Endoscopic ultrasound guided fine needle aspiration for the diagnosis of pancreatic cystic neoplasms: a meta-analysis.

BACKGROUND AND OBJECTIVES: Mucinous cystic neoplasms and intraductal papillary mucinous tumours have greater malignant potential than serous cystic neoplasms. EUS alone is inadequate for characterising these lesions but the addition of FNA may significantly improve diagnostic accuracy. The performance of EUS-FNA is highly variable in published studies. AIM: To determine the diagnostic accuracy of EUS-FNA to differentiate mucinous versus non-mucinous cystic lesions with cyst fluid analysis for cytology and carcinoembryonic antigen (CEA) by performing a meta-analysis of published studies. METHODS: Relevant studies were identified via structured database search and included if they used a reference standard of definitive surgical histology or clinical follow-up of at least 6 months. Data from selected studies were pooled to give summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio and Receiver Operating Characteristic (ROC) curve. Pre-defined subgroup analysis was performed. RESULTS: Eighteen studies (published 2002-2011) were included, with a total of 1438 patients. For cytology, pooled sensitivity was 54(95%CI 49-59)% and specificity 93(90-95)%. The diagnostic odds ratio (DOR) was 13.3 (4.37-49.43), with I(2) of 77.1%. For CEA sensitivity was 63(59-67)% and specificity 88(83-91)%. The DOR was 10.76(6.29-18.41) with an I(2) of 25.4%. The diagnostic accuracy of EUS-FNA was enhanced in prospective studies and studies of <36 months duration. No impact of publication bias on our results was demonstrated. CONCLUSIONS: Fine-needle aspiration has moderate sensitivity but high specificity for mucinous lesions. EUS-FNA, when used in conjunction with cross sectional imaging, is a useful diagnostic tool for the correct identification of mucinous cysts.

Women with peritoneal carcinomatosis of unknown origin: Efficacy of image-guided biopsy to determine site-specific diagnosis.

OBJECTIVES: To evaluate the use of image-guided biopsy (IGB) in routine clinical practice to obtain site-specific diagnoses in women presenting with peritoneal carcinomatosis (PC). STUDY DESIGN: Retrospective case study. SETTING: Tertiary referral centre. POPULATION: A total of 149 consecutive women with PC who underwent IGB. METHODS: Biopsy was performed in women considered unsuitable for primary surgery because of poor performance status or disease unlikely to be optimally debulked, with a prior history of malignancy or where there was clinicoradiological uncertainty about primary tumour site. Standard haematoxylin-eosin histological analysis was supplemented with immunohistochemistry. MAIN OUTCOME MEASURES: The rate of site-specific diagnosis. RESULTS: A total of 149 women underwent IGB using computed tomography or ultrasound over a 6-year period. The only complication was one rectus sheath haematoma. In 138 (93%) women, a site-specific cancer diagnosis was made on the IGB (including 111 müllerian tract, 8 gastrointestinal tract, 4 breast and 3 lymphoma); in ten women, a repeat biopsy was necessary, giving an overall failure rate of 7%. In a further six women, malignancy was confirmed but a site-specific diagnosis could not be made, and in four women, biopsy showed benign tissue. A site-specific diagnosis was obtained in 29 of the 32 women (94%) with previous malignancy, of which 18/32 (56%) showed a new primary cancer. CONCLUSIONS: IGB is a safe and accurate technique for providing site-specific diagnoses in women with PC in routine clinical practice, including those with a previous relevant malignancy. IGB can replace laparoscopic or open biopsy in defining primary therapeutic options. The data would suggest that the biopsy should be performed with ultrasound where feasible.

The detection of microsatellite instability in blind endometrial samples--a potential novel screening tool for endometrial cancer in women from hereditary nonpolyposis colorectal cancer families?

