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PURPOSE: The aim of this study was to assess potential physician work efficiencies when more than one diagnostic imaging study is interpreted by the same provider during the same session. METHODS: Medicare Physician Fee Schedule data from the American Medical Association Resource-Based Relative Value Scale Data Manager for 2011 were analyzed to quantify relative contributions of preservice, intraservice, and postservice physician work to the total work of rendering diagnostic imaging services. An expert panel review identified potential duplications in preservice and postservice work when multiple examinations are performed on the same patient during the same session. Maximum potential percentage work duplication for various diagnostic imaging modalities was calculated and compared to US Government Accountability Office estimates. RESULTS: The relative contributions of preservice and postservice work to total work varied by modality, ranging from 20% [computed tomography (CT)] to 33% (ultrasound). The maximum percentage of potentially duplicated preservice and postservice activity ranged from 19% (nuclear medicine) to 24% (ultrasound). Maximum mean potentially duplicated work relative value units ranged from 0.0212 for radiography to 0.0953 for magnetic resonance imaging (MRI). Maximum percentage work reduction ranged from 4.32% for CT to 8.15% for ultrasound. This corresponds to maximum professional Physician Fee Schedule reductions of only 2.96% (CT) to 5.45% (ultrasound), approximating an order of magnitude less than the Government Accountability Office's recommendations. CONCLUSION: Although potential efficiencies in physician work occur when multiple services are provided to the same patient during the same session, these are highly variable and considerably less than previously estimated. [ABSTRACT FROM AUTHOR]

1 3-hydroxy-5-trifluoromethyl-N-[2-(2-thienyl)-2-phenyl-ethenyl]- benzo(B) thiophene-2-carboxamide (L-652,343) is a 5-lipoxygenase and cyclo-oxygenase inhibitor in vitro. 2 In psoriasis increased concentrations of arachidonic acid transformation products are found in the lesional skin which may be important in the pathogenesis of the disease. We have measured the effect of orally administered L-652,343 on the concentration of LTB4 and prostaglandins in the lesional skin. 3 Eight patients with stable chronic plaque psoriasis received 500 and 250 mg of L-652,343, 12 h apart. A chamber technique was used to collect skin exudate samples from abraded plaques before and at 4, 24 and 48 h after the first dose. Exudates were analysed for LTB4 by a neutrophil chemokinesis assay and for PGE2 and PGD2 by RIA. 4 PGE2 and PGD2 levels were significantly reduced at 4 and 24 h after the first dose of L-652,343 but LTB4 levels were not affected indicating inhibition of the cyclo-oxygenase pathway but not of the 5-lipoxygenase pathway. This shows the importance of confirming that the action of 5- lipoxygenase inhibiting drugs in vitro occurs in vivo. [ABSTRACT FROM AUTHOR]

Topical clobetasol propionate or vehicle ointment was applied daily for 3 days to psoriatic plaques on eight patients. Skin chamber exudates from untreated, steroid and vehicle treated lesions were assayed for arachidonic acid (AA), leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) before, and at 24 h and 72 h after treatment. Significant reductions in AA and LTB4 were observed at 72 h in steroid treated lesions. The reduction in 12- HETE levels observed after steroid treatment was not statistically significant. PGE2 levels in lesional psoriatic skin were unaltered. The reduction of AA, and LTB4 was associated with clinical improvement of psoriasis. [ABSTRACT FROM AUTHOR]

Monohydroxy acids (HETEs) and leukotriene B4 (LTB4) metabolites of arachidonic acid were measured in skin of healthy volunteers after ultraviolet B irradiation, and in the uninvolved skin of psoriatics after topical dithranol application. Exudate was collected from suction bullae on control and inflamed abdominal skin, and analysed for 12-HETE and PGE2 by GC-MS and LTB4 by bioassay. 12-HETE and PGE2 were raised at 24 h but not at 72 h after u.v.B irradiation: control and 24 h values were 13.7 and 41.5 ng ml-1 (P less than 0.05, n = 6) for 12-HETE respectively, and 4.5 and 30.2 ng ml-1 (P less than 0.01, n = 6) for PGE2. Dithranol application raised PGE2 levels from 23.1 ng ml-1 in control exudate to 62 ng ml-1 (P less than 0.01, n = 6) at 24 h before declining to base levels at 72 h. However, 12-HETE was raised at 72 h (200 ng ml-1, P less than 0.01, n = 5) but not at 24 h (104 ng ml-1) compared to control levels (50 ng ml-1, n = 5). The levels of the LTB4 were low (less than 100 pg ml-1), and no significant increases were observed. Arachidonic acid in inflamed skin can be metabolised by the cyclo-oxygenase and lipoxygenase pathway. It is probable that the lipoxygenase product 12-HETE is involved in these inflammatory reactions. [ABSTRACT FROM AUTHOR]

