The clinical strategy for the Barrett's esophagus

The treatment of Barrett's esophagus is controversial. Current treatments include endoscopic therapy, surgical procedures, gastric acid-suppressive therapy with proton pump inhibitors (PPIs), and cancer chemoprevention such as nonsteroidal anti-inflammatory drugs. Endoscopic therapy combined with gastric acid suppressive therapy can result in squamous reepithelialization of the Barrett's mucosa. Antireflux surgery and PPIs therapy are potential options for the treatment of gastroesophageal reflux symptoms in patients with Barrett's esophagus. But there are no prospective studies that support any alternative approach to treatment. Although chemoprevention therapy may reduce cancer risk in Barrett's esophagus, no randomized controlled trials that prove its efficacy have been reported.     

Neuronal plasticity in the deafferented hypothalamic arcuate nucleus of adult female rats and its enhancement by treatment with estrogen

The hypothalamic arcuate nucleus (ARCN) was examined ultrastructurally 3 or 21 days after complete deafferentation of the medial basal hypothalamus (MBH) in ovariectomized adult female rats. Axodendritic shaft (SHS) and spine synapses (SPS) were counted in a field of 18,000 μm² in the middle part of the ARCN in each brain. The mean numbers of SHS and SPS at 3 or 21 days after deafferentation were reduced to about half of those in intact control animals. When the ARCNs of the ovariectomized MBH-island rats were examined 3 days after treatment with estradiol benzoate (EB, 2 μg/day), the numbers of SHS and SPS did not differ from those in ovariectomized MBH-island rats without EB treatment. However, EB treatment for 21 days produced a marked increase in the number of both SHS and SPS in the ovariectomized MBH-island females, with the number of SHS in these females being restored to almost 75% of the intact level; the incidence of SPS was also significantly greater than that in the intact control animals. In these EB-treated, ovariectomized MBH-island rats, double synapses (spine-spine and spine-shaft double synapses) were frequently observed. In ovariectomized females without MBH deafferentation, however, estrogen failed to increase the numbers of SHS, SPS, and double synapses, which were almost comparable to those in intact and ovariectomized controls. These results suggest that estrogen has a facilitatory effect on SHS and SPS formation in the deafferented ARCN, presumably stimulating not only axonal sprouting but also dendritic spine formation by intact arcuate neurons in the MBH island.     

Efficacy of STI571 for a patient with metastatic gastrointestinal stromal tumor

A 65-year-old man was referred to our hospital for evaluation of his huge abdominal tumor. He was diagnosed as having a gastrointestinal stromal tumor arising from the stomach. Seven months after surgery, multiple liver metastases and mesenteric dissemination occurred. He was medicated with STI571, which works by blocking proliferation of malignant cells with expression of c-kit. The tumors shrank and serum lactate dehydrogenase and alkaline phosphatase concentrations fell to below the normal limit three months later. STI571 was effective medicine for the metastatic gastrointestinal stromal tumor for six months in this case.     

The relationship between coronary artery calcification detected by non-gated multi-detector CT in patients with suspected ischemic heart disease and myocardial ischemia detected by thallium exercise stress testing

OBJECTIVE: To examine whether we could predict myocardial ischemia when coronary artery calcification is detected by non-gated multidetector CT in patients with suspected ischemic heart disease. METHODS: Eighty-three patients suspected of having ischemic heart disease (55 men, 28 women; age range 36-83 years; mean age 68 years) underwent multidetector CT and T1-201 single photon emission computed tomography. Prediction of myocardial ischemia by coronary arterial calcification detected on CT was evaluated by comparing the coronary artery territories that showed calcification with the area of myocardial ischemia determined by SPECT. The sensitivity, specificity, positive predictive value, and negative predictive value of multidetector CT for predicting myocardial ischemia were calculated. Coronary angiography was also examined and compared with multidetector CT. Risk factors, including hypertension, smoking, hyperlipidemia, diabetes, and family history, were compared for evidence of coronary artery calcification detected by multidetector CT and myocardial ischemia detected by thallium nuclear scans. RESULTS: For analysis by patients, the sensitivity, specificity, positive predictive value, and negative predictive value of coronary artery calcification for myocardial ischemia detection were 65, 63, 56, and 71%, respectively. Similarly, for analysis by coronary arterial territories, those values were 56, 77, 41 and 86%, respectively. Coronary stenosis on CAG was also related to the ischemia determined by SPECT and calcification on multidetector CT. Ischemia was better influenced by risk factors than was coronary arterial calcification. CONCLUSIONS: For analysis by coronary arterial territories, the specificity and negative predictive value of coronary arterial calcification seen by multidetector CT are relatively high.     

