Modulation of the transformed and neoplastic phenotype of rat fibroblasts by MHC-I gene expression.

Transfection of the activated ras oncogene (Ha-ras) into second passage rat embryo fibroblasts can induce the metastatic phenotype, while cotransfection of Ha-ras with the adenovirus type 2 E1a gene (Ad2-E1a) yields cells which are tumorigenic but nonmetastatic in nude mice. Because of the presence in nude mice of natural killer cells and B-lymphocytes, which might account for the different metastatic behavior of single versus double transfectants, we used triple deficient mutants as recipient animals in tumorigenicity assays. These mice carry two additional mutations resulting in the deficiency of natural killer cells and activated B-lymphocytes. We observed that the rat embryo fibroblast transfectants exhibit the same metastatic behavior in nude as well as in triple deficient mice, indicating that natural killer and B-cells are not responsible for the observed difference in metastatic phenotype between Ha-ras and Ha-ras plus Ad2-E1a transfectants. Double transfectants were found to express higher levels of major histocompatibility complex class I genes and the degree of expression appeared to correlate inversely with in vitro and in vivo parameters such as the ability to grow in agar-containing semisolid media and rate of tumor formation in triple deficient mice. Our observations are consistent with the concept that expression of major histocompatibility class I genes may be involved in regulating and modifying cell behavior by mechanisms independent of their role in immune recognition.

Association of Helicobacter pylori infection with dyspeptic symptoms in patients undergoing gastroduodenoscopy.

PURPOSE: To determine the prevalence of Helicobacter pylori in patients with non-ulcer dyspepsia and ulcer disease as well as in a control population undergoing endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic or biliary disease. PATIENTS AND METHODS: Forty-six eligible patients undergoing upper endoscopy at Massachusetts General Hospital were studied over a period of 18 months, as well as 24 patients undergoing ERCP for presumed pancreatic or biliary disease. Two biopsy specimens from the fundus and two from the antrum were taken for microbiologic and histopathologic analysis. Sera were examined by enzyme-linked immunoabsorbent assay. All specimens were processed in a blind fashion. Chi-square test with Yates' correction was used for statistical analysis. RESULTS: H. pylori was found in 31 of 46 (67%) study patients and in six of 24 (25%) control patients (by microbiologic or histologic techniques) (p less than 0.01). H. pylori was found in all patients with peptic ulcer disease and in 60% of patients without ulcers. No association between H. pylori and any specific gastrointestinal symptom was observed. H. pylori was identified in the fundus as often as in the antrum, although in the antrum the organism was more often associated with histologic gastritis. Compared with histology, serologic assays for IgG and IgA antibodies to H. pylori had sensitivities of 100% and 94%, and specificities of 86% and 76%, respectively. Reexamination of selected specimens without knowledge of their identity revealed that the specificity of serology exceeded 94% while the sensitivity of histologic and microbiologic studies may have been closer to 80%. CONCLUSIONS: H. pylori was more common in dyspeptic patients than in our control subjects undergoing ERCP. Multiple biopsy sites from fundus and antrum are required to exclude infection. Serologies of IgG and IgA were sensitive and specific for H. pylori, suggesting a possible role for non-endoscopic diagnosis of this infection. The frequent association of H. pylori with active inflammation rather than with quiescent gastritis is consistent with a pathologic role of this organism.

Serum hyaluronic acid in patients with veno-occlusive disease following bone marrow transplantation.

The development of hepatic veno-occlusive disease following bone marrow transplantation is associated with high-dose combination cytoreductive therapy. Experimental models have suggested that drug-induced injury to hepatic sinusoidal endothelial cells is involved in the pathogenesis of this syndrome. Hyaluronic acid is a polysaccharide that is metabolized, almost exclusively, by hepatic sinusoidal endothelial cells. The aim of the present study was to evaluate serum hyaluronic acid as a marker for endothelial cell injury in patients with veno-occlusive disease following bone marrow transplantation. Hyaluronic acid was measured in sera from patients with and without veno-occlusive disease using an enzyme-linked protein binding assay. Mean peak serum hyaluronic acid levels were significantly greater in patients who had a diagnosis of VOD compared to those transplant patients who did not, 1173.4 +/- 982.9 vs 444.9 +/- 735.6 ng/ml (P = 0.01). Serial serum samples obtained from a separate cohort of patients also demonstrated that serum hyaluronic acid levels were higher in patients with moderate or severe veno-occlusive disease compared to those with none or mild disease at days 7, 17 and 25 following transplantation (greatest difference at day 25: 366 +/- 327 vs 126 +/- 151, P = 0.01). Serum hyaluronic acid levels are increased in veno-occlusive disease and increase over time in patients with severe disease. Further studies are required to determine if elevated serum hyaluronic acid levels are due to decreased clearance by injured hepatic sinusoidal endothelial cells or increased production from early hepatic fibrogenesis associated with the acute liver injury.

