The Gut Microbiome: Human Health and Inflammatory Skin Diseases

The human microbiome is a rich environment consisting ofbacteria, fungi and other commensal microorganisms of thegut, mucosa and skin. The functional role of the gut microbiomeincludes facilitation in metabolism of macronutrients,maturation of the immune system, and production of pro- oranti-inflammatory signaling molecules and peptides. Theidentification of these resident organisms has brought abouta new understanding of disease processes. Nevertheless,more questions remain regarding the interactions within themicrobiome, its interactions with the host, and its contributionsto the pathophysiology of disease. The purpose of thisreview is to examine the existing medical literature to highlightthe role of the gut microbiome in human health, alsopaying attention to its role in several inflammatory skin diseases,namely atopic dermatitis, psoriasis, and rosacea.

Comparisons of dosimetric approaches for fractionated radioimmunotherapy of non-Hodgkin lymphoma.

AIM: The aim of this study was to compare different dosimetric approaches on therapy naïve patients enrolled in a multicentre fractionated radioimmunotherapy trial, to determine which methodological approach correlates with bone marrow toxicity. METHODS: Twenty-height non-Hodgkin lymphoma patients were treated with one or two fractions of 90Y-Ibritumomab-Tiuxetan (11.1 MBq/kg) 8 to 12 weeks apart in four different institutions. Quantitative imaging with 111In-Ibritumomab-Tiuxetan (185 MBq) was performed at 0, 1, 4 and 7 days after infusion, starting two weeks before the therapeutic administration. A whole-body (WB) CT scan was also acquired prior to the 111In-Ibritumomab injection, for attenuation correction purposes and was segmented to derive patient-specific organ masses. All dosimetry processing was centralized in a single institution. The first method (M_2D) was based on geometric mean WB scans, corrected for attenuation, scatter and organs superposition. The second method (M_2.5D) was based on the computed assisted matrix inversion approach and used segmented CT scans. The third method (M_3D) used iterative reconstruction of tomographic scans, corrected for attenuation, scatter and collimator response. Absorbed doses were estimated for lungs, liver, kidneys and spleen using MIRD S values adjusted for organ masses. Bone marrow (BM) absorbed doses were evaluated according to imaging methods (3) and compared to blood-based approaches. RESULTS: For some patients, organ masses such as liver or spleen significantly differed from male/female reference masses, whereas lungs and kidneys masses were relatively constant. Except for lungs, absorbed doses estimated by M_2D were higher than those from M_2.5D and these, in turn, were higher that those calculated from M_3D (Wilcoxon P<8.6e-4). Median organ absorbed dose estimates were equivalent for both fractions except for the spleen. In fact, spleen absorbed doses for the second fraction were lower than those for the first fraction, regardless of the approach. Possible explanations are that patient spleen masses were kept constant for analysis of both fractions and/or that spleen uptake was lowered after the first fraction. Estimation of BM absorbed doses from blood sampling was unable to predict platelet toxicity, but image-based methods performed better. Additionally, for most organs, the absorbed dose delivered by the first fraction could predict that delivered by the second fraction. CONCLUSION: These results confirm that different acquisition/processing protocols will lead to statistically different absorbed doses. Additionally, image-based dosimetric approaches are needed in order to correlate absorbed dose to bone marrow toxicity.

A retrospective analysis of selective internal radiation therapy (SIRT) with yttrium-90 microspheres in patients with unresectable hepatic malignancies.

AIM: To evaluate the efficacy and safety of selective internal radiation therapy (SIRT). MATERIALS AND METHODS: A retrospective analysis was undertaken of all patients who underwent SIRT at a single institution. Diagnostic and therapeutic angiograms, computed tomography (CT) images, positron-emission tomography (PET) images, and planar isotope images were analysed. The response to SIRT was analysed using radiological data and tumour markers. Overall survival, complications, and side effects of SIRT were also analysed. RESULTS: The initial 12 patients were included on an intention-to-treat basis, between 21/09/2005 and 07/05/2008. All patients had advanced disease and multiple prior courses of chemotherapy. One patient did not receive yttrium-90 due to complex vascular anatomy; the remaining 11 patients underwent 13 SIRT treatment episodes following work-up angiography. A response was seen using PET in 80% of patients. Using CT, the response of the tumour to therapy in the treated hepatic segments demonstrated a 20% partial response, stable disease in 50%, and progressive disease in 30%. Estimated median survival was 229 days, with 64% of patients still alive at the time of writing. No major complications were observed, although 82% of patients experienced side-effects following SIRT, mainly nausea, vomiting, and abdominal pain. CONCLUSIONS: There have been no complications in the 12 SIRT patients. Tumour response was seen in four out of five patients who underwent PET. Objective CT response rates were mixed and are perhaps partially explained by advanced disease and limitations of using measurements to assess response. This complex and potentially hazardous service has been successfully and safely established.

