Clinical phenotypes and therapeutic responses in cutaneous-predominant sarcoidosis: 6-year experience in a tertiary referral service.

BACKGROUND: There is a limited evidence base for the treatment of cutaneous sarcoidosis. OBJECTIVE: To describe treatment modalities and responses in patients with predominantly cutaneous sarcoidosis, in addition to clinical characteristics and prevalence of systemic disease. METHODS: Data were prospectively collected over a 6-year period. The Cutaneous Sarcoidosis Activity and Morphology Index was used to assess treatment effectiveness. RESULTS: In total, 47 patients with biopsy-confirmed cutaneous sarcoidosis were identified. Morphologically, the most common lesions were papules (49%) and plaques (42.6%). The most commonly affected sites were the head and neck (79%); 89.4% had systemic as well as cutaneous disease; 77% received systemic corticosteroid therapy, while 87% required further steroid-sparing treatment; 40% achieved clinical remission with hydroxychloroquine (HCQ) and 88% achieved clinical remission with methotrexate (MTX). OR of achieving remission on MTX compared with HCQ was 9.8 (95% CI 2.4-40.4, P = 0.001). MTX was superior to both azathioprine (AZA) (OR = 22; 95% CI 1.7-285.9; P = 0.02) and mycophenolate mofetil (MMF) (OR = 22; 95% CI 1.7-285.9; P = 0.02) in achieving remission. CONCLUSION: HCQ is effective and well-tolerated. MTX was associated with significantly increased probability of achieving clinical remission compared with AZA and MMF.

Environmental signatures and effects of an oil and gas wastewater spill in the Williston Basin, North Dakota.

Wastewaters from oil and gas development pose largely unknown risks to environmental resources. In January 2015, 11.4ML (million liters) of wastewater (300g/L TDS) from oil production in the Williston Basin was reported to have leaked from a pipeline, spilling into Blacktail Creek, North Dakota. Geochemical and biological samples were collected in February and June 2015 to identify geochemical signatures of spilled wastewaters as well as biological responses along a 44-km river reach. February water samples had elevated chloride (1030mg/L) and bromide (7.8mg/L) downstream from the spill, compared to upstream levels (11mg/L and <0.4mg/L, respectively). Lithium (0.25mg/L), boron (1.75mg/L) and strontium (7.1mg/L) were present downstream at 5-10 times upstream concentrations. Light hydrocarbon measurements indicated a persistent thermogenic source of methane in the stream. Semi-volatile hydrocarbons indicative of oil were not detected in filtered samples but low levels, including tetramethylbenzenes and di-methylnaphthalenes, were detected in unfiltered water samples downstream from the spill. Labile sediment-bound barium and strontium concentrations (June 2015) were higher downstream from the Spill Site. Radium activities in sediment downstream from the Spill Site were up to 15 times the upstream activities and, combined with Sr isotope ratios, suggest contributions from the pipeline fluid and support the conclusion that elevated concentrations in Blacktail Creek water are from the leaking pipeline. Results from June 2015 demonstrate the persistence of wastewater effects in Blacktail Creek several months after remediation efforts started. Aquatic health effects were observed in June 2015; fish bioassays showed only 2.5% survival at 7.1km downstream from the spill compared to 89% at the upstream reference site. Additional potential biological impacts were indicated by estrogenic inhibition in downstream waters. Our findings demonstrate that environmental signatures from wastewater spills are persistent and create the potential for long-term environmental health effects.

Nano- and micro-patterning biotemplated magnetic CoPt arrays.

Patterned thin-films of magnetic nanoparticles (MNPs) can be used to make: surfaces for manipulating and sorting cells, sensors, 2D spin-ices and high-density data storage devices. Conventional manufacture of patterned magnetic thin-films is not environmentally friendly because it uses high temperatures (hundreds of degrees Celsius) and high vacuum, which requires expensive specialised equipment. To tackle these issues, we have taken inspiration from nature to create environmentally friendly patterns of ferromagnetic CoPt using a biotemplating peptide under mild conditions and simple apparatus. Nano-patterning via interference lithography (IL) and micro-patterning using micro-contact printing (µCP) were used to create a peptide resistant mask onto a gold surface under ambient conditions. We redesigned a biotemplating peptide (CGSGKTHEIHSPLLHK) to self-assemble onto gold surfaces, and mineralised the patterns with CoPt at 18 °C in water. Ferromagnetic CoPt is biotemplated by the immobilised peptides, and the patterned MNPs maintain stable magnetic domains. This bioinspired study offers an ecological route towards developing biotemplated magnetic thin-films for use in applications such as sensing, cell manipulation and data storage.

