-dose aldehydes. We exposed Xpa-/-p53+/- knock-out mice either intermittently or semi-continuously to mixed acetaldehyde, formaldehyde, and acrolein. The intermittent regimen entailed exposure to the aldehydes 7 min every 45 min, 12 times/day, 5 days/week, corresponding to concentrations inhaled by smokers. Semi-continuously exposed animals received half the dose of aldehydes in 8h/day, 5 days/week. Some mice in each group were sacrificed after 13 weeks of exposure; the rest breathed clean air until the end of 1 year. Mice injected intratracheally with benzo[a]pyrene formed a positive control group. The nasal cavity, lungs, and any macroscopically abnormal organs of all mice were analysed histopathologically. After 13 weeks of exposure, the subacute, overall, histopathological changes induced by the inhalation differed noticeably between the intermittently and semi-continuously treated Xpa-/-p53+/- knock-out mice. After 13 weeks of mixed aldehyde exposure, atrophy of the olfactory epithelium generally appeared, but disappeared after 1 year (adaptation and/or recovery). Respiratory epithelial metaplasia of the olfactory epithelium occurred at a higher incidence at 1 year. Except for a significantly greater number of tumours observed in knock-out mice compared to wild mice (semi-continuous aldehyde exposure and controls), no differences between the semi-continuous and intermittent exposure groups were observed.

Lung permeability, antioxidant status, and NO2 inhalation: a selenium supplementation study in rats.

Little is known about antioxidant status, selenium status in particular, and lung response to NO2, which acts as a proinflammatory air pollutant. The effects of a low selenium diet (1.3 microg Se/d) with or without selenium supplementation were therefore studied in 128 Wistar rats, 2 mo old, male exposed to either acute (50 ppm, 30 min), intermittent subacute (5 ppm, 6 h/d, 5 d), intermittent long-term NO2 (1 ppm, 10 ppm, 6 h/d, 5 d/wk, 28 d), or normal atmospheric air (controls). Following sacrifice, measurements of lipid peroxidation (thiobarbituric acid-reactive substances, chemiluminescence), antioxidative protective enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD], glutathione S-transferase [GST], ceruloplasmin), lung damage (lactate dehydrogenase, alkaline and acid phosphatases), lung permeability (total protein, albumin), and inflammation (cell populations), along with the determination of new biomarkers such as CC16 (Clara-cell protein), were performed in serum and bronchoalveolar lavage fluid (BALF). While selenium-supplemented animals had increased GPx activity in serum prior to inhalation experiments, they also had decreased BALF CC16, blood SOD, and GST levels. Nevertheless, the protective role of normal selenium status with respect to NO2 lung toxicity was evident both for long-term and acute exposures, as the increase in BALF total proteins and corresponding decrease in serum (indicating increased lung permeability) was significantly more pronounced in selenium-deficient animals. During the various inhalation experiments, serum CC16 demonstrated its key role as an early marker of increased lung permeability. These findings corroborate the important role of selenium status in NO2 oxidative damage modulation, but also indicate, in view of its negative impact on CC16, a natural anti-inflammatory and immunosuppressor, that caution should be used prior to advocating selenium supplementation.

Autologous costochondral cartilage implant in two cases of velopharyngeal insufficiency.

The velopharyngeal sphincter is critical in enabling the functions of speaking and swallowing. Velopharyngeal insufficiency (VPI) results in hypernasal speech and nasal regurgitation. A frequent cause of VPI is congenital cleft palate, but otolaryngologists sometimes encounter iatrogenic VPI after surgery. Treatment of VPI with prostheses is often successful but not always well tolerated. Many surgical procedures have been proposed to correct palatal length or to enlarge the posterior pharyngeal wall. We report two cases in which autologous costochondral cartilage was used as implant augmentation. This approach is indicated and efficient when the velopharyngeal deficit is less than 5 mm. An autologous costochondral cartilage implant procedure is safe and reversible and can be expected to incite minimal host reaction.

Predictive factors of thyroid carcinoma in non-toxic multinodular goitre.

