Effects of Salt Loading on the Regulation of Rat Hypothalamic Magnocellular Neurosecretory Cells by Ionotropic GABA and Glycine Receptors.

Synaptic and extrasynaptic transmission mediated by ionotropic GABA and glycine receptors plays a critical role in shaping the action potential firing (spiking) activity of hypothalamic magnocellular neurosecretory cells and therefore determines the rate at which vasopressin and oxytocin are released from the neurohypophysis. The inhibitory effect of these transmitters relies on the maintenance of a low concentration of intracellular chloride ions such that, when activated by GABA or glycine, a hyperpolarisation of the neuronal membrane potential results. In this review, we highlight the various ways by which the two types of inhibitory receptors contribute to homeostasis by fine-tuning the spiking rate of vasopressin-releasing magnocellular neurosecretory cells in a manner dependent on the hydration state of the animal. In addition, we review the currently available evidence on how the strength of these inhibitory pathways can be regulated during chronic hypernatraemia via a form of activity-dependent depolarisation of the chloride reversal potential, leading to an abolition of these inhibitory pathways potentially causing sodium-dependent elevations in blood pressure.

Effects of Salt Loading on the Morphology of Astrocytes in the Ventral Glia Limitans of the Rat Supraoptic Nucleus.

In the ventral glial limitans (VGL) of the supraoptic nucleus (SON) of the rat, a unique astrocyte type is found with an ability to undergo striking morphological plasticity in response to a wide range of physiological stimulations such as chronic hypernatraemia. This includes a thinning of the VGL, which contains the somata and proximal processes of these astrocytes, as well as an almost complete withdrawal of their vertically-oriented distal processes. Currently, there is little information available on the types of astrocytes that reside in the SON-VGL and which of these exhibit state-dependent structural plasticity. To address this, we enabled the visualisation of single SON-VGL glia using two novel cell labelling techniques with fluorescence microscopy. First, we used an inducible genetic reporter mouse line that allowed the specific labelling of a low density of astrocytes expressing glutamate and aspartate transporter (GLAST)/excitatory amino acid transporter 1. This approach revealed a high degree of variability in the morphology of mouse SON-VGL astrocytes, in contrast to what has been reported for cortical astrocytes. Next, we used the DiOlistlic labelling approach to label single glial cells with DiI in the SON-VGL of rats. Astrocytes observed using this approach shared the morphological features of GLAST-expressing astrocytes in the mouse SON-VGL. Specific structural aspects of these cells were modified by chronic hypernatraemia achieved by 7-day salt loading. Notably, the average area of cells exhibiting protoplasmic features was significantly reduced in the horizontal plane, and the size of varicosities present on fibrous projections was significantly enlarged. These observations indicate that novel cell labelling methods can significantly advance our understanding of SON-VGL cells and reveal specific forms of morphological plasticity that can be driven by chronic hypernatraemia.

Biomarker analysis in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant 5-fluorouracil and cisplatin chemotherapy: epidermal growth factor receptor (EGFR) associated with favourable survival.

The aim of this study was to analyse the impact of epidermal growth factor receptor (EGFR), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), aurora kinase (ARK) A/B, and excision repair cross-complementing gene 1 (ERCC1) on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Normal and cancer tissue were separately obtained from gastrectomy samples of 153 patients with AJCC stage III-IV (M0) who subsequently treated with adjuvant FP chemotherapy. TS, DPD, TP, ERCC1, and ARK proteins were measured by immunohistochemistry (IHC). EGFR expression was investigated using a standardized IHC with the EGFR PharmDx assay. Amplification of EGFR gene was analysed using fluorescent in situ hybridisation (FISH). In multivariate analysis, stage, ratio of positive to removed lymph nodes, and EGFR expression were significant prognostic factors for overall survival. Patients with higher EGFR expression had better overall survival than those with lower expression (relative risk: 0.475 (95% confidence interval, 0.282-0.791, P=0.005). Low EGFR expression might be a predictive marker for relapse in curative resected stage III-IV (M0) gastric cancer patients who received adjuvant FP chemotherapy.