Eight psoriatic patients were treated with etretinate (50 mg daily) for 6 weeks. Skin chamber exudates from involved and uninvolved skin were assayed for arachidonic acid, 12-HETE, PGE2 and for neutrophil chemokinetic activity co-chromatographing with leukotriene B4, before and at weekly intervals during therapy. Pre-treatment concentrations of arachidonic acid, 12-HETE and leukotriene B4-like chemokinetic activity but not of PGE2 were elevated in involved skin when compared to uninvolved skin. The concentrations of arachidonic acid and 12-HETE declined during therapy but changes in PGE2 were minimal. LTB4-like activity was detectable in involved skin both before and after etretinate treatment. Clinically, scaling and infiltration improved but erythema was still evident. [ABSTRACT FROM AUTHOR]

Arachidonic acid and prostaglandins were measured in uninvolved psoriatic skin before and after treatment for up to 24 h with dithranol. Prior to treatment, skin exudate contained 2744 ng ml-1 arachidonic acid and 26.4 ng ml-1 PGE2. After treatment with dithranol, the arachidonic acid concentration increased to a maximum of 5556 ng ml- 1 at 48 h whilst PGE2 increased to 93.4 ng ml-1 at 12 h and then declined. The erythemal response was apparent at 6-12 h and maximal at 72 h. These results suggest that PGE2 mediates the early development of dithranol erythema. [ABSTRACT FROM AUTHOR]

A collision tumor is a rare neoplastic lesion consisting of two or more coexisting, distinct cell line entities. In this report, we present the case of a 56-year-old male patient with a history of colon cancer who presented to the emergency room with visual deficits that had started about eight months earlier. An ophthalmologic examination reported left homonymous hemianopsia, prompting a brain MRI, which showed a right posterior temporal extra-axial mass concerning intracerebral metastatic colon cancer, in consideration of patient history. A right parietal craniotomy was performed, achieving gross total safe resection. The patient's preoperative left homonymous hemianopsia persisted, but no new neurological deficits were reported postoperatively. Pathologic examination revealed a solitary fibrous tumor in collision with metastatic colonic adenocarcinoma. The patient's family opted for comfort-directed care, given the patient's poor prognosis., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Le et al.)

On April 13, 2023, the American Board of Radiology (ABR) announced plans to replace the current computer-based diagnostic radiology (DR) certifying examination with a new oral examination to be administered remotely, beginning in 2028. This article describes the planned changes and the process that led to those changes. In keeping with its commitment to continuous improvement, the ABR gathered input regarding the DR initial certification process. Respondents generally agreed that the qualifying (core) examination was satisfactory but expressed concerns regarding the computer-based certifying examination's effectiveness and impact on training. Examination redesign was conducted using input from key groups with a goal of effectively evaluating competence and incentivizing study behaviors that best prepare candidates for radiology practice. Major design elements included examination structure, breadth and depth of content, and timing. The new oral examination will focus on critical findings as well as common and important diagnoses routinely encountered in all diagnostic specialties, including radiology procedures. Candidates will first be eligible for the examination in the calendar year after residency graduation. Additional details will be finalized and announced in coming years. The ABR will continue to engage with interested parties throughout the implementation process.

On 8 November 2016 the American electorate voted Donald Trump into the Presidency and a majority of Republicans into both houses of Congress. Since many Republicans ran for elected office on the promise to 'repeal and replace' Obamacare, this election result came with an expectation that campaign rhetoric would result in legislative action on healthcare. The American Health Care Act (AHCA) represented the Republican effort to repeal and replace the Affordable Care Act (ACA). Key elements of the AHCA included modifications of Medicaid expansion, repeal of the individual mandate, replacement of ACA subsidies with tax credits, and a broadening of the opportunity to use healthcare savings accounts. Details of the bill and the political issues which ultimately impeded its passage are discussed here., Competing Interests: Competing interests: ABR and RD are supported by research grants from the Harvey L Neiman Health Policy Institute., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The year 1965 was critical for US health care policy. In that year, Medicare was created as part of the Social Security Act under President Lyndon B. Johnson after several earlier attempts by Presidents Franklin Roosevelt and Harry Truman. In 1966, the American Medical Association first published a set of standard terms and descriptors to document medical procedures, known as Current Procedural Terminology, or CPT. Fifty years later, though providers have certainly heard the term "CPT code," most would benefit from an enhanced understanding of the historical basis, current structure, and relationship to valuation of Current Procedural Terminology. This article will highlight this evolution, particularly as it relates to neuroradiology., (© 2016 by American Journal of Neuroradiology.)

