Association of prurigo nodularis and infectious disease hospitalizations: a national cross-sectional study.

BACKGROUND: Prurigo nodularis (PN) is associated with a variety of systemic comorbidities, including infectious diseases such as HIV and viral hepatitis. There are limited data on other infectious disease comorbidities in patients with PN. AIM: To characterize infectious disease hospitalizations among patients with PN and the associated cost burden. METHODS: We searched the 2016-2017 National Inpatient Sample, a cross-sectional sample of 20% of all US hospitalizations, for infectious disease hospitalizations among patients with PN. Associations of PN with infections and related costs were determined using multivariable logistic and linear regression, adjusting for age, race, sex and insurance type. RESULTS: PN was associated with any infection overall (OR = 2.98, 95% CI 2.49-3.56), and with HIV, cutaneous, hepatobiliary, central nervous system, bacterial, viral and fungal/parasitic infections and for sepsis. Patients with PN had a higher mean cost of care (US$11 667 vs. US$8893, P < 0.001) and length of stay (5.5 vs. 4.2 days, P < 0.001) for any infection overall and for 7 of 13 other infections. Adjusting for age, race, sex and insurance coverage, PN was associated with higher cost (+30%, 95% CI +17 to +44%) and higher length of stay (+30%, 95% CI +18 to +44%) for any infection overall, and for several specific infections. These associations remained with alternate regression models adjusting for severity of illness. CONCLUSION: There is a high infectious disease burden among patients with PN, corresponding to higher healthcare utilization and spending. Clinicians must be aware of these associations when treating these patients with immunomodulatory drugs.

Epithelioid hemangioendothelioma of the spine: report of two cases and review of the literature.

We report two patients with spinal epithelioid hemangioendothelioma (EH), an uncommon vascular, potentially malignant tumour. Neurological signs, diagnostic images, surgical techniques and complications, histology and the role of adjuvant therapy are discussed. Primary manifestation of EH of the vertebral column is rare. Thorough preoperative clinical and radiological workup, radical surgical excision, and close postoperative follow-up are recommended.

The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract.

Red and processed meat (PM) consumption increases the risk of large bowel cancer and it has been demonstrated that haem in red meat (RM) stimulates the endogenous production of N-nitroso compounds (NOCs) within the human intestine. To investigate whether N-nitrosation occurs in the upper gastrointestinal tract, 27 ileostomists were fed diets containing no meat, or 240 g RM or 240 g PM in a randomly assigned crossover intervention design carried out in a volunteer suite. Endogenous NOC were assessed as apparent total N-nitroso compounds (ATNC) in the ileostomy output. ATNC concentration in the diets was 22 microg ATNC/kg (RM) and 37 microg ATNC/kg (PM), and 9 microg ATNC/kg in the no meat diet. Levels significantly increased to 1175 microg ATNC/kg SEM = 226 microg ATNC/kg) following the RM (P=0.001) and 1832 microg ATNC/kg (SEM=294 microg ATNC/kg) following PM (P<0.001) compared to the no meat diet (283 microg ATNC/kg, SEM=74 microg ATNC/kg). ATNC concentrations in the ileal output were equivalent to those measured in faeces in similarly designed feeding studies. Supplementation with either 1 g ascorbic acid or 400 IU alpha-tocopherol had no effect on the concentration of ATNC detected in the ileal output. In in vitro experiments, N-nitrosomorpholine (NMor) was formed in the presence of nitrosated haemoglobin, at pH 6.8 but not in the absence of nitrosated haemoglobin. These findings demonstrate that haem may facilitate the formation of NOC in the absence of colonic flora in the upper human gastrointestinal tract.

A spectrum of behaviour in silent corticotroph pituitary adenomas.