Congenital cystic adenomatoid malformation (Type II) with active tuberculosis in an adult.

Cystic adenomatoid malformation (CAM) is a congenital disorder similar to bronchopulmonary sequestration. Most cases of CAM are diagnosed during the neonatal period and infancy. The histological classification of the vast majority of reported cases of CAM is Stocker's Type I. We present an adult patient with Stocker's Type II CAM with active tuberculosis.

Retrobulbar optic neuritis and meningoencephalitis following progressive outer retinal necrosis due to CMV in a patient with AIDS.

We report on a 34-year-old male patient with AIDS who developed retrobulbar optic neuritis and meningoencephalitis following bilateral progressive outer retinal necrosis (PORN) caused by cytomegalovirus (CMV). This case documents the presumed association of PORN with retrobulbar optic neuritis, and CMV meningoencephalitis in an AIDS patient.

Clinical features and outcome of community-onset bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli.

This study was conducted to evaluate the epidemiology and clinical features of bloodstream infections caused by extended-spectrum beta-lactamase-producing E. coli (ESBL-EC) in community-onset bacteremia. Of 929 episodes of community-onset E. coli bacteremia, 4.1% (38/929) had bacteremia with ESBL producers. Of these, 63.2% (24/38) were further classified as healthcare-associated infections. Although most patients had risk factors for infection due to ESBL producers, three patients with urinary tract infection, four patients with cholangitis, and one patient with a liver abscess had no identified predisposing risk factors. The 30-day mortality was 21.1% (8/38). ESBL-EC is a significant cause of bloodstream infection, even in patients with community-onset infection.

One-year adherence to clinic visits after highly active antiretroviral therapy: a predictor of clinical progress in HIV patients.

OBJECTIVE: To determine whether adherence to clinic visits early after initiation of highly active antiretroviral therapy (HAART) is predictive of long-term clinical outcome. DESIGN: Observational cohort study. SETTING: A tertiary referral hospital. SUBJECTS: A total of 387 adult HIV patients who were followed for at least 1 year after initiation of HAART between January 1998 and December 2004. MAIN OUTCOME MEASUREMENTS: The effect of 1-year adherence to clinic visits on the occurrence of new AIDS-defining illness or death was assessed using Kaplan-Meier survival estimates, and hazard ratios were estimated using Cox proportional hazards regression model. RESULTS: Multivariate analysis revealed that advanced clinical stage, fewer new drugs in HAART, and longer total elapsed time without clinical visits for 1 year after HAART were all significant risk factors for the occurrence of new AIDS-defining illnesses or death. Compared with no missed visits, the hazard ratio adjusted by clinical stage and number of new drugs in HAART was 2.87 (95% confidence interval [CI], 1.34-6.16, P = 0.007) for one missed appointment, 4.37 (95% CI: 1.74-10.98, P = 0.002) for two, and 8.19 (95% CI: 2.95-22.78, P < 0.001) for three or more. CONCLUSION: Adherence to clinic visits early after initiation of HAART is an independent predictor for long-term clinical progression in HIV patients.

The persistence of humoral and cellular immunities more than three decades after smallpox vaccination.

This study assessed the persistence of humoral (neutralising antibody titre to vaccinia virus) and cellular (immediate vaccinia-specific interferon (IFN)-gamma-producing T-cell) immunities to smallpox in a Korean population. Individuals who were vaccinated 25-60 years previously had higher neutralising antibody titres (geometric mean titre (GMT) 13.7; 95% CI 11.0-17.2) than vaccinia-naive individuals (GMT 6.7; 95% CI 5.5-8.0; p <0.001). However, there was no significant difference in cellular immunity between individuals vaccinated previously and vaccinia-naive individuals, and only 15% of the individuals vaccinated previously displayed an immediate IFN-gamma-producing effector-memory response in ELISPOT assays.