Many patients with Pierre Robin sequence (PRS) have associated birth defects, most commonly in association with abnormalities in bone or cartilage formation. Depending on severity, treatment of PRS ranges from nonoperative management with prone positioning to surgical intervention such as distraction osteogenesis. Generally, if a surgical approach is needed, these patients undergo nasal endoscopy or direct laryngoscopy with their intubation, which puts the cervical spine in a position of extreme extension. The authors present a patient with syndromic PRS secondary to Sticklers syndrome, with a cervical abnormality diagnosed with three-dimensional computed tomography and further evaluated with dynamic lateral plain x-rays to assess cervical instability. The goal of this report is to highlight the need to include cervical spine evaluation in the preoperation workup of patients with PRS, especially those with suspected abnormalities in bone or collagen formation.

The legislative branch of government took many by surprise when it announced the Medicare Access and CHIP Reauthorization Act of 2015. Once the Act was passed, President Obama quickly signed this bipartisan, bicameral effort into law. A foundational element of this legislation was the permanent repeal of the sustainable growth rate formula. Physicians and their patients were appropriately enthusiastic about this development. The Medicare Access and CHIP Reauthorization Act of 2015 included additional elements of considerable interest to neurointerventional specialists., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The use of alloplastic material in cranial reconstruction has been well described in the adult population, especially when a paucity of autologous tissue exists. In children it is unknown how long-term growth, however, may be affected by the implantation of nonexpansible alloplastic material. Therefore, the authors sought to compare the outcomes of pediatric patients undergoing alloplastic versus autologous cranial reconstruction., Methods: To assess the safety and long-term outcomes of alloplastic cranioplasty in children, an institutional review board-approved, retrospective, single institution review of pediatric patients undergoing cranioplasty was performed from 2000 to 2014. The age at surgery, cause of the cranial defect, defect size, time since initial surgery to reconstruction, implant type, and complications were assessed. Postreconstruction imaging was reviewed if available., Results: A reconstructive cranioplasty was performed in 41 pediatric patients (ages 1-19 years, average 7.35 years). Thirty patients underwent alloplastic reconstruction (age 4.37 ± 5.57 years), and 11 underwent autologous reconstruction (age 2.00 ± 3.74 years). The size of the cranial defects was 144.01 ± 393.04 cm for autologous and 405.31 ± 572.96 cm for alloplastic reconstructions. Follow-up for all patients was an average of 2.33 ± 2.76 years (0.1-9 years). No patients in either group showed evidence of elevated intracranial pressure after cranioplasty. In long-term follow-up, none of the implants were exposed or lost because of infection. Computed tomography and physical examination demonstrated that there was no skull growth restriction in either group., Conclusions: Our data show that alloplastic cranioplasty in the pediatric population is a safe alternative, when autologous cranial bone is not available.

The Affordable Care Act enters its fifth year firmly entrenched in our national consciousness. One method that has entered the vernacular for achieving cost savings is accountable care. There are other approaches that are less well known. The Bundled Payments for Care Improvement Initiative has the potential to significantly impact neurointerventionalists. We review that initiative here., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

In January 2015 the current Secretary of the Department of Health and Human Services (HHS) outlined a bold initiative to shape the delivery of healthcare through a set of strategies aimed at improving the quality of care and reducing the growth of healthcare costs. The strategies include increasing payment incentives tied to higher value care, increasing care coordination and integration, and increasing access to information to guide patients and clinicians. Significantly, the proposal includes specific goals for alternative payment models and value-based payments for the first time in the history of the Medicare program., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

In recent months, organized medicine has been consumed by the anticipated transition to the 10th iteration of the International Classification of Disease system. Implementation has come and gone without the disruptive effects predicted by many. Despite the fundamental role the International Classification of Disease system plays in health care delivery and payment policy, few neuroradiologists are familiar with the history of its implementation and implications beyond coding for diseases., (© 2016 by American Journal of Neuroradiology.)