Does salivary gland scintigraphy predict response to pilocarpine in patients with post-radiotherapy xerostomia?

This study was undertaken to determine whether standard salivary gland scintigraphy may be used for the objective assessment of salivary gland sialogogues, in particular oral pilocarpine, in the treatment of post-radiotherapy xerostomia. Nine patients, with xerostomia following radiotherapy to the head and neck region underwent salivary gland scintigraphy with technetium-99m pertechnetate (40 MBq) both before and following 1 month of oral pilocarpine (5 mg tds). For each scan, the percentage uptake in the first 14 min, the peak uptake, time to peak uptake and the percentage of activity excreted following lemon juice stimulation were calculated. The results were correlated with the subjective response as assessed by questionnaire and visual analogue scale. We found no correlation between subjective response and any of the four scan parameters analysed. We could not identify any parameter that predicted those patients who would respond to pilocarpine. In addition, only one parameter, the percentage of activity excreted following stimulation, correlated with previous dose of radiotherapy to the gland. In conclusion, in this study salivary gland scintigraphy did not appear to correlate with or predict response to oral pilocarpine. However, future studies might consider performing salivary gland scintigraphy prior to radiotherapy as well as at differing time points following the commencement of pilocarpine.

An assessment of finger doses received by staff while preparing and injecting radiopharmaceuticals.

Good working practice and legal obligation impose a duty on nuclear medicine departments to check syringe activities before administration to a patient. If syringe guards are used to reduce staff exposure while drawing up injections, the guard has to be removed to measure the activity in a conventional reentrant ionization chamber type calibrator. Alternatively, the activity may be checked in a purpose-built syringe calibrator which allows the assay of the activity in the syringe without the need to remove the syringe guard. Finger doses received during the dose preparation and injection are a cause for concern. This study investigated the finger and whole-body doses received when using each of these calibrators, and compared the results with those obtained by an operator who did not measure the dose at all. The results demonstrated that although the finger doses are small, measurement of the syringe activities in a conventional ionization chamber increases the dose by a factor of 2 above that which would occur if no activity measurements were made, whereas the use of the specialized syringe calibrator gave finger doses only marginally above those obtained with no activity measurement.

The effect on diagnostic quality of using dual isotope imaging for 81Krm ventilation and 99Tcm-MAA perfusion lung scanning.

It is the practice in some centres to use dual isotope imaging to reduce imaging times in lung ventilation and perfusion studies with 81Krm gas and 99Tcm-macroaggregated albumin (99Tcm-MAA) by simultaneous acquisition of the two images. The resulting loss of image caused by cross-talk between the two energy windows was investigated using two phantoms, one with cold 99Tcm lesions of varying size and contrast, and the other a uniform field of 81Krm. It was found that, under scatter conditions typical of a patient study, the use of dual isotope acquisition and a krypton generator of 470 MBq or greater resulted in a perceptible loss of image quality with lesions up to 4 cm in diameter being missed. On an older camera system, without modern energy and linearity correction facilities, a lower generator activity of only 120 MBq was sufficient to cause image degradation even under very low scatter conditions. Seventy-five patient studies were performed using both single and dual isotope imaging with generator activities ranging from 80 to 282 MBq. At these low generator activities, the studies did not demonstrate any differences between the images that would result in a different diagnosis. We conclude that the use of dual isotope V/Q scanning reduces the diagnostic value of the perfusion image if the activity of the 81Krm generator is too high, although at generator activities of 300 MBq or less no loss of image quality will occur on modern camera systems.

An investigation of the radiation dose to staff during cardiac radiological studies.

Measurements of radiation distributions in the vicinity of the couch were undertaken for a number of projections commonly employed during cardiac radiological studies. Three types of investigations were considered; cardiac catheterisations, pacemaker implants and percutaneous transluminal coronary angioplasties. The radiation dose to staff involved in these procedures was estimated. For each group of staff, the maximum annual workload and the workload which would necessitate an individual becoming a classified radiation worker may be deduced from an expression given in the text.