Does cardiovascular phenotype explain the association between diabetes and incident heart failure? The Strong Heart Study.

BACKGROUND AND AIMS: Diabetes remains a predictor of incident heart failure (HF), independent of intercurrent myocardial infarction (MI) and concomitant risk factors. Initial cardiovascular (CV) characteristics, associated with incident heart failure (HF) might explain the association of diabetes with incident HF. METHODS AND RESULTS: Participants to the 2nd Strong Heart Study exam, without prevalent HF or coronary heart disease, or glomerular filtration rate <30 mL/min/1.73 m(2), were analyzed (n = 2757, 1777 women, 1278 diabetic). Cox regression of incident HF (follow-up 8.91 ± 2.76 years) included incident MI censored as a competing risk event. Acute MI occurred in 96 diabetic (7%) and 84 non-diabetic participants (6%, p = ns). HF occurred in 156 diabetic (12%) and in 68 non-diabetic participants (5%; OR = 2.89, p < 0.001). After accounting for competing MI and controlling for age, gender, BMI, systolic blood pressure, smoking habit, plasma cholesterol, antihypertensive treatment, heart rate, fibrinogen and C-reactive protein, incident HF was predicted by greater LV mass index, larger left atrium, lower systolic function, greater left atrial systolic force and urinary albumin/creatinine excretion. Risk of HF was reduced with more rapid LV relaxation and anti-hypertensive therapy. Diabetes increases hazard of HF by 66% (0.02 < p < 0.001). The effect of diabetes could be explained by the level of HbA1c. CONCLUSIONS: Incident HF occurs more frequently in diabetes, independent of intercurrent MI, abnormal LV geometry, subclinical systolic dysfunction and indicators of less rapid LV relaxation, and is influenced by poor metabolic control. Identification of CV phenotype at high-risk for HF in diabetes should be advised.

Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVES: To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 881 anti-TNF-treated and 3673 non-biological disease-modifying antirheumatic drug (nbDMARD)-treated patients. RESULTS: 199 patients had at least one episode of SA (anti-TNF: 179, nbDMARD: 20). Incidence rates were: anti-TNF 4.2/1000 patient years (pyrs) follow-up (95% CI 3.6 to 4.8), nbDMARD 1.8/1000 pyrs (95% CI 1.1 to 2.7). The adjusted HR for SA in the anti-TNF cohort was 2.3 (95% CI 1.2 to 4.4). The risk did not differ significantly between the three agents: adalimumab, etanercept and infliximab. The risk was highest in the early months of therapy. The patterns of reported organisms differed in the anti-TNF cohort. Prior joint replacement surgery was a risk factor for SA in all patients. The rate of postoperative joint infection (within 90 days of surgery) was 0.7%. This risk was not significantly influenced by anti-TNF therapy. CONCLUSIONS: Anti-TNF therapy use in RA is associated with a doubling in the risk of SA. Physicians and surgeons assessing the RA patient should be aware of this potentially life-threatening complication.

Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR).

