Good Samaritan Hospital

<h3>BACKGROUND AND PURPOSE:</h3> The World Health Organization has recently placed new emphasis on the integration of genetic information for gliomas. While tissue sampling remains the criterion standard, noninvasive imaging techniques may provide complimentary insight into clinically relevant genetic mutations. Our aim was to train a convolutional neural network to independently predict underlying molecular genetic mutation status in gliomas with high accuracy and identify the most predictive imaging features for each mutation. <h3>MATERIALS AND METHODS:</h3> MR imaging data and molecular information were retrospectively obtained from The Cancer Imaging Archives for 259 patients with either low- or high-grade gliomas. A convolutional neural network was trained to classify <i>isocitrate dehydrogenase 1</i> (<i>IDH1</i>) mutation status, 1p/19q codeletion, and <i>O6-methylguanine-DNA methyltransferase</i> (<i>MGMT</i>) promotor methylation status. Principal component analysis of the final convolutional neural network layer was used to extract the key imaging features critical for successful classification. <h3>RESULTS:</h3> Classification had high accuracy: <i>IDH1</i> mutation status, 94%; 1p/19q codeletion, 92%; and <i>MGMT</i> promotor methylation status, 83%. Each genetic category was also associated with distinctive imaging features such as definition of tumor margins, T1 and FLAIR suppression, extent of edema, extent of necrosis, and textural features. <h3>CONCLUSIONS:</h3> Our results indicate that for The Cancer Imaging Archives dataset, machine-learning approaches allow classification of individual genetic mutations of both low- and high-grade gliomas. We show that relevant MR imaging features acquired from an added dimensionality-reduction technique demonstrate that neural networks are capable of learning key imaging components without prior feature selection or human-directed training.

In 1985 a 5-year multicenter Veterans Administration Cooperative Study was completed that compared the efficacy and toxicity of phenobarbital, carbamazepine, phenytoin, and primidone in a double-blind prospective study design. A total of 622 patients, either previously untreated or undertreated, were entered into the study. Strict exclusion criteria limited confounding factors such as drug or alcohol abuse. Results showed that each of the four drugs used as monotherapy were similarly effective in the treatment of generalized tonic clonic seizures, but carbamazepine was significantly more effective in the treatment of complex partial seizures as measured by 100% control. When the results for all four drugs were combined, the data showed that approximately 80% of the patients were adequately managed on monotherapy. Differences in toxicity were the most significant factor that discriminated between these four drugs. Both carbamazepine and phenytoin were associated with significantly lower incidences of intolerable side effects than were primidone or phenobarbital. A behavioral toxicity battery was performed whenever possible prior to administration of any antiepileptic drug and at 1, 3, 6, and 12 months after initiation of monotherapy. Significant differences in performance on all subtests of the battery were found between patients with epilepsy and a control group matched by age, sex, and education. When the differential effects of all four drugs on behavioral toxicity were compared, few statistically significant differences emerged. However, carbamazepine consistently produced fewer adverse effects on tests of attention/concentration and motor performance than did the other three antiepileptic drugs.

1. Microneurography was used to search for primary afferents responsive to innocuous low temperature in human nerves supplying the hairy skin of the hand or foot. Eighteen units were identified as cold-specific units: they displayed a steady-state discharge at skin temperatures in the range 28-30 degrees C, they were sensitive to small changes in temperature, and they responded vigorously when a cool metal probe touched their receptive fields (RFs). They were insensitive to mechanical stimuli and sympathetic activation. Their RFs comprised one, or at most two, spots less than 5 mm in diameter. 2. Nine units were characterised in detail by a series of 10 s cooling and warming pulses from a holding temperature of 35 degrees C. The threshold temperature for activation by cooling was 29.4 +/- 2.0 degrees C (mean +/- S.D.). Adaptation of the responses to supra-threshold cooling pulses was partial: mean peak and plateau firing rates were maximal on steps to 15 degrees C (35.9 and 19.9 impulses x s(-1), respectively). Three of these units also displayed a paradoxical response to warming, with a mean threshold of 42.3 degrees C. 3. Sixteen of the eighteen cold-specific units were also studied by electrical stimulation of their RFs. They conducted in the velocity range 0.8-3.0 m x s(-1). When stimulated at 2 Hz, their latency increased according to a characteristic time course, reaching a plateau within 3 min (mean slowing (+/- S.D.) 5.2 +/- 1.1 %) and recovering quickly (50 % recovery in 17.8 +/- 4.5 s). 4. To reconcile these findings with previous studies of reaction times and the effects of nerve compression on sensation, it is concluded that either human cold-specific afferent fibres are incompletely myelinated 'BC' fibres, or else there are C as well as A(delta) cold fibres, with the C fibre group contributing little to sensation.

