Huge submucosal hematoma of the stomach after accidental removal of the PErcutaneous endoscopic gastrostomy tube

We report a case of massive hemorrhage and aspiration pneumonia as complications of percutaneous endoscopic gastrostomy (PEG). Three months after insertion of a PEG tube, the patient accidentally pulled out the tube by himself. After the accident, the patient experienced hematemesis, which caused aspiration pneumonia. The button‐type tube was reinserted into the PEG fistula for hemostasis. The bleeding stopped temporarily; however, 21 days later, the patient relapsed into a condition of massive PEG site bleeding and hematemesis. He was transferred to our hospital, Kuniyoshi Hospital, to control the bleeding and aspiration pneumonia. Endoscopy revealed a sliding type of large hiatal hernia and a huge submucosal hematoma with an ulceration at the lower part of the gastric body. Emergency surgery including local gastrectomy, gastrostomy, jejunostomy and tracheostomy were helpful to treat these complications. Endoscopists should be aware how to treat these complications. One should not hesitate to perform open surgery when other treatments fail.     

A flip-flop model for nitrofurantoin disposition in the rabbit following oral administration

The influence of route of administration on the absorption of nitrofurantoin and the effect of factors influencing the absorption, such as water volume taken with the drug, change of gastric emptying rate, and effect of particle size, were investigated in rabbits. To clarify the absorption behavior of nitrofurantoin, the Martis-Levy method analogous to the Wagner-Nelson method was used to obtain the absorption kinetics of the drug. Moment analysis was also used to estimate the absorption behavior of the drug.The rate constants of absorption following oral administration of the drug were significantly smaller than those of elimination following intravenous administration. The results of moment analysis (based on a linear approximation) showed that the mean residence time following intravenous administration was much less than the mean absorption time of any oral dosage form. These results clearly show that the pharmacokinetic profile of nitrofurantoin following oral administration is of flip-flop type. Although this result was obtained in the rabbit, the implications of a flip-flop situation for the human case are discussed on the basis of the available published data.     

Nonlinear assessment of nitrofurantoin bioavailability in rabbits

The influence of route of administration on the absolute bioavailability and GI tract absorption of nitrofurantoin was investigated in rabbits. The disposition of nitrofurantoin was described by a one-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics, and bioavailability was estimated by nonlinear assessment. The plasma levels following oral administration were significantly lower than those after intravenous administration, and absolute Fvalues for oral administration were approximately 0.3. However, Fvalues following intraduodenal administration and portal vein infusion were nearly unity, and it was concluded that the reduction of bioavailability following oral administration could not be attributed to metabolism by intestinal microflora or to the hepatic first-pass effect. Thus, reduction of Fvalues following oral administration is probably due to gastric degradation of the drug. The effects of factors influencing bioavailability, such as water volume taken with the drug, change of gastric emptying rate and effect of particle size, were also investigated. Increase of volume of water administered tended to improve the bioavailability, and a particle size dependency was also observed.     

Does reaching the back reflect the actual internal rotation of the shoulder?

To clarify the relationship between the vertebral level reached by the thumb and the internal rotation angle of the humerus, 7 shoulders in healthy volunteers were examined by use of an electromagnetic tracking device. Measurements were repeated in the hanging-arm position with the thumb pointing anteriorly and at the buttock, sacrum, and each vertebral level up to T6. From the hanging-arm position to the buttock, 54.3% of internal rotation occurred (mean, 39.8 degrees ), and from the buttock to the sacrum, 11.7% occurred (mean, 8.6 degrees ). In total, 66% of internal rotation occurred from the hanging-arm position to the sacrum. Above the sacrum, the contribution of elbow flexion to the level of the vertebral spine became much greater, and internal rotation of the shoulder did not change significantly above the T12 level. We recommend that the level of the thumb below the buttock be subdivided for more accurate assessment of internal rotation.     

Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis

We studied the effects of fasudil, a selective Rho-kinase inhibitor, on experimental autoimmune neuritis (EAN). Continuous parenteral administration of fasudil prevented the development of EAN induced by P0 peptide 180-199 in Lewis rats while it also reduced EAN severity when administered after disease onset. Immunohistochemical examination disclosed a marked decrease in the amount of inflammatory cell infiltration and attenuation of demyelination and axonal degeneration. Specific proliferation of lymphocytes from fasudil-treated rats in response to P0 peptide was significantly reduced as compared with those from phosphate-buffered saline (PBS)-treated rats. Fasudil treatment was associated with a significant reduction in secretion of IFN-γ; by contrast, secretion of IL-4 was almost the same in the fasudil- and PBS-treated groups. As a result, the IFN-γ/IL-4 ratio in the supernatant was significantly deceased in fasudil-treated rats compared with PBS-treated ones. Therefore, our results indicate a beneficial effect of selective blockade of Rho-kinase in animals with autoimmune inflammation of the peripheral nerves, and may provide a rationale for the selective blockade of Rho-kinase as a new therapy for Guillain-Barré syndrome.     

Correlation of cerebral spinal fluid pH and HCO3- with disease progression in ALS

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease, which is characterized by progressive degeneration of spinal and bulbar innervating motor neurons. However, the underlying mechanisms of motor neuron death remain poorly understood. Several candidate disease biomarkers have been detected in cerebrospinal fluid of ALS patients. The present study analyzed various cerebral spinal fluid gas parameters in ALS patients and compared these values to controls, as well as patients with cervical spondylosis, Parkinson syndrome, and spinocerebellar degeneration. Cerebral spinal fluid pH positively correlated with the ALS functional rating scale in total and limb-type ALS patients. In addition, cerebral spinal fluid pH positively correlated with shorter disease duration (less than 22 weeks). These results suggested that cerebral spinal fluid pH provides a biomarker for ALS and could reflect mechanisms of disease progression in ALS patients.     

Pyogenic liver abscess caused by direct invasion of esophageal squamous cell carcinoma to the liver: Report of a case

We report a case of esophageal squamous cell carcinoma (ESCC) directly invading the liver and causing a pyogenic liver abscess. The patient was a 66-year-old man who presented with dysphagia. Esophagography, endoscopic study, and computed tomography (CT) showed a mass lesion in the lower third of the esophagus. A high fever developed on hospital day 17 and another CT scan revealed a liver abscess, 50 × 45 mm, in the left lateral lobe of the liver. Although imaging demonstrated a liver abscess continuous with the tumor, we performed percutaneous transhepatic drainage, followed thereafter by distal esophagectomy and total gastrectomy with a left lateral segmental resection of the liver. The pathological findings confirmed a diagnosis of ESCC with direct invasion (T4N1M0, stage IVa in the TNM classification). The patient had an uneventful postoperative recovery. Microscopic examination of the resected specimen revealed the expansive growth of tumor cells into the hepatocellular tissues. To our knowledge, this is the first report of the direct invasion of esophageal cancer to the liver causing a pyogenic liver abscess; however, it should be borne in mind when a patient with esophageal cancer becomes febrile.     

Multiple effects of hypothermia on inflammatory response following ischemia-reperfusion injury in experimental ischemic neuropathy

Hypothermia is neuroprotective in peripheral nerve ischemia, but the mechanism(s) of neuroprotection are not well known. A major mechanism of ischemia-reperfusion (IR) injury is the inflammatory response. We therefore dissected the effects of hypothermia on inflammatory mediators in peripheral nerve ischemia of rats. Following functional and pathological evaluations for the effect of hypothermia on IR injury, we undertook immunohistochemical studies of inflammatory cells, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor kappa B (NF-kappaB) in nerve subjected to IR under defined hypothermic conditions with varying time delays (0, 1, 3, and 4 h) and depth of hypothermia (28 degrees C, 32 degrees C, and 35 degrees C). Functionally and pathologically, significant hypothermic neuroprotection was confirmed in the intraischemically treated groups but not in the postischemically treated groups. In endoneurial microvessels, intraischemic hypothermia inhibited ICAM-1 upregulation but not TNF-alpha, NF-kappaB, and IL-6 expressions. We demonstrated significantly reduced granulocyte and mononuclear phagocyte infiltration into nerve with intraischemic hypothermia but not with postischemic hypothermia. Cytokine (TNF-alpha and IL-6) positive cells were significantly decreased in both epineurium and endoneurium with intraischemic hypothermia. Excess NF-kappaB expression was seen in both Schwann cell and axon under normothermia (35 degrees C) but was inhibitable with deep hypothermia (28 degrees C). We conclude that intraischemic hypothermia significantly attenuates the inflammatory response by its effect on multiple key mediators including cytokines, ICAM-1, and NF-kappaB.