Depolarization thresholds for hippocampal damage, ischemic preconditioning, and changes in gene expression after global ischemia in the rat

Induced ischemic tolerance in rat hippocampus was investigated in a forebrain ischemia model of repeated 4-vessel occlusion (4-VO). Ischemic insult variability was reduced by the use of dc potential measurements to determine the duration of ischemic depolarization in hippocampus. The results demonstrate a depolarization threshold for ischemic injury to CA1 neurons of 4-6 min and a window for optimal preconditioning of 2.5-3.5 min. Levels of induced mRNAs encoding hsp72 and several immediate-early genes were also shown to vary with depolarization interval. Immediate-early genes were maximally induced after depolarization periods inducing optimal preconditioning, while hsp72 expression increased with insult severity over the range leading to neuron loss. These results are similar to those obtained in gerbil studies indicating that preconditioning does not require large increases in hsp72 expression, and demonstrate the fundamental comparability of rodent global ischemia models when monitored by this approach.     

"True" posterior communicating artery aneurysm presenting the abducens nerve palsy

Most of "so-called" posterior communicating artery aneurysms previously reported, originated from the internal carotid-posterior communicating junction. Aneurysms arising from the posterior communicating artery itself are very rare. The abducens nerve palsy caused by cerebral aneurysm is also very rare. We are reporting a case with the saccular aneurysm arising directly from the distal half of the posterior communicating artery presenting the abducens nerve palsy. This 73-year-old woman who had no treatment with hypertension for several years was admitted for sudden onset of severe headache, vomitting and unconsciousness on March 1, 1984. She opened her eyes when addressed and had disorientation, urinary incontinence, right-hemiparesis and left-abducens nerve palsy. A 4-vessel angiography revealed the saccular aneurysm originating directly from the distal half of the posterior communicating artery. The patient underwent left-frontotemporal craniotomy on the 27th day after subarachnoid hemorrhage under Hunt & Kosnic Grade 3. The aneurysm originated directly from the distal half of the posterior communicating artery and directed inferior-posterior-laterally below the oculomotor nerve. The neck was successfully clipped. Immediate post-operative course was uneventful until the 7th day after surgery. On the 8th day she had hypertensive intraventricular hemorrhage and expired. The autopsy could not be obtained. The saccular "true" posterior communicating artery aneurysm with isolated unilateral abducens nerve palsy as seen in our case has not been reported. Considering the operative findings, we thought the aneurysmal dome contacted directly with the abducens nerve.     

Treatment of advanced bladder cancer with intra-arterial infusion of cisplatinum (CDDP) and aclacinomycin (ACR), combined with angiotensin II

Ten patients with advanced bladder cancer were treated with intra-arterial infusion therapy. The patients consisted of nine males and one female between 55 and 82 years old (median: 70 years). In all patients, cisplatinum (CDDP) (2 mg/kg), aclacinomycin (ACR) (0.5 mg/kg) and Angiotensin II (25 mg) were infused via the internal iliac artery for a period of about 30 minutes. Seven patients also received X-ray therapy with a linac. The efficacy of this therapy was assessed by computed tomographic scanning, sonography and cystoscopy. As a result of this assessment, 2 patients were rated complete response "(CR)", 6 partial response (PR) (showing 50% or more reduction in the lesion) and 2 no change "(NC)". To compare the efficacy of this therapy for two histopathologically defined groups of patients (patients with grades 2 and 3 cancer), one patient was rated "CR", four "PR" and two "NC" in the grade 3 group (total 7 patients), while one was rated "CR" and two "PR", in the grade 2 group (total 3 patients). In effective cases, pollakiuria and miction pain disappeared shortly following intra-arterial infusion therapy. As for side effects of the therapy, mild nausea or vomiting was observed in all patients, while leukopenia was noted in one patient.     

Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

     

Predictive factors of recurrence in adenocarcinoma of the esophagogastric junction in the multimodal era

IntroductionAdenocarcinoma of the esophagogastric junction (AEGJ) represents a poor prognostic tumor. We evaluated the recurrence pattern and risk factors associated with recurrence in patients undergoing surgical resection by AEJG.MethodsRecurrences were categorized as locoregional, peritoneal, or distant. These three recurrence groups and a non-recurrence group were compared, and overall survival (OS) and disease-free survival (DFS) for each one was obtained.ResultsWe analyzed 188 patients with curative surgical treatment. Recurrence was observed in 72 (38.3%) patients. Locoregional recurrence was observed in 17 (23.6%); 20 (27.8%) peritoneal recurrence and 35 (48.6%) distant metastasis. DFS was 9, 5, and 8 months, and OS was 21.8, 13.2, and 20.8, respectively. Tumors larger than 5 cm are risk factors for peritoneal recurrence (OR:2.88, p = 0.012). Positive lymph nodes were related to distant metastasis (OR:9.15, p = 0.040), and lymphatic invasion for locoregional recurrence (OR:3.81, p = 0.028).ConclusionAEGJ is associated with high rates of early recurrence.     

