Vitamin D and autoimmunity.

OBJECTIVES: To review and evaluate the role of vitamin D in autoimmune diseases based on current studies. METHOD: We searched PubMed using keywords such as 'vitamin D', 'autoimmune disease', and 'autoimmunity'. We compiled and reviewed various studies including prospective cohorts, cross-sectional studies, longitudinal evaluations, genetic studies, and experimental models that investigated the role of vitamin D in autoimmune diseases. RESULTS: There is evidence based on these various studies that several key autoimmune diseases are modulated by vitamin D. These diseases include, but are not limited to, multiple sclerosis (MS), scleroderma or systemic sclerosis (SSc), autoimmune thyroid diseases, rheumatoid arthritis (RA), and primary biliary cirrhosis (PBC). CONCLUSIONS: Although there is evidence for vitamin D as a factor in the pathophysiology of autoimmune diseases, the mechanism for this association has yet to be elucidated. Additional data are needed to corroborate these findings.

MEMS and microfluidics for diagnostics devices.

There are conditions in clinical medicine demanding critical therapeutic decisions. These conditions necessitate accuracy, rapidity, accessibility, cost-effectiveness and mobility. New technologies have been developed in order to address these challenges. Microfluidics and Micro Electro-Mechanical Systems are two of such technologies. Microfluidics, a discipline that involves processing fluids at the microscale in etched microchannels, is being used to build lab- on-a-chip systems to run chemical and biological assays. These systems are being transformed into handheld devices designed to be used at remote settings or at the bedside. MEMS are microscale electromechanical elements integrated in lab chip systems or used as individual components. MEMS based sensors represents a highly developed field with successful commercialized products currently being incorporated into vitro,ex vivo and in vivo devices. In the present paper several examples of microfluidic devices and MEMS sensors are introduced together with some current examples of commercialized products. Future challenges and trends will be discussed.

[Pulmonary adenocarcinoma in myasthenia gravis--autoimmunity and late development of malignancy].

We report a 75-year-old man with myasthenia gravis for many years, who was hospitalized because of cough, fever, and dyspnea. Chest x-ray revealed a bilateral pleural effusion. Adenocarcinomatous cells were found in the pleural fluid. Computerized tomography of the chest showed widespread pulmonary dissemination of the tumor. The relationship between myasthenia gravis, an autoimmune disease involving the motor end-plate, and malignancy (thymoma) has been widely recognized. Current literature documents few reports of lung malignancies with concurrent development of myasthenia gravis. A tentative explanation, based on current research, is provided for the possible role of myasthenia gravis and the late development of lung cancer. Moreover, a model for the autoimmune phenomenon and the development of late malignancies is provided with explicit explanations. It is important to search for occult, developing malignancies in newly diagnosed autoimmune diseases.

An acute ischaemic event associated with the use of venlafaxine: a case report and proposed pathophysiological mechanisms.

Venlafaxine, a structurally novel antidepressant, belongs to a new generation of antidepressants--the serotonin/noradrenaline reuptake inhibitors. In clinical trials, venlafaxine was found safe and effective in most patients. However, significant changes in vital signs (hyper- and hypotension) and cardiac conduction abnormalities were observed in a few patients, notably in elderly patients. We present a case of an elderly woman with a pre-existing history of ischaemic heart disease, who was treated with venlafaxine, and developed acute myocardial ischaemia within the first week of treatment. This is the first report of a possible association between an acute cardiovascular event and venlafaxine. The association of venlafaxine treatment with ischaemic events could be explained by its unique pharmacological and haemodynamic properties.

Recurrent aphthous stomatitis in Behçet's disease: clinical features and correlation with systemic disease expression and severity.

Behçet's disease (BD) is a multisystem disease, in which recurrent aphthous stomatitis (RAS) is a universal finding. We studied the expression of RAS in patients with BD, and the correlation between major or minor RAS and systemic expression and severity of the disease. Thirty-five patients with BD were studied, of whom 13 (37%) had major, 21 (60%) had minor and one (3%) had herpetiform RAS. The frequency of major RAS was significantly higher compared with a control group of patients with idiopathic RAS (37% vs 9%, P < 0.05). The BD patients with major RAS had significantly more relapses of oral ulceration in a year, higher numbers of oral ulcers per relapse, and longer duration of aphthous episodes, compared with patients with minor RAS. Oral ulcers also appeared at a significantly younger age in patients with major than with minor RAS. However, the systemic expression of the disease, as well as the disease severity score, were similar in patients with major and minor RAS. The results of this study indicate that major RAS is common in patients with BD, and is associated with a more severe, repeated and prolonged oral disease. Nevertheless, the presence of major RAS in BD does not predict a more severe systemic illness.