In 1966, The American Medical Association (AMA) working with multiple major medical specialty societies developed an iterative coding system for describing medical procedures and services using uniform language, the Current Procedural Terminology (CPT) system. The current code set, CPT IV, forms the basis of reporting most of the services performed by healthcare providers, physicians and non-physicians as well as facilities allowing effective, reliable communication among physician and other providers, third parties and patients. This coding system and its maintenance has evolved significantly since its inception, and now goes well beyond its readily perceived role in reimbursement. Additional roles include administrative management, tracking new and investigational procedures, and evolving aspects of 'pay for performance'. The system also allows for local, regional and national utilization comparisons for medical education and research. Neurointerventional specialists use CPT category I codes regularly--for example, 36,215 for first-order cerebrovascular angiography, 36,216 for second-order vessels, and 37,184 for acute stroke treatment by mechanical means. Additionally, physicians add relevant modifiers to the CPT codes, such as '-26' to indicate 'professional charge only,' or '-59' to indicate a distinct procedural service performed on the same day., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The Patient Protection and Affordable Care Act (ACA) became law on 23 March 2010. As part of the law, two independent boards were established. The Patient-Centered Outcomes Research Institute embodies national aspirations for employing comparative effectiveness research in healthcare decision-making, and the Independent Payment Advisory Board is focused on the need for a group of impartial experts to establish anticipatable growth rates for Medicare. Approximately 4 years after the bill was passed into law, these independent boards are at very different points in their life cycles. This article provides a status update., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Carotid and cerebral angiography have been a mainstay of neurointerventional and neuroradiologic practice for years. Centers for Medicare and Medicaid Services (CMS) and Relative Value Scale Update Committee (RUC) initiatives have compelled the professional societies to bundle component codes under threat of unilateral CMS revision and revaluation. Code bundling usually results in a decrease in the professional Relative Value Unit (RVU) valuation, and thus the MD reimbursement. The year 2013 saw a dramatic revision to the Current Procedural Terminology (CPT) code set that defines carotid and cerebral procedures. This paper reviews the process that led to that code set being revised and estimates the impact on professional reimbursement. We show the current and previous carotid angiography CPT codes and use clinical examples to assess professional RVU valuation before and after code revision., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The Relative Value Scale Update Committee (RUC) plays a critical role in determining physician payment. When the Centers for Medicare and Medicaid Services (CMS) transitioned to paying physicians based on the Resource-Based Relative Value Scale, the American Medical Association developed this unique multispecialty committee. Physicians at the RUC determine the resources required to provide physician services and recommend appropriate payment for those services. The RUC then submits its recommendations to CMS. Physicians have thus been important in determining relative value and hence payment for the services they provide.

Purpose: The aim of this study was to quantify potential physician work efficiencies and appropriate multiple procedure payment reductions for different same-session diagnostic imaging studies interpreted by different physicians in the same group practice., Methods: Medicare Resource-Based Relative Value Scale data were analyzed to determine the relative contributions of various preservice, intraservice, and postservice physician diagnostic imaging work activities. An expert panel quantified potential duplications in professional work activities when separate examinations were performed during the same session by different physicians within the same group practice. Maximum potential work duplications for various imaging modalities were calculated and compared with those used as the basis of CMS payment policy., Results: No potential intraservice work duplication was identified when different examination interpretations were rendered by different physicians in the same group practice. When multiple interpretations within the same modality were rendered by different physicians, maximum potential duplicated preservice and postservice activities ranged from 5% (radiography, fluoroscopy, and nuclear medicine) to 13.6% (CT). Maximum mean potential duplicated work relative value units ranged from 0.0049 (radiography and fluoroscopy) to 0.0413 (CT). This equates to overall potential total work reductions ranging from 1.39% (nuclear medicine) to 2.73% (CT). Across all modalities, this corresponds to maximum Medicare professional component physician fee reductions of 1.23 ± 0.38% (range, 0.95%-1.87%) for services within the same modality, much less than an order of magnitude smaller than those implemented by CMS. For services from different modalities, potential duplications were too small to quantify., Conclusions: Although potential efficiencies exist in physician preservice and postservice work when same-session, same-modality imaging services are rendered by different physicians in the same group practice, these are relatively minuscule and have been grossly overestimated by current CMS payment policy. Greater transparency and methodologic rigor in government payment policy development are warranted., (Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Teleradiology services are now embedded into the workflow of many radiology practices in the United States, driven largely by an expanding corporate model of services. This has brought opportunities and challenges to both providers and recipients of teleradiology services and has heightened the need to create best-practice guidelines for teleradiology to ensure patient primacy. To this end, the ACR Task Force on Teleradiology Practice has created this white paper to update the prior ACR communication on teleradiology and discuss the current and possible future state of teleradiology in the United States. This white paper proposes comprehensive best-practice guidelines for the practice of teleradiology, with recommendations offered regarding future actions., (Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Physician spending is complex and intrinsically related to national health care spending, government regulations, health care reform, private insurers, physician practice and patient utilization patterns. Consequently, since the inception of Medicare programs in 1965, several methods have been used to determine the amounts paid to physicians for each covered service. The sustainable growth rate (SGR) was enacted in 1997 to determine physician payment updates under Medicare part B with an intent to reduce Medicare physician payment updates to offset the growth and utilization of physician services that exceeds the gross domestic product growth. This is achieved by setting an overall target amount of spending for physicians' services and adjusting payment rates annually to reflect differences between actual spending and the spending target. Since 2002, the SGR has annually recommended reductions in Medicare reimbursements. Payments were cut by 4.8% in 2002. Since then, Congress has intervened on 13 separate occasions to prevent additional cuts from being imposed. This manuscript describes certain important aspects of the 2012 physician fee schedule.