Rationale: Giant cell arteritis (GCA)—a primary vasculitis of medium and large arteries—is associated with vessel wall damage, elastic membrane fragmentation, and vascular remodeling. Proteinases are believed to contribute to pathogenesis by degrading extracellular matrix and causing tissue injury. Objective: The MMP (matrix metalloproteinase)-9—a type IV collagenase—is produced in the vasculitic lesions of GCA. It is unknown which pathogenic processes are MMP-9 dependent. Methods and Results: The tissue transcriptome of GCA-affected temporal arteries contained high amounts of MMP-9 transcripts, and immunostaining for pro-MMP-9 localized the enzyme to wall-infiltrating macrophages. MMP-2 and MMP-9 transcripts were also abundant in monocytes and monocyte-derived macrophages from patients with GCA. Patient-derived monocytes outperformed healthy monocytes in passing through engineered basement membranes. GCA CD (cluster of differentiation) 4 + T cells required MMP-9–producing monocytes to penetrate through matrix built from type IV collagen. In vivo functions of MMP-9 were tested in a human artery-SCID (severe combined immunodeficiency) chimera model by blocking enzyme activity with a highly specific monoclonal antibody or by injecting rMMP-9 (recombinant MMP-9). Inhibiting MMP-9 activity profoundly suppressed vascular injury, decreased the density of inflammatory infiltrates ( P &lt;0.001), reduced intramural neoangiogenesis ( P &lt;0.001), and prevented intimal layer hyperplasia ( P &lt;0.001). rMMP-9 amplified all domains of vasculitic activity, promoted assembly of T-cell infiltrates ( P &lt;0.05), intensified formation of new microvessels ( P &lt;0.001), and worsened intimal thickening ( P &lt;0.001). Systemic delivery of N-acetyl-proline-glycine-proline—a matrikine produced by MMP-9–mediated gelatinolysis—had limited vasculitogenic effects. Conclusions: In large vessel vasculitis, MMP-9 controls the access of monocytes and T cells to the vascular wall. T cells depend on MMP-9–producing monocytes to pass through collagen IV-containing basement membrane. Invasion of vasculitogenic T cells and monocytes, formation of neoangiogenic networks, and neointimal growth all require the enzymatic activity of MMP-9, identifying this protease as a potential therapeutic target to restore the immunoprivilege of the arterial wall in large vessel vasculitis.

Differential A-fibre block of human peripheral nerves changes the sensation evoked by innocuous cooling (approximately 24 degrees C) of the skin from 'cold' to 'hot' or 'burning', and this has been attributed to activity in unidentified unmyelinated fibres that is normally masked or inhibited by activity in Adelta cold fibres. Application of the TRPM8 agonist menthol to the skin evokes 'burning/stinging' as well as 'cold', and the unpleasant sensations are also enhanced by A-fibre block. In this study we used microneurography to search for C fibres in human skin activated by cooling and menthol, which could be responsible for these phenomena. Afferent C fibres were classified by activity-dependent slowing as Type 1A (polymodal nociceptor), Type 1B (mechanically insensitive nociceptor) or Type 2 (cold sensitive), and their responses to heating and cooling ramps were measured before and after topical application of menthol preparations (2-50%). The only C fibres activated by menthol were the Type 2 fibres, which discharged vigorously with innocuous cooling and were strongly activated and sensitized to cooling by menthol. Unlike an Adelta cold fibre, they continued to discharge at skin temperatures down to 0 degrees C, and most (13/15) were also activated by heating. We propose that the Type 2 C fibres, although resembling Adelta cold fibres in their responses to innocuous cooling and menthol, have a more complex sensory function, colouring with a 'hot-burning' quality the perceptions of low and high temperatures. Their bimodal thermoreceptive properties may help account for several puzzling psychophysical phenomena, such as 'innocuous cold nociception', 'paradoxical heat' and the thermal grill illusion, and also for some neuropathic pains.