BACKGROUND: The risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) is thought to be increased following anti-tumour necrosis factor (anti-TNF) therapy, with a proposed differential risk between the anti-TNF drugs etanercept (ETA), infliximab (INF) and adalimumab (ADA). OBJECTIVE: To compare directly the risk between drugs, to explore time to event, site of infection and the role of ethnicity. METHODS: Data from the British Society for Rheumatology Biologics Register (BSRBR), a national prospective observational study, were used to compare TB rates in 10 712 anti-TNF treated patients (3913 ETA, 3295 INF, 3504 ADA) and 3232 patients with active RA treated with traditional disease-modifying antirheumatic drugs. RESULTS: To April 2008, 40 cases of TB were reported, all in the anti-TNF cohort. The rate of TB was higher for the monoclonal antibodies ADA (144 events/100,000 person-years) and INF (136/100,000 person-years) than for ETA (39/100,000 person-years). After adjustment, the incidence rate ratio compared with ETA-treated patients was 3.1 (95% CI 1.0 to 9.5) for INF and 4.2 (1.4 to 12.4) for ADA. The median time to event was lowest for INF (5.5 months) compared with ETA (13.4 months) and ADA (18.5 months). 13/40 cases occurred after stopping treatment. 25/40 (62%) cases were extrapulmonary, of which 11 were disseminated. Patients of non-white ethnicity had a sixfold increased risk of TB compared with white patients treated with anti-TNF therapy. CONCLUSION: The rate of TB in patients with RA treated with anti-TNF therapy was three- to fourfold higher in patients receiving INF and ADA than in those receiving ETA.

A reference range for endogenous gamma-hydroxybutyrate in urine by gas chromatography-mass spectrometry.

Gamma-hydroxybutyrate (GHB) has been implicated in drug-facilitated sexual assault (DFSA). The interpretation of GHB levels in biological samples collected for evidence is complicated by the natural presence of this compound in the body, and by its extremely rapid elimination after ingestion. There is a lack of agreement regarding a suitable cut-off concentration, which can reliably separate endogenous concentrations in urine from those reflecting ingestion. We have developed a method for the analysis of low levels of GHB in urine and have used it to establish a reference range for normal females. The method uses liquid-liquid extraction, silyl-derivatization, and gas chromatographic-mass spectrometric analysis. The limit of detection was 0.1 mg/L, and the method was linear from 0.1 to 5.0 mg/L. Our analysis of 50 urine samples donated by normal women indicates an upper limit of normal for urinary GHB of 1.46 mg/L or 323 microg GHB/mmol of creatinine. We propose that a 5 mg/L cut-off for urine GHB concentration, or 1000 microg GHB/mmol creatinine, will separate endogenous GHB concentrations from those reflecting GHB ingestion in antemortem samples with greater than 99% confidence, providing that a specific assay method comparable with that we describe is used. We demonstrate that urinary GHB concentrations fall with age and that this can be corrected for by measurement of the GHB/creatinine ratio.

Are the favorable outcomes of splenectomy predictable inpatients with idiopathic thrombocytopenic purpura (ITP)?

BACKGROUND: Historically, splenectomy has been an accepted procedure in the management of immune thrombocytopenic purpura (ITP). However, it is also true that the response to splenectomy in patients with ITP seems to be unpredictable. Therefore, the purpose of this study was to identify clinical variables that might predict a favorable response to splenectomy in patients with ITP. METHODS: Data were collected retrospectively for 40 adult patients with ITP who underwent laparoscopic (LS) and open (OS) splenectomy at Emory University Hospital between 1992 and 1999. Demographics and outcomes were recorded. Age, sex, disease duration, comorbidities (ASA > 2), previous response to steroids and/or other medications, and preoperative platelet count were analyzed by univariate (t-test, Fisher's exact test) and multivariate statistical methods. RESULTS: Of the 20 patients in each group, improved platelet counts were noted in 18 patients (90%) in the LS group and 20 patients (100%) in the OS group. Follow-up (16 +/- 3 months) was obtained in 19 LS patients (95%) and 16 OS patients (80%), with 84% and 87.5% sustained response rates, respectively. After univariate analysis, two variables (age and disease duration) were found to be significantly related to the outcome of splenectomy (p

Plasma antioxidant status after high-dose chemotherapy: a randomized trial of parenteral nutrition in bone marrow transplantation patients.