Recognizing and interpreting artifacts and pitfalls in MR imaging of the breast.

Magnetic resonance (MR) imaging of the breast has evolved into an important adjunctive tool in breast imaging with multiple and ever-increasing indications for its use. As with other types of MR imaging, there are a number of technical artifacts and pitfalls that can potentially limit interpretation of the images by masking or simulating disease. Because of the coils and computer-aided detection software specific to breast MR imaging, there are additional technical considerations that are unique to this type of MR imaging. Motion and misregistration artifacts, wraparound artifact, susceptibility artifact, poor fat saturation, lack of contrast material, and poor timing of the contrast material bolus are some of the artifacts and pitfalls that can make interpretation of breast MR images challenging and lead to misdiagnosis. Other important considerations in proper interpretation of breast MR images include acquisition of a sufficient medical history, knowledge of benign and abnormal lesion enhancement, morphologic versus kinetic assessment, evaluation of areas outside the breast, and positioning. By using the recommended strategies, one can reduce or eliminate common artifacts and pitfalls in breast MR imaging that prevent proper interpretation of the results of this important diagnostic tool.

Pulmonary tuberculosis in young Korean soldiers: incidence, drug resistance and treatment outcomes.

OBJECTIVE: To determine the incidence and treatment outcomes of pulmonary tuberculosis (PTB) in young soldiers of South Korea. DESIGN: From 2000 to 2004, all soldiers with a new diagnosis of tuberculosis (TB) were enrolled in the study, based on the official records of the Armed Forces Medical Command. The demographic and clinical data of the cases were evaluated retrospectively. RESULTS: A total of 3115 TB cases were reported during the study period, of whom 2071 (66.5%) were reported as PTB. The annual incidence rates of PTB were 96.4 per 100,000 population in 2000, 89.3 in 2001, 67.6 in 2002, 60.2 in 2003, and 63.1 in 2004. A total of 270 patients diagnosed and treated at the Armed Forces Capital Hospital were analysed. Of the Mycobacterium tuberculosis isolates, 87.4% were susceptible to all available anti-tuberculosis drugs; 253 (93.7%) patients eventually completed initial anti-tuberculosis treatment. Among the patients with smear-positive PTB, the cure rate was 89.3% (100/112). CONCLUSION: Our results demonstrate that the incidence of PTB in Korean soldiers, although still high, was declining steadily. With good case management, the overall success rate of initial treatment was approximately 90%.

Outcome of inappropriate empirical antibiotic therapy in patients with Staphylococcus aureus bacteraemia: analytical strategy using propensity scores.

Patients with Staphylococcus aureus bacteraemia (SAB) who received either inappropriate or appropriate empirical therapy were compared by using two risk stratification models: (1) a cohort study using a propensity score to adjust for confounding by empirical treatment assignment; and (2) a propensity-matched case-control study. Inappropriate empirical therapy was modelled on the basis of patient characteristics, and included in the multivariate model to adjust for confounding. For case-matching analysis, patients with inappropriate empirical therapy (cases) were matched to those with appropriate empirical therapy (controls) on the basis of the propensity score (within 0.03 on a scale of 0-1). In total, 238 patients with SAB were enrolled in the cohort study. Characteristics associated with inappropriate empirical therapy were methicillin resistance, underlying haematological malignancy, no history of colonisation with methicillin-resistant S. aureus, and a long hospital stay before SAB. These variables were included in the propensity score, which had an area under the receiver operating characteristics curve of 85%. In the cohort study, SAB-related mortality was 39% (45/117) for inappropriate empirical therapy vs. 28% (34/121) for appropriate empirical therapy (odds ratio (OR) 1.60; 95% CI 0.93-2.76). After adjustment for independent predictors for mortality and the propensity score, inappropriate empirical therapy was not associated with mortality (adjusted OR 1.39; 95% CI 0.62-3.15). In the matched case-control study (50 pairs), SAB-related mortality was 32% (16/50) for inappropriate empirical therapy and 28% (14/50) for appropriate empirical therapy (McNemar's test; p 0.85; OR 1.15; 95% CI 0.51-2.64). In conclusion, inappropriate empirical therapy resulted in only a slight tendency towards increased mortality in patients with SAB.

