Nontryptase Urinary and Hematologic Biomarkers of Mast Cell Expansion and Mast Cell Activation: Status 2022.

Quantitation of urinary metabolites of histamine, prostaglandin D2, and leukotriene E4 can fill the gap in our current efforts to improve diagnosis and management of symptomatic patients with systemic mastocytosis, and/or mast cell activation syndrome, In addition, patients symptomatic due to mast cell activation but who do not meet all the criteria for mast cell activation syndrome can have elevated baseline mediator metabolites. Serum tryptase levels have been the workhorse in diagnosing these disorders, but it has several drawbacks including the need to obtain acute and baseline samples, which require 2 visits to health care facilities and 2 venipunctures. Recently, increased baseline tryptase level has been reported in hereditary alpha tryptasemia, complicating diagnostic possibilities of an increased baseline tryptase level. Furthermore, no treatment can specifically be targeted at tryptase itself. In contrast, the finding of 1 or more elevated urinary levels of histamine, prostaglandin D2, and/or leukotriene E4 metabolites (1) greatly narrows diagnostic possibilities for causes of symptoms; (2) informs the practitioner what specific metabolic pathways are involved; and (3) targets the treatment in a specific, direct fashion. As a bonus, baseline spot/random urine samples can be obtained by the patients themselves and repeated at exactly the correct time when symptoms occur.

Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis.

OBJECTIVES: Systemic mastocytosis (SM) is a disorder characterized by the excessive accumulation of clonally derived mast cells in various tissues. When triggered, mast cells release large amounts of histamine, prostaglandins and leukotrienes. Leukotriene E4 (LTE4) is the primary stable metabolite of total cysteinyl leukotrienes. We hypothesized that secretion of LTE4 would be increased in SM and could be used alone or in combination with current urinary biomarkers to optimize screening for SM. DESIGN AND METHODS: LTE4 was measured by liquid chromatography followed by tandem mass spectrometry (LC-MS/MS). Analytical assay validation was performed using residual urine specimens. LTE4 results were normalized to urine creatinine for clinical use. Reference interval was established using a healthy volunteer cohort. Clinical sensitivity and specificity for SM detection were determined by measuring urinary biomarkers (LTE4, N-methyl histamine [NMH] and 11ß-prostaglandin F2α [BPG]) in a cohort of 409 patients referred to allergy specialists, 66 (16%) of which were diagnosed with SM. RESULTS: Urinary LTE4 measurement was accurate, precise and linear across a range of 31-3020pg/mL. The 95th percentile of the reference interval population was <104pg/mg creatinine. Median urine LTE4 concentrations were significantly higher among patients with SM (97pg/mg cr. vs. 50pg/mg cr.; p<0.01). Elevated urinary LTE4 was 48% sensitive and 84% specific for SM. Clinical sensitivity was 53% for BPG (>1000ng/mL) and 71% for NMH (>200ng/mL). Incorporating all three urinary metabolites improved the SM diagnostic sensitivity to 97%, with minimal change in specificity. CONCLUSIONS: We have developed a sensitive and precise LC-MS/MS assay for quantitation of LTE4 in urine. Incorporating LTE4 into a panel including BPG and NMH provides a much-needed screening tool for a complicated disease with non-specific symptoms and invasive confirmatory testing.

Urinary 11ß-PGF2α and N-methyl histamine correlate with bone marrow biopsy findings in mast cell disorders.

BACKGROUND: The utility of measuring histamine and prostaglandin metabolites in the urine of patients with mastocytosis has not been critically examined in a large series of patients. This study examined the relationship between the extent of increase in urinary excretion of 11ß-prostaglandinF2α and N-methyl histamine, with serum tryptase, whole blood serotonin, and bone marrow findings including morphology, percentage involvement, and abnormal mast cell phenotype. METHODS: This was a retrospective analysis of 90 patients who were continuously enrolled in the study for a period of 6 years (2008-2014). We recorded serum tryptase, whole blood serotonin, levels of urinary mast cell metabolites 11ß-prostaglandinF2α and N-methyl histamine (NMH), and bone marrow findings. RESULTS: Urinary mast cell metabolites 11ß-prostaglandinF2α and N-methyl histamine correlated with levels of serum tryptase, mast cell burden in the bone marrow, the presence of mast cell aggregates, and atypical mast cells on bone marrow biopsy. Whole blood serotonin did not have a significant correlation with the serum tryptase or mast cell burden in the bone marrow. Urinary NMH was significantly different between c-kit D816V-positive and c-kit D816V-negative patients, while 11ß-prostaglandinF2α was not. Urinary 11ß-prostaglandinF2α 24-h excretion >3500 ng and NMH levels >400 µg/gm Cr corresponded with the high degree of bone marrow biopsies positive for atypical mast cells, the presence of aggregates, and c-kit mutation. CONCLUSIONS: Easily obtained and quantified urinary metabolites of histamine (greater than twice the upper limit of normal) and prostaglandin D2 (>3.4 times the upper limit of normal) correlate well with bone marrow findings of mastocytosis.

Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis.

Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator-related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator-related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25-30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of 'occult' mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow-up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.

Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal.

Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011-2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%-19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials.

The Oxford Questions on the foundations of quantum physics.

The twentieth century saw two fundamental revolutions in physics-relativity and quantum. Daily use of these theories can numb the sense of wonder at their immense empirical success. Does their instrumental effectiveness stand on the rock of secure concepts or the sand of unresolved fundamentals? Does measuring a quantum system probe, or even create, reality or merely change belief? Must relativity and quantum theory just coexist or might we find a new theory which unifies the two? To bring such questions into sharper focus, we convened a conference on Quantum Physics and the Nature of Reality. Some issues remain as controversial as ever, but some are being nudged by theory's secret weapon of experiment.

Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections.

While extended infusions of piperacillin-tazobactam (TZP) are increasingly used in practice, the effect of infusion on the pharmacokinetic (PK) profile of TZP has not been widely assessed. To assess its effect on the pharmacokinetic profile of TZP, seven serum samples were collected from 11 hospitalized patients who received 3.375 g TZP intravenously for 4 h every 8 h. Population pharmacokinetic models were fit to the PK data utilizing first-order, Michaelis-Menten (MM), and parallel first-order/MM clearance. A population PK model with first-order clearance was fit to the tazobactam PK data. Monte Carlo simulations (MCSs) were used to determine the most effective administration schedule to ensure that free piperacillin concentrations were above the MIC for at least 50% of the dosing interval (50% fT>MIC) and to quantify the extent of the nonlinear clearance. The model incorporating parallel linear/MM clearance best fit the piperacillin PK data. The MCSs demonstrated that approximately 50% of the administered piperacillin is cleared by the nonlinear clearance mechanism. The results of the MCSs also revealed that more intensive TZP extended infusion dosing schemes (3.375 to 4.5 g intravenously [3-h infusion] every 6 h) than those commonly used in clinical practice were needed to maximize the 50% fT>MIC for MICs of ≥8 mg/liter. This study suggests that extended infusion of TZP is the most effective method of administration for patients with nosocomial infections. Due to the hyperclearance nature of the hospitalized patient populations studied, more intensive TZP dosing regimens may be needed to maximize fT>MIC in certain hospitalized populations.

Treatment of hypereosinophilic syndromes--the first 100 years.

Treatment of the hypereosinophilic syndrome (HES) has advanced rapidly and prevention of end organ damage previously associated with the disorders is now possible in most patients who have had a timely diagnosis. Tried and true medications such as prednisone, hydroxyurea, and interferon-alpha (IFN-aα) continue to play a valuable role in treating HES and their cost is modest. Newer medications included pegylated forms of IFN-aα and IFN-α2b, first- and second-generation tyrosine kinase inhibitors (imatinib mesylate, nilotinib), and monoclonal antibodies to interleukin (IL)-5 and CD52. The combination of better understanding of HES and better medications now provide the clinician with an improved ability to control unregulated proliferation of eosinophils.

Telavancin pharmacokinetics and pharmacodynamics in patients with complicated skin and skin structure infections and various degrees of renal function.

