A comparison of gastric gas volumes measured by computed tomography after high-flow nasal oxygen therapy or conventional facemask ventilation.

High-flow nasal oxygen therapy is increasingly used to improve peri-intubation oxygenation. However, it is unknown whether it may cause or exacerbate insufflation of gas into the stomach. High-flow nasal oxygen therapy is now standard practice in our hospital for adult patients undergoing percutaneous thermal ablation of liver cancer under general anaesthesia with tracheal intubation. We compared gastric gas volumes measured from computed tomography images that had been acquired immediately after intubation in two series of patients: 50 received peri-intubation high-flow nasal oxygen therapy and another 50 received conventional facemask pre-oxygenation and ventilation before intubation and before high-flow nasal oxygen therapy became standard practice in our unit. Median (IQR [range]) gastric gas volume was 24.0 (14.2-59.9 [3-167]) cm3 in the high-flow nasal oxygen therapy group and 23.8 (12.6-38.8 [0-185]) cm3 in the facemask group. There was no difference between the two groups in the volume of gastric gas measured by computed tomography imaging (Mann-Whitney U-test, U = 1136, p = 0.432, n1  = n2  = 50). Our results demonstrate that a small volume of gastric gas is commonly present after induction of anaesthesia, but that the use of peri-intubation high-flow nasal oxygen therapy for pre-oxygenation and during apnoea does not increase this volume compared with conventional facemask pre-oxygenation and ventilation. This is clinically relevant, as high-flow nasal oxygen therapy is increasingly being used in a peri-intubation context and in patients at higher risk of aspiration.

No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication.

HIV persistence during combination antiretroviral therapy (cART) is the principal obstacle to cure. Mechanisms responsible for persistence remain uncertain; infections may be maintained by persistence and clonal expansion of infected cells or by ongoing replication in anatomic locations with poor antiretroviral penetration. These mechanisms require different strategies for eradication, and determining their contributions to HIV persistence is essential. We used phylogenetic approaches to investigate, at the DNA level, HIV populations in blood, lymphoid, and other infected tissues obtained at colonoscopy or autopsy in individuals who were on cART for 8 to 16 years. We found no evidence of ongoing replication or compartmentalization of HIV; we did detect clonal expansion of infected cells that were present before cART. Long-term persistence, and not ongoing replication, is primarily responsible for maintaining HIV. HIV-infected cells present when cART is initiated represent the only identifiable source of persistence and is the appropriate focus for eradication.

Chronic unpredictable stress promotes cell-specific plasticity in prefrontal cortex D1 and D2 pyramidal neurons.

Exposure to unpredictable environmental stress is widely recognized as a major determinant for risk and severity in neuropsychiatric disorders such as major depressive disorder, anxiety, schizophrenia, and PTSD. The ability of ostensibly unrelated disorders to give rise to seemingly similar psychiatric phenotypes highlights a need to identify circuit-level concepts that could unify diverse factors under a common pathophysiology. Although difficult to disentangle a causative effect of stress from other factors on medial prefrontal cortex (PFC) dysfunction, a wealth of data from humans and rodents demonstrates that the PFC is a key target of stress. The present study sought to identify a model of chronic unpredictable stress (CUS) which induces affective behaviors in C57BL6J mice and once established, measure stress-related alterations in intrinsic excitability and synaptic regulation of mPFC layer 5/6 pyramidal neurons. Adult male mice received 2 weeks of 'less intense' stress or 2 or 4 weeks of 'more intense' CUS followed by sucrose preference for assessment of anhedonia, elevated plus maze for assessment of anxiety and forced swim test for assessment of depressive-like behaviors. Our findings indicate that more intense CUS exposure results in increased anhedonia, anxiety, and depressive behaviors, while the less intense stress results in no measured behavioral phenotypes. Once a behavioral model was established, mice were euthanized approximately 21 days post-stress for whole-cell patch clamp recordings from layer 5/6 pyramidal neurons in the prelimbic (PrL) and infralimbic (IL) cortices. No significant differences were initially observed in intrinsic cell excitability in either region. However, post-hoc analysis and subsequent confirmation using transgenic mice expressing tdtomato or eGFP under control of dopamine D1-or D2-type receptor showed that D1-expressing pyramidal neurons (D1-PYR) in the PrL exhibit reduced thresholds to fire an action potential (increased excitability) but impaired firing capacity at more depolarized potentials, whereas D2-expressing pyramidal neurons (D2-PYR) showed an overall reduction in excitability and spike firing frequency. Examination of synaptic transmission showed that D1-and D2-PYR exhibit differences in basal excitatory and inhibitory signaling under naïve conditions. In CUS mice, D1-PYR showed increased frequency of both miniature excitatory and inhibitory postsynaptic currents, whereas D2-PYR only showed a reduction in excitatory currents. These findings demonstrate that D1-and D2-PYR subpopulations differentially undergo stress-induced intrinsic and synaptic plasticity that may have functional implications for stress-related pathology, and that these adaptations may reflect unique differences in basal properties regulating output of these cells.