Microsatellite instability (MSI) is the phenotypic molecular characteristic of the majority of tumors associated with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC). Women in this group have an increased risk of endometrial cancer (EC). This study aimed to determine whether MSI could be demonstrated in blind endometrial samples from women with EC, HNPCC kindreds undergoing screening for EC, and women with normal endometrium. Twenty-four women with EC, 20 women from HNPCC kindreds, and 20 women undergoing gynecological surgery for benign indications underwent blind sampling. MSI analysis was performed by conventional polymerase chain reaction using fluorescent-labeled primers and automated analysis. Twelve microsatellites were studied with MSI defined as evident when novel alleles were seen in endometrial biopsy samples compared to genomic DNA. Of the 24 EC samples obtained, sufficient DNA for analysis was extracted in 17 cases. Three cases had evidence of MSI in at least 7/12 loci. None of the endometrium from the two other study groups revealed evidence of MSI. This is the first demonstration of MSI in blind endometrial biopsies. The ability to demonstrate MSI in heterogeneous endometrial samples suggests potential for the development of a novel EC screening tool for women in HNPCC kindreds.

Image-guided biopsy in women with breast cancer presenting with peritoneal carcinomatosis.

When women with a history of breast cancer present with peritoneal carcinomatosis, the differential diagnosis lies between recurrent breast cancer or a new primary tumor. This scenario is of particular relevance to women with a BRCA gene mutation, who have a genetic predisposition to develop second primary tumors of the ovary, fallopian tube, and peritoneum. We describe the use of image-guided core biopsy as an alternative to laparoscopy or exploratory laparotomy in providing minimally invasive diagnosis in this increasingly common clinical dilemma.

The use of whole rat embryo culture as a technique for investigating potential serum toxicity in recurrent miscarriage patients.

Previously, the rat embryo model has been used as an experimental technique in investigations of the aetiology of idiopathic recurrent miscarriage. The aim of the present study was to validate it as a tool in the investigation of the aetiology of this condition. Subjects (n = 36) with a history of recurrent miscarriage were recruited from two dedicated recurrent miscarriage clinics and compared with control women with at least one previous pregnancy resulting in a live birth (n = 23). Serum from each woman was used as culture medium in the rat embryo model. Cultured embryos were scored for growth and differentiation. No statistical difference was found in any parameter between the two groups. Furthermore, patients from the recurrent miscarriage group whose serum demonstrated a trend towards lower scores, subsequently conceived and underwent uncomplicated pregnancies.

Recommending exercise to healthy older adults: the preparticipation evaluation and exercise prescription.

The office-based preparticipation evaluation for older adults addresses cardiovascular status, muscle strength, flexibility, balance, and agility. The Kasch pulse-recovery test and the sit-and-reach test are practical methods for evaluating aerobic capacity and flexibility, respectively. Other measures, such as assessment of body composition or bone density, help establish goals and provide baselines for measuring exercise progress. The prescription for older people is aimed at maintaining current function and moving patients to the next activity level. The prescription specifies type, frequency, duration, and intensity of exercise. Case reports describe how key pieces of information from the preparticipation exam can lead to specific exercise recommendations.

Cellular proliferation in the placenta in normal human pregnancy and pregnancy complicated by intrauterine growth restriction.

OBJECTIVE: To determine the incidence of cellular proliferation in the placenta throughout the three trimesters of normal pregnancy, and in the third trimester of pregnancy complicated by intrauterine growth restriction (IUGR). METHODS: Placental samples were obtained from 17 first-trimester pregnancies, 9 second-trimester pregnancies, 33 uncomplicated third-trimester pregnancies, and 21 third-trimester pregnancies complicated by IUGR. These samples were then stained by immunohistochemical technique, using the monoclonal antibody MIB-1. RESULTS: The incidences of cellular proliferation in the four groups were as follows: first trimester (n = 17): 11.8% of cells (8.51-17.04); second trimester (n = 9): 9.88% of cells (5.04-10.99); normal third trimester (n = 33): 3.15% of cells (2.07-3.7); IUGR third trimester (n = 21): 3.7% of cells (3.02-4.85). The decline in cellular proliferation throughout the three trimesters of pregnancy was statistically significant (P < .0001 Kruskall-Wallis test). The Spearman rank correlation for proliferative index against gestational age had a P value less than .0001 (Rho corrected for ties = -0.81). There was no statistically significant difference in the incidence of cellular proliferation between normal third-trimester and IUGR third-trimester samples. CONCLUSION: The incidence of cellular proliferation in the placenta declines as pregnancy progresses, a finding that agrees with previous work by others. The incidence of cellular proliferation was not altered in cases of IUGR.