Purpose: The aim of this study was to assess the association of patient encounter complexity and the utilization of CT of the abdomen and pelvis (CTAP) in the emergency department (ED) setting., Methods: Using 5% research identifiable files for 2007, ED visits for Medicare fee-for-service beneficiaries were identified. Contemporaneous ED physician evaluation and management codes were used as the basis for patient complexity categorization. Encounters in which CTAP was performed on the same date of service were identified, and variables affecting the utilization of CTAP were analyzed., Results: Of 1,081,000 ED encounters, 306,401 (28.3%) were of lower complexity and 774,599 (71.7%) were of higher complexity. CT of the abdomen and pelvis was performed in 65,273 of all encounters (6.0%), corresponding to 4,069 (1.3%) of lower complexity and 61,204 (7.9%) of higher complexity encounters (odds ratio, 5.95; 95% confidence interval, 5.76-6.14). Of the 65,273 ED encounters associated with CTAP, 61,204 (93.8%) were of higher complexity., Conclusions: Of patients undergoing CTAP in the ED setting, a very large majority (93.8%) are clinically complex. CT of the abdomen and pelvis is 5.95 times more likely to be utilized in higher than lower complexity ED patient encounters., (Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Several reports have suggested a benefit for recombinant Factor VIIa (rFVIIa) in nonhematological conditions, including liver disease and transplantation. However, there are few reports of its use in children with liver failure. Recently, we used rFVIIa in four patients with liver failure and severe coagulopathy with bleeding who demonstrated significant laboratory and clinical improvement following its use with no side effects., Patients and Methods: All four patients were hospitalized with liver failure, coagulopathy, and bleeding that was controlled with fresh frozen plasma, platelets, and other therapies, as indicated. Their international normalization ratios (INR) ranged from 1.7 to 5.8 (normal 0.9-1.1). All four patients received rFVIIa for bleeding episodes that were not responding to their usual therapy, for procedures with a high risk of bleeding, or both. The dose of rFVIIa ranged from 0.067 to 0.3 mg/kg. The INR improved to normal or near normal in all four patients. In all cases, bleeding stopped within 10 minutes of receiving the rFVIIa, and there were no complications observed., Conclusions: rFVIIa provided significant benefit in these children with liver failure and severe coagulopathy, in terms of clinical and laboratory improvement in their bleeding and coagulation profiles. There were no obvious side effects from the rFVIIa. This drug may be an important tool in the treatment of children with liver failure and more study is needed to define the optimal dosing for children.

Background: Circulating autoantibodies against FcepsilonRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release., Objective: We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity., Methods: Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcepsilonRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview., Results: We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcepsilonRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcepsilonRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcepsilonRI autoantibodies but not with non-histamine-releasing anti-FcepsilonRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcepsilonRI autoantibodies., Conclusion: These data support the specificity of functional anti-FcepsilonRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcepsilonRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU.

Objective: To report the first case of ciprofloxacin-associated hemolytic-uremic syndrome (HUS)., Case Summary: A 53-year-old white man was treated with chemotherapy for acute lymphoblastic leukemia. Four weeks after initiation of treatment, he recovered his blood cell counts, but developed fever and was prescribed oral ciprofloxacin 500 mg twice daily. After 4 doses, he developed the typical features of HUS manifested by microangiopathic hemolytic anemia, oliguric renal failure, and thrombocytopenia. The medication was withdrawn, and he received 5 sessions of plasma exchange. He recovered completely and has normal renal function., Discussion: Secondary HUS or its related syndrome, thrombotic thrombocytopenic purpura (TTP), is uncommon, but has been reported in association with cancer, chemotherapy, and a variety of medications. Our case represents a possible adverse drug reaction to ciprofloxacin according to the Naranjo probability scale. It is the first reported case of HUS associated with ciprofloxacin., Conclusions: Ciprofloxacin use was followed by HUS in our patient and was possibly causally related. Early detection, discontinuation of the offending medication, and treatment of HUS/TTP is critical.

Phenolic compounds used in pharmaceutical and industrial products can cause irritant contact dermatitis. We studied the effects of resorcinol, phenol, 3,5-xylenol, chloroxylenol, and 4-hexyl-resorcinol on normal human epidermal keratinocytes and dermal fibroblasts for cytotoxicity and cytokine release, determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide methodology and enzyme-linked immunosorbent assay, respectively. An inverse correlation between phenol concentrations causing a 50% reduction in keratinocyte and fibroblast viability at 24 h and their octanol water-partition coefficients (i.e., hydrophobicity) was observed. 3,5-xylenol, chloroxylenol, hexyl-resorcinol, and sodium dodecyl sulfate, but not resorcinol or phenol, induced release of interleukin-1alpha from keratinocytes at cytotoxic concentrations. Variable release of tumor necrosis factor-alpha and interleukin-8 from keratinocytes occurred only at toxic threshold concentrations of the phenols or sodium dodecyl sulfate. Subtoxic concentrations of phenols or sodium dodecyl sulfate did not induce cytokine release from keratinocytes. Neither the phenols nor sodium dodecyl sulfate induced release of the chemokines interleukin-8, growth-related oncogene-alpha or monocyte chemotactic protein-1 from fibroblasts. Conditioned media from keratinocytes treated with cytotoxic concentrations of 3,5-xylenol, chloroxylenol, hexyl-resorcinol, or sodium dodecyl sulfate stimulated further release of the chemokines from fibroblasts above that obtained with control media. Rabbit anti-interleukin-1alpha serum inhibited keratinocyte-conditioned media induction of chemokine release. We have shown a structure-cytotoxicity relationship for a series of phenols as well as an association of interleukin-1alpha release with a cytotoxic effect. We demonstrated a cytokine cascade amplification step by the actions of stimulated keratinocyte media on cultured dermal fibroblasts, identifying interleukin-1alpha as the principal initiator of chemokine synthesis.

