The diagnostic value of fine needle aspiration in parotid lumps

Introduction

Fine needle aspiration (FNA) is a safe and quick method of diagnosing superficial lumps, which aids preoperative planning. However, FNA of the parotid gland has not gained the widespread acceptance noted in other head and neck lumps. The aim of this study was to determine the ability of FNA of the parotid gland to differentiate benign and malignant disease, and to determine the impact on surgical outcome.

Methods

A retrospective analysis of 201 consecutive parotid operations with preoperative FNA in a large district hospital in the UK was performed. The diagnostic characteristics were calculated for benign and malignant disease, and the impact on surgical procedure was determined.

Results

In identifying benign disease, FNA has a sensitivity of 85% and a specificity of 76%. In detecting malignant disease, FNA has a sensitivity and specificity of 52% and 92% respectively. A false positive on FNA was associated with a higher incidence of neck dissection.

Conclusions

FNA is a useful diagnostic test. However, owing to low sensitivity, it is necessary to interpret it in the context of all other clinical information.     

Genetic risk score predicting accelerated progression from mild cognitive impairment to Alzheimer’s disease

Aside from APOE, the genetic factors that influence the progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) remain largely unknown. We assessed whether a genetic risk score (GRS), based on eight non-APOE genetic variants previously associated with AD risk in genome-wide association studies, is associated with either risk of conversion or with rapid progression from MCI to AD. Among 288 subjects with MCI, follow-up (mean 26.3 months) identified 118 MCI-converters to AD and 170 MCI-nonconverters. We genotyped ABCA7 rs3764650, BIN1 rs744373, CD2AP rs9296559, CLU rs1113600, CR1 rs1408077, MS4A4E rs670139, MS4A6A rs610932, and PICALM rs3851179. For each subject we calculated a cumulative GRS, defined as the number of risk alleles (range 0–16) with each allele weighted by the AD risk odds ratio. GRS was not associated with risk of conversion from MCI to AD. However, MCI-converters to AD harboring six or more risk alleles (second and third GRS tertiles) progressed twofold more rapidly to AD when compared with those with less than six risk alleles (first GRS tertile). Our GRS is a first step toward development of prediction models for conversion from MCI to AD that incorporate aggregate genetic factors.     

Cardiac Disease Burden and Risk of Mortality in Hospitalized Muscular Dystrophy Patients

As treatments of the extra-cardiac complications of muscular dystrophy (MD) improve, males with MD are more likely to develop cardiac disease. The impact of cardiomyopathy or heart failure (HF) and ventricular tachycardia (VT) on hospitalizations and in hospital mortality are not known. We performed an analysis of inpatient admission data for patients with MD using the Pediatric Health Information System database. We selected males who were 6 years or older with diagnosis codes of MD and cardiac disease including cardiomyopathy/HF and VT between 2003 and 2013. We created a logistic regression model to identify predictors of subsequent cardiac arrest or death in MD patients. We also compared hospital charges, lengths of stay and ages among MD patients with or without cardiac disease. Our logistic regression model showed that VT (OR 5.41, 95 % CI 2.83, 10.34) and cardiomyopathy/HF (OR 1.79, 95 % CI 1.05, 3.04) were risk factors for cardiac arrest or death. Of the 84 cardiac arrests or deaths in 3363 MD patients, 49 (58 %) were related to cardiac disease. Nineteen (39 %) of these events occurred in MD patients with VT. The mean hospital charges and the mean length of stay were greater and longer in MD patients with VT compared to those without cardiac disease and those with only cardiomyopathy/HF (p < 0.05). Cardiac disease is a significant burden in hospitalized MD patients. Our results suggest that VT and cardiomyopathy/HF are associated with an increased risk of cardiac arrest or death in MD patients.     