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence.MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA).Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower.ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.     

Combined treatment with vitamin k2 and bisphosphonate in postmenopausal women with osteoporosis

Vitamin K2, as well as bisphosphonates, such as etidronate, alendronate, and risedronate, is widely used in the treatment with osteoporosis in Japan. Etidronate increases the lumbar bone mineral density (BMD), and prevents new vertebral fractures, in patients with osteoporosis, while alendronate and risedronate increase the lumbar and femoral neck BMDs, and prevent new vertebral and femoral neck fractures. Vitamin K2 enhances gamma-carboxylation of bone glutamic acid residues and the secretion of osteocalcin, sustains the lumbar BMD, and prevents osteoporotic fractures in patients with osteoporosis. Bisphosphonates, such as alendronate and risedronate, rather than vitamin K2, should be initially chosen for the treatment of osteoporosis, because they are more efficacious than vitamin K2. Available evidence suggest that risedronate prevents deterioration of the connectivity of the trabeculae in ovariectomized rats, whereas vitamin K2 increase the trabecular thickness, and that a combination of risedronate and vitamin K2 has a synergistic effect on preventing the deterioration of trabecular bone architecture induced by estrogen deficiency. Some studies have shown that combined treatment with etidronate and vitamin K2 appears to be more effective than etidronate alone in the prevention of new osteoporotic vertebral fractures. Based on these findings, combined treatment with vitamin K2 and bisphosphonates may be more efficacious in the prevention new vertebral fractures than a single treatment with bisphosphonate in postmenopausal women with osteoporosis. Thus, this combined treatment should be recommended for the treatment of postmenopausal osteoporosis. It is proposed that the role of vitamin K2 should be emphasized, when used in combination with bisphosphonates, especially in patients with vitamin K deficiency.     

Acoustic evaluation of postoperative hoarseness in adult patients

The present study was performed to evaluate postoperative hoarseness quantitatively by means of acoustic wave form analysis. Pitch and amplitude perturbation (PPQ, and APQ), and normalized noise energy (NNE) were measured along with the frequency characteristics in 51 adult patients undergoing elective surgery. The normal values for these acoustic parameters were less than 0.5%, less than 2.0%, and less than -10 dB, respectively. Vowel sound "E" was recorded and evaluated before the induction of anesthesia and on the morning of the day after the surgery. PPQ increased from 0.39% to 1.00% (P less than 0.05), APQ increased from 3.34% to 6.62% (P less than 0.05), and NNE increased from -9.19 dB to -4.74 dB (P less than 0.05). Eighteen percent of the patients showed abnormal values in all parameters preoperatively, but 45% of the patients postoperatively (P less than 0.05). These findings suggest that even the short term intubation resulted in the postoperative hoarseness, and this method is a useful and non-invasive bed-side test to evaluate postoperative hoarseness quantitatively.     

Experimental and clinical evaluation of the splenic capping method in the treatment of injured spleens

Polyglycolic acid elastic mesh was tailored and wrapped around the entire surface of experimentally injured spleens in 11 dogs, while carefully avoiding the splenic hilum, like a "hair-net", to achieve complete hemostasis by compression. All 11 dogs survived the experiment with no postoperative bleeding observed. Histological examination, performed 6 weeks postoperatively, revealed histiocytes, fibroblastic proliferation with collagen and cellular collagenized fibrous tissue forming a neocapsule covering the spleen. Hematologically, the platelet count was increased at 2 weeks postoperatively, but subsequently decreased to within the normal levels by 4 weeks. We employed this splenic capping method clinically in four cases to avoid splenectomy and sufficient hemostasis with ultimate splenic recovery was achieved in each case without any abscess formation, postoperative bleeding, or complications related to the use of the mesh. These experimental and clinical results thus indicate the efficacy and safety of the splenic capping method for preserving the injured spleen.     

Assessment of high-energy phosphorus compounds in the rat kidney by in situ31P nuclear magnetic resonance spectroscopy: effect of ischemia and furosemide

Summary ³¹P nuclear magnetic resonance (NMR) spectroscopy of the in situ rat kidney was performed by a surface coil method, and the effects of ischemia and furosemide infusion were assessed.³¹P NMR spectra of the kidney subjected to 30 min of ischemia returned completely to the pre-ischemic level after 60 min of reperfusion. But the³¹P NMR spectra after 60 min of ischemia did not recover, even after 120 min of reperfusion. Levels of -ATP and inorganic phosphate (Pi) decreased and the chemical shift of Pi increased after intravenous infusion of furosemide. This increase in chemical shift might signal an alkalotic change in intracellular pH. Furosemide infusion prior to ischemia is thought to protect the kidney from injury induced by 60 min of warm ischemia. The chemical shift of Pi returned to the pre-ischemic level earlier than -ATP and Pi. In conclusion, according to the findings of³¹P NMR spectroscopy, furosemide infusion prior to ischemia may be effective in protecting the kidney against ischemic injury. But the change in Pi peak and the causes of the dissociation of Pi and -ATP should be examined further.