Selected drug complications and treatment conflicts in the presence of coexistent diseases.

The presence of different coexistent systemic diseases often times complicates the selection of the appropriate treatment of an underlying rheumatologic condition. In this article, some controversial treatment conflicts that are frequently encountered in the daily practice of rheumatology are clarified and guidelines for the best available therapeutic options are provided.

Successful treatment of molluscum contagiosum with topical imiquimod in a severely immunocompromised HIV-positive patient.

Molluscum contagiosum is a common viral infection in the immuno-compromised HIV-positive patient where it is often severe and affecting the face and neck. It is frequently resistant to conventional, locally destructive therapies. Anecdotal evidence suggests that the immunomodulatory drug imiquimod might be a valid therapeutic option in this group of patients. We report the case of a severely immunocompromised HIV-positive patient with resistant facial molluscum contagiosum lesions that responded to topical imiquimod. The response to therapy and the possible implications for pathogenesis are discussed.

Mountaineer's heel.

Mountaineers are at risk of skin lesions caused by constant boot friction. This is the case of a 35 year old mountaineer who presented with large and deeply ulcerated lesions over the medial aspects of both heels after a two and a half day climb using crampons. A number of factors such as the length of the climb in cold and thin air and the impossibility of removal of the footwear to allow rapid rewarming may have contributed to a more acute presentation of these lesions.

A retrospective study addressed to understanding what predicts severe histological dysplasia/early melanoma in excised atypical melanocytic lesions.

BACKGROUND: Atypical naevi are common benign skin lesions but are also recognized both as precursors of and risk factors for melanoma. It is therefore imperative to excise those lesions that are either likely to progress or are already progressing to melanoma. Clinically, however, it may be difficult to distinguish these from benign atypical naevi with bland histology. OBJECTIVES: To analyse the clinical characteristics of excised melanocytic lesions and to identify the predictors of severe histological atypia/melanoma in situ and invasive melanoma. METHODS: The case notes of 434 patients who had melanocytic lesions removed at a pigmented lesion clinic were studied retrospectively. A single pathologist reviewed the excised lesions and clinical characteristics predictive of malignancy were identified. RESULTS: The best predictors of melanoma were older age, history of change and site on an extremity, but only older age was predictive of severe histological atypia/melanoma in situ as opposed to mild to moderate atypical histology. CONCLUSIONS: These results confirm the difficulty of differentiating accurately between benign atypical naevi and borderline lesions or early melanoma in a clinical setting. It is therefore necessary to have a sufficiently low threshold for excision to avoid missing early melanomas, particularly in older patients presenting with lesions on the extremities.

Is minocycline therapy in acne associated with antineutrophil cytoplasmic antibody positivity? A cross-sectional study.

BACKGROUND: Minocycline (MN), one of the commonly prescribed therapies for acne, is known to be associated with autoimmune disorders including drug-induced lupus. However, data are sparse regarding the prevalence of autoimmune disease in acne or in patients with acne treated with MN. OBJECTIVES: To establish the prevalence of antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA) and new autoimmune syndromes in an MN-exposed and unexposed population with acne. METHODS: In a cross-sectional study, 252 patients with acne vulgaris were assessed. Sixty-nine per cent had been exposed to MN at some point or were taking the drug at the time of the interview. Data recorded included duration of disease (acne) and drug history as well as possible side-effects of drugs, in particular joint symptoms (pain and swelling). In addition, blood was taken for ANA, ANCA, liver function tests and HLA analysis. RESULTS: There was no statistical difference in the prevalence of ANA positivity between patients exposed (13%) or not exposed (11%) to MN. However, higher titres of ANA (1/160 or higher) were found in the MN-exposed group (45% compared with 12% in the unexposed group). ANCA positivity was found in 7% of the MN-exposed group but no positivity was found in the unexposed cohort (P = 0.022). In 58% of cases, the ANCA detected were of the perinuclear pattern (p-ANCA) with myeloperoxidase specificity, and this finding was associated with clinical symptoms in the majority of cases. Two p-ANCA-positive patients were thought in retrospect to have developed a drug-induced lupus syndrome. CONCLUSIONS: ANA positivity is seen in patients with acne irrespective of exposure to MN; however, p-ANCA appear to be a serological marker for developing autoimmune disease in patients receiving MN.

Unilateral naevoid trichoepitheliomas on the face of a child.

Trichoepitheliomas are benign epidermal appendage tumours that present most commonly as solitary lesions, and less often as multiple, symmetrically distributed lesions on the face, scalp, neck and trunk. Only a few patients have been reported in whom trichoepitheliomas were found as unusually configured linear or plaque-like confluent lesions, all of which occurred in patients with skin types V or VI. We describe a white girl with a hemifacial plaque of confluent naevoid trichoepitheliomas, the first report of such lesions in a white patient.