BACKGROUND: Chemotherapy and radiation therapy result in increased free radical formation and depletion of tissue antioxidants. It is not known whether parenteral nutrition (PN) administered during bone marrow transplantation (BMT) supports systemic antioxidant status. OBJECTIVE: The aims of the study were to determine 1) whether high-dose chemotherapy decreases concentrations of major circulating antioxidants in patients undergoing BMT and 2) whether administration of standard PN maintains systemic antioxidant concentrations compared with PN containing micronutrients and minimal lipids alone. DESIGN: Twenty-four BMT patients were randomly assigned to receive either standard PN containing conventional amounts of dextrose, amino acids, micronutrients, and lipid (120 kJ/d) or a solution containing only micronutrients (identical to those in standard PN) and a small amount of lipid (12 kJ/d). Plasma antioxidant status was measured before conditioning therapy and serially at days 1, 3, 7, 10, and 14 after BMT. RESULTS: Plasma glutathione (GSH) and alpha- and gamma-tocopherol concentrations decreased and the GSH redox state became more oxidized after conditioning chemotherapy. Plasma cysteine concentrations were unchanged, whereas cystine concentrations increased. Plasma vitamin C and zinc concentrations and GSH peroxidase activity increased over time. Plasma alpha-tocopherol concentrations were lower in patients given standard PN. There were no differences in other plasma antioxidants between groups. CONCLUSIONS: A significant decline in GSH-glutathione disulfide, cysteine-cystine, and vitamin E status occurs after chemotherapy and BMT. Standard PN does not improve antioxidant status compared with administration of micronutrients alone. Further evaluation of PN formulations to support patients undergoing high-dose chemotherapy and BMT are needed.

The role of tissue expansion in abdominal wall reconstruction.

Abdominal wall reconstruction of ventral hernia defects with loss of visceral domain and inadequate soft-tissue coverage presents a surgical challenge. Four patients with large, skin grafted ventral hernia defects were treated by staged abdominal wall reconstruction. During the initial stage, tissue expanders were placed under the skin and subcutaneous tissue lateral to the defects. After adequate interval expansion, the second stage was performed. The expanders were removed, the visceral contents reduced easily, and the fascia reapproximated with polypropylene mesh. The expanded skin was closed easily over the fascial repair. All four patients were reconstructed successfully without complications. Tissue expansion can restore abdominal domain and allow soft-tissue closure in complicated ventral hernia defects.

Arrhythmogenic right ventricular dysplasia in an American Indian woman.

Arrhythmogenic right ventricular (RV) dysplasia consists of a dilatation of the right ventricle with a reduction of RV ejection fraction with fibrofatty replacement of the RV myocardium in the face of a well-preserved left ventricular systolic function. Arrhythmogenic RV dysplasia, which is a cause of sudden unexpected death, has been reported from many geographic areas, including the United States, Europe, and the Far East. This case report presents the first case of arrhythmogenic RV dysplasia in an American Indian (Native American) patient.

Vascular surgical society of great britain and ireland: limb outcome following failed femoropopliteal polytetrafluoroethylene bypass for intermittent claudication

BACKGROUND: Femoropopliteal (FP) bypass using polytetrafluoroethylene (PTFE) is still considered by many surgeons to be a reasonable procedure for severe intermittent claudication (IC) without limb-threatening ischaemia. The consequences of FP graft failure were examined. METHODS: Over 8 years, 54 patients had 55 FP grafts (that subsequently occluded) inserted for severe IC (42 PTFE and 13 vein grafts) above (30) or below (25) the knee. There were no operative deaths. During the same interval a total of 191 FP grafts were placed, 100 of which were vein grafts. Patient demography and risk factor analysis was similar for both groups. RESULTS: Nineteen patients required amputation subsequent to a failed graft, all of these following PTFE grafts. Mean time to occlusion was 12.2 (range 0-79) months. For PTFE grafts, the mean(s. d.) ankle index rose from 0.51(0.14) to 0.95(0.15) after operation but fell to 0.25(0.15) after occlusion, confirming a highly significant deterioration from preoperative levels, which was not seen in vein graft occlusions. CONCLUSION: Long-term FP bypass patency rates with vein are superior to those obtained with PTFE. Failed PTFE grafts show a significant deterioration in pressure indices compared with preoperative values. FP grafts for IC carry an intrinsic risk of limb loss which is much greater when vein is not used (P < 0.001).

Rising tide of cardiovascular disease in American Indians. The Strong Heart Study.