Local control, safety, and survival following image-guided percutaneous microwave thermal ablation in primary lung malignancy.

AIM: To determine local control, safety, and survival following percutaneous computed tomography (CT)-guided high-power microwave ablation (MWA) in the treatment of primary lung malignancy at a single institution. MATERIAL AND METHODS: From July 2010 to June 2016, 52 patients (mean age 76.3 years, range 55-91 years) with 61 unresectable primary lung cancers of mean diameter 23.8 mm (range 26-55 mm) underwent MWA in 55 ablation sessions. Tumours were diagnosed at biopsy, or positron-emission tomography (PET) avidity (mean SUV max = 10.51) and interval growth. Statistical analysis was performed by Kaplan-Meier modelling and Cox and logistic regression. RESULTS: Local tumour progression (LTP) was diagnosed in six lesions (10%). Median time to local recurrence was 3 months (range 2-14 months). There was a near 12-fold increased odds of local recurrence if the lesion size was >3 cm (95% confidence interval [CI]: 1.84-75.14; p=0.009). The median inpatient stay was 1 day, with no intra-procedural deaths and a 0% 30-day post-ablation mortality rate. Pneumothorax requiring drain was the most serious complication, occurring in 22% (n=12) of patients. Presence of severe emphysema and predicted forced expiratory volume in 1 second (FEV1) of <50% were found to predict future requirement of a drain (odds ratio [OR] 8.17, 95% CI: 1.62-41.37, p=0.01 and OR: 5.14, 95% CI: 1.28-20.68, p=0.02 respectively), when adjusted for age and gender. Tumour size >3 cm had a hazard ratio of 4.37 compared with tumour size ≤3 cm (95% CI: 1.45-13.17, p=0.009) of risk of cancer death at any time, by Cox regression. CONCLUSION: MWA for primary lung malignancy is a safe and effective treatment for primary lung tumours with outcomes that may be comparable to stereotactic body radiation therapy.

Evaluation of a single-pass with biphasic intravenous contrast medium injection CT protocol for the assessment of complications post-simultaneous pancreas-kidney transplant.

AIM: To evaluate the use of a single-pass with biphasic intravenous contrast medium injection computed tomography (CT) protocol to provide diagnostic quality CT studies for the assessment of complications post-simultaneous pancreas-kidney transplant (SPK). MATERIALS AND METHODS: This was an audit of practice and the need for informed consent was waived. The protocol was used in consecutive patients undergoing CT to exclude intra-abdominal sepsis post-SPK between June and December 2015. Single CT acquisition of the abdomen and pelvis was initiated 70 seconds after the start of biphasic contrast medium injection (66 ml at 1.2 ml/s, followed by 34 ml at 2.4 ml/s, 370 mg iodine/ml). The named transplant pancreas vessels were identified and the attenuation values of the blood within were measured. Diagnostic quality was confirmed if values were >211 HU and >80 HU in the arteries and veins, respectively. RESULTS: Thirteen CT studies were performed in 10 patients. CT studies were excluded due to complete pancreatic necrosis, and transplant superior mesenteric artery (SMA) thrombus with pancreatic head ischaemia causing effacement of the transplant superior mesenteric vein (SMV). Diagnostic quality of the analysed CT studies were confirmed with mean attenuation value of blood >211 HU in the transplant pancreatic arteries (SMA=259.0±51.4 HU, splenic artery=245.3±37.5 HU), and >80 HU in the pancreatic veins (SMV=195.4±36.2 HU, splenic vein=185.1±54.2 HU). CONCLUSION: Diagnostic quality CT studies were obtained using the single-pass CT protocol. Radiation exposure to patients may be reduced with this protocol, while permitting simultaneous assessment of parenchymal and vascular complications post-SPK.

Does perfusion CT play a role in the evaluation of percutaneous microwave-ablated lung tumours?

