A model for antiHelicobacter pylori chemotherapy using an experimental murine infection withHelicobacter felis

Colonization ofHelicobacter felis was observed to continue for at least 24 weeks in a BALB/c mouse stomach after oral inoculation of the bacteria. Bacteria were observed on the surface of the gastric mucosa and in the gastric pits as is typically seen withHelicobacter pylori infection in the human stomach.H. felis-colonized mice were treated for 5 consecutive days with various chemotherapeutic regimens used againstH. pylori for humans. The status ofH. felis infection was then assessed by the urease test 2 weeks after the final treatment. The clearance rates were 100% for a triple combination of amoxicillin (15 mg/kg), metronidazole (10 mg/kg) and bismuth subnitrate (5 mg/kg), 71% for amoxicillin alone (15 mg/kg), 80% for metronidazole alone (15 mg/kg), and 0% for bismuth subnitrate (60 mg/kg) or omeprazole (60 mg/kg) alone. Bacterial recurrence occurred more often in mice treated with amoxicillin alone than with the triple regimen during the 24-week posttreatment period. These results were very similar to the efficacy of each regimen obtained in clinical trials. Thus, this mouse model usingH. felis may be useful for evaluating drugs or regimens for the treatment of humanH. pylori infections.     

Atherosclerosis is accelerated in patients with long-term well-controlled systemic lupus erythematosus (SLE)

BACKGROUND: It is uncertain whether atherosclerosis is accelerated in premenopausal and postmenopausal patients with long-term well-controlled systemic lupus erythematosus (SLE). METHODS: We measured the intima-media thickness (IMT) of the carotid arteries and the cardio-ankle vascular index (CAVI) in 39 women with SLE and in age- and sex-matched controls. RESULTS: In the premenopausal state, carotid plaque was detected only in SLE patients (36%). In the postmenopausal state, the maximum IMT was about 2-fold greater in SLE patients than in control subjects (1.3+/-0.7 vs. 0.7+/-0.2 mm, p<0.001). CAVI was higher in both the premenopausal and postmenopausal SLE patients. The serum amyloid A protein (SAA) was higher in SLE patients in the premenopausal state (p=0.025), while remnant like particle-cholesterol (RLP-C), the homeostasis model assessment of insulin resistance (HOMA-IR), and SAA were significantly increased in postmenopausal SLE patients (p=0.001, p<0.001 and p<0.05, respectively). Multiple regression analysis revealed that the maximum IMT was associated with cumulative PSL dosage (p=0.027) and SAA (p=0.074) in the premenopausal SLE patients, and with HOMA-IR (p<0.001) in the postmenopausal SLE patients. CONCLUSION: Atherosclerosis is accelerated in long-term well-controlled SLE. More attention should be given to subclinical inflammation and insulin resistance in the management of SLE patients.     

Issues in cancer pain management

In this article, three aspects of recent issues in cancer pain management such as pain assessment, drowsiness with morphine, and problem in home care setting. First, the assessment of 'impact of pain' is to assess whether the treatment is sufficient for the patient. On the other hand, assessment of 'pain intensity' is the effectiveness of the treatment. Therefore, to reduce the gap in pain evaluations between cancer patients and medical stuffs by assessing the 'impact of pain' in addition to 'intensity of pain'. Second, increasing dosage of morphine often reduces pain, at the same time patients become drowsy. This is often observed soon after starting morphine administration, especially, patients who have renal dysfunction. An active morphine metabolite morphine-6-Glucuronide is excreted into urine, so that, renal dysfunction causes drowsiness. Third, at home care setting, patients tend to be into poor pain control condition. It is necessary that paying attention on patient's knowledge of medications and having support program for pain management for home care setting.     

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: report of five cases.

To minimize the adverse effects of high-dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO-ANCA-associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 +/- 0.15 mg/kg/day (mean +/- SD) (range 0.18-0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 +/- 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low-dose or intermediate-dose PSL regimen, is effective in the treatment of ANCA-associated vasculitis.     

Intraperitoneal seeding of ruptured hepatocellular carcinoma: case report

We report a solitary intraperitoneal recurrence in a long-term survivor after rupture of hepatocellular carcinoma. Ultrasonography demonstrated the finding of a lobulated mass with a "mosaic" appearance. The patient underwent resection of this implant and is currently disease free. We emphasize the importance of periodic surveillance of disseminated metastases of this condition.     

Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice

Several lines of evidence show the importance of angiotensin II (AII) in renal injuries, especially when hemodynamic abnormalities are involved. To elucidate the role of AII in immune-mediated renal injury, we studied anti-glomerular basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice. A transient activation of the renin-angiotensin system (RAS) was observed in both groups of mice at around day 1. A renal expression of monocyte chemoattractant protein-1 (MCP-1) was transiently induced at six hours in both groups, which was then downregulated at day 1. In the AT1a+/+ mice, after RAS activation, the glomerular expression of MCP-1 was exacerbated at days 7 and 14. Thereafter, severe proteinuria developed, and the renal expressions of transforming growth factor-beta1 (TGF-beta1) and collagen type I increased, resulting in severe glomerulosclerosis and interstitial fibrosis. In contrast, glomerular expression of MCP-1, proteinuria, and tissue damage were markedly ameliorated in the AT1a-/- mice. Because this amelioration is likely due to the lack of AT1a, we can conclude that AII action, mediated by AT1a, plays a pathogenic role in anti-GBM nephritis, in which AII may contribute to the exacerbation of glomerular MCP-1 expression. These results suggest the involvement of AII in immune-mediated renal injuries.     