A new complex variant Philadelphia chromosome was detected in a 65-year-old man with acute, pre-B, lymphoblastic leukemia (ALL). The classic cytogenetic analysis identified an apparently balanced three-way translocation t(1;9;22)(q25;q34;q11.2). Fluorescence in situ hybridization (FISH) studies confirmed the translocation and showed bcr/abl fusion on the der(22). However, these studies revealed that the distal part of the bcr gene was not translocated onto chromosome 1 at 1q25, but inserted into chromosome 17 at 17p12-13. This complex variant translocation was described as a t(1;9;22)(q25;q34;q11.2)ins(17;22)(p12-13;q11.2q11.2). Secondary changes including +8, an inversion of the derivative chromosome 9, a translocation t(14;20)(q11;q13), and an additional derivative 22 were also identified in most of the abnormal cells. The patient died from systemic fungemia and multiorgan failure 9 months after the diagnosis of ALL. The clinical significance of complex variant Philadelphia chromosomes in ALL is reviewed and discussed.

The major histocompatibility complex (MHC) acts as a marker for self during T-cell ontogeny and is associated with the pathogenesis of many autoimmune diseases. Recent investigations have shown about 30% of patients with chronic idiopathic urticaria (CIU) have IgG autoantibodies against the high-affinity IgE receptor, FcepsilonRI, or IgE. A link between MHC class II alleles and CIU has not been reported previously. DNA was extracted from blood of 100 Caucasian patients with CIU, and the MHC class II type determined using the polymerase chain reaction with sequence-specific primers, testing for DRB and DQB1 alleles. The frequency of alleles in CIU patients was compared with that found in 603 controls. Further human leucocyte antigen (HLA) typing on patient subsets, classified by the patients' responses to intradermal injection of autologous serum and their serum-induced histamine release from basophil leucocytes of healthy donors, was undertaken. HLA DRB1*04 (DR4) and its associated allele, DQB1*0302 (DQ8), are raised in CIU patients compared with a control population (P = 2 x 10-5 and P = 2 x 10-4, respectively). HLA DRB1*15 (DR15) and its associated allele, DQB1*06 (DQ6), are significantly less frequently associated with CIU. The HLA DRB1*04 association is particularly strong (corrected P = 3.6 x 10-6) for patients whose serum has in vivo and in vitro histamine-releasing activity. HLA class II typing is consistent with the concept that CIU is a heterogeneous disease, and supports an autoimmune pathogenesis in a subset of patients.

Cytokines induced in skin by ultraviolet radiation cause local and systemic immunosuppression. Tumor necrosis factor alpha, interleukin-1, and interleukin-10 are key mediators in the mouse, but less is known about cytokine synthesis and function in ultraviolet-irradiated human skin. We exposed human skin to 3 minimal erythema doses of solar-simulated radiation and raised suction blisters at intervals to 72 h. Alloantigen presentation was suppressed in a mixed epidermal cell-lymphocyte reaction by 69% from 4 to 15 h post-solar-simulated radiation, but recovered to control values by 24 h. Tumor necrosis factor alpha was raised at 4 h after solar-simulated radiation, reached a maximum 8-fold increase at 15 h, then rapidly declined to control values. Interleukin-1alpha and interleukin-1beta were first increased at 15 h, and remained raised to 72 h, although interleukin-1beta declined from its 15 h maximum. Interleukin-10 increased a maximum 2-fold between 15 and 24 h, coincident with recovery of mixed epidermal cell-lymphocyte reaction responses and downregulation of tumor necrosis factor alpha and interleukin-1beta. Solar-simulated radiation differentially affected soluble tumor necrosis factor alpha receptors; soluble tumor necrosis factor-RI was suppressed 33% at 8-15 h whereas soluble tumor necrosis factor-RII increased 2-fold from 15 to 48 h. Interleukin-1 receptor antagonist was raised at all times post-irradiation. Interleukin-12 was not detectable in control or irradiated skin. These kinetics suggest the tumor necrosis factor alpha network has primary importance in ultraviolet-damaged human skin. The small increase in interleukin-10 implies that 3 minimal erythema doses of solar-simulated radiation is the threshold dose for its induction and local, rather than systemic, functions for interleukin-10 in immunosuppression and regulation of other cytokines.