AIM: To assess the clinical utility of perfusion computed tomography (pCT) parameters in microwave ablation (MWA) of lung tumours. MATERIALS AND METHODS: Patients were included who had primary or metastatic lung tumours and underwent pCT studies immediately pre- and post-MWA. Perfusion maps of the tumours were constructed using CT perfusion software (GE, Milwaukee, WI, USA). Regions of interest were drawn on sequential axial sections to extract the pCT parameters, blood volume (BV), average blood flow (BF), and mean transit time (MTT) from the entire tumour volume. Direct visualisation of perfusion maps were performed by two experienced readers blinded to outcome. Data were analysed using the Mann-Whitney test. RESULTS: Thirty-one patients with 34 lung tumours had follow-up data at 12 months. The median tumour diameter was 19 mm (10-52 mm). Seven patients developed local tumour progression (LTP) at 12 months. There was no statistical difference between patients with LTP and complete treatment based on quantitative pCT parameters. Using radiologist visualisation of perfusion maps, there was moderate agreement between the two readers (kappa coefficient 0.53) with a combined 96% sensitivity, 62% specificity, 91% positive predictive value, and 80% negative predictive value. CONCLUSION: Quantitative pCT parameters do not help differentiate between LTP and complete treatment, but subjective analysis of perfusion maps may be a useful assessment tool for identifying treatment adequacy potentially enabling identification of areas requiring further treatment at the time of the procedure.

Transanal endoscopic microsurgery for rectal cancer.

Since its introduction in the 1980s, total mesorectal excision (TME) has been the standard surgical technique for treating rectal cancer. This procedure involves removing the rectum and the surrounding envelope of fat along the plane of the mesorectal fascia. Resecting this embryological unit reduces the local recurrence rate by removing all local lymph nodes, including those with occult metastatic disease; however, this surgery is associated with mortality and morbidity. Complications include incontinence for patients given an anastomosis, long-term stoma formation, and sexual and bladder dysfunction. Local excision of rectal cancer using the transanal endoscopic microsurgery (TEM) technique is associated with fewer complications, and therefore, is used as an alternative in specific circumstances. We outline the technique, its indications, imaging appearances and complications.

Field evaluation of the response of Aedes albopictus (Stegomyia albopicta) to three oviposition attractants and different ovitrap placements using black and clear autocidal ovitraps in a rural area of Same, Timor-Leste.

Known oviposition attractants or stimulants were compared, singly and in combination, using inexpensive autocidal ovitraps designed to trap emerging adults, in a rural area of Timor-Leste during the dry season. In this area, the dengue vector Aedes albopictus (Stegomyia albopicta) Skuse (Diptera: Culicidae) was abundant, but Aedes aegypti (Stegomyia aegypti) L. was not detected. The attractants were: (a) a compound found in Aedes eggs (dodecanoic acid); (b) components of nitrogen, phosphorous and potassium-based (NPK) fertilizer, and (c) infusions of discarded cigarette butts. A solution of ammonium phosphate and potassium nitrate was significantly more attractive to gravid Ae. albopictus than water only. Dodecanoic acid and cigarette butt infusions were not significantly more attractive than the control; however, they attracted various other Diptera and many non-culicid larvae developed in ovitraps in which these substances were used; thus, the presence of eggs or larvae of other species may have deterred Aedes oviposition. Significantly more Aedes eggs were found in ovitraps under vegetation than in ovitraps placed inside houses or against external walls. Clear-sided ovitraps in which black mesh was placed over a black ring floating on the water surface collected significantly fewer eggs than black ovitraps with identically placed mesh and rings.

Baseline corticosterone in wintering marine birds: methodological considerations and ecological patterns.

Previous studies have related levels of plasma corticosterone (CORT) of seabirds to variation in foraging conditions during the breeding period, but it is unclear whether similar relationships between foraging conditions and baseline CORT exist during other life stages. We validated methods for identifying baseline CORT of lethally sampled birds and assessed variation in baseline CORT relative to winter habitat conditions. We collected free-living white-winged scoters (Melanitta fusca) at four wintering sites during December and February. We found increasing CORT values beyond 3 min after time since flush (the duration between initial flush and death), presumably reflecting acute stress responses. Our results demonstrate that it is possible to obtain baseline CORT from lethally sampled birds if the time from initial flush until death is measured. Our study sites varied appreciably in exposure to wind and waves, predation danger, diving depths, and the fraction of preferred foods in scoter diets. Despite these habitat differences, baseline CORT did not vary across sites or winter periods. We interpret this lack of variation as evidence that birds select wintering areas where they can successfully manage site-specific costs and maintain physiological homeostasis.