A computer model of dorsal cochlear nucleus pyramidal cells: intrinsic membrane properties.

Manis [P. B. Manis, J. Neurosci. 10, 2338-2351 (1990)] studied "simple spiking," pyramidal cells of the dorsal cochlear nucleus (DCN) maintained in vitro. Response profiles to hyperpolarizing and depolarizing current pulses were generated. Hyperpolarization of the cell membrane followed by depolarization produced markedly different response profiles from those generated when no prehyperpolarization was imposed. By manipulating the magnitude of the hyperpolarizing and depolarizing pulses, "chopper," "pauser" and "build-up" response patterns, similar to those in vivo, could be generated by individual cells. Manis concluded that the different response profiles resulted from the modulation of intrinsic membrane conductances by the prehyperpolarizing pulses. Here a computer model is used to show that (a) steady-state hyperpolarization can influence cell responding to subsequent depolarization in a manner consistent with the data reported by Manis; and (b) the effects reported can be generated by the addition of a modeled transient potassium conductance to the standard Hodgkin-Huxley model of spike generation [A. L. Hodgkin and A. F. Huxley, J. Physiol. 117, 500-544 (1952)]. The model will be of use to those who wish to consider the role of various excitatory and inhibitory inputs to pyramidal cells and to establish their functional role within the DCN.

A computer model of amplitude-modulation sensitivity of single units in the inferior colliculus.

A computer model is presented of a neural circuit that replicates amplitude-modulation (AM) sensitivity of cells in the central nucleus of the inferior colliculus (ICC). The ICC cell is modeled as a point neuron whose input consists of spike trains from a number of simulated ventral cochlear nucleus (VCN) chopper cells. Input to the VCN chopper cells is provided by simulated spike trains from a model of the auditory periphery [Hewitt et al., J. Acoust. Soc. Am. 91, 2096-2109 (1992)]. The performance of the model at the output of the auditory nerve, the cochlear nucleus and ICC simulations in response to amplitude-modulated stimuli is described. The results are presented in terms of both temporal and rate modulation transfer functions (MTFs) and compared with data from physiological studies in the literature. Qualitative matches were obtained to the following main empirical findings: (a) Auditory nerve temporal-MTFs are low pass, (b) VCN chopper temporal-MTFs are low pass at low signal levels and bandpass at moderate and high signal levels, (c) ICC unit temporal-MTFs are low pass at low signal levels and broadly tuned bandpass at moderate and high signal levels, and (d) ICC unit rate-MTFs are sharply tuned bandpass at low and moderate signal levels and flat at high levels. VCN and ICC units preferentially sensitive to different rates of modulation are presented. The model supports the hypothesis that cells in the ICC decode temporal information into a rate code [Langner and Schreiner, J. Neurophysiol. 60, 1799-1822 (1988)], and provides a candidate wiring diagram of how this may be achieved.

Behavioural effects of scopolamine and the TRH analogue RX77368 on radial arm maze performance in the rat.

Effects of repeated intracerebroventricular administration of the thyrotrophin-releasing hormone (TRH) analogue, RX77368 (3,3'-dimethyl-TRH, 2 µg, once daily), on a scopolamine-induced performance deficit in an eight-arm radial maze were evaluated in adult rats. Scopolamine (0.3 mg/kg i.p.-30 min) pre-treatment produced a significant deficit in the number of unrepeated arm entries and total arm entries and increased the percentage of incorrect arm entries and the total time on the maze, compared with saline-treated controls. Prior treatment with RX77368 (40 min before maze testing) produced a partial but significant attenuation of the scopolamine-induced performance deficit on the maze during the first five trials but RX77368 also enhanced maze performance during the same period when given alone. These results suggest that the observed scopolamine-induced performance deficit on the radial arm maze partly results from a reduction in locomotion and maze exploration rather than solely impairment of memory, and that RX77368 treatment may improve radial maze performance by increasing arousal and exploratory behaviour in rats rather than directly enhancing cognition.