This study characterized the pharmacokinetic/pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved telavancin renal dose adjustment schemes. A previously published two-compartment open model with first-order elimination and a combined additive and proportional residual error model derived from 749 adult subjects in 11 clinical trials was used to simulate the individual concentration-time profiles for 10,260 subjects (NONMEM). The dosing regimens simulated were 10 mg/kg of body weight once daily for individuals with creatinine clearances (CL(CR)s) of >50 ml/min, 7.5 mg/kg once daily for individuals with CL(CR)s of 30 to 50 ml/min, and 10 mg/kg every 2 days for those with CL(CR)s of <30 ml/min. The area under the concentration-time curve (AUC) under one dosing interval (AUC(τ)) was computed as dose/CL. The probability of achieving an AUC(τ)/MIC ratio of ≥ 219 was evaluated separately for each renal dosing scheme. Evaluation of the dosing regimens demonstrated similar AUC values across the different renal function groups. For all renal dosing strata, >90% of the simulated subjects achieved an AUC(τ)/MIC ratio of ≥ 219 for MIC values as high as 2 mg/liter. For patients with CL(CR)s of <30 ml/min, the probability of target attainment (PTA) exceeded 90% for both the AUC0₋24 (AUC from 0 to 24 h) and AUC24₋48 intervals for MICs of ≤ 1 mg/liter. At a MIC of 2 mg/liter, the PTAs were 89.3% and 23.6% for the AUC0₋24 and AUC24₋48 intervals, respectively. The comparable PTA profiles for the three dosing regimens across their respective dosing intervals indicate that the dose adjustments employed in phase III trials for complicated skin and skin structure infections were appropriate.

Individual patient meta-analysis of exercise training effects on systemic brain natriuretic peptide expression in heart failure.

BACKGROUND: Brain natriuretic peptide (BNP) predicts exercise performance and exercise training may modulate BNP and its N-terminal portion (NT-pro-BNP), we therefore conducted an individual patient analysis of exercise training effects on BNP and NT-pro-BNP. AIMS: To use an individual patient meta-analysis to relate changes in BNP, NT-pro-BNP, and peak VO(2); to link these changes to volume parameters of exercise training programmes (intensity etc.); and to identify patient characteristics likely to lead to greater improvements in BNP, NT-pro-BNP, and peak VO(2). DESIGN: Individual patient meta-analysis. METHODS: A systematic search was conducted of Medline (Ovid), Embase.com, Cochrane Central Register of Controlled Trials, and CINAHL (until July 2008) to identify randomized controlled trials of aerobic and/or resistance exercise training in systolic heart failure patients measuring BNP and/or NT-pro-BNP. Primary outcome measures were change in BNP, NT-pro-BNP, and peak VO2. Subanalyses were conducted to identify (1) patient groups that benefit most and (2) exercise programme parameters enhancing favourable changes in primary outcome measures. RESULTS: Ten randomized controlled studies measuring BNP or NT-pro-BNP met eligibility criteria, authors provided individual patient data for 565 patients (313 exercise and 252 controls). Exercise training had favourable effects on BNP (-28.3%, p < 0.0001), NT-pro-BNP (-37.4%, p = < 0.0001), and peak VO(2) (17.8%, p < 0.0001). The analysis showed a significant change in primary outcome measures; moreover, change in BNP (r = -0.31, p < 0.0001) and NT-pro-BNP (r = -0.22, p < 0.0001) were correlated with peak VO(2) change. CONCLUSION: Exercise training has favourable effects on BNP, NT-pro-BNP, and peak VO(2) in heart failure patients and BNP/NT-pro-BNP changes were correlated with peak VO(2) changes.

'Idiopathic' eosinophilia with an Occult T-cell clone: prevalence and clinical course.

In a study of 99 consecutive patients with "idiopathic" eosinophilia, clonal T-cells were demonstrated in blood, bone marrow, or other tissue samples of 14 patients including 6 who had an overt T-cell malignancy. The remaining eight patients (approximately 8%) with an "Occult" T-cell clone had predominantly cutaneous disease and FIP1L1-PDGFRA was absent in all six evaluable patients. Two patients were effectively treated with low-dose oral cyclophosphamide or methotrexate whereas Gleevec treatment was ineffective in another two patients. Two patients (25%) transformed into cutaneous T-cell lymphoma after 3-8 years of eosinophilic prodrome.

Outpatient angioplasty and stenting facilitated by percutaneous arterial suture closure devices.