Effects of pretraining and water temperature on female rats' performance in the Morris water maze.

The water maze is a complex spatial task that requires the coordination of multiple systems to perform efficiently. Various factors have been shown to influence performance in this task, including motivational state and prior experience. Although a consistent sex difference has been observed in acquiring the water maze in rats, the contribution of the various factors in female rat performance has not been fully assessed. Therefore, the current study tested the effects of motivation as manipulated by water temperature of the maze and prior experience in the maze on the performance of female rats. It was hypothesized that females pretrained in the maze would perform better than those without exposure to the water maze, regardless of water temperature, but in naïve rats, colder water would improve performance as shown previously in male rats. For pretraining, female rats were taught to find a visible platform in cold (19 °C, 4 trials on one day) and warm (25 °C, 4 trials on one day) water before acquisition trials, with the order of the water temperature randomly assigned. Control rats were not given any training and were naïve to the water maze procedure. Pretrained and control rats were then tested to locate a hidden platform in either cold or warm water for 5 consecutive days. Overall, pretraining had a significant effect on distance, latency, and directness of path to the platform. Water temperature did not show a significant effect on any measure or a significant interaction with pretraining. Thus, while our hypothesis that pretraining would improve performance was supported, the results did not support the prediction that water temperature would also significantly influence performance. These results show that non-spatial pretraining can critically improve the performance of females in acquiring a place strategy for the hidden platform, irrespective of water temperature.

Oncogenic B-Raf signaling in melanoma cells controls a network of microRNAs with combinatorial functions.

Over two-thirds of melanomas have activating mutations in B-Raf, leading to constitutive activation of the B-Raf/MKK/ERK signaling pathway. The most prevalent mutation, B-RafV600E, promotes cancer cell behavior through mechanisms that are still incompletely defined. Here, we used a sensitive microarray profiling platform to compare microRNA (miRNA) expression levels between primary melanocytes and B-RafV600E-positive melanoma cell lines, and between melanoma cells treated in the presence and absence of an MKK1/2 inhibitor. We identified a network of >20 miRNAs deregulated by B-Raf/MKK/ERK in melanoma cells, the majority of which modulate the expression of key cancer regulatory genes and functions. Importantly, miRNAs within the network converge on protein regulation and cancer phenotypes, suggesting that these miRNAs might function combinatorially. We show that miRNAs augment effects on protein repression and cell invasion when co-expressed, and gene-specific latency and interference effects between miRNAs were also observed. Thus, B-Raf/MKK/ERK controls key aspects of cancer cell behavior and gene expression by modulating a network of miRNAs with cross-regulatory functions. The findings highlight the potential for complex interactions between coordinately regulated miRNAs within a network.

Long-term changes in reward-seeking following morphine withdrawal are associated with altered N-methyl-D-aspartate receptor 1 splice variants in the amygdala.

The NR1 subunit of the NMDA receptor can be alternatively spliced by the insertion or removal of the N1, C1, C2, or C2' regions. Morphine dependence and withdrawal were previously demonstrated to lower N1 and C2' in the accumbens and lower N1, C1, and C2' in the amygdala (AMY). Withdrawal has also been demonstrated to increase motivational and anxiety/stress behaviors in rats. We tested the hypothesis that NR1 splicing would be associated with these behaviors during an extended withdrawal period of 2 months. Motivation was measured using an operant orofacial assay at non-aversive temperatures (37°C) while anxiety and stress were measured by examining this behavior at aversive temperatures (46°C). Lower C1 and C2 expression levels were observed in the AMY in a subset of the population of withdrawn rats even after 2 months of morphine withdrawal. These subsets were associated with a hypersensitivity to adverse conditions which may reflect long-term alterations in the withdrawn population.

A computer-aided algorithm to quantitatively predict lymph node status on MRI in rectal cancer.