Plasma and Mucosal Fatty Acid Pattern in Colectomized Ulcerative Colitis Patients

Patients with inflammatory bowel disease (IBD)have increased plasma n3 polyunsaturated fatty acids(PUFAs), which in ulcerative colitis (UC) patientspersists six months after colectomy, suggesting aprimary abnormality in fatty acid (FA) metabolism inIBD. This finding needed to be confirmed in a largerseries of UC long-term colectomized patients. We aimedto assess the plasma FA pattern in UC colectomized patients with either Brooke's ileostomy (UC-BI)or ileal pouch anal anastomosis (UC-IPAA) and themucosal FA pattern in the ileal reservoir of the UC-IPAApatients. Plasma FAs were assessed in 63 UC colectomized patients (31 with BI and 32 with IPAA) and 30controls. In 26 UC-IPAA (8 with pouchitis and 18 withoutpouchitis) and in 13 healthy controls gut mucosal FAswere also investigated. FAs were detected by capillary column gas-liquid chromatography.Increased levels of saturated fatty acids (SFAs) anddecreased percentages of monounsaturated fatty acids(MUFAs) were observed in both groups of patients. There were no changes in plasma n3 and n6 PUFAs. Themucosal FA pattern of the ileal reservoir consisted ofincreased long-chain PUFAs, specially n6 PUFA, and adecrease of their essential precursors. High percentages of SFAs and low percentages of MUFAs were alsoseen. The plasma FA profile previously described in IBDis not observed long-term after colectomy in UC,suggesting that it is related with the presence of inflamed intestine. High concentrations of SFAsand decreased percentages of MUFAs might represent earlyevents in disturbed FA metabolism in IBD. The changes inFAs of the ileal reservoir, which closely resemble those found in human and experimentalIBD, probably represent a common pattern of intestinalinflammation.     

Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: a urocortin1-independent mechanism

A common expression of neuroadaptations induced by repeated exposure to addictive drugs is a persistent sensitized behavioral response to their stimulant properties. Neuroplasticity underlying drug-induced sensitization has been proposed to explain compulsive drug pursuit and consumption characteristic of addiction. The hypothalamic-pituitary-adrenal (HPA) axis-activating neuropeptide, corticotropin-releasing factor (CRF), may be the keystone in drug-induced neuroadaptation. Corticosterone-activated glucocorticoid receptors (GRs) mediate the development of sensitization to ethanol (EtOH), implicating the HPA axis in this process. EtOH-induced increases in corticosterone require CRF activation of CRF1 receptors. We posited that CRF1 signaling pathways are crucial for EtOH-induced sensitization. We demonstrate that mice lacking CRF1 receptors do not show psychomotor sensitization to EtOH, a phenomenon that was also absent in CRF1 + 2 receptor double-knockout mice. Deletion of CRF2 receptors alone did not prevent sensitization. A blunted endocrine response to EtOH was found only in the genotypes showing no sensitization. The CRF1 receptor antagonist CP-154,526 attenuated the acquisition and prevented the expression of EtOH-induced psychomotor sensitization. Because CRF1 receptors are also activated by urocortin-1 (Ucn1), we tested Ucn1 knockout mice for EtOH sensitization and found normal sensitization in this genotype. Finally, we show that the GR antagonist mifepristone does not block the expression of EtOH sensitization. CRF and CRF1 receptors, therefore, are involved in the neurobiological adaptations that underlie the development and expression of psychomotor sensitization to EtOH. A CRF/CRF1-mediated mechanism involving the HPA axis is proposed for acquisition, whereas an extrahypothalamic CRF/CRF1 participation is suggested for expression of sensitization to EtOH.     

Immunogenicity and protective efficacy of yeast extracts containing rotavirus-like particles: A potential veterinary vaccine

Rotavirus is the most common cause of severe diarrhea in many animal species of economic interest. A simple, safe and cost-effective vaccine is required for the control and prevention of rotavirus in animals. In this study, we evaluated the use of Saccharomyces cerevisiae extracts containing rotavirus-like particles (RLP) as a vaccine candidate in an adult mice model. Two doses of 1 mg of yeast extract containing rotavirus proteins (between 0.3 and 3 μg) resulted in an immunological response capable of reducing the replication of rotavirus after infection. Viral shedding in all mice groups diminished in comparison with the control group when challenged with 100 50% diarrhea doses (DD₅₀) of murine rotavirus strain EDIM. Interestingly, when immunizing intranasally protection against rotavirus infection was observed even when no increase in rotavirus-specific antibody titers was evident, suggesting that cellular responses were responsible of protection. Our results indicate that raw yeast extracts containing rotavirus proteins and RLP are a simple, cost-effective alternative for veterinary vaccines against rotavirus.     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.