The management of nontoxic multinodular goitre (NMNG) remains controversial. The challenge for the clinician is to identify the small proportion of NMNG patients with associated thyroid carcinoma who would thus benefit from surgery. We studied retrospectively the medical records of 80 patients with NMNG and coexisting thyroid carcinoma who underwent total thyroidectomy. Eighty total thyroidectomy patients with NMNG whose histology was benign were then randomnly chosen as controls. In univariate analysis, the following parameters were significantly more frequent in the carcinoma group: rapid growth of the goitre (p = 0.002), presence of microcalcifications (p = 0.01), hypoechogenicity (p = 0.02), firm consistency of a nodule (p = 0.03), and presence of a dominant cold nodule on scintigraphy (p = 0.03). In the multiple regression analysis, the variables significantly associated with carcinoma were rapid growth (Odds ratio (OR) = 4.13, 95% confidence interval(CI): 1.72-9.89), hypo-echogenicity (OR = 3.11, 95% CI: 1.13-8.51) and the presence of a dominant nodule (OR = 2.26, 95% CI: 1.06-4.79)). In the cancer group, tumour size was positively correlated with compression signs (p = 0.01), age (p = 0.02), the presence of a dominant nodule on scintigraphy (p = 0.02), and with rapid growth (p = 0.04). Concerning nodule size estimated on US (ultrasound), the majority (65%) of patients without carcinoma had nodules < 3 cm, whereas 73% of patients with clinical thyroid carcinoma (> or = 1 cm on histology) had nodules with a diameter of > or = 3 cm on US (p = 0.02). In conclusion, our study suggests that surgical treatment of NMNG should be proposed in the presence of rapid nodular growth, compression signs, dominant nodule on scintigraphy, nodule size > or 3 cm and hypo-echogenicity.

Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas.

Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na(+)/I(-) symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H(2)O(2)-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T(4)-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T(4)-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H(2)O(2)-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T(4)-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.

Prevalence of thyroid cancer in Graves' disease: a retrospective study of a cohort of 103 patients treated surgically.

BACKGROUND: Thyroid nodules in patients with Graves' disease (GD) are common, and the incidence of coexisting thyroid carcinoma is a much debated subject, which is addressed in this study. METHODS: In order to determine the incidence rate of coexisting malignancy, a retrospective study was conducted on 103 patients who underwent surgery for GD between 1990 and 2000 at the Cliniques Universitaires Saint-Luc in Brussels, Belgium. The patients were classified into groups. Those in group I had a solitary palpable nodule (4.9%), those in group II multiple palpable nodules (12.6%), group IIIa had nodule(s) revealed by imaging techniques (incidentalomas: 17.5%), and group IIIb had diffuse non-nodular goiter (65%). RESULTS: Patients with nodules (groups I, II, and IIIa) were found to have significantly more thyroid carcinomas than those with diffuse non-nodular goiters (P=0.02), and the rate of malignancy was significantly increased when the nodules were palpable (groups I and II; P=0.03). Eight patients (7.8%) were diagnosed as having coexisting carcinomas, all but one being microcarcinomas. CONCLUSIONS: Well-differentiated papillary carcinomas are found to coexist with GD surgically treated (7.8%) and occur most frequently in GD with palpable nodular lesions (35%). Even though the majority (88%) of coexisting carcinomas are microcarcinomas, the presence of palpable nodules justifies further evaluation and follow-up.

Lung hyperpermeability and asthma prevalence in schoolchildren: unexpected associations with the attendance at indoor chlorinated swimming pools.

AIMS: To study whether exposure to nitrogen trichloride in indoor chlorinated pools may affect the respiratory epithelium of children and increase the risk of some lung diseases such as asthma. METHODS: In 226 healthy children, serum surfactant associated proteins A and B (SP-A and SP-B), 16 kDa Clara cell protein (CC16), and IgE were measured. Lung specific proteins were measured in the serum of 16 children and 13 adults before and after exposure to NCl(3) in an indoor chlorinated pool. Relations between pool attendance and asthma prevalence were studied in 1881 children. Asthma was screened with the exercise induced bronchoconstriction test (EIB). RESULTS: Pool attendance was the most consistent predictor of lung epithelium permeability. A positive dose-effect relation was found with cumulated pool attendance and serum SP-A and SP-B. Serum IgE was unrelated to pool attendance, but correlated positively with lung hyperpermeability as assessed by serum SP-B. Changes in serum levels of lung proteins were reproduced in children and adults attending an indoor pool. Serum SP-A and SP-B were already significantly increased after one hour on the pool side without swimming. Positive EIB and total asthma prevalence were significantly correlated with cumulated pool attendance indices. CONCLUSIONS: Regular attendance at chlorinated pools by young children is associated with an exposure dependent increase in lung epithelium permeability and increase in the risk of developing asthma, especially in association with other risk factors. We therefore postulate that the increasing exposure of children to chlorination products in indoor pools might be an important cause of the rising incidence of childhood asthma and allergic diseases in industrialised countries. Further epidemiological studies should be undertaken to test this hypothesis.

Relationships between cell division, expression of growth factors and microcirculation in the thyroids of Tg-A2aR transgenic mice and patients with Graves' disease.