OBJECTIVE: The aim of this study was to demonstrate the principle of supporting radiologists by using a computer algorithm to quantitatively analyse MRI morphological features used by radiologists to predict the presence or absence of metastatic disease in local lymph nodes in rectal cancer. METHODS: A computer algorithm was developed to extract and quantify the following morphological features from MR images: chemical shift artefact; relative mean signal intensity; signal heterogeneity; and nodal size (volume or maximum diameter). Computed predictions on nodal involvement were generated using quantified features in isolation or in combinations. Accuracies of the predictions were assessed against a set of 43 lymph nodes, determined by radiologists as benign (20 nodes) or malignant (23 nodes). RESULTS: Predictions using combinations of quantified features were more accurate than predictions using individual features (0.67-0.86 vs 0.58-0.77, respectively). The algorithm was more accurate when three-dimensional images were used (0.58-0.86) than when only middle image slices (two-dimensional) were used (0.47-0.72). Maximum node diameter was more accurate than node volume in representing the nodal size feature; combinations including maximum node diameter gave accuracies up to 0.91. CONCLUSION: We have developed a computer algorithm that can support radiologists by quantitatively analysing morphological features of lymph nodes on MRI in the context of rectal cancer nodal staging. We have shown that this algorithm can combine these quantitative indices to generate computed predictions of nodal status which closely match radiological assessment. This study provides support for the feasibility of computer-assisted reading in nodal staging, but requires further refinement and validation with larger data sets.

Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

Morphine and MK-801 administration leads to alternative N-methyl-D-aspartate receptor 1 splicing and associated changes in reward seeking behavior and nociception on an operant orofacial assay.

The NMDA receptor plays a large role in opioid-induced plastic changes in the nervous system. The expression levels of its NR1 subunit are altered dramatically by morphine but no changes in its alternative splicing have been reported. Changes in the splicing of the N1, C1, C2, and C2' cassettes can alter the pharmacology and regulation of this receptor. Western Blots run on brain tissue from rats made tolerant to morphine revealed altered splicing of the N1 cassettes in the accumbens and amygdala (AMY), and the C1 cassette in the AMY and the dorsal hippocampus (HIPP). After 3days of withdrawal C2'-containing NR1 subunits were down-regulated in each of these areas. These were not due to acute doses of morphine and may represent long-term alterations in drug-induced neuroplasticity. We also examined the effects of morphine tolerance on an operant orofacial nociception assay which forces an animal to endure an aversive heat stimulus in order to receive a sweet milk reward. Morphine decreased pain sensitivity as expected but also increased motivational reward seeking in this task. NMDAR antagonism potentiated this reward seeking behavior suggesting that instead of attenuating tolerance, MK-801 may actually alter the rewarding and/or motivational properties of morphine. When combined, MK-801 and morphine had an additive effect which led to altered splicing in the accumbens, AMY, and the HIPP. In conclusion, NR1 splicing may play a major role in the cognitive behavioral aspects especially in motivational reward-seeking behaviors.

MRI features of the complete histopathological response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy.

AIM: To describe the post-chemoradiotherapy magnetic resonance imaging (MRI) features of locally advanced rectal carcinoma (LARC) in which there has been a complete histopathological response to neoadjuvant chemoradiotherapy (CRT). MATERIALS AND METHODS: This retrospective cohort study was performed between January 2005 and November 2009 at a regional cancer centre. Consecutive patients with LARC and a histopathological complete response to long-course CRT were identified. Pre- and post-treatment MRI images were reviewed using a proforma for predefined features and response criteria. ymrT0 was defined as the absence of residual abnormality on MRI. RESULTS: Twenty patients were included in the study. Seven (35%) ypT0 tumours were ymrT0. All 13 ypT0 tumours not achieving ymrT0 appearances had a good radiological response, with at least 65% tumour reduction. The appearances were heterogeneous: in 11/13 patients the tumour was replaced by a region of at least 50% low signal on MRI, with 8/13 having ≥80% low signal, and 3/13 with 100% low signal. CONCLUSION: MRI may be useful in identifying a complete histopathological response. However, the MRI appearances of ypT0 tumours are heterogeneous and conventional MRI complete response criteria will not detect the majority of patients with a complete histopathological response.

Lesioning of TRPV1 expressing primary afferent neurons prevents PAR-2 induced motility, but not mechanical hypersensitivity in the rat colon.