Silent corticotroph adenomas (SCA) are pituitary tumours positive on immunohistochemical staining for ACTH but without clinical evidence of Cushing's disease in the patient. Previous reports suggest that these tumours may behave in a more aggressive way then other pituitary adenomas. We have followed the natural history of SCA and assessed whether histopathological indices predict tumour behaviour. We identified 22 patients in whom trans-sphenoidal surgery was performed for a non-functioning adenoma (NFA) with positive immunostaining for ACTH between 1990 and 2000 and examined the history of their disease. Patients were followed up for a mean of 4.8 years. A total of 86.7% of patients had documented visual deficits at presentation. In four cases hypercortisolaemia was observed later in the course of the disease. Two patients died as a result of their SCA and 33.3% of tumours recurred. Recurrence was more frequent in patients treated with adjuvant radiotherapy. Pathological indices (increased mitotic range and Ki-67) did not predict recurrence or malignant transformation. We suggest that certain 'silent' corticotroph tumours may have the potential for ACTH secretion leading to hypercortisolaemia at a later stage in the disease. The possibility of transformation to a more aggressive tumour needs to be considered in all SCA.

Adverse operative events in neurosurgical training: incidence, trends and proposals for prevention.

We prospectively studied the adverse operative events encountered during the first 4.5 years of a single neurosurgeon's career (JP). We investigated the incidence of these events and their distribution over time, and recorded risk factors in causation. Twenty-three adverse events were identified in 728 cases studied. These all occurred in one of four categories of operation: craniotomy, shunt placement, spinal surgery and stereotactic biopsy. The incidence of adverse operative events varied between 5.8% for spinal operations to 9.5% for stereotactic biopsy. There was evidence of a reducing incidence of adverse operative events over time in some operative groups. The two categories with the highest incidence of adverse operative events were the same two categories with the lowest number of assisted cases per 100 operations performed.

Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation.

Human male volunteers were studied in a metabolic facility whilst they were fed randomized controlled diets. In eight volunteers there was a significant increase in faecal apparent total N:-nitroso compounds (ATNC) and nitrite excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses of meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods. Mean (+/- SE) faecal ATNC levels were 54 +/- 7 microg/day when the diets contained no meat, 52 +/- 11 microg/day when the diets contained 60 g meat/day, 159 +/- 33 microg/day with 240 g meat and 199 +/- 36 microg/day with 420 g meat. Higher concentrations of NOC were associated with longer times of transit in the gut (r = 0.55, P = 0.001) and low faecal weight (r = -0.51, P = 0.004). There was no significant decline in levels in individuals fed 420 g meat for 40 days. The exposures found on the higher meat diets were comparable with other sources of N:-nitroso compounds (NOC), such as tobacco smoke. Many NOC are known large bowel initiators and promotors in colon cancer, inducing G-->A transitions in codons 12 and 13 of K-ras. Endogenous NOC formation, combined with prolonged transit times in the gut, may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk.

Effect of meat and resistant starch on fecal excretion of apparent N-nitroso compounds and ammonia from the human large bowel.

N-nitroso compounds are produced in the human large intestine, but little is known about the dietary modulation of their synthesis at this site. The effects of meat and resistant starch on the fecal excretion of N-nitroso compounds, measured as apparent total N-nitroso compounds (ATNC), were therefore investigated in a crossover study involving eight healthy men. Three controlled diets that differed in the amount of meat (40 or 600 g) and resistant starch (37 g added to 600 g meat diet) were fed in random order, and fecal ATNC, as well as fecal ammonia and parameters of bowel function, were measured after 19 days of dietary adaptation. Mean ATNC excretion during the high-meat period was 114 micrograms/day, three times that during the low-meat period of 35 micrograms/day (p = 0.02); ammonia excretion was twice that during the low-meat period: 2.9 vs. 1.4 mmol/day (p = 0.03). The fecal ATNC were dissolved in the fecal water, and 45% had a molecular weight < 3,000. The addition of readily fermentable resistant starch to the high-meat diet significantly increased stool output from 118 to 153 g/day and decreased fecal pH from 7.2 to 6.6 but had no significant effect on fecal ATNC (151 micrograms/day), ammonia (3.7 mmol/day), whole gut transit time, urinary nitrate, or plasma urea. ATNC produced in the large bowel in association with a high-meat intake could represent an important source of DNA-damaging alkylating agents in the human large bowel.