AIM: To review our practice of outpatient percutaneous vascular interventions facilitated by an arterial suture device. MATERIALS AND METHODS: A retrospective review of all patients attending this tertiary centre for iliac or femoral intervention was undertaken between February 2001 and December 2004. All patients who underwent angioplasty or stenting had their puncture sites closed using a Perclose suture. Patients were kept flat for 15min and allowed to fully mobilize at 60min. Puncture sites were scored for visible bruising, haematoma and pain at discharge and on outpatient follow-up. Patient preference for future outpatient treatment was assessed. RESULTS: Fifty-seven outpatients underwent 81 punctures. Forty-eight (84%) patients underwent iliac angioplasty; of those 42% underwent stent placement. Six patients (10%) required inpatient admission, five secondary to failed suture deployment. One patient had a non-closer-related puncture site intimal flap occlusion successfully repaired at surgery. Fifty-one (90%) patients discharged with a mean time of 157min (60-280min). Forty-six (92%) patients had no visible bruising or palpable haematoma on discharge. No patient had a haematoma greater than 2.5cm. No discharged patient required readmission. Thirty percent reported a moderate to severe groin pain score (2-5/5) at discharge, increasing to 40% at follow-up. Forty-seven (98%) of the 48 patients, who expressed a preference, would be happy to undergo outpatient treatment again. CONCLUSION: Outpatient treatment is feasible, well tolerated and preferable to patients, but 10% will require inpatient admission. A planned post-procedure analgesia regimen or advice should be considered.

Incidence and effect of bare suprarenal stent struts crossing renal ostia following EVAR.

OBJECTIVES: The incidence and effect of bare stent struts crossing the renal ostia following endovascular aortic aneurysm repair with the Talent stent-graft is not known. The study aims to establish the incidence in which bare stent struts cross the renal ostia and to assess any associated effects on renal function. METHODS: Fifty-five patients (51 men, mean age 73 years, range 57-90) who had endovascular repair of their abdominal aortic aneurysms with a Talent suprarenal stent-graft were included in the study. Patients were scanned at a variety of follow-up periods (median 24 months, range 3-102). The relationship between the bare stent struts and the renal ostia, together with renal function were retrospectively recorded. The presence and location of the bare stent struts was assessed using CT virtual intravascular endoscopy (CT VIE). Struts were defined as being absent, peripherally located or in the central channel of the renal ostia. Renal function was assessed from glomerular filtration rates (GFR) derived from serum creatinine levels and the Cockcroft and Gault formula. RESULTS: A total of 109 renal ostia were evaluated by CT VIE with one patient having a previous nephrectomy. Bare stent struts crossed 1 renal ostium in 22 (40%) patients and bilateral ostia in 5 (9%) patients. Of the 109 ostia assessed, 15 (14%) ostia were crossed centrally and 17 (16%) had struts crossing the ostium peripherally. There were no statistically significant differences in the change between pre-operative GFR and latest GFR in the group without any strut involvement (6 mLs/min +/- 7 mLs/min) and the group with struts crossing one or both renal ostia (2 mLs/min +/- 9 mLs/min; p > .05). CONCLUSION: Peripheral or central coverage of renal ostia by bare stent struts occurs in a third of all renal arteries following EVAR. Crossing of renal ostia by bare stent struts does not affect follow-up GFR.

Midterm follow-up of a single-center experience of endovascular repair of abdominal aortic aneurysms with use of the Talent stent-graft.

PURPOSE: To review the midterm results of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) with the Talent stent-graft. MATERIALS AND METHODS: All patients who underwent EVAR of AAAs with Talent stent-grafts from February 1998 to April 2002 at a single institution were monitored for a minimum of 2 years or until an endpoint of death or rupture was reached. RESULTS: There were 68 eligible patients, who were monitored for a mean period of 39 months (range, 24-72 months). Forty-nine (72.9%) were alive at 2 years; among the 19 deaths, two resulted from aneurysm rupture and the other 17 were unrelated to EVAR. There was one immediate conversion to open repair and five primary proximal endoleaks; the remaining 62 patients (91.2%) all had a technically successful procedure. There were 33 endoleaks during follow-up: 23 (69.7%) were treated conservatively and 10 (30.3%) underwent secondary intervention in the form of embolization (n=2), attempted embolization (n=2), endovascular stent-graft placement (n=3), combined stent-graft placement and embolization (n=1), or surgical conversion (n=2). Overall, there were five persistent endoleaks, and the remaining patients were free of endoleak at their last review or endpoint. Three stent-grafts migrated and required further endovascular intervention. Wire fracture was seen in two stents but presented no clinical sequelae. There was one case of graft limb thrombosis that required surgical thrombectomy. CONCLUSIONS: EVAR of AAAs with use of the Talent stent-graft is a promising and acceptable alternative to open surgery. Our 30-day mortality rate of zero compares extremely well with historical data from open surgery and the findings of more recently published trials. The risk of endoleak and uncertainty over durability require long-term surveillance.