Colonic obstruction due to sigmoid muscular hyperplasia.

We report a case of acute colonic obstruction initially presumed to be secondary to acute diverticulitis, necessitating emergent surgical intervention. Pathologic examination failed to reveal evidence of inflammation, fibrosis or neoplasia. Marked hypertrophy of the sigmoid circular muscle layer was documented and thought to be the etiology of the colonic obstruction.

Continuous avoidance measures with or without acaricide in dust mite-allergic asthmatic children.

BACKGROUND: Improvement in the quality of life in the Western world and increased time spent indoors by children have enhanced the spread of house dust mites and increased the exposure time for sensitive children. Also, exposure to house dust mites in infancy and subsequent development of childhood asthma have been clinically linked. Recently, new acaricides have been developed. OBJECTIVE: To test the efficacy of the new acaricide (esdepallethin and piperonyl butoxide--"Acardust") combined with environmental control compared with continuous house dust mite avoidance measures. METHOD: Forty-six house dust mite-allergic, asthmatic children were evaluated for 6 months in a prospective, randomized, double-blind, and placebo-controlled study. Patients were randomly allocated to active and placebo acaricide treatment combined with avoidance measures, whereas only continuous avoidance measures were taken in the third group. Symptom score, medication usage, and peak flow measurements were recorded daily. The amount of house dust mite allergen in the dust vacuumed from the bedrooms was also measured. RESULTS: Morning and evening peak expiratory flow rates and forced expiratory volume in one second remained unchanged throughout the study period. In all groups, the symptom scores improved significantly, whereas the amount of house dust mite allergen decreased significantly at the end of the trial. CONCLUSIONS: Continuous house dust mite avoidance measures have a significant positive effect on the symptomology of children with mild or moderate asthma. "Acardust" combined with continuous house dust mite avoidance measures is not more effective than continuous house dust mite avoidance measures alone in the treatment of house dust mite-allergic, asthmatic children.

Neurotropic desmoplastic melanoma: a rare vulvar malignancy.

Melanoma represents the second most frequent vulvar malignancy, and yet is still considered to be an uncommon neoplasm. Several varieties of melanoma exist. A patient who was diagnosed with a rare subtype of melanoma as a primary vulvar process is presented here. To date, there is only one other reported case of neurotropic desmoplastic melanoma as a primary vulvar lesion. Our management included wide local excision of the primary lesion with clinical follow-up. Microstaging of this lesion showed it to fall into the poor prognosis category as per Breslow's technique, with a thickness of 6.5 mm. Clinical follow-up has been greater than 30 months without evidence of recurrence.

The effect of intravesical instillations of thiotepa, mitomycin C, and adriamycin on normal urothelium: an experimental study in rats.

The effects of intravesical instillations of thiotepa, mitomycin C and adriamycin on the normal urothelium were studied in rats. Changes in the bladder wall in the form of fibroblastic atypia and submucous fibrous plaques were significant in the mitomycin C treated group. In 46% of mitomycin C treated animals there was urothelial atypia and in one animal, the atypia was severe enough to resemble carcinoma in situ. None of the rats treated with thiotepa showed intramural fibrous plaques or fibroblastic atypia and only 8% showed urothelial atypia. In the group treated by adriamycin instillation, 17% showed intramural fibrous plaques, but none showed urothelial atypia or fibroblastic atypia. The fibroblastic atypia and submucosal fibrous plaques seen in the mitomycin treated group may explain the reduced bladder capacity seen in the clinical setting.

Intraoperative pathologic diagnosis of thyroid neoplasms. Report on experience with 504 specimens.