OBJECTIVE: By surveying practitioners in our community, we hoped to determine what pediatricians and family physicians (FPs) perceive as barriers to the American Academy of Pediatrics (AAP) Recommendation on Domestic Violence Screening. BACKGROUND: When screened in the pediatric setting, as many as 40% of mothers will disclose domestic violence (DV) by their partner. Recognizing the profound effects of DV on children, the AAP recently recommended that all practitioners incorporate DV screening as a part of routine anticipatory guidance. Yet, there is little information about whether pediatricians have the training, the time to screen, or understand the magnitude of this problem. DESIGN/METHODS: A 22-question survey about attitudes, training, and current DV screening practice was sent to all general pediatricians and FPs with admitting privileges to Children's Hospital Medical Center in Cincinnati, Ohio. A copy of the AAP recommendation on screening was included. The vast majority of practitioners with an appreciable pediatric practice in the surrounding tri-state area of 1.8 million people have privileges at the institution. RESULTS: After 2 mailings, 310 (57%) of 547 of questionnaires were returned. The majority of practitioners (64%) were unaware of the AAP recommendation, but 51% of practitioners screened at least high-risk families for DV and 49% had identified a case of DV in their practice. Still, only 8.5% routinely screened for DV and 74% had received no specific DV training. Fifty-eight percent of practitioners estimated the incidence of DV to be <5% in their practice. The most commonly perceived barriers to screening were lack of education (61%), office protocol (60%), time (59%), and support staff (55%). FPs were significantly more likely to have DV training (64% vs 21%), more likely to screen at least high-risk women (79% vs 56%), and more likely to have identified a case of DV (92% vs 40%) than pediatricians. FPs were less likely to cite lack of education (46% vs 65%) and lack of time (50% vs 61%) than pediatricians. Physicians licensed in Ohio were less likely to have specific domestic violence training (23% vs 60%) as compared with Kentucky physicians, where domestic violence education is required for licensing. Kentucky physicians were less likely to cite lack of education as barrier to DV screening (20% vs 62%). When comparing the characteristics of those who screen to those who do not, those with DV training were 10.9 times (odds adjusted ratio) more likely to screen. CONCLUSIONS: Practitioners grossly underestimate the incidence of DV in their practices. Lack of education including knowledge of screening recommendations is a barrier to DV screening by pediatricians. Greater efforts are needed to educate pediatricians on DV for the AAP recommendations to be accepted.domestic violence, child abuse, screening, physician attitude.

BACKGROUND AND PURPOSE: The detection of microbleeds differs strongly between studies, due to differences in scan protocol. This study aims to compare the visualization of microbleeds with 3D T2*-weighted imaging at 1.5T with 3D dual-echo T2*-weighted imaging at 7T. MATERIALS AND METHODS: Thirty-four patients (29 male; mean age, 58 ± 12 years) with atherosclerotic disease from the Second Manifestations of ARTerial Disease study were included. 3D T2*-weighted imaging at 1.5T and dual-echo T2*-weighted imaging at 7T were done in all patients. The presence and number of definite microbleeds were recorded on minimal intensity projections. Inter- and intraobserver reliability was assessed with Cohen κ test and the ICC. The difference in presence and number of microbleeds was tested with the McNemar test and Wilcoxon signed rank test. RESULTS: The interobserver ICC at 7T was 0.61 and the intraobserver ICC was 0.94, whereas at 1.5T the interobserver ICC was 0.50 and the intraobserver ICC was 0.59. Microbleeds were detected in significantly more patients on 7T (50%) than on 1.5T scans (21%) (P = .001). The number of microbleeds was also higher at 7T (median, 0.5; range, 0-5) than on 1.5T (median, 0.0; range, 0-6) (P = .002). CONCLUSIONS: 3D dual-echo T2*-weighted imaging at 7T results in better and more reliable detection of microbleeds compared with 3D T2*-weighted imaging at 1.5T.

