TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.', 'Effects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing-remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of the peripheral blood.', 'Regulatory T cells (Tregs), which are induced locally in the skin-draining lymph nodes in response to UVB exposure, connect the cutaneous immune response to CNS immunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg-inducing tolerogenic dendritic cells (DCs) were further necessary for induction of this systemic immune regulation by UVB radiation, because ablation of Langerhans cells abolished the UVB-induced phenotype. MS patients treated with UVB phototherapy showed an increase in induced Tregs and tolerogenic DCs accompanied by the downregulation of the T-cell effector cytokine interleukin 21. The treatment further induced elevated serum levels of vitamin D.
Answer: Local UVB radiation of the skin influences systemic immune reactions and attenuates systemic autoimmunity via the induction of skin-derived tolerogenic DCs and Tregs. Our data could have implications for the understanding or therapeutic modulation of environmental factors that influence immune tolerance.

SOLUTION: Does ultraviolet B light attenuate the systemic immune response in central nervous system autoimmunity?

PROBLEM: Context: Hepatic resection is well established as a potentially curative treatment for hepatic colorectal cancer metastases. However, only a small proportion of patients with liver metastases are suitable for resection because they either have extrahepatic disease, or the extent and/or the distribution of their hepatic disease would make excision impossible. We have previously described the use of cryotherapy for inadequate resection margins and lesions in the remaining lobe of the liver. Combining such cryodestructive techniques with resection offers the possibility of increasing the proportion of patients to whom potentially curative treatment can be offered. The aim of this study was to compare survival in patients treated with resection and cryotherapy against those of patients treated with resection alone. Potential prognostic variables were also examined.', 'Patients undergoing a hepatic resection with or without cryotherapy at our unit between April 1990 and July 1997 were identified from our database and their notes reviewed. Survival was estimated using the Kaplan-Meier method and compared using the Log rank test.', 'One hundred and seven patients were treated in total: 32 underwent resection alone, and 75 underwent resection combined with cryotherapy. There was no significant difference between the survival of patients treated with resection alone and those treated with resection and cryotherapy.
Answer: Edge and contralobe cryotherapy can be combined with hepatic resection to allow a greater proportion of patients with hepatic colorectal metastases to be offered treatment, and results in similar survival figures comparable to hepatic resection for at least 3 years.

SOLUTION: Does resection with cryotherapy of colorectal hepatic metastases have the same survival as hepatic resection alone?

PROBLEM: Context: As metoclopramide stimulates aldosterone secretion, we tested its usefulness in the assessment of lateralization of primary aldosteronism by adrenal vein sampling (AVS).', 'Prospective within-patient study in consecutive patients undergoing AVS for primary aldosteronism subtyping.', 'We compared the diagnostic accuracy of baseline and postmetoclopramide lateralization index and relative (to cortisol) aldosterone secretion indices (RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined by the four corners criteria as the reference diagnosis.', 'We recruited 93 consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased plasma aldosterone in the inferior vena cava and in both adrenal veins. The postmetoclopramide lateralization index was accurate in identifying APA, but did not increase diagnostic accuracy over baseline lateralization index, because the RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to values more than 0.90 bilaterally in non-APA patients allowing accurate identification of factitious aldosterone suppression. In contrast, RASI was 0.90 or less in 48% contralateral to the tumor in APA patients. Regression analysis showed the APA patients with persistent suppression of RASI contralaterally showed a more florid primary aldosteronism phenotype.
Answer: Metoclopramide does not enhance lateralization of aldosterone excess in APA, but consistently increased the value of RASI in non-APA cases, thus unmasking potentially misleading suppression of aldosterone. Postmetoclopramide RASI may therefore allow a more precise diagnosis when AVS can be achieved only unilaterally.

SOLUTION:
Does metoclopramide unmask potentially misleading contralateral suppression in patients undergoing adrenal vein sampling for primary aldosteronism?