BACKGROUND: Although cardiovascular disease (CVD) used to be rare among American Indians, Indian Health Service data suggest that CVD mortality rates vary greatly among American Indian communities and appear to be increasing. The Strong Heart Study was initiated to investigate CVD and its risk factors in American Indians in 13 communities in Arizona, Oklahoma, and South/North Dakota. METHODS AND RESULTS: A total of 4549 participants (1846 men and 2703 women 45 to 74 years old) who were seen at the baseline (1989 to 1991) examination were subjected to surveillance (average 4.2 years, 1991 to 1995), and 88% of those remaining alive underwent a second examination (1993 to 1995). The medical records of all participants were exhaustively reviewed to ascertain nonfatal cardiovascular events that occurred since the baseline examination or to definitively determine cause of death. CVD morbidity and mortality rates were higher in men than in women and were similar in the 3 geographic areas. Coronary heart disease (CHD) incidence rates among American Indian men and women were almost 2-fold higher than those in the Atherosclerosis Risk in Communities Study. Significant independent predictors of CVD in women were diabetes, age, obesity (inverse), LDL cholesterol, albuminuria, triglycerides, and hypertension. In men, diabetes, age, LDL cholesterol, albuminuria, and hypertension were independent predictors of CVD. CONCLUSIONS: At present, CHD rates in American Indians exceed rates in other US populations and may more often be fatal. Unlike other ethnic groups, American Indians appear to have an increasing incidence of CHD, possibly related to the high prevalence of diabetes. In the general US population, the rising prevalence of obesity and diabetes may reverse the decline in CVD death rates. Therefore, aggressive programs to control diabetes and its risk factors are needed.

Detection of drug misuse--an addictive challenge.

It is now accepted that drug misuse is a large and growing problem in the United Kingdom, some estimates of the number of regular illicit drug users being as high as three million. The aim of this paper is to provide insight into the methods used to detect drug misuse. The strategy adopted by one laboratory is described and methods of screening for, and identification of, a wide range of compounds are provided. No claim is made that this is the best approach or that the list of drugs detected is comprehensive; the range of drugs encountered is always increasing and the lists are constantly updated. It is hoped that users of toxicology laboratory services will gain an appreciation of the capabilities and limitations of the techniques available; and that those who may wish to provide such a service will find the necessary information in a readily accessible format.

Compatibility and stability of fentanyl admixtures in polypropylene syringes.

OBJECTIVE: To determine the physicochemical stability of fentanyl in combination with midazolam and either hyoscine butylbromide or metoclopramide, and stored in 30 ml polypropylene syringes. METHODS: Solutions containing approximately 40 microg/ ml of fentanyl in combination with midazolam (approximately 600 microg/ml) and either metoclopramide (approximately 700 microg/l) or hyoscine (approximately 850 microg/ml) were prepared from commercial ampoules of the drugs. The solutions were stored, in triplicate, in the dark at 32 degrees C (to simulate usage conditions) for 10 days, and the concentration of each constituent drug was periodically determined using a stability-indicating high-performance liquid chromatography assay. RESULTS: The combinations were relatively stable, with all drugs maintaining over 90% of their initial chemical potency for at least 1 week. There were no evident changes in either the physical appearance or pH values of the solutions over the course of the study. CONCLUSIONS: On the basis of physicochemical stability, polypropylene syringes containing fentanyl with midazolam and either hyoscine butylbromide or metoclopramide can be safely prepared and stored at or below 32 degrees C for periods of up to 1 week prior to use by palliative care patients receiving the drugs via a portable subcutaneous infusion device.

A method for the confirmation and identification of drugs of misuse in urine using solid phase extraction and gas-liquid chromatography with mass spectrometry.

A method is described for the confirmation/identification of a range of commonly misused drugs in urine samples. The method has been used for two years without problems for a range of purposes including hospital/clinic drugs of misuse screening and for toxicology in coroner's cases. Urine samples which have given a positive result on immunochemical screening for a particular drug group or groups (for example, opiates) can be processed with identification of the drugs present using a single procedure. Bond ElutCertify columns are used for the extraction of drugs from the samples followed by propionylation and gas chromatography with mass selective detection.