Sharon Becker, RN, is coordinator of the Health Ministries Program at Good Samaritan Hospital in Dayton, Ohio. She attends Holy Trinity Church m Dayton. Reprinted with permission: Copyright© 2003 Good Samaritan Hospital. Date: April 7, 2003.The foregoing is not to be considered legal advice, for which readers should consult their own legal counsel. The views represent the views of the author and do not necessarily carry the endorsement of InterVarsity Christian Fellowship/USA®.

AIM: To determine how millennial nursing students perceive the effects of instructional technology on their attentiveness, knowledge, critical thinking, and satisfaction. BACKGROUND Millennial learners develop critical thinking through experimentation, active participation, and multitasking with rapid shifts between technological devices. They desire immediate feedback. METHOD; A descriptive, longitudinal, anonymous survey design was used with a convenience sample of 108 sophomore, junior, and senior baccalaureate nursing students (participation rates 95 percent, winter, 85 percent, spring). Audience response, virtual learning, simulation, and computerized testing technologies were used. An investigator-designed instrument measured attentiveness, knowledge, critical thinking, and satisfaction (Cronbach's alphas 0.73, winter; 0.84, spring). RESULTS: Participants positively rated the audience response, virtual learning, and simulation instructional technologies on their class participation, learning, attention, and satisfaction. They strongly preferred computerized testing. CONCLUSION: Consistent with other studies, these students engaged positively with new teaching strategies using contemporary instructional technology. Faculty should consider using instructional technologies.

The article describes a study that measured, over a 3-month period, staffing problems, including turnover rates; nurse incidents, including absenteeism, back injuries, and needle sticks; and patient incidents, including falls and medication errors. The self-reported stress of the nurses caring for these patients was recorded over the same 3-month period. Data showed that a relatively strong relationship exists between a hospital unit's Stress Continuum Scale (SCS) and the occurrence of patient incidents. The relationship between the SCS and personal incidents and nurse injuries appears weak, as does the relationship between staff turnover and stress. Lagging staff turnover by 1 month resulted in a moderate association with the SCS, however.

PURPOSE Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed &lt; 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred forty-two (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.

Among 47 patients with thrombotic thrombocytopenic purpura (TTP), 8 patients were diagnosed to have postoperative-TTP. Two patients underwent vascular surgery, 5 patients coronary artery bypass grafts, and 1 patient resection of myocardial sarcoma. Prior to surgery, all patients except one had normal hemograms and platelet counts, and blood smears showed no schistocytes. Five to 19 days after surgery, all 8 patients developed postoperative TTP, which clinical feature was characterized by unexplained progressive encephalopathy, thrombocytopenia, and microangiopathic hemolytic anemia. In addition, in 3 patients, progressive gangrene of the toes also developed. Four patients achieved complete remission following exchange plasmapheresis and 1 patient spontaneous remission. Due to complicated surgical settings after surgery, recognition of TTP was often delayed and it contributed to death in 3 patients despite treatment with exchange plasmapheresis. In view of occurrence of postoperative TTP following cardiac and vascular surgeries, pathogenic mechanism for postoperative TTP may be explained on the basis of injury of diseased endothelial surface and release of a humoral factor(s) that results in platelet aggregation in the capillaries and arterioles. Our experience with these cases indicates that TTP may occur as a serious complication of cardiac and vascular surgeries, and early recognition of the diagnosis and institution of exchange plasmapheresis are of paramount importance for favorable outcome.

OBJECTIVE: To report a case of fluconazole worsening of liver dysfunction. CASE SUMMARY: A patient with hepatitis experienced worsening of her liver function when treated with fluconazole for a Candida infection in her urine. Elevations in aspartate aminotransferase, alanine aminotransferase, and total bilirubin concentrations along with increased prothrombin time and activated partial thromboplastin time were noted as early as the second day of therapy. After discontinuation of the fluconazole, the liver parameters returned to their normal baseline level. DISCUSSION: Hepatotoxicity associated with azole antifungal therapy is reviewed. This patient experienced elevations in liver function enzymes; the literature relating to this topic is evaluated. CONCLUSIONS: It is probable that fluconazole therapy was involved in the worsening of this patient's liver function. Liver function should be monitored during the course of fluconazole therapy in patients with underlying liver dysfunction. It appears from the published reports that HIV-positive patients may be at risk for hepatotoxicity with fluconazole.