Intraoperative pathologic examination with frozen section (FS) was performed on 504 specimens of thyroid tissue obtained from 457 patients over a period of 9 years. After examination of permanent sections (PS) a malignant neoplasm was diagnosed in 57 specimens (11.3%); 50 (87%) of these were primary thyroid carcinoma, four (8%) metastatic carcinoma, and three (5%) malignant lymphoma. The FS diagnosis was "benign" in 448 (88.9%), "malignant" in (30) 5.9%, and "deferred" in 26 (5.2%). The sensitivity of FS diagnosis of malignancy was 53% and the specificity and positive predictive value 100%. The negative predictive value was 97.8% and overall accuracy 97.9%. The PS disclosed a malignant neoplasm in 62% of specimens in which FS diagnosis was "deferred." Sixty-eight percent of papillary carcinomas, 87% of undifferentiated carcinomas, and a single case of medullary carcinoma were diagnosed with FS examination. A FS diagnosis of malignancy was not made in any of the ten specimens containing follicular carcinoma; in all ten the neoplasms were well-differentiated and eight were encapsulated and minimally invasive. The inability to diagnose follicular carcinoma intraoperatively with FS is the most significant factor accounting for the relatively low sensitivity of FS diagnosis of malignant thyroid neoplasms.

Physical exercise conditioning in the absence of weight loss reduces fasting and postprandial triglyceride-rich lipoprotein levels.

The effect of physical exercise conditioning on fasting and postprandial lipoprotein levels was studied in six normolipidemic subjects. The study consisted of two phases: a baseline stabilization phase in which subjects maintained their regular physical activity and an exercise conditioning phase in which subjects had 29 exercise sessions during a 7-week period. Each of these sessions consisted of jogging on a treadmill for 30 minutes. The subjects averaged 15.2 miles/wk. To control for possible confounding factors, such as changes in diet composition and weight loss, we placed the subjects on a metabolic diet and increased their daily caloric intake during the exercise phase. At the end of each phase of the study, a vitamin A-fat loading test was done to specifically label and follow postprandial lipoprotein levels, and a maximum oxygen consumption test was done to evaluate the subjects' physical fitness. The exercise conditioning phase significantly increased the subjects' aerobic capacity and postheparin lipoprotein lipase activity, and the phase decreased fasting triglyceride levels. Physical exercise also significantly decreased chylomicron (Sf greater than 1,000) levels by 37%. In summary, this study suggests that physical exercise conditioning reduces fasting and postprandial lipoprotein levels by increasing the catabolism of triglyceride-rich particles. Because these particles may have a role in atherogenesis, this could be a major mechanism by which exercise prevents coronary heart disease.

Fine-needle aspiration biopsy of the thyroid nodule. Results of a start-up project in a general teaching hospital setting.

The results of the initial 102 fine-needle aspiration biopsies of the thyroid performed at a 795-bed general teaching hospital are reported. Eighty-four of the nodules (82%) were cytologically benign, 18 nodules (18%) were suspicious, and none of the nodules was diagnosed as malignant. Five nodules In the suspicious group (28%) were found to be malignant following microscopic examination of the surgical specimens. There was one false-negative result. Based on the data from 21 patients with both cytologic and histologic diagnoses, the positive predictive value of this procedure was 38% and the negative predictive value was 87% (sensitivity, 83%; specificity, 47%). Our results were comparable with those of major referral centers. Guidelines for establishing a fine-needle aspiration biopsy program at a general hospital are suggested.

Hyperglycemia associated with renal cell carcinoma.

A case of renal cell carcinoma presenting with uncontrolled diabetes mellitus is reported. After a radical nephrectomy, the diabetic state completely resolved. Laboratory studies failed to reveal any endocrinopathy responsible for the diabetic state. Thus it appears that hyperglycemia and diabetes mellitus can now be included with the other paraneoplastic endocrinopathies associated with renal cell carcinoma.

Pulmonary tuberculosis and bronchocentric granulomatosis.

Bronchocentric granulomatosis (BG) is an uncommon inflammatory lesion of unknown etiology defined on morphologic grounds by the presence of necrotizing granulomata centered on bronchi and bronchioles. We report the typical pathologic features of BG in a patient with tuberculosis. Mycobacterial and other types of infection should be excluded by appropriate stains and cultures in all patients with BG on lung biopsy, especially those who are nonasthmatic.

Inoperable gastric lymphosarcoma mistaken for carcinoma: response to radiation with twenty-year survival to date.

With suitable treatment, the potential for long survival with gastric lymphoma is well-documented. However, since these tumors constitute only about 1-3% of gastric malignancies, they may occur only rarely in a particular radiologist's experience. The present report of a remarkable therapeutic response is a reminder that the possibility of lymphosarcoma should be included in the differential diagnosis of every gastric neoplasm.