A child with laryngo-onychocutaneous syndrome partially responsive to treatment with thalidomide.

Laryngo-onychocutaneous syndrome (LOCS) is a condition characterized by erosive or ulcerative skin lesions associated with excessive granulation tissue, at sites of trauma such as the digits, elbows and knees. Similar lesions can occur within the conjunctival mucosa, leading to corneal scarring and blindness. The main complications, however, occur in the respiratory tract, where a similar process of erosions and subsequent formation of granulation tissue causes airway obstruction which may lead to premature death. LOCS is now believed to be a nonblistering variant of junctional epidermolysis bullosa and to date there are no efficacious treatments available. We report a 16-year-old girl with LOCS who failed to respond to methylprednisolone and cyclophosphamide, but had a partial response to oral thalidomide with marked decrease in granulation tissue and tracheal secretions. Interruption of treatment resulted in prompt resurgence of the granulation tissue which was again controlled by reintroduction of thalidomide. We propose that in the absence of effective therapies for LOCS, a trial of thalidomide in these patients should be considered.

Hepatic hydrothorax.

Ascites is a common manifestation of portal hypertension in patients with cirrhosis. Approximately 5% of patients with cirrhosis may develop a pleural effusion. This is usually right sided. In the absence of cardiac or lung disease, the presence of a pleural effusion in a cirrhotic patient is known as hepatic hydrothorax. Small volumes of fluid within the pleura may be associated with significant respiratory symptoms which require the clinician to rapidly remove the fluid. The development of hepatic hydrothorax is secondary to passage of ascites from the abdomen to the pleural space via defects in the diaphragm. Once the diagnosis of hepatic hydrothorax is established with certainty, medical therapy with salt restriction and diuretics is initiated. When these measures are ineffective the patient has refractory hepatic hydrothorax. Based on current studies, transjugular intrahepatic portal systemic shunts appear to be the most effective form of treatment for these patients.

Occupational contact dermatitis in nurses with hand eczema.

Occupationally related dermatitis is a common problem in nurses, who are exposed to a wide variety of allergenic and irritant substances. In a group of 44 nurses with hand dermatitis (40 female, 4 male), 18 were thought to have a predominantly allergic contact dermatitis, 15 an irritant dermatitis, 7 other form of eczema, 3 atopic dermatitis and one pompholyx. 10 of the 15 irritant cases were diagnosed as occupational. Of the 18 patients with allergic contact dermatitis, the allergens were thought to be occupationally relevant in 8 cases. In 6 of these 8 the dermatitis was due to natural rubber latex (3) or other rubber chemicals (3). 2 had additional evidence of immediate-type hypersensitivity to natural rubber latex (one was patch test allergic to latex, the other to thiuram mix). Natural rubber latex allergy, both delayed and immediate, is a significant problem, and nurses at risk should be tested for both types of hypersensitivity, as well as being patch tested to standard, rubber and medicaments series.

Digital imaging in clinical dermatology across the UK in the year 2001.

Colour photography is an important tool in the daily practice of dermatologists. Digital photography promises quicker acquisition and handling of clinical images. Despite increasing availability and falling costs, dermatologists have been slow in adopting this new technique. To establish to what degree digital photography has found its way into routine practice in dermatology departments in the UK during the year 2001, we conducted a postal survey of all dermatology departments in the UK about usage of digital cameras. A total of 65.4% of the questionnaires were returned. The responses indicated that 71% of departments in teaching hospitals vs. 56% of departments in district general hospitals (DGH) had access to a digital camera. Reasons for not having a digital camera were satisfaction with conventional photography and lack of resources. In 48% of the departments of teaching hospitals or DGH with access to a digital camera, less than 10% of all photos were taken digitally. However, 24% of departments in DGH and 22% in teaching hospitals took more than 80% of their clinical photos digitally, indicating that in many departments digital photography is still in an early phase and only occasionally used, whilst in others a change from conventional photography towards digital photography as the mainly used technique has already taken place. Overall, the main drawbacks of digital photography were poorer resolution in comparison with conventional photography, problems with storage and filing images and time required for downloading and storing images.

Skin abnormalities in the National Portrait Gallery.

Pathological changes in the human body have long been recognised in painting. To assess the frequency of potential physical abnormalities reflected in paintings, we reviewed portraits on display at one visit in the National Portrait Gallery in London. We identified a number of possible abnormalities, most of them dermatological, with the commonest finding being small facial papular lesions, most likely representing either common warts or dermal naevi. This exercise however, reflects a subjective interpretation of the different artists's perceptions of their models' physical appearances.