This study assessed differences in the psychological adjustment of gay men who tested positive for the antibody to the human immunodeficiency virus (HIV). Twenty‐one were symptomatic for AIDS, and 27 were asymptomatic. A group of 15 gay men who tested negative for the HIV was included as a comparison group. Men in the three groups were equivalent on demographic variables. Symptomatic men reported more health problems than either asymptomatic or seronegative men. Relative to men who were symptomatic, those who were asymptomatic reported more death anxiety, less optimism, and greater severity of psychological distress, and reported more frequent use of avoidance and distancing as coping strategies. The poor psychological functioning of asymptomatic subjects was attributed to the uncertainty regarding their future health status. Generally, positive psychological well‐being of symptomatic and asymptomatic men was related to the infrequent use of avoidance coping strategies and high satisfaction with perceived social support.

PURPOSE: To evaluate the safety and efficacy of a novel optical coherence tomography (OCT)-guided atherectomy catheter in treating patients with symptomatic femoropopliteal disease. METHODS: The VISION trial ( ClinicalTrials.gov identifier NCT01937351) was a single-arm, multicenter, global investigational device exemption study enrolling 158 subjects (mean age 67.2±10.5 years; 87 men) across 20 participating sites. In this cohort, 198 lesions were treated with an average length of 53±40 mm using the Pantheris catheter alone or Pantheris + adjunctive therapy. The primary safety endpoint was the composite of major adverse events (MAEs) through 6 months (objective performance goal 43.2%). Technical success (primary efficacy outcome) was defined as the percent of target lesions with a residual diameter stenosis ≤50% after treatment with the Pantheris device alone (objective performance goal 87.0%). Procedural success was defined as reduction in stenosis to ≤30% after Pantheris ± adjunctive therapy. Tissue specimens retrieved from each treated lesion were histologically analyzed to evaluate the accuracy and precision of OCT image guidance. RESULTS: The primary efficacy outcome was achieved in 192 (97.0%) of the 198 lesions treated with the Pantheris catheter. Across all lesions, mean diameter stenosis was reduced from 78.7%±15.1% at baseline to 30.3%±11.8% after Pantheris alone (p<0.001) and to 22.4%±9.9% after Pantheris ± adjunctive therapy (p<0.001). Of the 198 target lesions, 104 (52.5%) were treated with the Pantheris alone, 84 (42.4%) were treated with Pantheris + adjunctive angioplasty, and 10 (5.1%) with Pantheris + angioplasty + stenting. The composite MAE outcome through 6 months occurred in 25 (16.6%) of 151 subjects. There were no clinically significant perforations, 1 (0.5%) catheter-related dissection, 4 (2%) embolic events, and a 6.4% clinically driven target lesion revascularization rate at 6 months. The 40-lesion chronic total occlusion (CTO) subset (mean lesion length 82±38 mm) achieved a similar significant reduction in stenosis to 35.5%±13.6% after Pantheris alone (p<0.001). Histological analysis of atherectomy specimens confirmed <1% adventitia in 82.1% of the samples, highlighting the precision of OCT guidance. Characterization of the OCT-guided lesions revealed evidence of an underestimation of disease burden when using fluoroscopy. CONCLUSION: OCT-guided atherectomy for femoropopliteal disease is safe and effective. Additionally, the precision afforded by OCT guidance leads to greater removal of plaque during atherectomy while sparing the adventitia.