Accuracy of carotid duplex is laboratory specific and must be determined by internal audit.

OBJECTIVE: To assess the accuracy of carotid duplex in a single vascular laboratory at the prediction of an angiographic 70% internal carotid artery stenosis. DESIGN: A retrospective review of all patients who underwent both carotid duplex and angiography in a 1-year period at a vascular unit which participates in the ACST trial. METHODS: Peak systolic velocity was used as a primary end-point in carotid duplex examinations with a PSV > 130 cm/s used as an indication for angiographic assessment. Biplanar arch aortography and selective carotid catheterisation were performed as indicated and diameter reduction calculated by the ECST method. RESULTS: The sensitivity of 130 cm/s for the detection of a 70% stenosis was 96% and the specificity 67%. If a PSV of 250 cm/s were used the sensitivity would be only 37% and specificity 96%. CONCLUSIONS: Applying duplex criteria from one centre to another is inappropriate. Laboratory specific audit of duplex and angiography is essential before deciding to abandon preoperative angiography for carotid disease.

Pancreatic necrosis: results of necrosectomy, packing, and ultimate closure over drains.

OBJECTIVE: The treatment of pancreatic necrosis at a tertiary referral center was reviewed to effect better patient outcome. SUMMARY BACKGROUND DATA: Pancreatic necrosis is a devastating disease that leads to death in 10% to 50% of cases. Infected necrosis is particularly deadly because 80% of deaths from necrosis are due to infection or its complications. Therapeutic strategies center on aggressive support of organ systems and prevention and treatment of infectious complications. METHODS: Records of all patients who underwent pancreatic necrosectomy from 1990 to 1996 at Emory University Hospital were reviewed. Patients with infected necrosis were debrided as soon as the diagnosis was made. Reoperation for completion necrosectomy with ultimate closure over lavage catheters was performed as necessary. RESULTS: Of the 244 patients admitted with acute pancreatitis in the study period, 50 underwent pancreatic debridement. The mean age was 52 years, and 74% of patients were transferred from other institutions. Eighty-four percent of patients had infected necrosis, and all patients underwent sequential debridement with eventual closure over drains. Organ failure occurred in 72% of cases, and the overall mortality rate was 12%. The mean length of stay was 54 days. CONCLUSIONS: The management of pancreatic necrosis demands the allocation of extensive resources. An aggressive operative strategy of multiple debridements with ultimate closure over drains can lead to a low mortality rate in patients with this complex disease, but the determination of when to explore patients with sterile necrosis remains difficult.

Management of pancreatic pseudocysts.

BACKGROUND: Operative internal drainage has been standard treatment for chronic unresolved pancreatic pseudocysts (PPs). Recently, percutaneous external drainage (PED) has become the primary mode of treatment at many medical centers. STUDY DESIGN: A retrospective chart review was performed of 96 patients with PPs who were managed between 1987 and 1996. Longterm followup information was obtained by telephone and mail questionnaire. RESULTS: Twenty-seven patients underwent computed tomographic (CT)-guided PED. PP resolution occurred in 17 patients. Clinical deterioration or secondary infection mandated urgent pancreatic debridement in 7 (26%) patients and cystgastrostomy in 2 (7%) patients. There was one hospital death in this group. Thirty-two patients underwent cystgastrostomy or cystjejunostomy (n = 21), distal pancreatectomy (n = 8), pancreatic debridement and external drainage (n = 2), or cystectomy (n = 1). Two (6%) patients required postoperative pancreatic debridement for failure of resolution and peritonitis and two patients underwent PED of abscess. There was one hospital death in the expectantly managed group of 37 patients. Median followup of 3 years (range, 0.5-9.3 years) in 66 patients revealed that 6, 3, and 4 patients of PED, surgery, and expectantly managed groups, respectively, had radiologic evidence of recurrent PPs. CONCLUSIONS: Operative management for PPs appears to be superior to CT-guided PED. Although the later was often successful, it required major salvage procedures in one third of the patients. An expectant management protocol may be suitable for selected patients.