Sentinel node biopsy for cT1 and cT2a gastric cancer.

AIMS: To evaluate the feasibility and accuracy of sentinel node (SN) biopsy for gastric cancer. PATIENTS AND METHODS: One hundred patients with gastric cancer diagnosed as cT1 (n=80) or cT2a (n=20) were enrolled. Indocyanine green-stained SNs were analysed by hematoxylin and eosin staining (n=100) and by cytokeratin immunohistochemistry (n=50). RESULTS: SNs were identified in 94 of the 100 patients and the mean number of SNs was 4.4 (range, 1-12). Of these 94 patients, 14 patients had lymph node metastases. Two patients with T1 and one patient with T2 had metastases in non-SNs alone by hematoxylin and eosin staining (diagnostic accuracy =97.3% in T1 and 95.0% in T2). All three patients with a false negative result had a tumour, which was more than 4 cm in size and signet ring cell histology. In two of them, the tumour was located at lesser curvature. By immunohistochemical staining, three patients with T1 and one patient with T2 were found to have lymph node micrometastases in non-SNs alone among 45 patients (diagnostic accuracy =92.1% in T1, 85.7% in T2). CONCLUSION: SN biopsy using indocyanine green can be performed rapidly and easily with a high detection rate and accuracy in patients with T1 gastric cancer. However, it should be performed with caution for large tumours with a signet ring cell histology located at lesser curvature due to the possibility of a false negative result.

Intraoperative gastroscopy for gastric surgery.

BACKGROUND: Few reports are available on the use of intraoperative gastroscopy for gastric surgery. METHODS: The details of 33 patients (25 early gastric cancers and eight gastric submucosal tumors) who underwent intraoperative gastroscopy from June 2003 to June 2004 were analyzed. The type of operation or resection margin was determined by evaluating both sides of the stomach simultaneously by combined operative and gastroscopic methods. RESULTS: Preoperative endoscopic clipping was done preferentially for early gastric cancer. However, when precise localization was needed, intraoperative gastroscopy was used. Curative gastric resection was possible in 25 early gastric cancer patients after accurate lesion localization. Laparoscopic wedge resections of submucosal tumors were performed in seven patients without stenosis by combined laparoscopic and gastroscopic methods. CONCLUSIONS: Intraoperative gastroscopy can be used effectively during gastric surgery for early gastric cancer or submucosal tumors and can be regarded as a modern stethoscope to gastric surgeons.

Predictors of operative morbidity and mortality in gastric cancer surgery.

BACKGROUND: The aim of this study was to identify factors that predict morbidity and mortality in gastric cancer surgery. METHODS: Data on 719 consecutive patients who underwent operations for gastric cancer at Seoul National University Hospital between January and December 2002 were reviewed. RESULTS: Overall morbidity and mortality rates were 17.4 per cent (125 patients) and 0.6 per cent (four patients) respectively, and the rates of surgical and non-surgical complications were 14.7 per cent (106 patients) and 3.3 per cent (24 patients). Morbidity rates were higher in patients aged over 50 years (odds ratio (OR) 1.04 (95 per cent confidence interval (c.i.) 1.02 to 1.06)), when the gastric tumour was resected with another organ (36 per cent for combined resection versus 15.4 per cent for gastrectomy only; OR 3.25 (95 per cent c.i. 1.76 to 6.03)) and when gastrojejunostomy was used for reconstruction after subtotal gastrectomy (17.0 per cent for Billroth II versus 9.5 per cent for Billroth I; OR 2.00 (95 per cent c.i. 1.05 to 3.79)). Only three patients (2.8 per cent) with a surgical complication underwent reoperation, two for adhesive obstruction and one for intra-abdominal bleeding. CONCLUSION: Age, combined resection and Billroth II reconstruction after radical subtotal gastrectomy were independently associated with the development of complications after gastric cancer surgery.