AIMS: To describe and identify the function of a class of human C fibre with an unusual response to repetitive electrical stimulation. Other C fibres slow progressively at 2 Hz (type 1), reach a latency plateau (type 2) or hardly slow at all (type 3). METHODS: C fibres innervating hairy skin were recorded by microneurography in the superficial peroneal nerves of 19 healthy volunteers. Baseline electrical stimulation of the skin was at 0.25 Hz, and activity-dependent slowing recorded during stimulation at 2 Hz for 3 min and after a 3-min pause in stimulation. RESULTS: In 41 units, there was a partial recovery of latency during repetitive stimulation. These were classified as 'type-4' units, and identified as sympathetic efferents, since they exhibited spontaneously activity, which was enhanced by manoeuvres that increase sympathetic outflow (15 of 16 cases) and/or suppressed by a proximal anaesthetic block (eight of eight cases). The peak slowing during 2 Hz trains averaged 6.47 +/- 2.06% (mean +/- SD, n=41), but after 3 min the slowing had reduced to 4.90 +/- 2.20%, which was less than in all type 1 (nociceptor) fibres but similar to that in type 2 (cold) fibres. Compared with cold fibres, type-4 sympathetic fibres slowed more after the first 10 impulses at 2 Hz (2.57 +/- 0.45%) and also after a pause in stimulation (1.66 +/- 0.51%). CONCLUSIONS: The distinctive activity-dependent slowing profiles of these type-4 sympathetic C units may help identification in vitro, and suggest that hyperpolarization-activated channels have a particularly prominent role in the axonal membrane.

BACKGROUND: In this study we compared clinical findings with flow cytometric immunophenotypic results in a series of patients with aggressive and indolent gamma delta T-cell malignancies with peripheral blood and/or bone marrow involvement. METHODS: Gamma delta T-cell malignancies were detected based on flow cytometric demonstration of an abnormal T-cell population staining positive with T-cell receptor gamma delta and confirmed by morphologic and clinical reviews. Clinical data were obtained through chart review and discussion with the patients' physicians. RESULTS: Blood or bone marrow involvement was present in all patients. Hepatosplenic and cutaneous gamma delta T-cell lymphomas had an aggressive clinical course, whereas the gamma delta T-cell large granular lymphocyte (LGL) leukemias had an indolent course. Expressions of CD5, CD8, CD16, and CD57 differed in gamma delta T-cell LGL leukemia compared with hepatosplenic and cutaneous gamma delta T-cell lymphomas. CONCLUSIONS: Gamma delta T-cell malignancies have a poor prognosis with the exception of gamma delta T-cell LGL leukemia (indolent process). Because CD57 expression is specific for gamma delta T-cell LGL leukemias, expression of this antigen may be associated with a more indolent clinical course. Because cutaneous gamma delta T-cell lymphoma can present with peripheral blood involvement, flow cytometric evaluation of peripheral blood is important in staging these patients.

OBJECTIVE: To report a case of possible foscarnet-induced severe hypomagnesemia and other electrolyte disorders. CASE SUMMARY: An AIDS patient experienced an exacerbation of cytomegalovirus retinitis and was treated with foscarnet. The patient experienced muscle twitches, tremulousness, and anxiety on day 17 of foscarnet therapy. Laboratory results indicated hypomagnesemia, hypocalcemia, hypokalemia, and hypophosphatemia. After electrolyte supplementation and discontinuation of foscarnet, the symptoms resolved and laboratory indices returned to normal. DISCUSSION: Electrolyte disorders associated with foscarnet are reviewed. Severe hypomagnesemia occurred in this patient and published literature is highlighted. In addition, known and/or possible mechanisms of the disorders are discussed. CONCLUSIONS: It is probable that foscarnet contributed to the electrolyte disorders and symptomatology in this patient. Electrolytes must be monitored frequently during foscarnet therapy. Also, concomitant therapy with antianxiety medications that may mask the symptoms of electrolyte disorders should be undertaken with caution.