1H and 15N NMR resonance assignments and solution secondary structure of oxidized Desulfovibrio desulfuricans flavodoxin.

Sequence-specific 1H and 15N resonance assignments have been made for 137 of the 146 nonprolyl residues in oxidized Desulfovibrio desulfuricans [Essex 6] flavodoxin. Assignments were obtained by a concerted analysis of the heteronuclear three-dimensional 1H-15N NOESY-HMQC and TOCSY-HMQC data sets, recorded on uniformly 15N-enriched protein at 300 K. Numerous side-chain resonances have been partially or fully assigned. Residues with overlapping 1HN chemical shifts were resolved by a three-dimensional 1H-15N HMQC-NOESY-HMQC spectrum. Medium- and long-range NOEs, 3JNH alpha coupling constants, and 1HN exchange data indicate a secondary structure consisting of five parallel beta-strands and four alpha-helices with a topology similar to that of Desulfovibrio vulgaris [Hildenborough] flavodoxin. Prolines at positions 106 and 134, which are not conserved in D. vulgaris flavodoxin, contort the two C-terminal alpha-helices.

Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer?

High red meat diets have been linked with risk of sporadic colorectal cancer; but their effects on mutations which occur in this cancer are unknown. G-->A transitions in K-ras occur in colorectal cancer and are characteristic of the effects of alkylating agents such as N-nitroso compounds (NOC). We studied th effect of red meat consumption on faecal NOC levels in eight male volunteers who consumed diets low or high in meat (60 or 600 g/day), as beef, lamb or pork, whilst living in a metabolic suite. Increased intake of red meat induced a significant (P<0.024) 3-fold increase from 40 + or - 7 to ab average of 113 + or - 25 microgram/day NOC, a range of exposure in faeces similar to that from tobacco-specific NOC in cigarette smoke. THe diets were isoenergetic and contained equal amounts of fat, but concentrations of heterocyclic amines were low. Faecal excretion of the promotor ammonia was significantly increased to 6.5 + or - 1.08 mmol/day. When the high red meat diets were supplemented with 20 g phytate-free wheat bran in six volunteers there was no reduction in NOC levels (mean 138 + or - 41 microgram/day NOC), but faecal weight increased. Higher starch and non-starch polysaccharide intakes reduced intraluminal cross-linking in microcapsules (r=-0.77) and reduced faecal pH (r=-0.64). In two volunteers there was no effect of 600 g white meat and fish o faecal NOC (mean low white meat diet 68 + or - 10 microgram/day, high white meat 56 + or -6 microgram/day nor on faecal nitrate, nitrite and iron. Faecal nitrite levels increased on changing from a white to red meat diet (mean high white meat diet 46 + or - 7 mg/day, high red meat diet mean 80 + or - 7 mg/day.) Increased endogenous production of NOC and precursors from increased red meat, but not white meat and fish, consumption may be relevant to the aetiology of colorectal cancer.

Purification and structural characterization of the CD11b/CD18 integrin alpha subunit I domain reveals a folded conformation in solution.

The alpha subunits of the leukocyte CD11/CD18 integrins contain an approximately 200 amino acid 'inserted' or I domain. The I domain of the cell-surface Mac-1 (CD11b/CD18) integrin has been shown to be the major recognition site for several adhesion ligands, including iC3b, fibrinogen, factor X, and ICAM-1. The I domain from the Mac-1 alpha subunit has been expressed in Escherichia coli as a soluble GST-fusion protein containing a factor Xa sensitive cleavage site. Analytical characterization of the purified I domain reveals that it is obtained in very high quality at high yields. CD and NMR spectra indicate that I domain adopts a predominantly folded structure in solution, independent of the remainder of the alpha subunit. Addition of Ca2+ and Mg2+ did not significantly perturb the structural conformation.