Epidemiological characteristics of occupational blood exposures of healthcare workers in a university hospital in South Korea for 10 years.

This study investigated the epidemiological characteristics of occupational blood exposures (OBEs) of healthcare workers (HCWs) in South Korea, and examined trends of OBEs after implementing blood exposure prevention (BEP) programmes. The study was conducted between 1 January 1992 and 31 December 2001 at a university-affiliated acute care hospital in Seoul. The BEP programmes comprised in-service education, hepatitis B virus (HBV) vaccination, and postexposure evaluation and prophylaxis. From 959 reported cases of OBEs, the crude incidence density (ID) was 2.62 cases per 100 person-years. The major risk groups for OBEs were physicians (ID 4.34) and new employees. The major type of OBE was from sharps injuries, including needlesticks (94.0%). OBE cases occurred more frequently during the spring (36.4%). The frequency of the serological tests of anti-hepatitis B surface antigen of HCWs changed significantly each year (P<0.05). The major serological risk for source patients was HBV (52.1%), but the risks for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increased significantly each year (P<0.05). There were no seroconversion cases following OBEs among the tested HCWs. In summary, we established the epidemiological characteristics of OBEs in a South Korean university hospital, and reduced the risk of OBEs of major risk groups by BEP programmes. We also found an increase in the risk of HCV and HIV during the study period, suggesting that OBEs could be a serious threat to HCWs.

The significance and clinical factors associated with a subcentimeter resection of colorectal liver metastases.

BACKGROUND: Prognosis after resection of colorectal liver metastases is influenced by various factors. A positive margin of resection (MOR) has been shown to adversely influence prognosis. Although a 1-cm MOR has been accepted as adequate, the data to support this guideline are sparse. METHODS: Our hepatobiliary database was queried for patients who underwent liver resection for colorectal metastases between January 1992 and July 2003. All patients were divided into three groups: MOR <.5 cm (group A), .5 to 1 cm (group B), and >1 cm (group C). Operative reports from each hepatic resection were analyzed to determine local factors that may have contributed to a subcentimeter MOR. RESULTS: A total of 112 patients (67 men and 45 women) underwent liver resection for colorectal metastases with negative margins. Fifty-three patients were in group A, 26 patients were in group B, and 33 patients were in group C. Group C demonstrated decreased local recurrence (LR; P = .003), distant recurrence (DR; P = .008), and disease-free recurrence (P = .002). A significant difference in the overall time to LR (P = .003), time to DR (P = .003), and disease-free survival (P = .002) was also demonstrated. Factors associated with a subcentimeter MOR included nonanatomical resection (P = .043), proximity to a major vessel (P = .003), and central location (P = .002). CONCLUSIONS: A <1-cm resection for colorectal liver metastases is associated with increased LR and DR, as well as decreased disease-free survival. When a nonanatomical resection is performed, a MOR >1 cm should be attempted, because an adequate margin is often underestimated. Considerations should be made for extended resections when tumors are centrally located or near major vessels.

Clinical features and outcome of patients with community-acquired Pseudomonas aeruginosa bacteraemia.

Cases of community-acquired Pseudomonas aeruginosa bacteraemia (n = 39) that occurred at a tertiary-care hospital during a 5-year period were analysed retrospectively. The commonest underlying diseases were solid tumour (41%) and haematological malignancy (18%). Most (44%) of the patients were neutropenic, and 39% had septic shock at initial presentation. The 30-day attributable mortality rate was 39%. Two previously healthy patients were identified with fatal P. aeruginosa pneumonia with bacteraemia. P. aeruginosa bacteraemia is a fatal infection that should be considered in the differential diagnosis of patients presenting from the community with rapidly progressive sepsis.