Tissue heterogeneity and nodule formation are hallmarks of thyroid growth. This is accounted for by the clonality theory that acknowledges different individual cellular abilities to respond to trophic stimuli. In order to test the hypothesis that functional and mitotic properties of thyrocytes could be influenced by paracrine interactions with neighbour endothelial cells, studies were conducted in both mouse and human goitre models. In the first part of the study, homogenous goitres in C57 black mice were compared with heterogeneous goitres in transgenic hyperthyroid mice expressing the A2 adenosine receptor (Tg-A2aR). The second part of the study concentrated on comparing human thyroid tIssue of control individuals and of patients with Graves' disease. The rate of cell division was evaluated by immunohistochemical detection of cells positive for proliferating cell nuclear antigen (PCNA). Their spatial distribution was then correlated with immunohistochemical cellular expression of growth- and vasoactive-related factors (fibroblast growth factor-2, transforming growth factor-beta, endothelin-1, vascular endothelial growth factor, nitric oxide synthase III), and with microcirculation expansion. Observations were made on digitalised images of histological serial sections. The nearest-neighbour method was used to distinguish between random or clustered distribution. PCNA-positive cells were both randomly and uniformly distributed in homogenous goitres from C57 black mice, and were clustered in tIssue areas identified as papillary and hyperplastic zones in heterogeneous goitres from Tg-A2aR mice. However, they were absent in the so-called compact cellular zones featuring resting cells. Moreover, whereas papillary and hyperplastic zones were highly vascularised, compact zones were nearly free of microvessels. Spatial distribution of dividing cells was positively correlated with the expression of growth-related factors. A similar pattern was observed in the thyroids of patients with Graves' disease. In accordance with the recent demonstration of the presence of angiofollicular units in the thyroid, these data strongly support the hypothesis that functional and mitotic properties of each single thyrocyte, likely to be responsible for growth heterogeneity of hyperplastic glands, may be adjusted at tIssue level by specific interactions with neighbour endothelial cells that, in turn, could alter the mitotic rate of thyrocytes through paracrine signals.

Urinary homovanillic acid and serum prolactin levels in children with low environmental exposure to lead.

Current evidence suggests that the neurotoxic effects of lead may partially be mediated through interference with the dopaminergic system. The aim of this study was to assess the levels of two peripheral dopaminergic markers--serum prolactin (Pro-S) and urinary homovanillic acid (HVA-U)--in children living around two lead smelters, who are presumed to be exposed to high environmental lead pollution (n = 200), and compare their results with 200 age- and sex-matched controls living in an area unpolluted by heavy metals, giving a total of 400 children (200 boys and 200 girls). The influence of lead exposure on HVA-U and Pro-S was assessed by stepwise multiple regression, testing lead concentrations in blood (Pb-B), age, sex and area of residence as predictors. Though lead levels were significantly higher in boys and in the lead-polluted environment, mean Pb-B values were relatively low, indicating a low uptake of lead in the contaminated environment (39.5 micrograms l-1, range 4.6-165 micrograms l-1, n = 200), and no significant correlation could be found with either Pro-S or HVA-U. However, when the subgroup of 121 children with Pb-B levels above 50 micrograms l-1 were considered, a weak positive correlation was found between Pb-B and HVA-U (r2 = 0.04, p = 0.03), whilst in the even smaller subgroup of 15 children with Pb-B levels above 100 micrograms l-1, Pro-S appeared to be positively correlated with Pb-B, though the numbers of children were too small for the correlation to reach statistical significance (p = 0.095). These weak associations, probably not important in biological terms, indicate that Pro-S and HVA-U are not useful biomarkers at present exposure levels to lead in the environment. Nevertheless, the finding of subtle biochemical alterations in the dopaminergic system at Pb-B levels of around 100 micrograms l-1 supports the recommended setting of the action level at this value.

The distribution of ceroid in human atherosclerosis.

It has been suggested that macrophages in atherosclerotic plaques oxidize the lipid they contain, leading to necrosis in the plaque. Over 200 human aortic and coronary atherosclerotic plaques from 102 human necropsy subjects aged between 5 and 88 were, therefore, examined histologically for the presence of insoluble lipid (ceroid), thought to be a product of lipid oxidation. Ceroid was present in all the plaques but not in areas of diffuse intimal thickening. In early lesions the insoluble lipid was within membrane-bound vesicles in macrophage-like cells, many showing characteristic ring structures suggesting that membrane-associated oxidative systems might be responsible for rendering the lipid insoluble. Staining was increased by an oxidizing agent and abolished by a reducing agent. It is suggested that this distribution supports the concept of lipid oxidation by macrophages within the plaque.