BACKGROUND: Thrombotic microangiopathy (TM) is characterized by thrombocytopenia and microangiopathic hemolytic anemia in association with diffuse microthrombi in the arteriolar capillaries of various organs. Its clinical manifestation is protean, and a few well-defined clinical syndromes have been recognized. A clear understanding of the consequence of TM is needed to appreciate the unusual clinical syndromes due to atypical presentation of thrombotic thrombocytopenic purpura (TTP). METHODS: The medical records of patients with known diagnoses of TTP, hemolytic uremic syndrome (HUS), and the syndrome in which hemolysis, elevated liver enzymes, and low platelet count are found in association with pregnancy were examined retrospectively from 1981 to 1994 and prospectively from 1995 to 2000. Various thrombotic microangiopathic presentations were identified in these patients. Their response to exchange plasmapheresis was evaluated, and their clinical outcome was determined. RESULTS: A total of 74 patients were diagnosed with TM. Among these patients, several well-defined thrombotic microangiopathic presentations were identified. These presentations included TTP in 57 patients, acute respiratory distress syndrome (ARDS) in 13 patients, HUS in 9 patients, the syndrome in which hemolysis, elevated liver enzymes, and low platelet count are found in association with pregnancy in 9 patients, peripheral digit ischemic syndrome (PDIS) in 6 patients, pancreatitis in 3 patients, hepatitis in 3 patients, and nonocclusive mesenteric ischemia (NOMI) in 2 patients. Exchange plasmapheresis was an effective treatment, with a response rate of 79%. A poor prognosis was evident when ARDS was present, with an overall survival rate of 46%. CONCLUSION: Traditionally, TTP and HUS are considered the main entities of TM. It is evident that other manifestations of TM, if unrecognized in a timely fashion, can lead to fatality. The understanding of the pathophysiologic consequences of TM and the recognition of its atypical presentations are essential to achieve favorable outcomes in patients with this life-threatening disease.

Systemic vasculitis (SV) involving abdominal structures usually has a poor prognosis. Gallbladder vasculitis (GV) has been reported as part of SV (GB-SV) and focal single-organ vasculitis (GB-SOV). We analyzed clinical and histologic characteristics of patients with GV to identify features that differentiate GB-SOV from the systemic forms of GV. To identify affected patients with GV we used pathology databases from our institution and an English-language PubMed search. Clinical manifestations, laboratory and histologic features, treatment administered, and outcomes were recorded. Patients were divided in 2 groups, GB-SOV and GB-SV. As in previous studies of single-organ vasculitis, GB-SOV was only considered to be a sustainable diagnosis if disease beyond the gallbladder was not apparent after a follow-up period of at least 6 months. Sixty-one well-characterized patients with GV were included (6 from our institution). There was no significant sex bias (32 female patients, 29 male). Median age was 52 years (range, 18-94 yr). GB-SOV was found in 20 (33%) and GB-SV in 41 (67%) patients. No differences were observed in age, sex frequency, or duration of gallbladder symptoms between groups. Past episodes of recurrent right-upper quadrant or abdominal pain and lithiasic cholecystitis were more frequent in GB-SOV patients, whereas acalculous cholecystitis occurred more often in GB-SV. In GB-SV, gallbladder-related symptoms occurred more often concomitantly with or after the systemic features, but they sometimes appeared before SV was fully developed (13.5%). Constitutional and musculoskeletal symptoms were reported only in GB-SV patients. Compared to GB-SOV, GB-SV patients presented more often with fever (62.5% vs 20%; p = 0.003) and exhibited higher erythrocyte sedimentation rate levels (80 ± 28 vs 37 ± 25 mm/h, respectively; p = 0.006). All GB-SV patients required glucocorticoids and 50% of them also received cytotoxic agents. Mortality in GB-SV was higher than in GB-SOV (35.5% vs 10%; p = 0.05). Nongranulomatous inflammation with fibrinoid necrosis of medium-sized vessels occurred equally in both groups (>90%). Forms of SV affecting the gallbladder included polyarteritis nodosa (n = 10), hepatitis B virus-associated vasculitis (n = 8), cryoglobulinemic (essential or hepatitis C virus-associated) vasculitis (n = 6), vasculitis associated with autoimmune diseases (n = 6), microscopic polyangiitis (n = 4), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (n = 4), IgA vasculitis (Henoch-Schönlein) (n = 2), and giant cell arteritis (n = 1).GV is uncommon. Its histology most often consists of a nongranulomatous necrotizing vasculitis affecting medium-sized vessels. GB-SOV is usually discovered after routine cholecystectomy performed because of the presence of local symptoms, gallstone-associated cholecystitis, and contrary to GB-SV, GB-SOV is usually not associated with systemic symptoms. Acute phase reactants and surrogate markers of autoimmunity are usually normal or negative in GB-SOV. GB-SOV does not require systemic antiinflammatory or immunosuppressive therapy; surgery is adequate to achieve cure. GB-SV always warrants immunosuppressant therapy and is associated with high mortality. The finding of GV may precede the generalized manifestations of SV. Therefore, once GV is discovered, studies to determine disease extent and a vigilant follow-up are mandatory.