The impact of diabetes on current revascularisation practice and clinical outcome in patients with critical lower limb ischaemia.

OBJECTIVE: To compare current revascularisation practice and outcome in diabetic and non-diabetic patients presenting with critical limb ischaemia (CLI) to a single vascular surgeon. METHODS: Data for 113 patients presenting with CLI were collected prospectively over a 3-year period. Forty-four (39%) were diabetic. Treatment was classified as percutaneous angioplasty, arterial reconstruction, primary major amputation, and conservative therapy. Main outcome measures were 30-day mortality, major amputation, survival, and amputation-free survival. RESULTS: Diabetic patients were more likely to present with gangrene, give a history of angina, be treated with nitrates and statins, and have lower cholesterol levels. No significant differences were found in the initial treatment options between diabetics and non-diabetics: angioplasty 39 vs 26%, surgical revascularisation 34 vs 33%, primary major amputation 9% vs 17%, and conservative treatment 11 vs 19% (p = ns in all). There were eight deaths (7%) within 30-days. At follow-up (1-44 months, median 14 months), rates of major amputation and death for the entire population were 23 and 8%, respectively. The 12-month cumulative survival and amputation-free survival rates were 90 and 72%, respectively. When comparing diabetic to non-diabetic patients, there were no significant differences in the 30-day mortality (6.8 vs 7.2%, p = 0.4), cumulative survival (93 vs 89% at 12 months, log-rank test: 0.00, p = 0.9), amputation-free survival (71 vs 73% at 12 months, log-rank test: 0.00, p = 0.99), and major amputation rates (22.7 vs 23.1% at 12 months, p = 0.96). Similarly, there were no differences in limb salvage rates between diabetic and non-diabetic patients undergoing revascularisation procedures (78 vs 90% at 12 months, log-rank test: 2.04, p = 0.15). CONCLUSIONS: In current practice, an aggressive multidisciplinary approach in diabetic patients presenting with CLI leads to similar limb salvage, amputation-free survival, mortality, and major amputation rates to those seen in non-diabetic patients. The presence of diabetes should not deter clinicians from attempting revascularisation by means of angioplasty or surgical reconstruction.

FIP1L1-PDGFRA in eosinophilic disorders: prevalence in routine clinical practice, long-term experience with imatinib therapy, and a critical review of the literature.

We previously studied clinico-pathologic features of 89 consecutive adult patients with moderate-to-severe eosinophilia, and reported a FIP1L1-PDGFRA prevalence of 12%. In that series, all 11 FIP1L1-PDGFRA+ patients receiving imatinib achieved a complete response. We now extend our observations through a study of 741 unselected patients with eosinophilia for FIP1L1-PDGFRA, and present longer term follow up data for the imatinib-treated cohort. We also include data for three previously unreported FIP1L1-PDGFRA+ patients. Among the 741 requests, only 21 (3%) were found to carry the FIP1L1-PDGFRA mutation. While all 14 FIP1L1-PDGFRA+ patients receiving imatinib achieved a complete response, the 4 patients who attempted to discontinue imatinib all relapsed. We also find that it is possible to maintain patients in clinical remission with an empirically derived schedule of low-dose (50-100 mg), intermittent (once daily to once weekly) imatinib. Lastly, we present a comprehensive review of the literature pertaining to FIP1L1-PDGFRA in order to address several key aspects of this mutation from a clinical standpoint.

Patterns, incidence and predictive factors for pain after interventional radiology.