One-third of patients with chronic idiopathic urticaria (CIU) have circulating functional autoantibodies against the high affinity IgE receptor FcepsilonRI, or IgE. The intradermal injection of autologous serum causes a weal and flare reaction in many patients with CIU, and this reaction forms the basis of the autologous serum skin test (ASST). We have determined the parameters of the ASST which define the optimal sensitivity and specificity for the identification of patients with autoantibodies. Two physicians (R.A. S. and C.E.H.G.) performed ASSTs in a total of 155 patients with CIU, 40 healthy control subjects, 15 patients with dermographism, nine with cholinergic urticaria and 10 with atopic eczema. Patients were classified as having functional autoantibodies by demonstrating in vitro serum-evoked histamine release from the basophils of two healthy donors. There were significant differences (P < 0.001) in the mean weal diameter, weal volume, weal redness and flare area of the intradermal serum-induced cutaneous responses at 30 min between patients with CIU with autoantibodies and either those without autoantibodies or control subjects. The optimum combined sensitivity and specificity of the ASST was obtained if a positive test was defined as a red serum-induced weal with a diameter of >/= 1.5 mm than the saline-induced response at 30 min. For R.A.S. and C.E.H.G., the ASST sensitivity was 65% and 71% and specificity was 81% and 78%, respectively. Using these criteria, the following subjects had positive ASSTs: none of 15 dermographics, none of 10 atopics, one of nine cholinergics and one of 40 controls.

Background: Previous studies defining the clinical features of patients with chronic idiopathic urticaria (CIU) were performed before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU., Objective: Our purpose was to determine whether there are differences between patients with and those without autoantibodies in the clinical features or severity of CIU., Methods: The clinical features of 107 patients with CIU were evaluated prospectively. Patients were identified as having functional autoantibodies on the basis of the serum-evoked histamine release in vitro from the basophils of 2 healthy donors., Results: Patients with autoantibodies (31%) had more wheals (P = .005), a wider distribution of wheals (P = .009), higher itch scores for the most severe episodes of itching (P = .002), more systemic symptoms (P = .03), and lower serum IgE levels (P < .0005) than patients without autoantibodies., Conclusion: The presence of autoantibodies indicates a subset of patients with more severe CIU.

Background: Previous studies defining the histopathologic features of patients with chronic idiopathic urticaria (CIU) were performed on wheals of uncertain duration and before the identification of functional autoantibodies against FcepsilonRI and/or IgE, now known to be present in approximately 30% of patients with CIU., Objective: We sought to determine the timing of the inflammatory infiltrate in the wheals of patients with CIU and to detect differences between patients with and without autoantibodies., Methods: Immunohistochemistry was used to identify neutrophils (neutrophil elastase), T lymphocytes (CD3), and activated eosinophils (EG2) in biopsy specimens from uninvolved skin and wheals present for less than 4 hours and greater than 12 hours in 22 patients with CIU, as well as in biopsy specimens from the skin of 12 healthy control subjects. Patients were identified as having functional autoantibodies on the basis of their serum-evoked histamine release in vitro from the basophils of 2 healthy donors., Results: EG2(+), neutrophil elastase+, and, to a lesser extent, CD3(+) cells were found in greater numbers in wheals undergoing biopsy at less than 4 and greater than 12 hours than in uninvolved skin (P <.05). Patients without autoantibodies (n = 12) had significantly more EG2(+) cells in wheals of greater than 12 hours' duration than patients with autoantibodies (n = 10; P =.02). There was no other difference between patients with and without autoantibodies in the cutaneous cellular infiltrate., Conclusion: Neutrophil and eosinophil accumulation occurs early in the evolution of a wheal in patients with CIU, but eosinophil activation may occur later or be more persistent in patients without autoantibodies.

Background: Circulating functional autoantibodies to the high-affinity IgE receptor (Fc(epsilon)RI) or to IgE have been found in approximately one third of patients with chronic idiopathic urticaria (CIU)., Objective: We sought to compare basophil histamine release and basophil numbers in patients with CIU with and without autoantibodies., Methods: Basophil histamine release to the anti-Fc(epsilon)RI mAb 22E7, anti-IgE, and formyl-methionyl-leucyl-phenylalanine (fMLP); basophil numbers; and total cellular histamine were measured in 26 patients with CIU and 18 healthy control subjects. Twelve patients were classified as having functional anti-Fc(epsilon)RI and/or anti-IgE autoantibodies on the basis of their serum-evoked histamine release from the basophils of 2 healthy donors., Results: 22E7 and anti-IgE, but not fMLP, released less histamine from basophils of patients with CIU than from those of control subjects. Mean+/-SEM maximum histamine release to 22E7 from basophils of control subjects and patients with CIU with and without autoantibodies was 38.5%+/-5.0%, 17.9%+/-6.0% (P =.01), and 1.0%+/-0.3% (P <.0001), respectively. Similar results were obtained with anti-IgE, which is dependent on and cross-links cell bound IgE, and 22E7, which directly cross-links the IgE receptor. The mean+/-SEM basophil counts for control subjects and patients with CIU without and with autoantibodies were 52+/-7, 34+/-9 (P =.04), and 5+/-1 (P <.0001) x 10(6) cells/L, respectively, and similar changes were found in measurements of total cellular histamine., Conclusion: Patients with autoantibodies have both markedly reduced basophil numbers and basophil histamine release to factors acting through Fc(epsilon)RI, which indicates either a residual pool of functionally distinct basophils or may be a consequence of desensitization of the Fc(epsilon)RI pathway.