Pacinian Corpuscles in the Human Fetal Finger and Thumb: A Study Using 3D Reconstruction and Immunohistochemistry

The detailed distribution of Pacinian corpuscles was evaluated by viewing the transverse sections of all fingers and thumbs, including the interdigital areas, from eight hands of five fetuses of gestational age 28–33 weeks (crown‐rump length 230–290 mm). Among the 40 fingers and thumbs, serial sections were prepared for 3D reconstructions of nerve elements in the distal and middle phalangeal segments of three fifth fingers; in these three fingers, the distal segment contained 45–75 Pacinian corpuscles. These Pacinian corpuscles were 0.2–1.0 mm in length and 0.05–0.3 mm in thickness, oriented along the proximodistal axis and arranged along the palmar digital nerve branches. Other than beneath the digital skin, small corpuscles (<0.1 mm in thickness) were observed within the tendon sheath of the flexors in the middle or distal segment of five fetuses and in the nail beds of four fetuses. Clusters of 5–20 corpuscles formed bouquet‐ or tree‐like arrangements along neurovascular bundles in the fingers, thumbs and interdigital areas. Because the space beneath the skin was thick and loose in the interdigital area, trees in the interdigital area were up to 2 mm long. Regardless of site, the central core of each corpuscle was positive for S100 protein, while the core and parts of the capillaries in the corpuscle were weakly positive for nestin. Because corpuscles in the tendon sheath and nail bed, as well as bouquet‐ and tree‐like arrangements of corpuscles, have not been reported in adults, these morphologies are likely specific to fetuses. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:154–165, 2018. © 2017 Wiley Periodicals, Inc.     

The current status of gynecological laparoscopic surgery in educational facilities in Japan

A questionnaire survey was administered by Tohoku University hospital to investigate the current status of gynecological laparoscopic operations in teaching hospitals in which residents were trained as obstetricians and gynecologists. Thirty-eight senior doctors in 18 hospitals were sent a postal questionnaire. The response rates of facilities and doctors were 94.4% and 76.3% respectively. Diagnostic and operative laparoscopy was performed in all of the hospitals surveyed, however only a few hospitals performed more than 100 laparoscopies per year, and many surgeons did not perform advanced laparoscopic operations including hysterectomy, myomectomy and lymphadenectomy. Half of the doctors performed minilaparotomy, which is a so-called "open" technique. The standard surgical style involved the use of a carbon dioxide (CO2) pneumoperitoneum and an endoscope 10 mm in diameter. Unipolar endocoagulating instruments were generally used for hemostasis and incision. Most of the doctors surveyed thought that operative laparoscopy would become a necessary procedure in gynecological field, and half of them hoped to receive training in the technique. Instruction of expert endoscopic surgeons is necessary, especially in teaching hospitals, for the spread of safe and advanced laparoscopic surgery. An educational and training system for established surgeons as well as for young residents is urgently needed in Japan.     

Pyridoxalated haemoglobin polyoxyethylene conjugate,a nitric oxide scavenger,decreases dose-limiting hypotension associated with interleukin-2 (IL-2) therapy

Interleukin-2 (IL-2), a cytokine that induces natural killer cells termed lymphokine-activated killer (LAK) cells, is in use as an anticancer agent. During IL-2 therapy, adverse effects, such as vasodilatation and hypotension, are common. Previous studies suggest that these effects are due to nitric oxide (NO). Therefore a model of IL-2-induced hyperdynamic response in sheep was developed to test the effect of pyridoxalated haemoglobin polyoxyethylene conjugate (PHP; a NO scavenger), which is currently in clinical development for the treatment of shock associated with systemic inflammatory response syndrome. Twelve female sheep were divided into four groups (n =3 per group): sham control (Ringer's lactate solution), PHP alone (20 mg x kg(-1) x h(-1) for 96 h), IL-2 alone (recombinant human IL-2; 1,440,000 units/kg intravenously every 8 h) and a combination of PHP and IL-2. All of the sheep received Ringer's lactate solution to maintain haematocrit at baseline levels. The sheep had free access to food and water. A fall in the mean arterial pressure and systemic vascular resistance index by 20% was observed in the IL-2 group, but not in the PHP+IL-2 group. The fluid requirement to maintain the haematocrit was higher in the IL-2 group (5 ml x kg(-1) x h(-1)) than in the PHP+IL-2 group (4 ml x kg(-1) x h(-1)). The sham group showed no changes in any of the parameters. Scavenging NO by PHP prevented the hyperdynamic reaction induced by IL-2 administration in sheep. This activity of PHP may prevent the early discontinuation of IL-2 therapy that results because of these adverse events.