AIM: To evaluate prospectively the pattern, severity and predictive factors of pain after interventional radiological procedures. MATERIALS AND METHODS: All patients undergoing non-arterial radiological interventional procedures were assessed using a visual-analogue scale (VAS) for pain before and at regular intervals for 24 h after their procedure. RESULTS: One hundred and fifty patients (87 men, mean age 62 years, range 18-92 years) were entered into the study. Significant increases in VAS score occurred 8 h after percutaneous biliary procedures (+47.7 mm, SD 14.9 mm; p=0.001), 6 h after central venous access and gastrostomy insertion (+23.7 mm, SD 19.5 mm; p=0.001 and +28.4 mm, SD 9.7 mm; p=0.007, respectively) and 4h after oesophageal stenting (+27.8 mm, SD 20.2 mm, p=0.001). Non-significant increases in VAS pain score were observed after duodenal and colonic stenting (duodenal: +5.13 mm, SD 7.47 mm; p=0.055, colonic: +23.3 mm, SD 13.10 mm, p=0.250) at a mean of 5h (range 4-6h). Patients reported a significant reduction in pain score for nephrostomy insertion (-28.4mm, SD 7.11 mm, p=0.001). Post-procedural analgesia was required in 99 patients (69.2%), 40 (28.0%) requiring opiates. Maximum post-procedural VAS pain score was significantly higher in patients who had no pre-procedural analgesia (p=0.003). CONCLUSION: Post-procedural pain is common and the pattern and severity of pain between procedures is variable. Pain control after interventional procedures is often inadequate, and improvements in pain management are required.

Interferon treatment for hypereosinophilic syndromes and systemic mastocytosis.

Hypereosinophilic syndromes (HES) and systemic mastocytosis (SMCD) are heterogeneous disorders with clinical symptoms from local and remote effects of excessive proliferation of eosinophils and mast cells, respectively. Interferon alpha (IFN-alpha), alone or in combination with other medications, can be a useful, and at times life-saving, treatment for patients with HES. Receptors for IFN-alpha are present on eosinophils, and clinical benefits are due to its effect on eosinophil proliferation, migration, activation, and survival. These effects are likely mediated through multiple pathways including, but not limited to, inhibition of eosinophil colony-forming cells, upregulation of IFN-gamma synthesis, and inhibition of production of eosinophil-active cytokines by T cells, mast cells, and mononuclear cells. IFN-alpha has been life-saving for patients with intractable HES that were resistant to prednisone, hydroxyurea, and other agents. Resistance to the eosinopenic effect of IFN-alpha does not develop and the dose of IFN-alpha necessary to maintain control of eosinophilia often decreases with time. The combination of IFN-alpha and hydroxyurea is very useful and allows dosage reduction of IFN-alpha and better control of hypereosinophilia than with either agent alone. The efficacy of IFN-alpha for treatment of SMCD has been more difficult to establish, with both favorable and unfavorable results reported. The disparate results may have resulted from the small number of patients with SMCD treated with IFN-alpha, the use of various criteria for a "successful" treatment outcome, short duration of treatment and follow-up, and the use of modest dosages. In reported series, side effects from IFN-alpha have frequently been dose-limiting. IFN-alpha improves many of the clinical symptoms of SMCD including dermatological, hematological, gastrointestinal, and systemic symptoms associated with histamine release. IFN-alpha has a beneficial effect on skeletal symptoms because of its ability to increase bone density and reduce painful episodes from vertebral fractures. No consistent improvement in bone marrow infiltration by mast cells has been demonstrated except in a recent study employing high dosages of IFN-alpha. A beneficial effect from the combination of IFN-alpha and prednisone has been reported for several patients, suggesting that combined use of these two medications may provide synergism in treatment outcomes.

A cross-site vascular radiology on-call service: the Manchester experience.

AIM: A cross-site vascular radiology on-call service was established 5 years ago to cover two vascular centres in Manchester. We aimed to review the service. MATERIALS AND METHODS: A prospective audit of out-of hours referrals and procedures over a three month period (March-May 2003) was undertaken. RESULTS: There were 52 incidents in 49 patients (mean 4 calls per week). Nine involved telephone advice only, the remainder (82%) required a procedure. Angiography was performed on 88% of patients and therapeutic radiological intervention on 50%. 71% of calls occurred at a weekend. 50% of the calls were from vascular surgery and 50% from other sources. The consultant vascular radiologist was present for 93% of procedures. CONCLUSIONS: The workload suggests that a vascular radiology on call service is justified in Manchester. There have been no major problems with its implementation and operation. This is a consultant led service, with very few cases being devolved to a specialist registrar (SpR).