BACKGROUND: Proteinase activated receptor 2 (PAR-2) is expressed by many neurons in the colon, including primary afferent neurons that co-express transient receptor potential vanilloid 1 (TRPV1). Activation of PAR-2 receptors was previously found to enhance colonic motility, increase secretion and produce hypersensitivity to mechanical stimuli. This study examined the functional role of TRPV1/PAR-2 expressing neurons that innervate the colon by lesioning TRPV1 bearing neurons with the highly selective and potent TRPV1 agonist resiniferatoxin. METHODS: Colonic motility in response to PAR-2 activation was evaluated in vitro using isolated segments of descending colon and in vivo using manometry. Colonic mechanical nociceptive thresholds were measured using colorectal distension. Transient receptor potential vanilloid 1 expressing neurons were selectively lesioned with resiniferatoxin. KEY RESULTS: In vitro, the PAR-2 agonists, trypsin and SLIGRL did not alter contractions of colon segments when applied alone, however, the agents enhanced acetylcholine stimulated contraction. In vivo, PAR-2 agonists administered intraluminally induced contractions of the colon and produced hypersensitivity to colorectal distention. The PAR-2 agonist enhancement of colonic contraction was eliminated when TRPV1 expressing neurons were lesioned with resiniferatoxin, but the PAR-2 agonist induced hypersensitivity remained in the lesioned animals. CONCLUSIONS & INFERENCES: Our findings indicate that TRPV1/PAR-2 expressing primary afferent neurons mediate an extrinsic motor reflex pathway in the colon. These data, coupled with our previous studies, also indicate that the recently described colospinal afferent neurons are nociceptive, suggesting that these neurons may be useful targets for the pharmacological control of pain in diseases such as irritable bowel syndrome.

Steroid hormone content of seminal plasma influences fertilizing ability of sperm in White Leghorns.

Maternal and paternal influences before fertilization can significantly affect the ultimate reproductive output. In avian species, previous studies have shown that concentrations of testosterone (T) in seminal plasma vary greatly and are related to sperm quality. To our knowledge, the presence of other reproductive hormones in avian seminal plasma and their potential influences on fertility remain unstudied. We measured the concentrations of progesterone (P4), T, dihydrotestosterone, and estrogen in seminal and blood plasma collected from White Leghorn roosters. Progesterone was the most abundant hormone compared with all others measured, and concentrations of P4 in seminal plasma were significantly higher than concentrations found in circulation. Given the relatively high concentration of seminal plasma P4, we then attempted to determine its effect on fertility. Hens were inseminated with semen samples that were supplemented with either a high physiological dose of P4 or a control vehicle. Fertilization ability of all semen samples was then characterized using a perivitelline sperm hole penetration assay. Progesterone treatment significantly decreased the ability of sperm to reach and penetrate the egg, suggesting that males that deposit more P4 into seminal plasma may have a decreased capability to fertilize an egg.

Evaluation of a general practice based hepatitis C virus screening intervention.

BACKGROUND: In 2003 an estimated 37,500 of Scotland's population was chronically infected with HCV; 44% were undiagnosed former injecting drug users (IDU)--a priority group for antiviral therapy. AIM: To evaluate a hepatitis C virus (HCV) screening intervention. DESIGN: Outcome measures among two similar General Practice populations in an area of high HCV and drug use prevalence, one of which was exposed to an HCV screening intervention, were compared. METHODS: Thirty to fifty four year old attendees of the intervention practice were opportunistically offered testing and counselling, where clinically appropriate, (November 2003-April 2004). OUTCOMES: HCV test uptake, case detection, referral and treatment administration rates. RESULTS: Of 584 eligible attendees, 421 (72%) were offered and 117 (28%) accepted testing in the intervention practice; no testing was undertaken in the comparison practice. Prevalences of HCV antibody were 13% (15/117), 75% (3/4) and 91% (10/11) among all tested persons, current IDUs and former IDUs respectively. For 4/15 (27%) evidence of binge drinking following the receipt of their positive result, was available. Of the 11 referred to specialist care because they were HCV RNA positive, nine attended at least one appointment. Two received treatment: one had achieved a sustained viral response as of February 2008. CONCLUSION: While non targeted HCV screening in the general practice setting can detect infected former IDU, the low diagnostic yield among non IDUs limited the effectiveness of the intervention. A more targeted approach for identifying former IDUs is recommended. Additionally, the low uptake of treatment among chronically infected persons four years after diagnosis demonstrates the difficulties in clinically managing such individuals. Strategies, including support for those with a history of problem alcohol use, to improve treatment uptake are required.

Pancreas transplants.

Cadaveric, whole pancreas transplantation has proved an effective therapy in the treatment of long-standing type 1 diabetes mellitus and is capable of achieving an insulin-independent eugyclaemic state. As a result, this procedure is being increasingly performed. However, the surgical procedure is complex and unfamiliar to many radiologists. Imaging with computed tomography (CT) and magnetic resonance imaging (MRI) gives excellent results and can be used confidently to diagnose vascular, enteric, and immune-mediated complications. We present a review of the normal post-transplantation appearance and the features of early and late complications.