Transjugular intrahepatic portal systemic shunt for the management of symptomatic cirrhotic hydrothorax.

OBJECTIVE: To investigate the safety and effectiveness of performing transjugular intrahepatic portal systemic shunt (TIPS) for the management of symptomatic cirrhotic hydrothorax in patients with advanced cirrhosis. METHODS: TIPS was performed by standard technique after portal vein patency had been established by ultrasound. Portal-hepatic vein pressure gradient was determined before and after placement of the shunt. A portal-hepatic vein gradient of less than 12 mm Hg was the treatment goal. RESULTS: Five patients underwent TIPS placement over an 11-month period. Despite use of diuretics, the patients had required a median of seven thoracenteses (range 2-11) for control of symptoms preceding placement of the shunt. A TIPS was placed without serious complications in all five patients. In two patients, insertion of the shunt was associated with no further need for thoracentesis. The other three patients had recurrent need for thoracentesis. These three patients were found to have occluded shunts which were rendered patent by angioplasty and/or urokinase. Subsequently, two required no further thoracentesis, whereas, in the other patient, the need for thoracentesis was decreased dramatically. CONCLUSIONS: TIPS appears to be a safe and useful technique for the management of patients with symptomatic cirrhotic hydrothorax that is refractory to medical therapy. Recurrence of the pleural effusion after placement of TIPS may be an indication of shunt occlusion.

A case of childhood dermatofibrosarcoma protuberans without detected cytogenetic abnormality.

Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative skin tumour of intermediate malignancy, with a limited potential for metastasis but a high rate of recurrence; specific cytogenetic abnormalities are now known. Childhood DFSP has been considered a rarity in the past, but it is now recognized that many cases of childhood DFSP are diagnosed only in adulthood. Despite advances in the understanding of its pathogenesis as well as the development of valuable immunohistochemical and cytogenetic diagnostic techniques, there often remains a significant delay between the initial presentation and diagnosis of DFSP. We report a case of childhood DFSP in which the diagnosis was reached only after a nodular lesion developed in a plaque that was initially present. Causes for delay between initial presentation and diagnosis in childhood DFSP are discussed. Histology and immunostaining in our patient showed the typical features of DFSP, but the G-banded cytogenetic analysis of short-term tissue culture was negative. However, this technique offers only a detection rate between 50% and 80%. Clinicians should be aware of the limitations of newer diagnostic techniques. Increasing recognition amongst paediatricians and paediatric dermatologists that childhood DFSP is not as rare as once believed will probably lead to the use of newer diagnostic methods at an earlier stage, and so reduce the delay between the onset of symptoms and diagnosis.

Coexpression of galanin and adrenocorticotropic hormone in human pituitary and pituitary adenomas.

Galanin is a neuropeptide that regulates the secretion of several pituitary hormones, including prolactin (PRL) and growth hormone (GH). Galaninlike immunoreactivity (Gal-IR) and galanin mRNA in the rat anterior pituitary is cell lineage specific, with predominant expression in lactotrophs and somatotrophs. The authors examined the cellular distribution of human Gal-IR in seven normal postmortem pituitaries and 62 pituitary tumors by immunoperoxidase staining. In contrast to the rat, Gal-IR in human anterior pituitaries was present in corticotrophs scattered throughout the gland, but not in lactotrophs, somatotrophs, thyrotrophs, or gonadotrophs. Distinct Gal-IR also was present in hyperplastic and neoplastic corticotrophs in 19 of 22 patients with Cushing's disease. In noncorticotroph cell tumors, unequivocal Gal-IR was present in 5 of 11 GH-secreting tumors associated with clinical acromegaly, 9 of 18 nonfunctioning pituitary adenomas, and 2 of 14 prolactinomas. Of these galanin-positive tumors, four of the five GH-secreting adenomas, six of the nine nonfunctioning adenomas, and both of the prolactinomas also contained adrenocorticotropic hormone immunoreactivity (ACTH-IR). Immunostaining and in situ hybridization on adjacent sections using an 35S-labeled probe complementary to human galanin mRNA demonstrated predominant galanin expression in normal corticotrophs. Immunoelectron microscopy confirmed the presence of Gal-IR in pituitary cells characteristic of corticotrophs in both normal and neoplastic pituitaries. Thus, as in the rat, galanin gene expression in the human pituitary is cell-type specific. Unlike the rat, however, human galanin gene expression is restricted to the corticotroph lineage. Studies of tumors confirmed the observed coexpression of galanin and adrenocorticotropic hormone. The divergent cell type specificity of galanin production in human and rat pituitaries reflects different patterns of gene activation in these two species. In addition, these results suggest that galanin in the human pituitary may participate locally in the regulation of the hypothalamic-pituitary-adrenal axis.