A Framework for Regional Agroecosystems Characterization Using the National Resources Inventory.

An agroecological framework is used to examine the relations among natural resources and agriculture. Spatial representation of selected agroecosystems characteristics was accomplished using the National Resources Inventory (NRI). Natural resource and anthropogenic variables from the NRI were spatially aggregated to produce maps showing the regional variability in area-weighted values of agroecosystem components. Maps of natural vegetation, agricultural land use, crop diversity, artificial drainage, irrigation, net soil loss, and conservation practices show the extent to which resources have been modified to support agriculture in the Midwest. The frequency of land used for crops and pasture exceeds 70% in much of the region. Natural vegetation occupies less than 10% of the land in many areas. Subsurface and surface drainage, more than 35% of some areas, has contributed to loss of wetlands having a direct effect on water quality. Irrigation has diverted water from natural ecosystems and increased the potential for leaching of agrichemicals. Excess erosion may threaten long-term productivity in parts of the region even though conservation practices have been implemented. Examination of these and other elements in an agroecosystem framework may be useful in the search for systems to sustain agriculture and natural resources in the region. Such a framework can also be used to locate areas where mitigation of degraded resources is most needed; identify areas where research into causes of degradation can yield the most information; and where policies to improve off-site damage may be most effectively implemented.

Hydration of the fat-free body mass in children and adults: implications for body composition assessment.

Previous studies have shown that children have a higher aqueous fraction of the fat-free body mass (FFM) than young adults. In older adults, methodological differences among studies limit evaluation of potential age-related differences in the water content of the FFM (W/FFM). Therefore, we determined W/FFM in 28 healthy white prepubescent children (age = 5-10 yr), 31 young adults (age = 22-39 yr), and 62 older adults (age = 65-84 yr), using 2H2O dilution to estimate total body water and a multicomponent approach based on body density, total body water, and regional bone mineral density to estimate FFM. To quantify the extent to which variation in W/FFM affects percent fat estimation error, differences in percent fat between our multicomponent approach and the Siri two-component model were related to W/FFM. Prepubescent children (72.7 +/- 1.6%) and older adults (72.5 +/- 1.4%) were found to have significantly higher (P < 0.01) mean W/FFM than young adults (70.8 +/- 1.2%). Differences in percent fat between the multicomponent and two-component models ranged from -10 to 6% fat and were significantly associated with W/FFM (r = -0.62, P < 0.0001). We conclude that prepubescent children and older adults, on average, have a higher W/FFM than young adults, and that, in adults, individual differences in W/FFM account for a substantial portion of the percent fat estimation errors associated with the use of two-component body composition models.

Regularity of cochlear nucleus stellate cells: a computational modeling study.

This article reports on a computational modeling study designed to investigate the generation of the transient chopper response of cochlear nucleus stellate cells. The model is based on a simulation of the auditory periphery which feeds a generic stellate-cell model. Physiological recordings of transient chopper units in response to short, best frequency, tone bursts show a brief initial period (typically < 10 ms) of rapid rate adaptation as evidenced by a rapid rise in mean interspike interval. Associated with this rate adaptation is a significant increase in firing irregularity. The changes in rate and irregularity have recently been attributed to the activation of noisy inhibitory inputs on the cell [e.g., Banks and Sachs, J. Neurophysiol. 65, 606-629 (1991)]. However, the results show that the transient chopper response pattern can be generated without the need for inhibitory inputs. The transience of the initial chopping pattern is sensitive to the following model parameters: (a) the firing threshold of the cell, (b) the number of excitatory inputs that converge on the cell, and (c) the magnitude of the current delivered to the cell for each active input. The response was also found to be relatively insensitive to changes in the degree of dendritic filtering imposed on the auditory-nerve input. The results of each simulation can be explained by considering the pattern of depolarization the cell receives during the course of a tone burst.

A computer model of a cochlear-nucleus stellate cell: responses to amplitude-modulated and pure-tone stimuli.