We report the neonatal courses, early postnatal development, and neuroimaging findings of 17 patients with marked microcephaly and simplified cerebral gyral patterns, a condition that we call microlissencephaly. Retrospective analyses of the clinicoradiologic features of these patients allowed segregation of the patients into 5 distinct groups with varying outcomes. The apparent discreteness of these groups suggests multiple etiologies of this malformation, although there appears to be a strong genetic component with probable autosomal recessive inheritance. Utilizing the neonatal course and neuroradiologic features of these infants allows classification of specific subsets, which may be useful to predict outcome.

Purpose: To determine if fast spin-echo T2 (FSE) is of equal value to flow-sensitive 2D cine phase-contrast (CPC) to assess patency of endoscopic third ventriculocisternostomies (VC)., Patients and Methods: We reviewed clinical charts and MR scans of 27 patients who underwent third VC for treatment of obstructive hydrocephalus. Thirty-nine postoperative scans included both sequences and were assessed for the presence or absence of flow-related signal changes., Results: In 28 cases, FSE, CPC, and clinical findings suggested patency. In 1 case, CPC and FSE suggested occlusion, which was confirmed clinically and operatively. In the remaining cases, FSE showed better clinical correlation than did CPC., Conclusion: The assessment of third VC patency with FSE, a sequence available on most clinical scanners without a requirement for special hardware and software, is at least as sensitive in the qualitative assessment of VC function as CPC.

Histamine releasing autoantibodies play a central role in the pathogenesis of chronic urticaria (CU) in approximately 30% of affected patients. We investigated the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria was diagnosed by the development of a weal-and-flare reaction to the intradermal injection of autologous serum and by serum-induced histamine release from the basophil leucocytes of healthy donors in vitro. Ten patients with severe, autoimmune CU, poorly responsive to conventional treatment, were treated with IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was monitored using urticaria activity scores, visual analogue scales and autologous intradermal serum tests. Clinical benefit was noted in nine of 10 patients: three patients continue in prolonged complete remissions (3 years follow-up), two had temporary complete remissions, and symptoms in four patients improved subsequent to treatment. There was significant improvement in the urticaria activity scores and visual analogue scores at 2 (P < 0.01) and 6 weeks (P < 0.01) post-IVIG compared with the baseline values (Wilcoxon matched pairs). The diminution in urticarial activity in the majority of patients corresponded with a reduced weal-and-flare response to the intradermal injection of autologous post-treatment serum compared with the pretreatment serum. Minor side-effects were common, but there were no serious or long-term adverse effects. IVIG represents a novel therapeutic option in selected patients with recalcitrant CU associated with histamine releasing autoantibodies.

Background: Peripheral blood basophils are reduced in some chronic urticaria patients when counted with granule stains. Approximately 30% of patients with severe chronic urticaria have functional autoantibodies which release histamine from healthy donor basophils in vitro but the relationship between basophil numbers in vivo and serum histamine releasing activity has not been studied., Objective: To determine the relationship between basophil numbers and serum basophil histamine releasing activity and to assess whether basophils are present, but undetectable, in peripheral blood with granule stains by using a new flow cytometric method based on surface immunophenotype., Methods: Basophils were counted manually by a chamber method using a granule stain and by flow cytometry using dual staining with anti-IgE and anti-Fc epsilonRI in 25 chronic idiopathic urticaria patients and 25 healthy controls. Serum histamine releasing activity was assessed on healthy donor basophils in vitro and by the weal response to autologous serum skin testing in vivo (patients only)., Results: Basophils were significantly reduced in chronic urticaria by manual counting and flow cytometry. A subgroup of seven patients with in vitro histamine releasing activity showed a marked reduction or absence of basophils by both methods. There were no obvious distinguishing clinical characteristics between these patients and the others; six of them showed positive autologous serum skin-test responses. On comparing the two methods, the manual basophil counts were generally lower than flow cytometric counts. Agreement over the full range of values was not strong and therefore counts obtained by the two methods are not directly interchangeable., Conclusion: Basopenia in chronic idiopathic urticaria is associated with serum basophil histamine releasing activity in a subgroup of patients. The lack of granule and surface immunophenotype staining suggests a reduction in numbers rather than an inability to detect circulating degranulated cells by conventional counting methods.