A screening procedure for total N-nitroso contaminants in personal care products: results of collaborative studies undertaken by a CTPA Working Group.

Synopsis A modified procedure for the determination of total N-nitroso compounds in personal care products was evaluated in collaborative studies organized through the UK Cosmetic Toiletry and Perfumery Association (CTPA). The method offers a true 'totals'determination in that a solution of the whole sample is analysed. Samples are dissolved/suspended in water or aqueous THF, and nitrite/nitrite ester interferences are removed by prior treatment with sulphamic acid. The treated test solution is denitrosated in a single reaction with HBr/acetic acid, in refluxing n-propyl acetate, and 'total'N-nitroso compounds are determined in a chemiluminescence reaction of the released nitric oxide with ozone. The use of a propyl acetate denitrosation solvent and of higher concentrations of HBr have improved both the sensitivity (routine limit of determination at 10 mugkg(-1)) and water tolerance of the method. The method was shown to recover N-nitrosamines quantitatively, and to be sufficiently repeatable and reproducible to be used as a screening technique for N-nitroso compounds in personal care products.

Lactoperoxidase-catalyzed oxidation of thiocyanate ion: a carbon-13 nuclear magnetic resonance study of the oxidation products.

Products formed from the lactoperoxidase (LPO) catalyzed oxidation of thiocyanate ion (SCN-) with hydrogen peroxide (H2O2) have been studied by 13C-NMR at pH 6 and pH 7. Ultimate formation of hypothiocyanite ion (OSCN-) as the major product correlates well with the known optical studies. The oxidation rate of SCN- appears to be greater at pH < or = 6.0. At [H2O2]/[SCN-] ratios of < or = 0.5, OSCN- is not formed immediately, but an unidentified intermediate is produced. At [H2O2]/[SCN-] > 0.5, SCN- appears to be directly oxidized to OSCN-. Once formed, OSCN- slowly degrades over a period of days to carbon dioxide (CO2), bicarbonate ion (HCO3-), and hydrogen cyanide (HCN). An additional, previously unrecognized product also appears after formation of OSCN-. On the basis of carbon-13 chemical shift information this new species is suggested to result from rearrangement of OSCN- to yield the thiooxime isomer, SCNO- or SCNOH.

Peptide nitrosation in dilute acid.

Rates and products are reported for the nitrosation of simple dipeptides (glycylglycine, its ethyl ester and N-acetylglycylglycine) in dilute acid at 37 degrees C. The results suggest that conversion to a diazo derivative (which rapidly decomposes) is the most likely outcome of the gastric nitrosation of small proteins and peptides.

Possible underestimation of nitrosatable amine levels in artificial saliva extracts of children's rubber pacifiers and baby-bottle teats.

Children's pacifiers and baby-bottle nipples from various countries were analysed for their content of N-nitrosamines and nitrosatable amines. Using a method involving extraction with artificial saliva, several nitrosamines including N-nitrosodi-n-butylamine (NDBA), N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were detected in addition to the three nitrosatable amines dibutylamine (DBA), diethylamine (DEA) and dimethylamine (DMA). Upon nitrosation in artificial saliva, these amines produced not only the related N-nitrosamines but also relatively high levels of the corresponding nitramines--N-nitrodibutylamine (NTDBA), N-nitrodiethylamine (NTDEA) and N-nitrodimethylamine (NTDMA). Thus, both N-nitramines and N-nitrosamines should be measured after nitrosation; otherwise, the method probably underestimates the quantities of nitrosatable amines present in artificial saliva extracts. Whether N-nitramines, some of which have been shown to be both mutagenic and carcinogenic, are formed in the saliva of babies exposed to these products remains to be confirmed.

Formation of nitrosoiminodialkanoic acids during the nitrosation of peptides.

The nitrosation of dipeptides by nitrous acid in aqueous medium leads to a rearrangement, the products being N-nitrosoiminodialkanoic acids. Such reactions are likely to occur in gastric juice.