A computer model of a ventral-cochlear-nucleus (VCN) stellate cell with chop-S type response properties is presented and evaluated. The model is based on a simplified model of spike generation preceded by a stage that simulates dendritic low-pass filtering. Input to the model is in the form of simulated auditory-nerve spikes produced by a model of the auditory periphery [Meddis and Hewitt, J. Acoust. Soc. Am. 89, 2866-2882 (1991)]. Outputs from the stellate-cell model are shown to qualitatively replicate a wide range of typical in vivo responses. These include: (a) realistic onset and steady-state rate-level functions, (b) "chopper"-type post-stimulus time histogram responses; (c) typical "chop-S"-type neuron responses characterized by a low coefficient of variance (CV less than 0.3) of interspike intervals as a function of time; (d) level-dependent amplitude-modulation transfer functions; (e) intrinsic oscillations in responses to pure-tone stimuli; (f) amplitude-modulation encoding over a wide dynamic range; and (g) frequency-limited phase locking to pure tones. It is shown that these responses can be explained primarily by the membrane properties of the cells. More specifically, how the model encodes signal amplitude modulation was studied and an explanation was suggested for the generation of the bandpass modulation transfer functions. Such functions are observed neurally in response to amplitude-modulated stimuli presented at moderate to high signal levels.

Modeling the identification of concurrent vowels with different fundamental frequencies.

Human listeners are better able to identify two simultaneous vowels if the fundamental frequencies of the vowels are different. A computational model is presented which, for the first time, is able to simulate this phenomenon at least qualitatively. The first stage of the model is based upon a bank of bandpass filters and inner hair-cell simulators that simulate approximately the most relevant characteristics of the human auditory periphery. The output of each filter/hair-cell channel is then autocorrelated to extract pitch and timbre information. The pooled autocorrelation function (ACF) based on all channels is used to derive a pitch estimate for one of the component vowels from a signal composed of two vowels. Individual channel ACFs showing a pitch peak at this value are combined and used to identify the first vowel using a template matching procedure. The ACFs in the remaining channels are then combined and used to identify the second vowel. Model recognition performance shows a rapid improvement in correct vowel identification as the difference between the fundamental frequencies of two simultaneous vowels increases from zero to one semitone in a manner closely resembling human performance. As this difference increases up to four semitones, performance improves further only slowly, if at all.

An evaluation of eight computer models of mammalian inner hair-cell function.

Eight computer models of auditory inner hair cells have been evaluated. From an extensive literature on mammalian species, a subset of well-reported auditory-nerve properties in response to tone-burst stimuli were selected and tested for in the models. This subset included tests for: (a) rate-level functions for onset and steady-state responses; (b) two-component adaptation; (c) recovery of spontaneous activity; (d) physiological forward masking; (e) additivity; and (f) frequency-limited phase locking. As models of hair-cell functioning are increasingly used as the front end of speech-recognition devices, the computational efficiency of each model was also considered. The evaluation shows that no single model completely replicates the subset of tests. Reasons are given for our favoring the Meddis model [R. Meddis, J. Acoust. Soc. Am. 83, 1056-1063 (1988)] both in terms of its good agreement with physiological data and its computational efficiency. It is concluded that this model is well suited to provide the primary input to speech recognition devices and models of central auditory processing.

Coronary sinus atrial pacing: radiographic considerations.

Transvenous atrial pacing via an electrode placed in the coronary sinus has become an increasingly frequent procedure during the past 10 years for both diagnosis and therapy of cardiac arrhythmias. The coronary sinus has five major venous tributaries, any one of which can be entered by a pacing catheter. A catheter in the middle cardiac vein can mimic the usual ventricular pacemaker position, while an electrode in the coronary sinus or in a persistent left superior vena cava may be mistaken for myocardial perforation. A persistent left superior vena cava may also be catheterized. This anomaly is associated with a tenfold increased incidence of congenital atrioventricular conduction abnormalities and, therefore, is surprisingly common in patients having coronary sinus pacers placed because of cardiac arrhythmias.

Calyceal calculi simulating gallstones.

Multiple faceted stones can develop in any sacular structure. Five cases of renal stones are described, four cases with calculi in calyceal diverticuli and one case with calculi in a hydronephrotic sac. Emphasis is on the remarkably similar radiographic appearance these cases of renal stones have with gallstones.