Expression profiling with arrays of randomly disrupted genes in mouse embryonic stem cells leads to in vivo functional analysis

DNA arrays are capable of profiling the expression patterns of many genes in a single experiment. After finding a gene of interest in a DNA array, however, labor-intensive gene-targeting experiments sometimes must be performed for the in vivo analysis of the gene function. With random gene trapping, on the other hand, it is relatively easy to disrupt and retrieve hundreds of genes/gene candidates in mouse embryonic stem (ES) cells, but one could overlook potentially important gene-disruption events if only the nucleotide sequences and not the expression patterns of the trapped DNA segments are analyzed. To combine the benefits of the above two experimental systems, we first created approximately 900 genetrapped mouse ES cell clones and then constructed arrays of cDNAs derived from the disrupted genes. By using these arrays, we identified a novel gene predominantly expressed in the mouse brain, and the corresponding ES cell clone was used to produced mice homozygous for the disrupted allele of the gene. Detailed analysis of the knockout mice revealed that the gene trap vector completely abolished gene expression downstream of its integration site. Therefore, identification of a gene or novel gene candidate with an interesting expression pattern by using this type of DNA array immediately allows the production of knockout mice from an ES cell clone with a disrupted allele of the sequence of interest.     

A neuronal mechanism of propofol-induced central respiratory depression in newborn rats

The neural mechanisms of propofol-induced central respiratory depression remain poorly understood. In the present study, we studied these mechanisms and the involvement of gamma-aminobutyric acid (GABA)A receptors in propofol-induced central respiratory depression. The brainstem and the cervical spinal cord of 1- to 4-day-old rats were isolated, and preparations were maintained in vitro with oxygenated artificial cerebrospinal fluid. Rhythmic inspiratory burst activity was recorded from the C4 spinal ventral root. The activity of respiratory neurons in the ventrolateral medulla was recorded using a perforated patch-clamp technique. We found that bath-applied propofol decreased C4 inspiratory burst rate, which could be reversed by the administration of a GABAA antagonist, bicuculline. Propofol caused resting membrane potentials to hyperpolarize and suppressed the firing of action potentials in preinspiratory and expiratory neurons. In contrast, propofol had little effect on resting membrane potentials and action potential firing in inspiratory neurons. Our findings suggest that the depressive effects of propofol are, at least in part, mediated by the agonistic action of propofol on GABAA receptors. It is likely that the GABAA receptor-mediated hyperpolarization of preinspiratory neurons serves as the neuronal basis of propofol-induced respiratory depression in the newborn rat.     

Nutritional support in various disease states. B. Nutritional support in severe infection

Within one decade the concept of clinical nutritional support has changed. It was once thought that total parenteral nutrition was an all-purpose panacea, and then that role was played by enteral nutrition. Recently, however, immunonutrition has emerged as a new methodology for nutritional support. Because of the pathologic complexity, numerous problems remain in nutritional support for surgical patients with severe infection. The best route of nutrition in the acute phase, actual efficacy of immune system-enhancing diets, and the prevention of bacterial translocation (BT) and Ventilator-associated pneumonia (VAP) should be resolved. This paper describes concerns in the clinical nutritional management of patients with severe infection and examines how the remaining questions are being resolved.     

Detection of bone marrow and extramedullary involvement in patients with non-Hodgkin’s lymphoma by whole-body MRI: comparison with bone and <Superscript>67</Superscript>Ga scintigraphies

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkins lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from ⁶⁷Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and ⁶⁷Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkins lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by ⁶⁷Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than ⁶⁷Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by ⁶⁷Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkins lymphoma.     

Optical mapping of pontine chemosensitive regions of neonatal rat

We analyzed the neuronal response to hypercapnic acidosis, using an optical recording technique with a fluorescent voltage-sensitive dye (di-4-ANEPPS), in pontine slice preparations of neonatal rats, containing the locus coeruleus (LC), which has been electrophysiologically demonstrated to be chemosensitive. The dye-stained preparation was continuously superfused with artificial cerebrospinal fluid. Epifluorescence of the slice was detected using a high-sensitivity optical recording system. Changes in the intensity of fluorescence were serially analyzed while switching artificial cerebrospinal fluid from control to hypercapnic acidosis, or vice versa. The optical recording method revealed that the LC, as reported in previous studies, reversibly showed a depolarizing response to hypercapnic acidosis in 56% of the examined preparations. The A5 area (56%) also exhibited a reversible, depolarizing response to hypercapnic acidosis. The response was preserved under conditions in which chemical synaptic transmission was blocked by low Ca(2+)-high Mg(2+) solution. These results suggest that the optical recording method is applicable to identification of potentially chemosensitive areas, which deserve further electrophysiological analysis, and that the A5 area could be chemosensitive.